Assessment of estrogenic exposure in brown trout (Salmo trutta) in a Swiss midland river: integrated analysis of passive samplers, wild and caged fish, and vitellogenin mRNA and protein

This field study examined the vitellogenin (VTG) biomarker response under conditions of low and fluctuating activities of environmental estrogenicity. The present study was performed on immature brown trout (Salmo trutta) exposed to the small river Luetzelmurg, which is located in the prealpine Swiss midland region and receives effluents from a single sewage treatment plant (STP). To understand better factors influencing the relationship between estrogenic exposure and VTG induction, we compared VTG levels in caged (stationary) and feral (free-ranging) fish, VTG levels in fish from up- and downstream of the STP, and two different methods for quantifying VTG (enzyme-linked immunosorbent assay vs real-time reverse transcription-polymerase chain reaction), and we used passive samplers (polar organic chemical integrative sampler [POCIS]) to integrate the variable, bioaccumulative estrogenic load in the river water over time. The POCIS from the downstream site contained approximately 20-fold higher levels of bioassay-derived estrogen equivalents than the POCIS from the upstream site. In feral fish, this site difference in estrogenic exposure was reflected in VTG protein levels but not in VTG mRNA. In contrast, in caged fish, the site difference was evident only for VTG mRNA but not for VTG protein. Thus, the outcome of VTG biomarker measurements varied with the analytical detection method (protein vs mRNA) and with the exposure modus (caged vs feral). Our findings suggest that for environmental situations with low and variable estrogenic contamination, a multiple-assessment approach may be necessary for the assessment of estrogenic exposure in fish.

„Es war, als hätte das Virus mich geschwängert.“ Vertextungsformen in Aids-Autobiographien

Die vorliegende Untersuchung der Vertextung von Aids in Autobiografien fokussiert die Frage, welcher Darstellungsstrategien diese sich bedienen und welche Funktionen sie in den westlichen Kulturen übernehmen. Vier Autobiografien werden exemplarisch mit Hilfe der Systemtheorie und der Diskursanalyse analysiert und auf folgende Leitfragen hin untersucht: Sind die AutorInnen an Aids erkrankt oder nicht? Welche Lebenszeit steht ihnen zur Verfügung? Sind sie professionelle Schriftsteller oder Laien? Welche Rolle spielt ihr Geschlecht? Welche Werte werden wie vermittelt? Wird Akzeptabilität geschaffen? Wie wird mit den Grenzen des Akzeptablen umgegangen? Wie wird die Konstruktion und Destruktion des schreibenden Subjektes angesichts der Krankheitserfahrung verhandelt? Das untersuchte Material umfasst ein Spektrum, das • das schnelle Sterben an Aids, das lange Leben mit Aids sowie das Leben als HIV-Negativer in Gegenwart von Aids zeigt. • von gesellschaftlich orientierter Bewältigung der Krankheitserfahrung über individuelle Bewältigung bis hin zur Verweigerung der gesellschaftlichen Integration reicht. • den unterschiedlichen Einsatz von Metaphern bei der Sinngebung und der Vertextung von Körpererfahrung aufzeigt: Sterben als Geburt (Normalisierungsrhetorik), Sterben als Holocaust (Eskalationsrhetorik), Krankheitserfahrung als Generator immer neuer, überbordender Sprachbilder.

BTLA mediates inhibition of human tumor-specific CD8+ T cells that can be partially reversed by vaccination

The function of antigen-specific CD8+ T cells, which may protect against both infectious and malignant diseases, can be impaired by ligation of their inhibitory receptors, which include CTL-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1). Recently, B and T lymphocyte attenuator (BTLA) was identified as a novel inhibitory receptor with structural and functional similarities to CTLA-4 and PD-1. BTLA triggering leads to decreased antimicrobial and autoimmune T cell responses in mice, but its functions in humans are largely unknown. Here we have demonstrated that as human viral antigen-specific CD8+ T cells differentiated from naive to effector cells, their surface expression of BTLA was gradually downregulated. In marked contrast, human melanoma tumor antigen-specific effector CD8+ T cells persistently expressed high levels of BTLA in vivo and remained susceptible to functional inhibition by its ligand herpes virus entry mediator (HVEM). Such persistence of BTLA expression was also found in tumor antigen-specific CD8+ T cells from melanoma patients with spontaneous antitumor immune responses and after conventional peptide vaccination. Remarkably, addition of CpG oligodeoxynucleotides to the vaccine formulation led to progressive downregulation of BTLA in vivo and consequent resistance to BTLA-HVEM-mediated inhibition. Thus, BTLA activation inhibits the function of human CD8+ cancer-specific T cells, and appropriate immunotherapy may partially overcome this inhibition.