169 research outputs found

    LOW-COST, HOLISTIC APPROACH TO ACTIVE LEARNING IN INFORMATION TECHNOLOGY

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    ABSTRACT The curriculum of a program in information technolog

    Rim Pathway-Mediated Alterations in the Fungal Cell Wall Influence Immune Recognition and Inflammation

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    ACKNOWLEDGMENTS We acknowledge Jennifer Lodge, Woei Lam, and Rajendra Upadhya for developing and sharing the chitin and chitosan MTBH assay. We thank Todd Brennan of Duke University for providing MyD88-deficient mice. We acknowledge Neil Gow for providing access to the Dionex HPAEC-PAD instrumentation. We also acknowledge Connie Nichols for critical reading of the manuscript. These experiments were supported by an NIH grant to J.A.A. and F.L.W., Jr. (R01 AI074677). C.M.L.W. was supported by a fellowship provided through the Army Research Office of the Department of Defense (no. W911NF-11-1-0136 f) (F.L.W., Jr.). J.W., L.W., and C.M. were supported by the Wellcome Trust Strategic Award in Medical Mycology and Fungal Immunology (097377) and the MRC, Centre for Medical Mycology (MR/N006364/1). FUNDING INFORMATION MRC Centre for Medical MycologyMR/N006364/1 Carol A. Munro HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) https://doi.org/10.13039/100000060R01 AI074677J. Andrew Alspaugh Wellcome https://doi.org/10.13039/100010269097377 Carol A. Munro DOD | United States Army | RDECOM | Army Research Office (ARO) https://doi.org/10.13039/100000183W911NF-11-1-0136 f Chrissy M. Leopold WagerPeer reviewe

    Neurotensin NTS1 and NTS2 receptor agonists produce anxiolytic-like effects in the 22-kHz ultrasonic vocalization model in rats

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    Neurotensin is a neuropeptide neurotransmitter that interacts with multiple neurotransmitter systems, including those regulating amygdalar function, via NTS1 and NTS2 receptors. Both receptors are expressed in the amygdala and agonists for NTS1 or NTS2 receptors have exhibited anxiolytic effects in animal models. Systemic adminstration of NTS1 receptor agonist PD149163 was recently shown to reduce footshock conditioned 22-kHz ultrasonic vocalizations in rats, suggesting that PD149163 produced an anxiolytic effect. The effects that neurotensin may have or a selective NTS2receptor agonist may have on 22-kHz vocalizations has yet to be examined. The current study evaluated the effects of intracerebroventricularly administered neurotensin (0.1–10.0 μg), PD149163 (0.1–10.0 ng), or the NTS2 receptor agonist JMV-431 (0.1–1.0 μg) on footshock conditioned 22-kHz vocalizations in male Wistar rats. Neurotensin, PD149163, and JMV-431 all significantly reduced the number 22-kHz calls. No changes in call duration were found, suggesting that non-specific drug effects do not account for the reductions in 22-kHz calls. These data support anxiolytic effects produced by activation of NTS1 or NTS2 receptors, and suggest that neurotensin plays a natural role in the expression of conditioned USVs. These data suggest that both receptor subtypes are putative pharmacologic targets

    Neonatal vaccination of low birthweight infants in Ghana.

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    OBJECTIVES: Global vaccination policy advocates for identifying and targeting groups who are underserved by vaccination to increase equity and uptake. We investigated whether birth weight and other factors are determinants of neonatal BCG vaccination in order to identify infants underserved by vaccination. METHODS: We used logistic regression to calculate adjusted ORs (AORs) for the association between birth weight (categorised as non-low birth weight (NLBW) (≥2.50 kg) and low birth weight (LBW) (2-2.49 kg, 1.50-1.99 kg and 0.19). Facility-born infants were vaccinated at a mean of 6 days, suggesting that they were not vaccinated in the facility at birth but were referred for vaccination. CONCLUSIONS: LBW is a risk factor for neonatal under-vaccination, even for facility-born infants. Ensuring vaccination at facility births would substantively improve timing and equitable BCG vaccination

    Note and Comment

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    The Doctrine of Unfair Trade; Valuing Property and Franchises of Public Service Corporations for Fixing Rates; Right of the Interstate Commerce Commission to Adduce Testimony; Rule in Shelley\u27s Case controls Estate Created by Deed to Trustee; The Right of the Garnishee to Dispose of Goods in His Possession While the Litigation is Pending; The Police Power, Billboards and Sky Signs; How Far the Record of Voting Machines is Conclusive

    Radiation mitigating properties of the lignan component in flaxseed

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    BACKGROUND: Wholegrain flaxseed (FS), and its lignan component (FLC) consisting mainly of secoisolariciresinol diglucoside (SDG), have potent lung radioprotective properties while not abrogating the efficacy of radiotherapy. However, while the whole grain was recently shown to also have potent mitigating properties in a thoracic radiation pneumonopathy model, the bioactive component in the grain responsible for the mitigation of lung damage was never identified. Lungs may be exposed to radiation therapeutically for thoracic malignancies or incidentally following detonation of a radiological dispersion device. This could potentially lead to pulmonary inflammation, oxidative tissue injury, and fibrosis. This study aimed to evaluate the radiation mitigating effects of FLC in a mouse model of radiation pneumonopathy. METHODS: We evaluated FLC-supplemented diets containing SDG lignan levels comparable to those in 10% and 20% whole grain diets. 10% or 20% FLC diets as compared to an isocaloric control diet (0% FLC) were given to mice (C57/BL6) (n=15-30 mice/group) at 24, 48, or 72-hours after single-dose (13.5 Gy) thoracic x-ray treatment (XRT). Mice were evaluated 4 months post-XRT for blood oxygenation, lung inflammation, fibrosis, cytokine and oxidative damage levels, and survival. RESULTS: FLC significantly mitigated radiation-related animal death. Specifically, mice fed 0% FLC demonstrated 36.7% survival 4 months post-XRT compared to 60–73.3% survival in mice fed 10%-20% FLC initiated 24–72 hours post-XRT. FLC also mitigated radiation-induced lung fibrosis whereby 10% FLC initiated 24-hours post-XRT significantly decreased fibrosis as compared to mice fed control diet while the corresponding TGF-beta1 levels detected immunohistochemically were also decreased. Additionally, 10-20% FLC initiated at any time point post radiation exposure, mitigated radiation-induced lung injury evidenced by decreased bronchoalveolar lavage (BAL) protein and inflammatory cytokine/chemokine release at 16 weeks post-XRT. Importantly, neutrophilic and overall inflammatory cell infiltrate in airways and levels of nitrotyrosine and malondialdehyde (protein and lipid oxidation, respectively) were also mitigated by the lignan diet. CONCLUSIONS: Dietary FLC given early post-XRT mitigated radiation effects by decreasing inflammation, lung injury and eventual fibrosis while improving survival. FLC may be a useful agent, mitigating adverse effects of radiation in individuals exposed to incidental radiation, inhaled radioisotopes or even after the initiation of radiation therapy to treat malignancy

    Defects in intracellular trafficking of fungal cell wall synthases lead to aberrant host immune recognition

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    Acknowledgments We acknowledge Jeanette Wagener and Louise Walker for performing the HPAEC-PAD analysis and Neil Gow for providing access to the Dionex HPAEC-PAD instrumentation. We thank Mike Cook and the Duke University Cancer Center Flow Cytometry Shared Resource for assistance with the flow cytometry. We also acknowledge Michelle Plue and the Duke University Shared Materials Institute Facility for performing the transmission electron microscopy. We thank Marcel Wu¨thrich for providing the MyD88-/-and TLR2/4-/- mice, and Mari Shinohara and Elizabeth Deerhake for providing the Dectin-1-/- mice. Funding: These experiments were supported by a National Institutes of Health grant awarded to JAA and FLW, Jr. (R01 AI074677, https://grants.nih.gov/grants/oer.html). CM and colleagues Jeanette Wagener, Louise Walker, Neil Gow were supported by the Wellcome Trust Strategic Award in Medical Mycology and Fungal Immunology (097377, https://wellcome.ac.uk), Wellcome Trust Senior Investigator Award (101873) and the MRC Centre for Medical Mycology (MR/N006364/1, https://www.abdn.ac.uk/cmm/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

    IL-27 signaling activates skin cells to induce innate antiviral proteins and protects against Zika virus infection

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    In the skin, antiviral proteins and other immune molecules serve as the first line of innate antiviral defense. Here, we identify and characterize the induction of cutaneous innate antiviral proteins in response to IL-27 and its functional role during cutaneous defense against Zika virus infection. Transcriptional and phenotypic profiling of epidermal keratinocytes treated with IL-27 demonstrated activation of antiviral proteins OAS1, OAS2, OASL, and MX1 in the skin of both mice and humans. IL-27–mediated antiviral protein induction was found to occur in a STAT1- and IRF3-dependent but STAT2-independent manner. Moreover, using IL27ra mice, we demonstrate a significant role for IL-27 in inhibiting Zika virus morbidity and mortality following cutaneous, but not intravenous, inoculation. Together, our results demonstrate a critical and previously unrecognized role for IL-27 in cutaneous innate antiviral immunity against Zika virus

    Vaccination timing of low-birth-weight infants in rural Ghana: a population-based, prospective cohort study

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    Objective: To investigate delays in first and third dose diphtheria–tetanus–pertussis (DTP1 and DTP3) vaccination in low-birth-weight infants in Ghana, and the associated determinants. Methods: We used data from a large, population-based vitamin A trial in 2010–2013, with 22 955 enrolled infants. We measured vaccination rate and maternal and infant characteristics and compared three categories of low-birth-weight infants (2.0–2.4 kg; 1.5–1.9 kg; and <1.5 kg) with infants weighing ≥2.5 kg. Poisson regression was used to calculate vaccination rate ratios for DTP1 at 10, 14 and 18 weeks after birth, and for DTP3 at 18, 22 and 24 weeks (equivalent to 1, 2 and 3 months after the respective vaccination due dates of 6 and 14 weeks). Findings: Compared with non-low-birth-weight infants (n=18 979), those with low birth weight (n=3382) had an almost 40% lower DTP1 vaccination rate at age 10 weeks (adjusted rate ratio, aRR: 0.58; 95% confidence interval, CI: 0.43–0.77) and at age 18 weeks (aRR: 0.63; 95% CI: 0.50–0.80). Infants weighing 1.5–1.9 kg (n=386) had vaccination rates approximately 25% lower than infants weighing ≥2.5 kg at these time points. Similar results were observed for DTP3. Lower maternal age, educational attainment and longer distance to the nearest health facility were associated with lower DTP1 and DTP3 vaccination rates. Conclusion: Low-birth-weight infants are a high-risk group for delayed vaccination in Ghana. Efforts to improve the vaccination of these infants are warranted, alongside further research to understand the reasons for the delays
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