Persistence survey of Toxic Shock Syndrome toxin-1 producing Staphylococcus aureus and serum antibodies to this superantigen in five groups of menstruating women

Background: Menstrual Toxic Shock Syndrome (mTSS) is thought to be associated with the vaginal colonization with specific strains of Staphylococcus aureus TSST-1 in women who lack sufficient antibody titers to this toxin. There are no published studies that examine the seroconversion in women with various colonization patterns of this organism. Thus, the aim of this study was to evaluate the persistence of Staphylococcus aureus colonization at three body sites (vagina, nares, and anus) and serum antibody to toxic shock syndrome toxin-producing Staphylococcus aureus among a small group of healthy, menstruating women evaluated previously in a larger study. Methods: One year after the completion of that study, 311 subjects were recalled into 5 groups. Four samples were obtained from each participant at several visits over an additional 6-11 month period: 1) an anterior nares swab; 2) an anal swab; 3) a vagina swab; and 4) a blood sample. Gram stain, a catalase test, and a rapid S. aureus-specific latex agglutination test were performed to phenotypically identify S. aureus from sample swabs. A competitive ELISA was used to quantify TSST-1 production. Human TSST-1 IgG antibodies were determined from the blood samples using a sandwich ELISA method. Results: We found only 41% of toxigenic S. aureus and 35.5% of non-toxigenic nasal carriage could be classified as persistent. None of the toxigenic S. aureus vaginal or anal carriage could be classified as persistent. Despite the low persistence of S. aureus colonization, subjects colonized with a toxigenic strain were found to display distributions of antibody titers skewed toward higher titers than other subjects. Seven percent (5/75) of subjects became seropositive during recall, but none experienced toxic shock syndrome-like symptoms. Conclusions: Nasal carriage of S. aureus appears to be persistent and the best predicator of subsequent colonization, whereas vaginal and anal carriage appear to be more transient. From these findings, it appears that antibody titers in women found to be colonized with toxigenic S. aureus remained skewed toward higher titers whether or not the colonies were found to be persistent or transient in nature. This suggests that colonization at some point in time is sufficient to elevate antibody titer levels and those levels appear to be persistent. Results also indicate that women can become seropositive without experiencing signs or symptoms of toxic shock syndrome

184AA3: a xenograft model of ER+ breast adenocarcinoma

PURPOSE: Despite the prevalence and significant morbidity resulting from estrogen receptor positive (ER(+)) breast adenocarcinomas, there are only a few models of this cancer subtype available for drug development, and arguably none for studying etiology. Those models that do exist have questionable clinical relevance. METHODS: Given our goal of developing luminal models, we focused on six cell lines derived by minimal mutagenesis from normal human breast cells, and asked if any could generate clinically relevant xenografts, which we then extensively characterized. RESULTS: Xenografts of one cell line, 184AA3, consistently formed ER+ adenocarcinomas that had a high proliferative rate and other features consistent with “luminal B” intrinsic subtype. Squamous and spindle cell/mesenchymal differentiation was absent, in stark contrast to other cell lines that we examined or others have reported. We explored intratumoral heterogeneity produced by 184AA3 by immunophenotyping xenograft tumors and cultured cells, and characterized marker expression by immunofluorescence and flow cytometry. A CD44(High) subpopulation was discovered, yet their tumor forming ability was far less than CD44(Low) cells. Single cell cloning revealed the phenotypic plasticity of 184AA3, consistent with the intratumoral heterogeneity observed in xenografts. Characterization of ER expression in cultures revealed ER protein and signaling is intact, yet when estrogen was depleted in culture, and in vivo, it did not impact cell or tumor growth, analogous to therapeutically resistant ER+ cancers. CONCLUSIONS: This model is appropriate for studies of the etiology of ovarian hormone independent adenocarcinomas, for identification of therapeutic targets, predictive testing and drug development

Volcaniclastic stratigraphy of the Tiscapa maar crater walls (Managua, Nicaragua) : implications for volcanic and seismic hazards and Holocene climate changes

The Tiscapa maar in the center of Managua city formed by a phreatomagmatic eruption 60 ka old basaltic–andesitic formation F1 comprises mafic ignimbrites and phreatomagmatic tephras derived from the Las Sierras volcanic complex south of Managua. Formation F2 contains the ~60 ka basaltic–andesitic Fontana tephra erupted from the Las Nubes Caldera of the Las Sierras complex 15 km to the S, the 25 ka Upper Apoyo tephra from the Apoyo Caldera 35 km to the SE, and the Lower (~17 ka) and Upper (12.4 ka) Apoyeque tephras from the Chiltepe volcanic complex 15 km to the NW. These tephras are separated by weathering horizons and paleosols indicating dry climatic conditions. Fluvial deposits of a SSW-NNE running paleo-river system build formation F3. The fluvial sediments contain, from bottom to top, scoriae from the ~6 ka basaltic San Antonio tephra, pumice lapilli from the Apoyo and Apoyeque tephras and the 6.1 ka Xiloà tephra, and scoriae derived from the Fontana tephra. The fluvial sediment succession thus reflects progressively deeper carving erosion in the southern highlands (where a large-amplitude regional erosional unconformity exists at the appropriate stratigraphic level) that began after ~6 ka. This suggests that the mid-Holocene tropical high-precipitation climatic phase affected western Nicaragua about a thousand years later than other circum-Caribbean regions. The end of the wet climate phase ~3 ka ago is recorded by a deep weathering zone and paleosol atop formation F3 prior to the Tiscapa eruption. Formation F4 is the Tiscapa tuffring composed of pyroclastic surge and fallout deposits that cover a minimum area of 1.2 km2. The 4 × 109 kg of erupted basaltic magma is compositionally and genetically related to the low-Ti basalts of the N–S striking Nejapa-Miraflores volcanic–tectonic alignment 5 km to the West of Tiscapa. Ascent and eruption mode of the Tiscapa magma were controlled by the Tiscapa fault that has a very active seismic history as it achieved 12 m displacement in about 3000 years. Managua city is thus exposed to continued seismic and volcanic risks

MicroRNA-181a/b-1 Is Not Required for Innate γδ NKT Effector Cell Development

Thymic development of αβ T lymphocytes into invariant natural killer (NK) T cells depends on their selection via agonistic lipid antigen presented by CD1d. If successful, newly selected NKT cells gain effector functions already in the thymus. Some γδ T cell subsets also acquire effector functions in the thymus. However, it is not clear whether agonistic TCR stimulation is involved in thymic γδ T cell selection and development. Here we combine two genetic models to address this question. MiR-181a/b-1-/-mice, which show impaired agonistic T cell selection of invariant αβ NKT cells, were crossed to Tcrd-H2BeGFP reporter mice to monitor selection, intra-thymic expansion and differentiation of γδ T cells. We found that miR-181a/b-1-deficiency had no effect on numbers of thymic γδ T cell or on their differentiation towards an IL-17- or IFN-γ-producing effector phenotype. Also, the composition of peripheral lymph node γδ T cells was not affected by miR-181a/b-1-deficiency. Dendritic epidermal γδ T cells were normally present in knock-out animals. However, we observed elevated frequencies and numbers of γδ NKT cells in the liver, possibly because γδ NKT cells can expand and replace missing αβ NKT cells in peripheral niches. In summary, we investigated the role of miR-181a/b-1 for selection, intrathymic development and homeostasis of γδ T cells. We conclude that miR-181a/b-1-dependent modulation of T cell selection is not critically required for innate development of γδ NKT cells or of any other γδ T cell subtypes