ALBERT

Description: Article The life cycle of parasitic hookworms includes a developmental stage in the lungs, before reaching the gut where they mature into adults. Here Bouchery et al. show that Group 2 innate lymphoid cells (ILC2s) cooperate with CD4 + T cells to inhibit the development of a model hookworm in the lungs of mice. Nature Communications doi: 10.1038/ncomms7970 Authors: Tiffany Bouchery, Ryan Kyle, Mali Camberis, Amy Shepherd, Kara Filbey, Alexander Smith, Marina Harvie, Gavin Painter, Karen Johnston, Peter Ferguson, Rohit Jain, Ben Roediger, Brett Delahunt, Wolfgang Weninger, Elizabeth Forbes-Blom, Graham Le Gros

Description: This paper presents an experiment measuring how lab-induced group identity affects trust and trustworthiness in a repeated trust game with random matching. Identity had positive in-group and negative out-group effects on trust. However, the in-group effect was small and statistically insignificant, while the out-group effect was large. Trustworthiness was determined mainly by reciprocity effects.

Description: Author(s): Alexander Smith and Robert B. Mann We consider the behavior of bipartite and tripartite nonlocality between fermionic entangled states shared by observers, one of whom uniformly accelerates. We find that while fermionic entanglement persists for arbitrarily large acceleration, the Bell–Clauser-Horne-Shimony-Holt inequalities cannot b... [Phys. Rev. A 86, 012306] Published Fri Jul 06, 2012

Description: Introduction Most cases of acquired idiopathic severe aplastic anemia (SAA) are immune mediated. Following an insult which is likely to be viral, there is an increase in auto-reactive oligoclonal T-cells that result in apoptotic death of stem and progenitor cells, due to lack or absence of regulatory T-cells (Tregs) and a pro-inflammatory environment with clonal expansion of Th1 cells and increased Th17 cells. We have previously shown a correlation between low Treg numbers and disease severity, and that Tregs are not only reduced in number but are also unable to effectively suppress T effectors (Teff)1. The only curative treatment option for SAA is hematopoietic stem cell transplantation (HSCT) but this option is not accessible to everyone because of lack of donor or unfitness for the procedure. Moreover, patients who fail standard immunosuppressive treatment (ATG and Cyclosporine A) have limited alternative therapeutic options. The aim of this study was to investigate the expandability of Tregs in AA, their subsequent function and stability following expansion. Such data may provide the rationale for a novel future approach to treatment of refractory SAA. Methods and results IL-2 sensitivity assay One of the hallmarks of response to IL-2 by Tregs is STAT5 phosphorylation. To evaluate AA Tregs response to IL-2, freshly isolated cells from 6 AA patients were cultured in the presence of IL-2 (ranging from 0.1 to 1000 IU/ml). STAT5 phosphorylation was assessed by intracellular staining for pSTAT5 after 15 and 30 minutes. Tregs from AA patients have shown an increase in STAT5 phosphorylation similar to 2 healthy donors (HD) Tregs, confirming their responsiveness to IL-2. Tregs expansion Peripheral blood mononuclear cells (PBMCs) were obtained from six AA patients and eight HDs and enriched for Tregs using a magnetic beads regulatory T cells isolation kit according to the manufacturer instructions. Tregs were then stimulated with anti CD3/CD28 beads (1:1 ratio) and high dose IL-2 (1,000 IU/ml) for four weeks in a "Treg friendly" culture with all-trans retinoic acid 2 mM and rapamycin 100 nM. After four weeks of culture, expanded Tregs were then 'rested' for 5 days with decreasing doses of IL-2. Tregs from AA patients were expanded in a comparable rate to HD Tregs, with a median fold increase of 33 (range 29-149) compared to 21 fold increase (range 8-36) in HD. There was no significant difference between AA and HDs in terms of fold increase after 4 weeks. The expanded Tregs demonstrated more than 90% FoxP3+ expression in both AA and HDs. To assess IL-2 dependency of the expanded Tregs, Tregs were gradually deprived of IL-2 following expansion and STAT5 phosphorylation evaluated in both AA and HDs Tregs. Although expanded AA Tregs showed slightly lower pSTAT5 level following IL-2 deprivation, they responded to low dose IL-2 and pSTAT5 returned to similar level as in HDs. Expanded Tregs function and methylation status of TSDR To assess the suppressive activity of expanded Tregs, Teff were stained with a fluorescent proliferation dye (CellTrace Violet, Life Technologies) and co-cultured with autologous expanded Tregs (1:1 ratio) for 5 days in the presence of anti CD3/CD28 beads (Teff:Treg:beads = 20:20:1). The expanded Tregs from AA patients suppressed the proliferation of both autologous and allogeneic CD4+ T effectors (43% versus 5%, respectively, p = 0.009) and the suppressive function of expanded AA Tregs was not significantly different from expanded HD Tregs. In order to assess the stability of our Tregs we investigated the methylation status of 15 CpG sites within the Foxp3 Treg-specific demethylated region (TSDR) by amplicon sequencing of bisulfite treated DNA on an Illumina MiSeq instrument. The TSDR CpG sites in expanded Tregs from HDs and AA patients were found to be 〉98% unmethylated (no significant difference between AA and HD), which confirms the stability of expanded Tregs. Conclusions Our data show that Tregs from AA patients can be expanded efficiently ex vivo. Importantly, expanded Tregs are functional and stable with similar phenotypic characteristics to HD Tregs. These results may lead to the development of a novel treatment option for patients who fail/relapse after standard immunosuppression and for those who are not eligible for HSCT. References 1. Kordasti, S., et al. Functional characterization of CD4+ T cells in aplastic anemia. Blood119, 2033-2043 (2012). Disclosures Mufti: Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Description: After the dissolution of the Austro-Hungarian Monarchy, Austria transformed itself from an empire to a small Central European country. Formerly an important player in international affairs, the new republic was quickly sidelined by the European concert of powers. Austria's post-Habsburg state suffered from enormous losses of territory and population. However, these losses did not hamper the country's innovative spirit. The essays in this twentieth anniversary volume of Contemporary Austrian Studies argue that Austria found its place in the global arena of the twentieth century, making its mark on both Europe and the world. From Freudian psychoanalysis to Auto-Marxist thought and the Austrian School of Economics, Austrian ideas continued to be vital to the intellectual community at large. Vienna remained the Austrian capital and reasserted its strong position in Central European and international business and finance. This volume also examines how increasing globalization in the 20th century impacted Austrian demography, society, and political life. Specifically, the essays discuss how Austria's place in the contemporary world became increasingly determined by the European integration process.

Description: In his day, Raphael Cilento was one of the most prominent and controversial figures in Australian medicine. As a senior medical officer in the Commonwealth and Queensland governments, he was an active participant in public health reform during the inter-war years and is best known for his vocal engagement with public discourse on the relationship between hygiene, race and Australian nationhood. Yet Cilento’s work on tropical hygiene and social welfare ranged beyond Australia, especially when he served as a colonial medical officer in British Malaya and in the Mandated Territory of New Guinea. He also worked with the League of Nations Health Organization in the Pacific Islands and oversaw international social welfare programs for the United Nations. On one level, this professional mobility allowed ideas and practices of public health and government to circulate between colonial spaces of northern Australia, the Pacific Islands and Asia. On another, it meant that Cilento’s Pacific colonialism and colonial experience shaped his understanding of Australian national health and welfare. Rather than attempt a comprehensive biography of Cilento, this book instead uses this border-crossing career as a means to explore several material and discursive facets of Australia’s relationships to the Pacific and the world.