623 research outputs found

    The Soul of Politics: The Reverend Jim Wallis\u27s Attempt to Transcend the Religious/Secular Left and the Religious Right

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    Preacher and social activist Jim Wallis has written and spoke out against what he identified as the polarizing effects between the Religious/Secular Left and the Religious Right. His first hook The Soul of Politics: A Practical and Prophetic Vision for Change (1995) reveals Wallis\u27s attempt to create a rhetorical vision that transcends the polarizing political ideologies of the Left and Right. An analysis of Wallis\u27s rhetoric reveals that while his rhetorical goal was laudable the message, built in the form of a jeremiad, lacked consistency and failed to transcend the Frames of Acceptance of both the Left and the Right

    Drivers of bird species richness within moist high-altitude grasslands in eastern South Africa

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    Moist high-altitude grasslands in South Africa are renowned for high avifaunal diversity and are priority areas for conservation. Conservation management of these areas conflicts with management for other uses, such as intensive livestock agriculture, which requires annual burning and leads to heavy grazing. Recently the area has become target for water storage schemes and renewable electricity energy projects. There is therefore an urgent need to investigate environmental factors and habitat factors that affect bird species richness in order to optimise management of those areas set aside for conservation. A particularly good opportunity to study these issues arose at Ingula in the eastern South African high-altitude grasslands. An area that had been subject to intense grazing was bought by the national power utility that constructed a pumped storage scheme on part of the land and set aside the rest for bird conservation. Since the new management took over in 2005 the area has been mostly annually burned with relatively little grazing. The new management seeks scientific advice on how to maintain avian species richness of the study area. We collected bird occurrence and vegetation data along random transects between 2006 and 2010 to monitor the impact of the new management, and to study the effect of the habitat changes on bird species richness. To achieve these, we convert bird transect data to presence only data to investigate how bird species richness were related to key transect vegetation attributes under this new grassland management. First we used generalised linear mixed models, to examine changes in vegetation grass height and cover and between burned and unburned habitats. Secondly, we examined how total bird species richness varied across seasons and years. And finally we investigated which habitat vegetation attributes were correlated with species richness of a group of grassland depended bird species only. Transects that were burned showed a larger decrease in vegetation cover compared to transects that were not burned. Grass height increased over time. Bird species richness was highest in summer compared to other seasons and increased over time. Overall bird species richness increased over the three summer surveys but species richness of birds that prefer heavily grazed habitat showed little change over the three years. Changes in bird species richness were best explained by the model with grass height for combined species richness of grassland depended birds but also for birds that prefer heavy grazing when treated alone. On one hand birds that prefer moderate grazing were best explained by a null model. However, overall bird species richness was better positively correlated to grass height than grass cover or dead grass. We conclude that frequent burning alone with relatively reduced grazing led to higher but less dense grass, which benefited some species and disadvantaged others. We suggest that management of this grassland use combination of fire and grazing and leave some areas unburned to accommodates birds of various habitat needs

    A role for the JAK-STAT1 pathway in blocking replication of HSV-1 in dendritic cells and macrophages

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    <p>Abstract</p> <p>Background</p> <p>Macrophages and dendritic cells (DCs) play key roles in host defense against HSV-1 infection. Although macrophages and DCs can be infected by herpes simplex virus type 1 (HSV-1), both cell types are resistant to HSV-1 replication. The aim of our study was to determine factor (s) that are involved in the resistance of DCs and macrophages to productive HSV-1 infection.</p> <p>Results</p> <p>We report here that, in contrast to bone marrow-derived DCs and macrophages from wild type mice, DCs and macrophages isolated from signal transducers and activators of transcription-1 deficient (STAT1<sup>-/-</sup>) mice were susceptible to HSV-1 replication and the production of viral mRNAs and DNA. There were differences in expression of immediate early, early, and late gene transcripts between STAT1<sup>+/+ </sup>and STAT1<sup>-/- </sup>infected APCs.</p> <p>Conclusion</p> <p>These results suggest for the first time that the JAK-STAT1 pathway is involved in blocking replication of HSV-1 in DCs and macrophages.</p

    Macrophages exposed continuously to lipopolysaccharide and other agonists that act via toll-like receptors exhibit a sustained and additive activation state

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    BACKGROUND: Macrophages sense microorganisms through activation of members of the Toll-like receptor family, which initiate signals linked to transcription of many inflammation associated genes. In this paper we examine whether the signal from Toll-like receptors [TLRs] is sustained for as long as the ligand is present, and whether responses to different TLR agonists are additive. RESULTS: RAW264 macrophage cells were doubly-transfected with reporter genes in which the IL-12p40, ELAM or IL-6 promoter controls firefly luciferase, and the human IL-1β promoter drives renilla luciferase. The resultant stable lines provide robust assays of macrophage activation by TLR stimuli including LPS [TLR4], lipopeptide [TLR2], and bacterial DNA [TLR9], with each promoter demonstrating its own intrinsic characteristics. With each of the promoters, luciferase activity was induced over an 8 hr period, and thereafter reached a new steady state. Elevated expression required the continued presence of agonist. Sustained responses to different classes of agonist were perfectly additive. This pattern was confirmed by measuring inducible cytokine production in the same cells. While homodimerization of TLR4 mediates responses to LPS, TLR2 appears to require heterodimerization with another receptor such as TLR6. Transient expression of constitutively active forms of TLR4 or TLR2 plus TLR6 stimulated IL-12 promoter activity. The effect of LPS, a TLR4 agonist, was additive with that of TLR2/6 but not TLR4, whilst that of lipopeptide, a TLR2 agonist, was additive with TLR4 but not TLR2/6. Actions of bacterial DNA were additive with either TLR4 or TLR2/6. CONCLUSIONS: These findings indicate that maximal activation by any one TLR pathway does not preclude further activation by another, suggesting that common downstream regulatory components are not limiting. Upon exposure to a TLR agonist, macrophages enter a state of sustained activation in which they continuously sense the presence of a microbial challenge

    Optimization of DNA extraction from human urinary samples for mycobiome community profiling.

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    IntroductionRecent data suggest the urinary tract hosts a microbial community of varying composition, even in the absence of infection. Culture-independent methodologies, such as next-generation sequencing of conserved ribosomal DNA sequences, provide an expansive look at these communities, identifying both common commensals and fastidious organisms. A fundamental challenge has been the isolation of DNA representative of the entire resident microbial community, including fungi.Materials and methodsWe evaluated multiple modifications of commonly-used DNA extraction procedures using standardized male and female urine samples, comparing resulting overall, fungal and bacterial DNA yields by quantitative PCR. After identifying protocol modifications that increased DNA yields (lyticase/lysozyme digestion, bead beating, boil/freeze cycles, proteinase K treatment, and carrier DNA use), all modifications were combined for systematic confirmation of optimal protocol conditions. This optimized protocol was tested against commercially available methodologies to compare overall and microbial DNA yields, community representation and diversity by next-generation sequencing (NGS).ResultsOverall and fungal-specific DNA yields from standardized urine samples demonstrated that microbial abundances differed significantly among the eight methods used. Methodologies that included multiple disruption steps, including enzymatic, mechanical, and thermal disruption and proteinase digestion, particularly in combination with small volume processing and pooling steps, provided more comprehensive representation of the range of bacterial and fungal species. Concentration of larger volume urine specimens at low speed centrifugation proved highly effective, increasing resulting DNA levels and providing greater microbial representation and diversity.ConclusionsAlterations in the methodology of urine storage, preparation, and DNA processing improve microbial community profiling using culture-independent sequencing methods. Our optimized protocol for DNA extraction from urine samples provided improved fungal community representation. Use of this technique resulted in equivalent representation of the bacterial populations as well, making this a useful technique for the concurrent evaluation of bacterial and fungal populations by NGS

    Collaborative Induction of Inflammatory Responses by Dectin-1 and Toll-like Receptor 2

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    Toll-like receptors (TLRs) mediate recognition of a wide range of microbial products including lipopolysaccharides, lipoproteins, flagellin, and bacterial DNA, and signaling through TLRs leads to the production of inflammatory mediators. In addition to TLRs, many other surface receptors have been proposed to participate in innate immunity and microbial recognition, and signaling through some of these receptors is likely to cooperate with TLR signaling in defining inflammatory responses. In this report we have examined how dectin-1, a lectin family receptor for β-glucans, collaborates with TLRs in recognizing microbes. Dectin-1, which is expressed at low levels on macrophages and high levels on dendritic cells, contains an immunoreceptor tyrosine-based activation motif–like signaling motif that is tyrosine phosphorylated upon activation. The receptor is recruited to phagosomes containing zymosan particles but not to phagosomes containing immunoglobulin G–opsonized particles. Dectin-1 expression enhances TLR-mediated activation of nuclear factor κB by β-glucan–containing particles, and in macrophages and dendritic cells dectin-1 and TLRs are synergistic in mediating production of cytokines such as interleukin 12 and tumor necrosis factor α. Additionally, dectin-1 triggers production of reactive oxygen species, an inflammatory response that is primed by TLR activation. The data demonstrate that collaborative recognition of distinct microbial components by different classes of innate immune receptors is crucial in orchestrating inflammatory responses

    Amphetamine Modulates Excitatory Neurotransmission through Endocytosis of the Glutamate Transporter EAAT3 in Dopamine Neurons

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    SummaryAmphetamines modify the brain and alter behavior through mechanisms generally attributed to their ability to regulate extracellular dopamine concentrations. However, the actions of amphetamine are also linked to adaptations in glutamatergic signaling. We report here that when amphetamine enters dopamine neurons through the dopamine transporter, it stimulates endocytosis of an excitatory amino acid transporter, EAAT3, in dopamine neurons. Consistent with this decrease in surface EAAT3, amphetamine potentiates excitatory synaptic responses in dopamine neurons. We also show that the process of internalization is dynamin- and Rho-mediated and requires a unique sequence in the cytosolic C terminus of EAAT3. Introduction of a peptide based on this motif into dopamine neurons blocks the effects of amphetamine on EAAT3 internalization and its action on excitatory responses. These data indicate that the internalization of EAAT3 triggered by amphetamine increases glutamatergic signaling and thus contributes to the effects of amphetamine on neurotransmission

    Immunoglobulin Replacement Therapy During COVID-19 Pandemic: Practical and Psychological Impact in Patients with Antibody Deficiency

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    Purpose: The COVID-19 pandemic has impacted on how health services deliver care and the mental health of the population. Due to their clinical vulnerability, to reduce in-hospital attendances during the COVID-19 pandemic, modifications in immunoglobulin treatment regimens were made for patients with antibody deficiency. These patients were also likely to experience social isolation due to shielding measure that were advised. We aimed to investigate the impact of modifying immunoglobulin treatment regimen on infection and mental health burden during shielding restrictions.// Method: Patients on immunoglobulin replacement therapy (IGRT) responded to a standardised questionnaire examining self-reported infection frequency, anxiety (GAD-7), depression (PHQ-8), fatigue (FACIT), and quality of life during the pandemic. Infection frequency and immunoglobulin trough levels were compared to pre-pandemic levels.// Results: Patients who did not change treatment modality or those who received immunoglobulin replacement at home during the pandemic reported fewer infections. In patients who received less frequent hospital infusions, there was no significant increase in infections whilst immunoglobulin trough levels remained stable. There was no significant difference in anxiety, or depression scores between the treatment modality groups. Patients reported higher fatigue scores compared to the pre-COVID general population and in those discharged following hospitalisation for COVID.// Conclusion: Changing immunoglobulin treatment regimen did not negatively impact infection rates or psychological wellbeing. However, psychological welfare should be prioritised for this group particularly given uncertainties around COVID-19 vaccination responsiveness and continued social isolation for many
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