229 research outputs found

    CD4+ T cell expression of the IL-10 receptor is necessary for facial motoneuron survival after axotomy

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    BACKGROUND: After peripheral nerve transection, facial motoneuron (FMN) survival depends on an intact CD4+ T cell population and a central source of interleukin-10 (IL-10). However, it has not been determined previously whether CD4+ T cells participate in the central neuroprotective IL-10 cascade after facial nerve axotomy (FNA). METHODS: Immunohistochemical labeling of CD4+ T cells, pontine vasculature, and central microglia was used to determine whether CD4+ T cells cross the blood-brain barrier and enter the facial motor nucleus (FMNuc) after FNA. The importance of IL-10 signaling in CD4+ T cells was assessed by performing adoptive transfer of IL-10 receptor beta (IL-10RB)-deficient CD4+ T cells into immunodeficient mice prior to injury. Histology and qPCR were utilized to determine the impact of IL-10RB-deficient T cells on FMN survival and central gene expression after FNA. Flow cytometry was used to determine whether IL-10 signaling in T cells was necessary for their differentiation into neuroprotective subsets. RESULTS: CD4+ T cells were capable of crossing the blood-brain barrier and associating with reactive microglial nodules in the axotomized FMNuc. Full induction of central IL-10R gene expression after FNA was dependent on CD4+ T cells, regardless of their own IL-10R signaling capability. Surprisingly, CD4+ T cells lacking IL-10RB were incapable of mediating neuroprotection after axotomy and promoted increased central expression of genes associated with microglial activation, antigen presentation, T cell co-stimulation, and complement deposition. There was reduced differentiation of IL-10RB-deficient CD4+ T cells into regulatory CD4+ T cells in vitro. CONCLUSIONS: These findings support the interdependence of IL-10- and CD4+ T cell-mediated mechanisms of neuroprotection after axotomy. CD4+ T cells may potentiate central responsiveness to IL-10, while IL-10 signaling within CD4+ T cells is necessary for their ability to rescue axotomized motoneuron survival. We propose that loss of IL-10 signaling in CD4+ T cells promotes non-neuroprotective autoimmunity after FNA

    Cellular sources and neuroprotective roles of interleukin-10 in the facial motor nucleus after axotomy

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    Facial motoneuron (FMN) survival is mediated by CD4+ T cells in an interleukin-10 (IL-10)-dependent manner after facial nerve axotomy (FNA), but CD4+ T cells themselves are not the source of this neuroprotective IL-10. The aims of this study were to (1) identify the temporal and cell-specific induction of IL-10 expression in the facial motor nucleus and (2) elucidate the neuroprotective capacity of this expression after axotomy. Immunohistochemistry revealed that FMN constitutively produced IL-10, whereas astrocytes were induced to make IL-10 after FNA

    Identification of a resilient mouse facial motoneuron population following target disconnection by injury or disease

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    Background: When nerve transection is performed on adult rodents, a substantial population of neurons survives short-term disconnection from target, and the immune system supports this neuronal survival, however long-term survival remains unknown. Understanding the effects of permanent axotomy on cell body survival is important as target disconnection is the first pathological occurrence in fatal motoneuron diseases such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). Objective: The goal of this study was to determine if facial motoneurons (FMN) could survive permanent target disconnection up to 26 weeks post-operation (wpo) after facial nerve axotomy (FNA). In addition, the potentially additive effects of immunodeficiency and motoneuron disease on post-axotomy FMN survival were examined. Methods: This study included three wild type (WT) mouse strains (C57BL/6J, B6SJL, and FVB/NJ) and three experimental models (RAG-2-/-: immunodeficiency; mSOD1: ALS; Smn-/-/SMN2+/+: SMA). All animals received a unilateral FNA, and FMN survival was quantified at early and extended post-operative timepoints. Results: In the C57BL/6J WT group, FMN survival significantly decreased at 10 wpo (55 ± 6%), and then remained stable out to 26 wpo (47 ± 6%). In the RAG-2-/- and mSOD1 groups, FMN death occurred much earlier at 4 wpo, and survival plateaued at approximately 50% at 10 wpo. The SMA model and other WT strains also exhibited approximately 50% FMN survival after FNA. Conclusion: These results indicate that immunodeficiency and motoneuron disease accelerate axotomy-induced neuron death, but do not increase total neuron death in the context of permanent target disconnection. This consistent finding of a target disconnection-resilient motoneuron population is prevalent in other peripheral nerve injury models and in neurodegenerative disease models as well. Characterization of the distinct populations of vulnerable and resilient motoneurons may reveal new therapeutic approaches for injury and disease

    Polar phonons in some compressively stressed epitaxial and polycrystalline SrTiO3 thin films

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    Several SrTiO3 (STO) thin films without electrodes processed by pulsed laser deposition, of thicknesses down to 40 nm, were studied using infrared transmission and reflection spectroscopy. The complex dielectric responses of polar phonon modes, particularly ferroelectric soft mode, in the films were determined quantitatively. The compressed epitaxial STO films on (100) La0.18Sr0.82Al0.59-Ta0.41O3 substrates (strain 0.9%) show strongly stiffened phonon responses, whereas the soft mode in polycrystalline film on (0001) sapphire substrate shows a strong broadening due to grain boundaries and/or other inhomogeneities and defects. The stiffened soft mode is responsible for a much lower static permittivity in the plane of the compressed film than in the bulk samples.Comment: 11 page

    Impact of peripheral immune status on central molecular responses to facial nerve axotomy

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    When facial nerve axotomy (FNA) is performed on immunodeficient recombinase activating gene-2 knockout (RAG-2-/-) mice, there is greater facial motoneuron (FMN) death relative to wild type (WT) mice. Reconstituting RAG-2-/- mice with whole splenocytes rescues FMN survival after FNA, and CD4+ T cells specifically drive immune-mediated neuroprotection. Evidence suggests that immunodysregulation may contribute to motoneuron death in amyotrophic lateral sclerosis (ALS). Immunoreconstitution of RAG-2-/- mice with lymphocytes from the mutant superoxide dismutase (mSOD1) mouse model of ALS revealed that the mSOD1 whole splenocyte environment suppresses mSOD1 CD4+ T cell-mediated neuroprotection after FNA. The objective of the current study was to characterize the effect of CD4+ T cells on the central molecular response to FNA and then identify if mSOD1 whole splenocytes blocked these regulatory pathways. Gene expression profiles of the axotomized facial motor nucleus were assessed from RAG-2-/- mice immunoreconstituted with either CD4+ T cells or whole splenocytes from WT or mSOD1 donors. The findings indicate that immunodeficient mice have suppressed glial activation after axotomy, and cell transfer of WT CD4+ T cells rescues microenvironment responses. Additionally, mSOD1 whole splenocyte recipients exhibit an increased astrocyte activation response to FNA. In RAG-2-/- + mSOD1 whole splenocyte mice, an elevation of motoneuron-specific Fas cell death pathways is also observed. Altogether, these findings suggest that mSOD1 whole splenocytes do not suppress mSOD1 CD4+ T cell regulation of the microenvironment, and instead, mSOD1 whole splenocytes may promote motoneuron death by either promoting a neurotoxic astrocyte phenotype or inducing Fas-mediated cell death pathways. This study demonstrates that peripheral immune status significantly affects central responses to nerve injury. Future studies will elucidate the mechanisms by which mSOD1 whole splenocytes promote cell death and if inhibiting this mechanism can preserve motoneuron survival in injury and disease

    Dielectric properties of PbBO₃ perovskites with mixed-valence substitution in the B position

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    Dielectric properties of PbBO₃ perovskites with mixed-valence substitution in the B position / V. G. Zalesskiĭ, V. V. LemanovThis paper reports on the synthesis of PbBO3 perovskites with mixed-valence substitution in the B position in which the number of ions n in different valence states occupying oxygen octahedra varies from 2 to 6. The dielectric properties of ceramic samples have been studied at frequencies in the range from 12 Hz to 100 kHz and in the temperature interval 77–450 K. The new compounds have been shown to possess relaxor properties. Original Russian Text © V.G. Zalesskiĭ, V.V. Lemanov, 2010, published in Fizika Tverdogo Tela, 2010, Vol. 52, No. 7, pp. 1365–1369

    Crop Updates 2000 - Lupins

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    This session covers nineteen papers from different authors: 1.1999 Lupin Highlights, Bill O’Neill, LUPIN PRODUCTIVITY IMPROVEMENTS AND INDUSTRY DEVELOPMENT LUPIN ANTHRACNOSE 2. Anthracnose – 1999/2000, Geoff Thomas and Mark Sweetingham, Agriculture Western Australia LUPIN BREEDING AND AGRONOMY 3. The genetic control of mildly restricted branching in narrow-leafed lupin (Lupinus augustifolius L), Kedar Adhikari1,3, Nick Galwey1,3 and Miles Dracup2,3 1Plant Sciences, University of Western Australia 2Agriculture Western Australia 3Cooperative Research Centre for Legumes in Mediterranean Agriculture, University of Western Australia 4. Genotype x time of sowing interaction in lupins – Mingenew, Bob French, Agriculture Western Australia 5. Genotype x time of sowing interaction in lupins – Wongan Hills, Bob French, Agriculture Western Australia 6. Genetic variation in lupin tolerance to Brown Leaf Spot, Bob French, Agriculture Western Australia 7. Yellow lupin management in Western Australia, Bob French, Agriculture Western Australia APHIDS AND VIRUS CONTROL 8. Forecasting aphid and virus risk in lupins, Debbie Thackray, Jenny Hawkes and Roger Jones, Centre for Legumes in Mediterranean Agriculture and Agriculture Western Australia 9. When should lupin crops be sprayed for aphids to achieve maximum yield response? Françoise Berlandier, Agriculture Western Australia 10. Yield limiting potential of the new, non-necrotic strain of bean yellow mosaic virus in narrow-leafed lupin, Roger Jones, Yvonne Cheng and Lisa Smith, Crop Improvement Institute, Agriculture Western Australia, and Centre for Legumes in Mediterranean Agriculture LUPIN NUTRITION 11. Increasing the value of a rotation by applying lime, Chris Gazey and Michael O’Connell, Agriculture Western Australia HERBICIDE TOLERANCE AND WEED CONTROL 12. Herbicide damage does not mean lower yield in Lupins, Peter Carlton, Trials Coordinator, Elders Limited 13. Effect of herbicides Tordonä 75D and Lontrelä, used for eradication of Skeleton Weed, on production of Lupins in following seasons, John R. Peirce and Brad J. Rayner, Agriculture Western Australia 14. Herbicide tolerance of lupins, Terry Piper, Agriculture Western Australia 15. Tanjil lupins will tolerate metribuzin under the right conditions, Peter Newman, Agronomist Elders Limited and Cameron Weeks, Mingenew/Irwin Group LUPIN ESTABLISHMENT 16. A new seed pressing system for ryegrass suppression and healthy lupin establishment, Mohammad Amjad and Glen Riethmuller,Agriculture Western Australia 17. Banded surfactant for better lupin yield on non-wetting sand, Dr Paul Blackwell, Agriculture Western Australia DROUGHT TOLERANCE 18. Drought tolerance of lupin genotypes in Western Australia, Jairo A. Palta1,2,, Neil C. Turner1,2, Robert J. French2,3 ,1CSIRO Plant Industry, Centre for Mediterranean Agricultural Research, 2Centre for Legumes in Mediterranean Agriculture, University of Western Australia, 3Agriculture Western Australia, 19. Stem carbohydrate in lupins: a possible buffer to maintain seed growth under adverse conditions, Bob French1, Tim Setter2, Jairo Palta3 , 1Agriculture Western Australia, and CLIMA, 2Agriculture Western Australia, 3CSIRO, Floreat Park, and CLIM

    Thermodynamic theory of epitaxial ferroelectric thin films with dense domain structures

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    A Landau-Ginsburg-Devonshire-type nonlinear phenomenological theory is presented, which enables the thermodynamic description of dense laminar polydomain states in epitaxial ferroelectric thin films. The theory explicitly takes into account the mechanical substrate effect on the polarizations and lattice strains in dissimilar elastic domains (twins). Numerical calculations are performed for PbTiO3 and BaTiO3 films grown on (001)-oriented cubic substrates. The "misfit strain-temperature" phase diagrams are developed for these films, showing stability ranges of various possible polydomain and single-domain states. Three types of polarization instabilities are revealed for polydomain epitaxial ferroelectric films, which may lead to the formation of new polydomain states forbidden in bulk crystals. The total dielectric and piezoelectric small-signal responses of polydomain films are calculated, resulting from both the volume and domain-wall contributions. For BaTiO3 films, strong dielectric anomalies are predicted at room temperature near special values of the misfit strain.Comment: 19 pages, 8 figure
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