Does Male Circumcision Prevent HIV Infection?

Siegfried discusses the first reported randomized controlled trial of whether circumcision protects against HIV, published in PLoS Medicine

Recreation and mission: an empirical-theological study of the impact Christian camps have on the emergence of faith of young people based on the example of SOLA

In dieser Forschungsarbeit wurde die Auswirkung von christlicher Freizeitarbeit auf die Glaubensgenese von Jugendlichen erforscht. Die Umsetzung erfolgte mithilfe einer empirisch-theologischen Untersuchung am Beispiel eines SOLAs. Es wurden qualitative Interviews mit Jugendlichen durchgefuhrt, die uber die SOLA-Arbeit eine Glaubensgenese erlebt haben. Die erhobenen Daten wurden mit der Grounded-Theory-Methodik nach Breuer (2009) ausgewertet und mit den Theorien zur Glaubensgenese von Engel (1989), Grom (1992) und Zulehner (2008) in Beziehung gesetzt. Die Ergebnisse wurden auf die einzelnen Elemente angewendet, die bei der Gestaltung einer Freizeit zur Verfugung stehen. Damit ist eine Hilfestellung entstanden, die Veranstaltern von Freizeiten eine Orientierung geben kann, auf welche Elemente einer Freizeit besonders zu achten ist, wenn eine Glaubensgenese erwunscht ist.This research paper analyzes the impact Christian recreational activities have on the emergence of young people’s faith. Using the example of SOLA, the analysis is based on empiric-theological research. Young people, whose faith has emerged through SOLA were interviewed qualitatively. The data retrieved was analyzed using the grounded theory method by Breuer (2009) and put into relation to the theories of Engel (1989), Grom (1992) and Zulehner (2008) about how faith emerges. Furthermore, these results were applied to the individual elements available through the organization of camps. The outcomes the author has established are of assistance to all parties involved in the organization of christian recreational activities, who want to improve their programs toward impacting the emergence of faith in their participants.Christian Spirituality, Church History and MissiologyM. Th. (Missiology

Murine Toll-Like Receptor 2 Activation Induces Type I Interferon Responses from Endolysosomal Compartments

Background: Toll-like receptors (TLRs) are among the first-line sentinels for immune detection and responsiveness to pathogens. The TLR2 subfamily of TLRs (TLR1, TLR2, TLR6) form heterodimers with each other and are thus able to recognize a broad range of components from several microbes such as yeast, Gram-positive bacteria and protozoa. Until now, TLR2 activation by bacterial ligands has long been associated with pro-inflammatory cytokines but not type I interferon responses. Methodology/Principal Findings: Using a variety of transgenic mice, here we provide in vivo and in vitro data showing that TLR2 activation does in fact induce interferon-beta and that this occurs via MyD88-IRF1 and-IRF7 pathways. Interestingly, by microscopy we demonstrate that although a cell surface receptor, TLR2 dependent induction of type I interferons occurs in endolysosomal compartments where it is translocated to upon ligand engagement. Furthermore, we could show that blocking receptor internalization or endolysosomal acidification inhibits the ability of TLR2 to trigger the induction type I interferon but not pro-inflammatory responses. Conclusion/Significance: The results indicate that TLR2 activation induces pro-inflammatory and type I interferon responses from distinct subcellular sites: the plasma membrane and endolysosomal compartments respectively. Apart from identifying and characterizing a novel pathway for induction of type I interferons, the present study offers new insights into how TLR signaling discriminates and regulates the nature of responses to be elicited against extracellular and endocytosed microbes

Hormonal receptors in lung adenocarcinoma: expression and difference in outcome by sex

Background: Lung cancer seems to have different epidemiological, biomolecular and clinical characteristics in females than in males, with a better prognosis for women. The aim of the study is to determine gender differences in lung adenocarcinoma in terms of androgen (AR), estrogen (ER)α and progesterone (PgR) receptors expression and their impact on outcome. Results: Overall survival was significantly better in ERα and in PgR positive lung adenocarcinoma patients (median survival 45 vs. 19 months). Eight out of 62 patients showed positive expression of nuclear (n) AR and 18 of cytoplasmic (c) AR with a significantly better survival (49 vs. 19 and 45 vs. 19 months, respectively). There was a significant difference in survival between patients with vs. without c-AR expression (30 vs. 17 months). Finally, in the subgroup of women, median survival was greater in positive expression of c-AR than for women with negative c-AR (45 vs. 21 months). Materials and Methods: We conducted an analysis on a cohort of 62 patients with advanced NSCLC treated at our institution. We investigated the immunohistochemical expression of n/c AR, ERα and PgR in 62 NSCLC and we correlated it with patients’ clinic-pathologic characteristics and with prognosis. Conclusions: Our results showed that the positive expression of one hormonal receptor could represent a prognostic factor. Furthermore our study suggests that AR should become object of close examination in a larger series of lung adenocarcinoma patients, also for selection of the patients with best prognosis that can perform more chemotherapy lines

Influence of Internalin A murinisation on host resistance to orally acquired listeriosis in mice

Background: The bacterial surface protein internalin (InlA) is a major virulence factor of the food-born pathogen Listeria monocytogenes. It plays a critical role in the bacteria crossing the host intestinal barrier by a species-specific interaction with the cell adhesion molecule E-cadherin. In mice, the interaction of InlA with murine E-cadherin is impaired due to sequence-specific binding incompatibilities. We have previously used the approach of ‘murinisation’ to establish an oral listeriosis infection model in mice by exchanging two amino acid residues in InlA. This dramatically increases binding to mouse E-cadherin. In the present study, we have used bioluminescent murinised and non-murinised Listeria strains to examine the spatiotemporal dissemination of Listeria in four diverse mouse genetic backgrounds after oral inoculation. Results: The murinised Listeria monocytogenes strain showed enhanced invasiveness and induced more severe infections in all four investigated mouse inbred strains compared to the non-murinised Listeria strain. We identified C57BL/6J mice as being most resistant to orally acquired listeriosis whereas C3HeB/FeJ, A/J and BALB/cJ mice were found to be most susceptible to infection. This was reflected in faster kinetics of Listeria dissemination, higher bacterial loads in internal organs, and elevated serum levels of IL-6, IFN-γ, TNF-α and CCL2 in the susceptible strains as compared to the resistant C57BL/6J strain. Importantly, murinisation of InlA did not cause enhanced invasion of Listeria monocytogenes into the brain. Conclusion: Murinised Listeria are able to efficiently cross the intestinal barrier in mice from diverse genetic backgrounds. However, expression of murinized InlA does not enhance listerial brain invasion suggesting that crossing of the blood brain barrier and crossing of the intestinal epithelium are achieved by Listeria monocytogenes through different molecular mechanisms

Displacement Effects of Conservation Grazing on Red Deer (Cervus elaphus) Spatial Behaviour

Conservation grazing uses semi-feral or domesticated herbivores to limit encroachment in open areas and to promote biodiversity. However, we are still unaware of its effects on wild herbivores. This study investigates the influence of herded sheep and goats on red deer (Cervus elaphus) spatial behavior by testing three a-priori hypotheses: (i) red deer are expected to avoid areas used by livestock, as well as adjacent areas, when livestock are present, albeit (ii) red deer increase the use of these areas when sheep and goats are temporarily absent and (iii) there is a time-lagged disruption in red deer spatial behavior when conservation grazing practice ends. Using GPS-telemetry data on red deer from a German heathland area, we modelled their use of areas grazed by sheep and goats, using mixed-effect logistic regression. Additionally, we developed seasonal resource selection functions (use-availability design) to depict habitat selection by red deer before, during, and after conservation grazing. Red deer used areas less during conservation grazing throughout all times of the day and there was no compensatory use during nighttime. This effect mostly persisted within 21 days after conservation grazing. Effects on habitat selection of red deer were detectable up to 3000 meters away from the conservation grazing sites, with no signs of either habituation or adaption. For the first time, we demonstrate that conservation grazing can affect the spatio-temporal behavior of wild herbivores. Our findings are relevant for optimizing landscape and wildlife management when conservation grazing is used in areas where wild herbivores are present.publishedVersio

Severe Developmental B Lymphopoietic Defects in Foxp3-Deficient Mice are Refractory to Adoptive Regulatory T Cell Therapy

The role of Foxp3-expressing regulatory T (Treg) cells in tolerance and autoimmunity is well-established. However, although of considerable clinical interest, the role of Treg cells in the regulation of hematopoietic homeostasis remains poorly understood. Thus, we analysed B and T lymphopoiesis in the scurfy (Sf) mouse model of Treg cell deficiency. In these experiments, the near-complete block of B lymphopoiesis in the BM of adolescent Sf mice was attributed to autoimmune T cells. We could exclude a constitutive lympho-hematopoietic defect or a B cell-intrinsic function of Foxp3. Efficient B cell development in the BM early in ontogeny and pronounced extramedullary B lymphopoietic activity resulted in a peripheral pool of mature B cells in adolescent Sf mice. However, marginal zone B and B-1a cells were absent throughout ontogeny. Developmental B lymphopoietic defects largely correlated with defective thymopoiesis. Importantly, neonatal adoptive Treg cell therapy suppressed exacerbated production of inflammatory cytokines and restored thymopoiesis but was ineffective in recovering defective B lymphopoiesis, probably due to a failure to compensate production of stroma cell-derived IL-7 and CXCL12. Our observations on autoimmune-mediated incapacitation of the BM environment in Foxp3-deficient mice will have direct implications for the rational design of BM transplantation protocols for patients with severe genetic deficiencies in functional Foxp3+ Treg cells

Identification of tumor-specific Salmonella Typhimurium promoters and their regulatory logic

Conventional cancer therapies are often limited in effectiveness and exhibit strong side effects. Therefore, alternative therapeutic strategies are demanded. The employment of tumor-colonizing bacteria that exert anticancer effects is such a novel approach that attracts increasing attention. For instance, Salmonella enterica serovar Typhimurium has been used in many animal tumor models as well as in first clinical studies. These bacteria exhibit inherent tumoricidal effects. In addition, they can be used to deliver therapeutic agents. However, bacterial expression has to be restricted to the tumor to prevent toxic substances from harming healthy tissue. Therefore, we screened an S. Typhimurium promoter-trap library to identify promoters that exclusively drive gene expression in the cancerous tissue. Twelve elements could be detected that show reporter gene expression in tumors but not in spleen and liver. In addition, a DNA motif was identified that appears to be necessary for tumor specificity. Now, such tumor-specific promoters can be used to safely express therapeutic proteins by tumor-colonizing S. Typhimurium directly in the neoplasi

FEM simulations of fatigue crack initiation in the oligocrystalline microstructure of stents

For over two decades, vascular stents have been widely used to treat clogged vessels, serving as a scaffold to enlarge the narrowed lumen and recover the arterial flow area. High-purity oligocrystalline austenitic steel is usually applied for the production of stents. Despite the popularity and benefit of stenting, it still may cause serious clinical adverse issues, such as in-stent restenosis and stent fracture. Therefore, the study of the mechanical properties of stents and in particular the prediction of their life cycles are in the focus of materials research. In our contribution, within the finite element method, a two-scale model of crack initiation in the microstructure of stents is elaborated. The approach is developed on the basis of the physically based Tanaka-Mura model (TMM), considering the evolution of shear bands during the crack initiation phase. The model allows for the analysis of the microstructure with respect to the life cycles of real materials. The effects of different loading conditions, grain orientation, and thickness of the specimen on Wöhler curves were analysed. It was found that the microstructural features of oligocrystals are very sensitive to different loading conditions with respect to their fatigue behaviour and play a major role in fatigue crack initiation. Different grain-orientation distributions result in qualitative and quantitative differences in stress distribution and in the number of cycles for crack initiation. It was found that presence of a neutral zone in the cut-out of the microstructure under three-point-bending loading conditions changes the qualitative and quantitative patterns of stress distribution and affects the number of cycles for crack initiation. It was found that under both tensile and bending loading conditions, thicker specimens require more cycles for crack initiation. The Wöhler curves for crack initiation in oligocrystalline microstructures of stents could be compared with the ones in the experiment, taking into account that for high cyclic fatigue (HCF), typically, more than 70% of the cycles refer to crack initiation. The developed numerical tools could be used for the material design of stents.German Research Foundation (DFG

NK cell activation in visceral leishmaniasis requires TLR9, myeloid DCs, and IL-12, but is independent of plasmacytoid DCs

Natural killer (NK) cells are sentinel components of the innate response to pathogens, but the cell types, pathogen recognition receptors, and cytokines required for their activation in vivo are poorly defined. Here, we investigated the role of plasmacytoid dendritic cells (pDCs), myeloid DCs (mDCs), Toll-like receptors (TLRs), and of NK cell stimulatory cytokines for the induction of an NK cell response to the protozoan parasite Leishmania infantum. In vitro, pDCs did not endocytose Leishmania promastigotes but nevertheless released interferon (IFN)-α/β and interleukin (IL)-12 in a TLR9-dependent manner. mDCs rapidly internalized Leishmania and, in the presence of TLR9, produced IL-12, but not IFN-α/β. Depletion of pDCs did not impair the activation of NK cells in L. infantum–infected mice. In contrast, L. infantum–induced NK cell cytotoxicity and IFN-γ production were abolished in mDC-depleted mice. The same phenotype was observed in TLR9−/− mice, which lacked IL-12 expression by mDCs, and in IL-12−/− mice, whereas IFN-α/β receptor−/− mice showed only a minor reduction of NK cell IFN-γ expression. This study provides the first direct evidence that mDCs are essential for eliciting NK cell cytotoxicity and IFN-γ release in vivo and demonstrates that TLR9, mDCs, and IL-12 are functionally linked to the activation of NK cells in visceral leishmaniasis