Long Term Protection after Immunization with P. berghei Sporozoites Correlates with Sustained IFNγ Responses of Hepatic CD8+ Memory T Cells

Protection against P. berghei malaria can successfully be induced in mice by immunization with both radiation attenuated sporozoites (RAS) arresting early during liver stage development, or sporozoites combined with chloroquine chemoprophylaxis (CPS), resulting in complete intra-hepatic parasite development before killing of blood-stages by chloroquine takes place. We assessed the longevity of protective cellular immune responses by RAS and CPS P. berghei immunization of C57BL/6j mice. Strong effector and memory (TEM) CD8+ T cell responses were induced predominantly in the liver of both RAS and CPS immunized mice while CD4+ T cells with memory phenotype remained at base line levels. Compared to unprotected naïve mice, we found high sporozoite-specific IFNγ ex vivo responses that associated with induced levels of in vivo CD8+ TEM cells in the liver but not spleen. Long term evaluation over a period of 9 months showed a decline of malaria-specific IFNγ responses in RAS and CPS mice that significantly correlated with loss of protection (r2 = 0.60, p<0.0001). The reducing IFNγ response by hepatic memory CD8+ T cells could be boosted by re-exposure to wild-type sporozoites. Our data show that sustainable protection against malaria associates with distinct intra-hepatic immune responses characterized by strong IFNγ producing CD8+ memory T cells

Immune mechanisms in malaria: new insights in vaccine development.

Early data emerging from the first phase 3 trial of a malaria vaccine are raising hopes that a licensed vaccine will soon be available for use in endemic countries, but given the relatively low efficacy of the vaccine, this needs to be seen as a major step forward on the road to a malaria vaccine rather than as arrival at the final destination. The focus for vaccine developers now moves to the next generation of malaria vaccines, but it is not yet clear what characteristics these new vaccines should have or how they can be evaluated. Here we briefly review the epidemiological and immunological requirements for malaria vaccines and the recent history of malaria vaccine development and then put forward a manifesto for future research in this area. We argue that rational design of more effective malaria vaccines will be accelerated by a better understanding of the immune effector mechanisms involved in parasite regulation, control and elimination

Non-affirmative Theory of Education as a Foundation for Curriculum Studies, Didaktik and Educational Leadership

This chapter presents non-affirmative theory of education as the foundation for a new research program in education, allowing us to bridge educational leadership, curriculum studies and Didaktik. We demonstrate the strengths of this framework by analyzing literature from educational leadership and curriculum theory/didaktik. In contrast to both socialization-oriented explanations locating curriculum and leadership within existing society, and transformation-oriented models viewing education as revolutionary or super-ordinate to society, non-affirmative theory explains the relation between education and politics, economy and culture, respectively, as non-hierarchical. Here critical deliberation and discursive practices mediate between politics, culture, economy and education, driven by individual agency in historically developed cultural and societal institutions. While transformative and socialization models typically result in instrumental notions of leadership and teaching, non-affirmative education theory, previously developed within German and Nordic education, instead views leadership and teaching as relational and hermeneutic, drawing on ontological core concepts of modern education: recognition; summoning to self-activity and Bildsamkeit. Understanding educational leadership, school development and teaching then requires a comparative multi-level approach informed by discursive institutionalism and organization theory, in addition to theorizing leadership and teaching as cultural-historical and critical-hermeneutic activity. Globalisation and contemporary challenges to deliberative democracy also call for rethinking modern nation-state based theorizing of education in a cosmopolitan light. Non-affirmative education theory allows us to understand and promote recognition based democratic citizenship (political, economical and cultural) that respects cultural, ethical and epistemological variations in a globopolitan era. We hope an American-European-Asian comparative dialogue is enhanced by theorizing education with a non-affirmative approach

Assessment of the Mount Polley Mine site for potential passive or semi-passive treatment options

Passive water treatment is often sought as a component of long-term mine closure management. Passive water treatment promotes relatively self-sustaining conditions for the management of mine impacted water, with outcomes often being low maintenance and operational costs. However, owing to the sensitive biogeochemical nature of these technologies, a site-specific phased approach is necessary for evaluating passive treatment as a component of mine closure management, and ultimately, its successful implementation. The Mount Polley Mine (the “Mine”) was evaluated for the viability of constructed wetland treatment systems (CWTSs) as part of their long-term water management plan. A site assessment was conducted, which identified potential plant species for use in a CWTS, and evaluated the water, substrates, and plants in the context of a CWTS. Genetic microbial community profiling was used to assess natural wetlands, and components of the water management infrastructure at the Mine, and was paired with traditional growth-based microbial characterization and quantification. This information was evaluated in the context of water chemistry, treatment objectives, and biogeochemical processes to assess the feasibility for semi-passively or passively treating Mine water. Upon assessment of the natural treatment capacity at the Mine, natural conditions and processes were identified that could potentially benefit water quality.Non UBCUnreviewedOthe

Real-Time Volumetric Phase Monitoring: Advancing Chemical Analysis by Countercurrent Separation

Countercurrent separation (CCS) utilizes the differential partitioning behavior of analytes between two immiscible liquid phases. We introduce the first platform (“CherryOne”) capable of real-time monitoring, metering, and control of the dynamic liquid–liquid CCS process. Automated phase monitoring and volumetrics are made possible with an array of sensors, including the new permittivity-based phase metering apparatus (PMA). Volumetric data for each liquid phase are converted into a dynamic real-time display of stationary phase retention (Sf) and eluent partition coefficients (<i>K</i>), which represent critical parameters of CCS reproducibility. When coupled with the elution–extrusion operational mode (EECCC), automated Sf and <i>K</i> determination empowers untargeted and targeted applications ranging from metabolomic analysis to preparative purifications

Phylogenetic relationships of the heath dragons (Rankinia adelaidensis and R. parviceps) from the south-western Australian biodiversity hotspot

Although the south-western Australian region is recognised as a global biodiversity hotspot, there are still significant gaps in our understanding of the biodiversity of this region. We present a phylogenetic study of the heath dragons (Rankinia adelaidensis and R. parviceps) from this region, incorporating a 1612-bp section of mtDNA and two nuclear introns, Gapdh (~244 bp) and Enol (~330 bp). In addition, we present a generic-level analysis of three gene regions (mtDNA, Gapdh, BDNF), which provides clear evidence that Rankinia adelaidensis and R. parviceps are not closely related to Rankinia diemensis from eastern Australia. Instead, the heath dragons are strongly supported as forming a clade with the genus Ctenophorus. In addition, we find that there are significant levels of haplotype divergence between currently recognised subspecies of the heath dragons (R. a. adelaidensis, R. a. chapmani, R. p. parviceps, R. p. butleri). We suggest that the genetic divergences between subspecies result from geographic isolation in allopatry owing to habitat preferences, followed by drift and/or selection. On the basis of these deep divergences and consistent morphological differences between subspecies, we recommend elevating all taxa to full species, and provide a taxonomic revision of the genera Rankinia and Ctenophorus