3,079 research outputs found

    Pulmonary dendritic cells and alveolar macrophages are regulated by γδ T cells during the resolution of S. pneumoniae-induced inflammation

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    γδ T cells commonly associate with mucosal and epithelial sites, fulfilling a variety of immunoregulatory functions. While lung γδ T cells have well-characterized pro-inflammatory activity, their potential role in the resolution of lung inflammation has yet to be explored in any detail. Indeed, given the importance of minimizing inflammation, the cellular mechanisms driving the resolution of lung inflammation are poorly understood. Using a murine model of acute Streptococcus pneumoniae-mediated lung inflammation, we now show that resolution of inflammation following bacterial clearance is associated with a > 30-fold increase in γδ T-cell number. Although inflammation eventually resolves in TCRδ−/− mice, elevated numbers of alveolar macrophages and pulmonary dendritic cells, and the appearance of well-formed granulomas in lungs of TCRδ−/− mice, together indicated a role for γδ T cells in regulating mononuclear phagocyte number. Ex vivo, both alveolar macrophages and pulmonary dendritic cells were susceptible to lung γδ T cell-mediated cytotoxicity, the first demonstration of such activity against a dendritic cell population. These findings support a model whereby expansion of γδ T cells helps restore mononuclear phagocyte numbers to homeostatic levels, protecting the lung from the consequences of inappropriate inflammation. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd

    New mutations at the imprinted Gnas cluster show gene dosage effects of Gsα in postnatal growth and implicate XLαs in bone and fat metabolism, but not in suckling

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    The imprinted Gnas cluster is involved in obesity, energy metabolism, feeding behavior, and viability. Relative contribution of paternally expressed proteins XLαs, XLN1, and ALEX or a double dose of maternally expressed Gsα to phenotype has not been established. In this study, we have generated two new mutants (Ex1A-T-CON and Ex1A-T) at the Gnas cluster. Paternal inheritance of Ex1A-T-CON leads to loss of imprinting of Gsα, resulting in preweaning growth retardation followed by catch-up growth. Paternal inheritance of Ex1A-T leads to loss of imprinting of Gsα and loss of expression of XLαs and XLN1. These mice have severe preweaning growth retardation and incomplete catch-up growth. They are fully viable probably because suckling is unimpaired, unlike mutants in which the expression of all the known paternally expressed Gnasxl proteins (XLαs, XLN1 and ALEX) is compromised. We suggest that loss of ALEX is most likely responsible for the suckling defects previously observed. In adults, paternal inheritance of Ex1A-T results in an increased metabolic rate and reductions in fat mass, leptin, and bone mineral density attributable to loss of XLαs. This is, to our knowledge, the first report describing a role for XLαs in bone metabolism. We propose that XLαs is involved in the regulation of bone and adipocyte metabolism

    Multiplex quantitative PCR for single-reaction genetically modified (GM) plant detection and identification of false-positive GM plants linked to Cauliflower mosaic virus (CaMV) infection.

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    BACKGROUND:Most genetically modified (GM) plants contain a promoter, P35S, from the plant virus, Cauliflower mosaic virus (CaMV), and many have a terminator, TNOS, derived from the bacterium, Agrobacterium tumefaciens. Assays designed to detect GM plants often target the P35S and/or TNOS DNA sequences. However, because the P35S promoter is derived from CaMV, these detection assays can yield false-positives from non-GM plants infected by this naturally-occurring virus. RESULTS:Here we report the development of an assay designed to distinguish CaMV-infected plants from GM plants in a single multiplexed quantitative PCR (qPCR) reaction. Following initial testing and optimization via PCR and singleplex-to-multiplex qPCR on both plasmid and plant DNA, TaqMan qPCR probes with different fluorescence wavelengths were designed to target actin (a positive-control plant gene), P35S, P3 (a CaMV-specific gene), and TNOS. We tested the specificity of our quadruplex qPCR assay using different DNA extracts from organic watercress and both organic and GM canola, all with and without CaMV infection, and by using commercial and industrial samples. The limit of detection (LOD) of each target was determined to be 1% for actin, 0.001% for P35S, and 0.01% for both P3 and TNOS. CONCLUSIONS:This assay was able to distinguish CaMV-infected plants from GM plants in a single multiplexed qPCR reaction for all samples tested in this study, suggesting that this protocol is broadly applicable and readily transferrable to any interested parties with a qPCR platform

    Atom-by-Atom Substitution of Mn in GaAs and Visualization of their Hole-Mediated Interactions

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    The discovery of ferromagnetism in Mn doped GaAs [1] has ignited interest in the development of semiconductor technologies based on electron spin and has led to several proof-of-concept spintronic devices [2-4]. A major hurdle for realistic applications of (Ga,Mn)As, or other dilute magnetic semiconductors, remains their below room-temperature ferromagnetic transition temperature. Enhancing ferromagnetism in semiconductors requires understanding the mechanisms for interaction between magnetic dopants, such as Mn, and identifying the circumstances in which ferromagnetic interactions are maximized [5]. Here we report the use of a novel atom-by-atom substitution technique with the scanning tunnelling microscope (STM) to perform the first controlled atomic scale study of the interactions between isolated Mn acceptors mediated by the electronic states of GaAs. High-resolution STM measurements are used to visualize the GaAs electronic states that participate in the Mn-Mn interaction and to quantify the interaction strengths as a function of relative position and orientation. Our experimental findings, which can be explained using tight-binding model calculations, reveal a strong dependence of ferromagnetic interaction on crystallographic orientation. This anisotropic interaction can potentially be exploited by growing oriented Ga1-xMnxAs structures to enhance the ferromagnetic transition temperature beyond that achieved in randomly doped samples. Our experimental methods also provide a realistic approach to create precise arrangements of single spins as coupled quantum bits for memory or information processing purposes

    Broadband Antireflection and Light Extraction Enhancement in Fluorescent SiC with Nanodome Structures

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    We demonstrate a time-efficient and low-cost approach to fabricate Si3N4 coated nanodome structures in fluorescent SiC. Nanosphere lithography is used as the nanopatterning method and SiC nanodome structures with Si3N4 coating are formed via dry etching and thin film deposition process. By using this method, a significant broadband surface antireflection and a considerable omnidirectional luminescence enhancement are obtained. The experimental observations are then supported by numerical simulations. It is believed that our fabrication method will be well suitable for large-scale production in the future

    Bone marrow mesenchymal stem cells do not enhance intra-synovial tendon healing despite engraftment and homing to niches within the synovium

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    Intra-synovial tendon injuries display poor healing, which often results in reduced functionality and pain. A lack of effective therapeutic options has led to experimental approaches to augment natural tendon repair with autologous mesenchymal stem cells (MSCs) although the effects of the intra-synovial environment on the distribution, engraftment and functionality of implanted MSCs is not known. This study utilised a novel sheep model which, although in an anatomically different location, more accurately mimics the mechanical and synovial environment of the human rotator cuff, to determine the effects of intra-synovial implantation of MSCs

    Uterine selection of human embryos at implantation

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    Human embryos frequently harbor large-scale complex chromosomal errors that impede normal development. Affected embryos may fail to implant although many first breach the endometrial epithelium and embed in the decidualizing stroma before being rejected via mechanisms that are poorly understood. Here we show that developmentally impaired human embryos elicit an endoplasmic stress response in human decidual cells. A stress response was also evident upon in vivo exposure of mouse uteri to culture medium conditioned by low-quality human embryos. By contrast, signals emanating from developmentally competent embryos activated a focused gene network enriched in metabolic enzymes and implantation factors. We further show that trypsin, a serine protease released by pre-implantation embryos, elicits Ca2+ signaling in endometrial epithelial cells. Competent human embryos triggered short-lived oscillatory Ca2+ fluxes whereas low-quality embryos caused a heightened and prolonged Ca2+ response. Thus, distinct positive and negative mechanisms contribute to active selection of human embryos at implantation

    Analysis of the alcohol drinking behavior and influencing factors among emerging adults and young adults: A cross-sectional study in Wuhan, China

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    Background: The relationship between alcohol use in adolescents and young adults and outcomes has not been widely researched in China. The aim of the current study was to understand the current status of drinking behavior of Chinese youth transitioning into adulthood. Methods: The cross-sectional study included 1634 participants between 18 and 34 years of age. The participants were randomly chosen from 13 administrative districts in Wuhan, and invited to complete a questionnaire. Univariate analysis was performed to describe the demographic distribution of alcohol consumption and the association with drinking status. Stepwise Logistic regression analysis was undertaken analyzing the factors influencing the drinking behaviors. The data were weighted to the population in Wuhan and analyzed using SAS version 9.3. Results: For our sample of emerging and young Chinese adults the prevalence of drinking alcohol was 45.84%. The non-drinkers predominated, accounting for 54.16% and light drinkers accounted for 42.94%, while moderate and heavy drinkers were in the minority (2.90%). The earlier the age of first alcohol drinking or the age of first being intoxicated, the greater the likelihood of being a moderate or heavy drinker. People with high emerging adulthood were more likely to have moderate or heavy drinking behaviors. The logistic regression analysis indicated that heavy drinkers were more likely to not be married and to be classified as high emerging adulthood. Conclusions: Our findings suggested that the drinking pattern should be further evaluated over time to explore the ways in which social and cultural factors shape the drinking route of this age group. Effective drinking behavior prevention and interventions and appropriate guidance should be formulated to establish an appropriate attitude towards drinking alcohol and develop a drinking behavior which is conducive to physical and mental health between this particular demographic

    Responses of marine benthic microalgae to elevated CO<inf>2</inf>

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    Increasing anthropogenic CO2 emissions to the atmosphere are causing a rise in pCO2 concentrations in the ocean surface and lowering pH. To predict the effects of these changes, we need to improve our understanding of the responses of marine primary producers since these drive biogeochemical cycles and profoundly affect the structure and function of benthic habitats. The effects of increasing CO2 levels on the colonisation of artificial substrata by microalgal assemblages (periphyton) were examined across a CO2 gradient off the volcanic island of Vulcano (NE Sicily). We show that periphyton communities altered significantly as CO2 concentrations increased. CO2 enrichment caused significant increases in chlorophyll a concentrations and in diatom abundance although we did not detect any changes in cyanobacteria. SEM analysis revealed major shifts in diatom assemblage composition as CO2 levels increased. The responses of benthic microalgae to rising anthropogenic CO2 emissions are likely to have significant ecological ramifications for coastal systems. © 2011 Springer-Verlag
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