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.

Self-generated expressions of residual complaints following brain injury

Following brain injury there is often a prolonged period of deteriorating psychological condition, despite neurological stability or improvement. This is presumably consequent to the remission of anosognosia and the realisation of permanently worsened status. This change is hypothesised to be directed partially by the socially mediated processes which play a role in generating self-awareness and which here direct the reconstruction of the self as a permanently injured person. However, before we can understand this process of redevelopment, we need an unbiassed technique to monitor self-awareness. Semi-structured interviews were conducted with 30 individuals with long-standing brain injuries to capture their spontaneous complaints and their level of insight into the implications of their difficulties. The focus was on what the participants said in their own words, and the extent to which self-knowledge of difficulties was spontaneously salient to the participants. Their responses were subjected to content analysis. Most participants were able to say that they had brain injuries and physical difficulties, many mentioned memory and attentional problems and a few made references to a variety of emotional disturbances. Content analysis of data from unbiassed interviews can reveal the extent to which people with brain injuries know about their difficulties. Social constructionist accounts of self-awareness and recovery are supported.

mVps34 is activated following high-resistance contractions

Following resistance exercise in the fasted state, both protein synthesis and degradation in skeletal muscle are increased. The addition of essential amino acids potentiates the synthetic response suggesting that an amino acid sensor, which is involved in both synthesis and degradation, may be activated by resistance exercise. One such candidate protein is the class 3 phosphatidylinositol 3OH-kinase (PI3K) Vps34. To determine whether mammalian Vps34 (mVps34) is modulated by high-resistance contractions, mVps34 and S6K1 (an index of mTORC1) activity were measured in the distal hindlimb muscles of rats 0.5, 3, 6 and 18 h after acute unilateral high-resistance contractions with the contralateral muscles serving as a control. In the lengthening tibialis anterior (TA) muscle, S6K1 (0.5 h = 366.3 +/- 112.08%, 3 h = 124.7 +/- 15.96% and 6 h = 129.2 +/- 0%) and mVps34 (3 h = 68.8 +/- 15.1% and 6 h = 36.0 +/- 8.79%) activity both increased, whereas in the shortening soleus and plantaris (PLN) muscles the increase was significantly lower (PLN S6K1 0.5 h = 33.1 +/- 2.29% and 3 h = 47.0 +/- 6.65%; mVps34 3 h = 24.5 +/- 7.92%). HPLC analysis of the TA demonstrated a 25% increase in intramuscular leucine concentration in rats 1.5 h after exercise. A similar level of leucine added to C2C12 cells in vitro increased mVps34 activity 3.2-fold. These data suggest that, following high-resistance contractions, mVps34 activity is stimulated by an influx of essential amino acids such as leucine and this may prolong mTORC1 signalling and contribute to muscle hypertrophy.

Studies on the persistence of estradiol benzoate and nortestosterone decanoate in hair of cattle following treatment with growth promoters, determined by ultra-high-performance liquid chromatography-tandem mass spectrometry

Measurement of steroid esters in bovine hair samples, using sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS), provides a powerful tool for identifying animals treated illicitly with growth promoters. The successful application of such testing requires appropriate sampling of hair from treated animals. This paper describes the results of hair analysis by LC-MS/MS for two animal studies in which animals were treated with estradiol-3-benzoate and nortestosterone decanoate. The results from the first animal study indicate that animals treated with these anabolic steroids may not always be identified from analysis of hair samples; positive test results occur sporadically and only for some of the treated animals. The results from the second animal study identify conditions attaching to positive hair samples, such as, that concentrations of steroid esters in hair are related to distance of sampling from point of injection and to time post-treatment, that concentrations of steroid esters in hair are related to dose given to the animal but that this relationship may vary over time post-treatment, and that steroid esters may be measured in regrowth hair taken some weeks after treatment. Steroid esters are determined along the length of the hair, confirming that accumulation of steroid esters into hair occurs from various sources, including blood, sweat and sebum. The reported research provides some useful insights into the mechanisms governing the persistence of steroid esters in bovine hair following illicit treatment with growth promoters. (C) 2009 Elsevier B.V. All rights reserved.

ARE OECD MACROECONOMIC VARIABLES TREND STATIONARY? EVIDENCE FROM PANEL STATIONARITY TESTS ALLOWING FOR A STRUCTURAL BREAK AND CROSS-SECTIONAL DEPENDENCE

This article applies the panel stationarity test with a break proposed by Hadri and Rao (2008) to examine whether 14 macroeconomic variables of OECD countries can be best represented as random walk or stationary fluctuations around a deterministic trend. In contrast to previous studies, based essentially on visual inspection of the break type or just applying the most general break model, we use a model selection procedure based on BIC. We do this for each time series so that heterogeneous break models are allowed for in the panel. Our results suggest, overwhelmingly, that if we account for a structural break, cross-sectional dependence and choose the break models to be congruent with the data, then the null of stationarity cannot be rejected for all the 14 macroeconomic variables examined in this article. This is in sharp contrast with the results obtained by Hurlin (2004), using the same data but a different methodology.

Observation of Postsoliton Expansion Following Laser Propagation through an Underdense Plasma

The expansion of electromagnetic postsolitons emerging from the interaction of a 30 ps, 3 x 10(18) W cm(-2) laser pulse with an underdense deuterium plasma has been observed up to 100 ps after the pulse propagation, when large numbers of postsolitons were seen to remain in the plasma. The temporal evolution of the postsolitons has been accurately characterized with a high spatial and temporal resolution. The observed expansion is compared to analytical models and three-dimensional particle-in-cell results, revealing a polarization dependence of the postsoliton dynamics.

War, peace and suicide: The case of Northern Ireland

Durkheim’s idea that war reduces suicide through greater social and political integration has been used to explain suicide trends during the Northern Ireland conflict and in the period of peace. The applicability of Durkheim is critically evaluated through a case study of suicide trends by age, gender and cause of death over a forty year period. The key finding is that the cohort of children and young people who grew up in the worst years of violence during the 1970s, have the highest and most rapidly increasing suicide rates, and account for the steep upward trend in suicide following the 1998 Agreement. Contrary to Durkheim, the recent rise in suicide involves a complex of social and psychological factors. These include the growth in social isolation, poor mental health arising from the experience of conflict, and the greater political stability of the past decade. The transition to peace means that externalised aggression is no longer socially approved. It becomes internalised instead.