11,688 research outputs found

    Seminal fluid and cytokine control of regulatory T-cells in murine pregnancy.

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    For successful pregnancy, the maternal immune system must tolerate the presence of a fetus that expresses alloantigens. The appropriate and timely acquisition of this state of tolerance is critical and emerging evidence suggests that it needs to be present from the time the embryo implants into the uterus. Recently it has been demonstrated that a subpopulation of lymphocytes termed CD4⁺CD25⁺ regulatory T cells (Treg cells) are required for immune tolerance of the fetus during pregnancy. Despite their importance the factors that control regulatory T cells during pregnancy, and in particular in the peri-implantation period, are poorly understood. Using mouse models we have assessed the role of the ejaculate and its components (sperm and seminal plasma) in coordinating Treg cells in the period prior to embryo implantation. We have also used mice with a null mutation in the interleukin 10 (IL-10) gene to assess the role of this cytokine in coordination of Treg cell populations in later pregnancy. Experiments in the peri-implantation period just prior to implantation (day 3.5 postcoitum) showed that there was a significant increase (approximately 2-fold; p<0.05) in the total number of (CD4⁺Foxp3⁺) Treg cells in the iliac lymph nodes (LNs) that drain the uterus, but not in the distal inguinal LNs. This appeared not to be the result of a selective expansion in Treg cells but due to expansion of the entire CD4⁺ cell pool, since the percent of CD4+ cells expressing Foxp3 in any of the lymphoid tissues studied did not increase in response to mating. In addition, there was a similar increase in the density of these cells in the uterus just prior to implantation at day 3.5pc (p<0.05). By using males deficient in the sperm or seminal plasma components of the ejaculate we could show that the increase in both the lymph node and uterine Treg cell populations occurred in response to seminal plasma. The role of seminal plasma in regulating expression of mRNAs encoding migratory molecules in the peri-implantation uterus, and the involvement of these genes in recruiting Treg cells following mating, was then assessed. We analysed the mRNAs for the chemokines Ccl4, Ccl5, Ccl19, Ccl22, the chemokine receptors Ccr4, Ccr5, Ccr7 and the integrin Cd103 using qRT-PCR. We showed a significant elevation in Ccl19 and Ccr5 mRNA at day 3.5pc following mating to intact males. However the increase in mRNA was independent of factors associated with seminal fluid and might instead be regulated by ovarian steroid hormones. Using IL-10 null mutant (IL-10-/-) mice it was then shown that the cytokine IL-10 is involved in controlling Treg cell numbers in mid gestation. At gestational day (gd) 9.5, in IL-10-/- mice, there was an approximate 40% elevation in the proportion of CD4⁺ cells expressing Foxp3 compared with wild‐type control mice (p<0.01). This was seen in both the iliac LNs and inguinal LNs. In addition, there was a greater than 10-fold increase (p<0.0001) in the total number of Treg cells in the uterine-draining iliac LNs of IL-10-/- mice compared to wild-type mice. This was not seen in the inguinal LNs. Experiments comparing allogeneic and syngeneic mated mice showed that the proportional changes seen in the CD4⁺ cell population was dependent on fetal alloantigens, although the elevation in total numbers still occurred in the absence of fetal alloantigens. This study begins to unravel the process by which Treg cell populations are expanded and recruited into the uterus prior to embryo implantation and later in gestation. A greater understanding of this process may aid in the diagnosis and prevention of a range of pregnancy pathologies associated with immune dysregulation, such as preeclampsia and recurrent spontaneous abortion.Thesis (Ph.D.) -- University of Adelaide, School of Paediatrics and Reproductive Health, 201

    Genetic mapping of natural variation in potassium concentrations in shoots of Arabidopsis thaliana

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    Naturally-occurring variation in K+ concentrations between plant genotypes is potentially exploitable in a number of ways, including altering the relationship between K+ accumulation and growth, enhancing salinity resistance, or improving forage quality. However, achieving these requires greater insight into the genetic basis of the variation in tissue K+ concentrations. To this end, K+ concentrations were measured in the shoots of 70 Arabidopsis thaliana accessions and a Cape Verdi Island/Landsberg erecta recombinant inbred line (RIL) population. The shoot K+ concentrations expressed on the basis of fresh matter (KFM) or dry matter (KDM) were both broadly and normally distributed as was the shoot dry matter content per unit fresh weight (DMC). Using the data from the RILs, four quantitative trait loci (QTL) were identified for KFM and three for KDM. These were located on chromosomes 2, 3, 4, and 5. Two of the QTLs for KFM overlapped with those for KDM. None of these QTLs overlapped with those for fresh weight or dry weight, but the QTL for KDM located on chromosome 3 overlapped with one for DMC. In silico analysis was used to identify known or putative K+ and cation transporter genes whose loci overlapped with the QTLs. In most cases, multiple genes were identified and the possible role of their gene products in determining shoot K+ concentrations is discussed.Hisatomi Harada and Roger A. Leig

    The Memorability of Supernatural Concepts: Effects of Minimal Counterintuitiveness, Moral Valence, and Existential Anxiety on Recall

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    Within the cognitive science of religion, some scholars hypothesize (1) that minimally counterintuitive (MCI) concepts enjoy a transmission advantage over both intuitive and highly counterintuitive concepts, (2) that religions concern counterintuitive agents, objects, or events, and (3) that the transmission advantage of MCI concepts makes them more likely to be found in the world’s religions than other kinds of concepts. We hypothesized that the memorability of many MCI supernatural concepts was due in large part to other characteristics they possess, such as their frequent and salient association with moral concerns and the alleviation of existential anxieties, and that without such characteristics they would fail to be memorable. We report the results of three experiments designed to test the relative contributions of minimal counterintuitiveness, moral valence, and existential anxiety to the memorability of supernatural ideas. We observed no main effects for minimal counterintuitiveness but did observe main effects for both moral valence and existential anxiety. We also found that these effects did not seem to stem from the greater visualizability of morally valenced concepts or concepts that concerned existential anxieties. These findings challenge important claims made by leading researchers regarding MCI concepts within the cognitive science of religion

    Thermal control surfaces experiment: Initial flight data analysis

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    The behavior of materials in the space environment continues to be a limiting technology for spacecraft and experiments. The thermal control surfaces experiment (TCSE) aboard the Long Duration Exposure Facility (LDEF) is the most comprehensive experiment flown to study the effects of the space environment on thermal control surfaces. Selected thermal control surfaces were exposed to the LDEF orbital environment and the effects of this exposure were measured. The TCSE combined in-space orbital measurements with pre and post-flight analyses of flight materials to determine the effects of long term space exposure. The TCSE experiment objective, method, and measurements are described along with the results of the initial materials analysis. The TCSE flight system and its excellent performance on the LDEF mission is described. A few operational anomalies were encountered and are discussed

    Origin of the Mott Gap

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    We show exactly that the only charged excitations that exist in the strong-coupling limit of the half-filled Hubbard model are gapped composite excitations generated by the dynamics of the charge 2e2e boson that appears upon explicit integration of the high-energy scale. At every momentum, such excitations have non-zero spectral weight at two distinct energy scales separated by the on-site repulsion UU. The result is a gap in the spectrum for the composite excitations accompanied by a discontinuous vanishing of the density of states at the chemical potential when UU exceeds the bandwidth. Consequently, we resolve the long-standing problem of the cause of the charge gap in a half-filled band in the absence of symmetry breaking.Comment: 6 pages, 2 figures: Expanded Published versio
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