Langerhans Cells Prime IL-17-Producing T Cells and Dampen Genital Cytotoxic Responses following Mucosal Immunization

Langerhans cells (LCs) are dendritic cells (DCs) localized in stratified epithelia, such as those overlaying skin, buccal mucosa, and vagina. The contribution of LCs to the promotion or control of immunity initiated at epithelial sites remains debated. We report in this paper that an immunogen comprising OVA linked to the B subunit of cholera toxin, used as delivery vector, was efficient to generate CTLs after vaginal immunization. Using Lang-EGFP mice, we evaluated the contribution of distinct DC subsets to the generation of CD4 and CD8 T cell responses. We demonstrate that the vaginal epithelium, unlike the skin epidermis, includes a minor population of LCs and a major subset of langerin(-) DCs. Intravaginally administered Ag is taken up by LCs and langerin(-) DCs and carried up to draining lymph nodes, where both subsets prime CD8 T cells, unlike blood-derived DCs, although with distinct capabilities. LCs prime CD8 T cells with a cytokine profile dominated by IL-17, whereas Lang(-) DCs induce IFN-gamma-producing T cells. Using Lang-DTR-EGFP mice to ensure a transient ablation of LCs, we found that these cells not only are dispensable for the generation of genital CTL responses but also downregulate these responses, by a mechanism that may involve IL-10 and IL-17 cytokines. This finding has implications for the development of mucosal vaccines and immunotherapeutic strategies designed for the targeting of DCs.

Performance, représentation et (il)lisibilité du genre dans la fiction sandienne des années 1830

Dans son premier roman, Indiana (1832), Sand établit un réseau de correspondances entre la langue, la performance et l'identité sexuelle qui n'ont pas encore fait l'objet d'une étude approfondie. Or, ces correspondances sous-tendent d'autres romans des années 1830, notamment Lélia (1833), Le Secrétaire intime (1834) et Gabriel (1839). Deux concepts – la performance et la lisibilité – fondent en fait les réflexions de Sand sur la représentation et le genre. Il s'agit dans cet article d'étudier ce réseau d'associations et d'explorer son évolution dans la fiction sandienne des années 1830. Cette analyse permettra de souligner comment, chez Sand, la performativité du genre met en question et trouble la représentation mimétique.

Research priorities of adult intensive care nurses in 20 European countries: a Delphi study.

Aims: This paper is a report of a three round Delphi study of intensive care nursing research priorities in Europe (October 2006–April 2009).

Background: Internationally, priorities for research in intensive care nursing have received some attention focusing on healthcare interventions and patient needs. Studies as early as the 1980s identified priorities in the United States, United Kingdom, Hong Kong and Australia. Research priorities of intensive care nurses across the European Union are unknown.

Methods: The participants, invited in 2006, included 110 intensive care nurses, managers, educators and researchers from 20 European Critical Care Nursing Associations. Delphi round one was an emailed questionnaire inviting participants to list important areas for research. The list was content analysed and developed into an online questionnaire for rounds two and three. In round two, participants ranked the topics on a scale of 1–6 (not important to extremely important). Mean scores of round two were added to the questionnaire of round three and participants ranked the topics again.

Results: There were 52 research topics in 12 domains. There was a dominance of priorities in five main areas: patient safety; impact of evidence based practice on outcomes; impact of workforce on outcomes; well being of patients and relatives; and impact of end-of-life care on staff and practice.

Conclusions: The results reflect worldwide healthcare concerns and objectives and highlight topics that nurses view as fundamental to the care of critically ill patients. These topics provide a platform for future research efforts to improve clinical practice and care of patients in intensive care.

Mutational hotspot in Exon 20 of PIK3CA in breast cancer among Singapore Chinese

The recent identification of somatic mutations in the catalytic region of PIK3 (PIK3CA) in breast cancer and demonstration of their oncogenic function has implicated PIK3CA in mammary carcinogenesis. To investigate possible ethnic differences in patterns of PIK3CA mutations in Singaporean Chinese breast cancer and to characterize these in a panel of cell lines, we sequenced exons 9 and 20 in 80 primary tumors, 19 breast cancer cell lines and 7 normal human mammary epithelial cells (HMECs). Searching for novel hotspots of mutation, we sequenced additional exons ( 1, 2, 6, 7, 14 and 18) in 20 primary tumors and 6 breast cancer cell lines. We detected 33 point mutations in 31 of 80 (39%) breast cancers, and 11 mutations in 10 of 19 (53%) breast cancer cell lines. No mutations were detected in normal breast tissue adjacent to the tumor, or in the 6 normal HMECs. The exon 20 A3140G (H1047R) substitution was identified most frequently (22/31, 71%) and showed a significant association with patient age ( p = 0.043) and stage of the disease ( p = 0.025), but not with ER/PR status or histological grade of the tumor. The incidence of point mutations in PIK3CA, the A3140G substitution in particular, in Singapore breast cancers are among the most frequent reported to date for any gene in breast cancer. The results suggest that mutation of PIK3CA might contribute to development of early stage breast cancer and could provide a potent target for early diagnosis and therapy.

Peptide IC-20, encoded by skin kininogen-1 of the European yellow-bellied toad, Bombina variegata, antagonizes bradykinin-induced arterial smooth muscle relaxation

The objectives were to determine if the skin secretion of the European yellow-bellied toad (Bombina variegata), in common with other related species, contains a bradykinin inhibitor peptide and to isolate and structurally characterize this peptide. Materials and Methods: Lyophilized skin secretion obtained from this toad was subjected to reverse phase HPLC fractionation with subsequent bioassay of fractions for antagonism of the bradykinin activity using an isolated rat tail artery smooth muscle preparation. Subsequently, the primary structure of the peptide was established by a combination of microsequencing, mass spectroscopy, and molecular cloning, following which a synthetic replicate was chemically synthesised for bioassay. Results: A single peptide of molecular mass 2300.92 Da was resolved in HPLC fractions of skin secretion and its primary structure determined as IYNAIWP-KH-NK-KPGLL-. Database interrogation with this sequence indicated that this peptide was encoded by skin kininogen-1 previously cloned from B. variegata. The blank cycles were occupied by cysteinyl (C) residues and the peptide was located toward the C-terminus of the skin kininogen, and flanked N-terminally by a classical -KR- propeptide convertase processing site. The peptide was named IC-20 in accordance (I = N-terminal isoleucine, C = C-terminal cysteine, 20 = number of residues). Like the natural peptide, its synthetic replicate displayed an antagonism of bradykinin-induced arterial smooth muscle relaxation. Conclusion: IC-20 represents a novel bradykinin antagonizing peptide from amphibian skin secretions and is the third such peptide found to be co-encoded with bradykinins within skin kininogens.

Conditions for efficient and stable ion acceleration by moderate circularly polarized laser pulses at intensities of 10(20) W/cm(2)

Conditions for efficient and stable ion radiation pressure acceleration (RPA) from thin foils by circularly polarized laser pulses at moderate intensities are theoretically and numerically investigated. It is found that the unavoidable decompression of the co-moving electron layer in Light-Sail RPA leads to a change of the local electrostatic field from a

The Roads from Rio: Lessons From 20 Years of Multilateral Environmental Negotiations

A review of international environmental negotiations since the 'Earth Summit' in Rio de Janiero 1992