445 research outputs found

    The Integration of Research and Extension: A Preliminary Study

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    How are Research and Extension integrated in land-grant systems throughout the United States? This question was answered by Directors of Agriculture Experiment Stations and Cooperative Extension who completed an online survey. Ninety-two individuals responded to the survey; 53% were with AES, and 47% were with CES. Interaction tended to occur through joint appointments and cohousing of faculty. Best-integrated practices revolved around a commodity or specific issue such as water quality. Funding was a common catalyst for collaboration in the form of competitive RFPs, internal grants, or special accounts

    Using Optogenetic Dyadic Animal Models to Elucidate the Neural Basis for Human Parent-Infant Social Knowledge Transmission.

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    Healthy early development depends on a warm reciprocal relationship between parent and offspring, where parent and infant interact in close temporal co-ordination as if engaged in a “dyadic dance” of glances, gestures, smiles and words (Stern, 1985; Gianino and Tronick, 1988). Most, if not all, early learning takes place during these well-choreographed social exchanges, which support cultural knowledge transmission from parent to offspring using verbal and non-verbal forms of communication and behavioural modelling. Such vicarious knowledge transmission through social interaction (rather than direct experience) is known as social learning (Bandura, 1971; Csibra and Gergely, 2009). Tomasello (2014) argues that human mastery of these “second-personal social relations” (Darwall, 2006)—in which social partners share and create joint knowledge, intentionality and goals—has accelerated the rise of the human species through “cultural intelligence” (Herrmann et al., 2007).Ministry of Education (MOE)Published versionThis research is supported by the Ministry of Education, Singapore, under its Academic Research Fund Tier 1 [RG99/20 to VL and GA; RG152/18 (NS) to VL]

    Collateral contamination concomitant to the polonium-210 poisoning of Mr Alexander Litvinenko

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    Mr Litvinenko died on 23rd November 2006, having been poisoned with polonium-210 on 1st November, with evidence of a previous poisoning attempt during October 2006. Measurements of 210Po in urine samples were made for a large number of people to determine whether they may have been contaminated. In the majority of cases, measured levels were attributable to the presence of 210Po from normal dietary sources. For a small number of cases, elevated levels provided evidence of direct contamination associated with the poisonings. For one individual, while estimated doses were below thresholds for irreversible organ damage, a notably increased risk of cancer can be inferred. The use of the chelating agent, Unithiol, to increase 210Po excretion in this case was only moderately effective in reducing doses received

    Chemical biology in the embryo: In situ imaging of sulfur biochemistry in normal and proteoglycan-deficient cartilage matrix

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    © 2016 American Chemical Society. Proteoglycans (PGs) are heavily glycosylated proteins that play major structural and biological roles in many tissues. Proteoglycans are abundant in cartilage extracellular matrix; their loss is a main feature of the joint disease osteoarthritis. Proteoglycan function is regulated by sulfation-sulfate ester formation with specific sugar residues. Visualization of sulfation within cartilage matrix would yield vital insights into its biological roles. We present synchrotron-based X-ray fluorescence imaging of developing zebrafish cartilage, providing the first in situ maps of sulfate ester distribution. Levels of both sulfur and sulfate esters decrease as cartilage develops through late phase differentiation (maturation or hypertrophy), suggesting a functional link between cartilage matrix sulfur content and chondrocyte differentiation. Genetic experiments confirm that sulfate ester levels were due to cartilage proteoglycans and support the hypothesis that sulfate ester levels regulate chondrocyte differentiation. Surprisingly, in the PG synthesis mutant, the total level of sulfur was not significantly reduced, suggesting sulfur is distributed in an alternative chemical form during lowered cartilage proteoglycan production. Fourier transform infrared imaging indicated increased levels of protein in the mutant fish, suggesting that this alternative sulfur form might be ascribed to an increased level of protein synthesis in the mutant fish, as part of a compensatory mechanism

    Opportunities and challenges of self-binding directives: A comparison of empirical research with stakeholders in three European countries

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    BackgroundSelf-binding directives (SBDs) are psychiatric advance directives that include a clause in which mental health service users consent in advance to involuntary hospital admission and treatment under specified conditions. Medical ethicists and legal scholars identified various potential benefits of SBDs but have also raised ethical concerns. Until recently, little was known about the views of stakeholders on the opportunities and challenges of SBDs.AimsThis article aims to foster an international exchange on SBDs by comparing recent empirical findings on stakeholders’ views on the opportunities and challenges of SBDs from Germany, the Netherlands, and the United Kingdom.MethodComparisons between the empirical findings were drawn using a structured expert consensus process.ResultsFindings converged on many points. Perceived opportunities of SBDs include promotion of autonomy, avoidance of personally defined harms, early intervention, reduction of admission duration, improvement of the therapeutic relationship, involvement of persons of trust, avoidance of involuntary hospital admission, addressing trauma, destigmatization of involuntary treatment, increase of professionals’ confidence, and relief for proxy decision-makers. Perceived challenges include lack of awareness and knowledge, lack of support, undue influence, inaccessibility during crisis, lack of cross-agency coordination, problems of interpretation, difficulties in capacity assessment, restricted therapeutic flexibility, scarce resources, disappointment due to noncompliance, and outdated content. Stakeholders tended to focus on practical challenges and did not often raise fundamental ethical concerns.ConclusionsStakeholders tend to see the implementation of SBDs as ethically desirable, provided that the associated challenges are addressed.<br/

    Hexb enzyme deficiency leads to lysosomal abnormalities in radial glia and microglia in zebrafish brain development

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    Sphingolipidoses are severe, mostly infantile lysosomal storage disorders (LSDs) caused by defective glycosphingolipid degradation. Two of these sphingolipidoses, Tay Sachs and Sandhoff diseases, are caused by ÎČ-Hexosaminidase (HEXB) enzyme deficiency, resulting in ganglioside (GM2) accumulation and neuronal loss. The precise sequence of cellular events preceding, and leading to, neuropathology remains unclear, but likely involves inflammation and lysosomal accumulation of GM2 in multiple cell types. We aimed to determine the consequences of Hexb activity loss for different brain cell types using zebrafish. Hexb deficient zebrafish (hexb−/− ) showed lysosomal abnormalities already early in development both in radial glia, which are the neuronal and glial progenitors, and in microglia. Additionally, at 5 days postfertilization, hexb−/− zebrafish showed reduced locomotor activity. Although specific oligosaccharides accumulate in the adult brain, hexb−/− ) zebrafish are viable and apparently resistant to Hexb deficiency. In all, we identified cellular consequences of loss of Hexb enzyme activity during embryonic brain development, showing early effects on glia, which possibly underlie the behavioral aberrations. Hereby, we identified clues into the contribution of non-neuronal lysosomal abnormalities in LSDs affecting the brain and provide a tool to further study what underlies the relative resistance to Hexb deficiency in vivo

    Angiotensin II for the Treatment of Vasodilatory Shock

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    BACKGROUND Vasodilatory shock that does not respond to high-dose vasopressors is associated with high mortality. We investigated the effectiveness of angiotensin II for the treatment of patients with this condition. METHODS We randomly assigned patients with vasodilatory shock who were receiving more than 0.2 mu g of norepinephrine per kilogram of body weight per minute or the equivalent dose of another vasopressor to receive infusions of either angiotensin II or placebo. The primary end point was a response with respect to mean arterial pressure at hour 3 after the start of infusion, with response defined as an increase from baseline of at least 10 mm Hg or an increase to at least 75 mm Hg, without an increase in the dose of background vasopressors. RESULTS A total of 344 patients were assigned to one of the two regimens; 321 received a study intervention (163 received angiotensin II, and 158 received placebo) and were included in the analysis. The primary end point was reached by more patients in the angiotensin II group (114 of 163 patients, 69.9%) than in the placebo group (37 of 158 patients, 23.4%) (odds ratio, 7.95; 95% confidence interval [CI], 4.76 to 13.3; P<0.001). At 48 hours, the mean improvement in the cardiovascular Sequential Organ Failure Assessment (SOFA) score (scores range from 0 to 4, with higher scores indicating more severe dysfunction) was greater in the angiotensin II group than in the placebo group (-1.75 vs. -1.28, P = 0.01). Serious adverse events were reported in 60.7% of the patients in the angiotensin II group and in 67.1% in the placebo group. Death by day 28 occurred in 75 of 163 patients (46%) in the angiotensin II group and in 85 of 158 patients (54%) in the placebo group (hazard ratio, 0.78; 95% CI, 0.57 to 1.07; P = 0.12). CONCLUSIONS Angiotensin II effectively increased blood pressure in patients with vasodilatory shock that did not respond to high doses of conventional vasopressors. (Funded by La Jolla Pharmaceutical Company; ATHOS-3 ClinicalTrials.gov number, NCT02338843.)Peer reviewe

    Tissue-specific suppression of thyroid hormone signaling in various mouse models of aging

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    DNA damage contributes to the process of aging, as underscored by premature aging syndromes caused by defective DNA repair. Thyroid state changes during aging, but underlying mechanisms remain elusive. Since thyroid hormone (TH) is a key regulator of metabolism, changes in TH signaling have widespread effects. Here, we reveal a significant common transcriptomic signature in livers from hypothyroid mice, DNA repair-deficient mice with severe (Csbm/m/Xpa-/-) or intermediate (Ercc1-/Δ-7) progeria and naturally aged mice. A strong induction of TH-inactivating deiodinase D3 and decrease of TH-activating D1 activities are observed in Csbm/m/Xpa-/- livers. Similar findings are noticed in Ercc1-/Δ-7, in naturally aged animals and in wild-type mice exposed to a chronic subtoxic dose of DNAdamaging agents. In contrast, TH signaling in muscle, heart and brain appears unaltered. These data show a strong suppression of TH signaling in specific peripheral organs in premature and normal aging, probably lowering metabolism, while other tissues appear to preserve metabolism. D3-mediated TH inactivation is unexpected, given its expression mainly in fetal tissues. Our studies highlight the importance of DNA damage as the underlying mechanism of changes in thyroid state. Tissue-specific regulation of deiodinase activities, ensuring diminished TH signaling, may contribute importantly to the protective metabolic response in aging
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