135 research outputs found

    Geographic constraints on social network groups

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    Social groups are fundamental building blocks of human societies. While our social interactions have always been constrained by geography, it has been impossible, due to practical difficulties, to evaluate the nature of this restriction on social group structure. We construct a social network of individuals whose most frequent geographical locations are also known. We also classify the individuals into groups according to a community detection algorithm. We study the variation of geographical span for social groups of varying sizes, and explore the relationship between topological positions and geographic positions of their members. We find that small social groups are geographically very tight, but become much more clumped when the group size exceeds about 30 members. Also, we find no correlation between the topological positions and geographic positions of individuals within network communities. These results suggest that spreading processes face distinct structural and spatial constraints.Comment: 10 pages, 5 figure

    Structural analysis of MDM2 RING separates degradation from regulation of p53 transcription activity

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    MDM2–MDMX complexes bind the p53 tumor-suppressor protein, inhibiting p53's transcriptional activity and targeting p53 for proteasomal degradation. Inhibitors that disrupt binding between p53 and MDM2 efficiently activate a p53 response, but their use in the treatment of cancers that retain wild-type p53 may be limited by on-target toxicities due to p53 activation in normal tissue. Guided by a novel crystal structure of the MDM2–MDMX–E2(UbcH5B)–ubiquitin complex, we designed MDM2 mutants that prevent E2–ubiquitin binding without altering the RING-domain structure. These mutants lack MDM2's E3 activity but retain the ability to limit p53′s transcriptional activity and allow cell proliferation. Cells expressing these mutants respond more quickly to cellular stress than cells expressing wild-type MDM2, but basal p53 control is maintained. Targeting the MDM2 E3-ligase activity could therefore widen the therapeutic window of p53 activation in tumors

    Impaired expression of metallothioneins contributes to allergen-induced inflammation in patients with atopic dermatitis

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    Regulation of cutaneous immunity is severely compromised in inflammatory skin disease. To investigate the molecular crosstalk underpinning tolerance versus inflammation in atopic dermatitis, we utilise a human in vivo allergen challenge study, exposing atopic dermatitis patients to house dust mite. Here we analyse transcriptional programmes at the population and single cell levels in parallel with immunophenotyping of cutaneous immunocytes revealed a distinct dichotomy in atopic dermatitis patient responsiveness to house dust mite challenge. Our study shows that reactivity to house dust mite was associated with high basal levels of TNF-expressing cutaneous Th17 T cells, and documents the presence of hub structures where Langerhans cells and T cells co-localised. Mechanistically, we identify expression of metallothioneins and transcriptional programmes encoding antioxidant defences across all skin cell types, that appear to protect against allergen-induced inflammation. Furthermore, single nucleotide polymorphisms in the MTIX gene are associated with patients who did not react to house dust mite, opening up possibilities for therapeutic interventions modulating metallothionein expression in atopic dermatitis

    The view of teachers on bullying and implications for nursing

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    Objetivo: Compreender o bullying escolar, na perspectiva dos professores, e refletir sobre as possíveis ações da área da saúde em seu enfrentamento. Para tanto, tomaram- se por base as diretrizes do Programa Saúde na Escola, dos Ministérios da Saúde e da Educação. Método: Estudo de caso qualitativo, realizado com professores de uma escola pública de Minas Gerais. Foram utilizados grupos focais na coleta de dados e o material empírico foi decodificado a partir de técnica de análise temática de conteúdo, resultando em uma categoria analítica: concepções e experiências de professores diante do bullying. Resultados: Foram identificadas percepções pontuais sobre o fenômeno e utilização de recursos de intervenção pouco eficazes. No plano interpretativo, problematizaram-se as contribuições da saúde e da enfermagem no redimensionamento das intervenções e no processo de formação continuada dos professores. Conclusão: Os resultados apontam para a construção de práticas intersetoriais para o enfrentamento do bullying.To understand school bullying from the perspective of teachers and reflect about the possible actions of the health area when coping with it. The guidelines of the School Health Program of the Ministries of Health and Education were used to reach that purpose. Method: A qualitative study carried out with teachers of a public school in Minas Gerais. Focus groups were used to collect data and the empirical material was decoded from thematic analysis of content, resulting in an analytical category: conceptions and experiences of teachers on bullying. Results: Specific perceptions about the phenomenon and the use of ineffective intervention resources were identified. In the interpretive plan were problematized the health and nursing contributions with resizing the interventions and the continuing training process of teachers. Conclusion: The results point to the construction of intersectoral practices forcoping with bullying.Objetivo: Comprender el bullying escolar desde la perspectiva de los profesores, y reflexionar sobre las posibles acciones del área de salud en su enfrentamiento. Tomando como base los lineamientos del Programa de Salud Escolar, de los Ministerios de Salud y de Educación. Método: Estudio de caso cualitativo realizado con los profesores de una escuela pública en Minas Gerais. Para la recolección de datos se utilizaron grupos focales y el material empírico fue decodificado a partir de la técnica de análisis temático de contenido, dando lugar a una categoría analítica: concepciones y experiencias de los profesores sobre el acoso escolar. Resultados: Se identificaron percepciones específicas sobre el fenómeno y la utilización de recursos ineficaces de intervención. En el plano interpretativo, se problematizaron las contribuciones de la salud y de la enfermería en el redimensionamiento de las intervenciones y en el proceso de formación continua de los profesores. Conclusión: Los resultados apuntan a la construcción de prácticas intersectoriales para el enfrentamiento del bullying.CIEC - Centro de Investigação em Estudos da Criança, UM (UI 317 da FCT

    A Metric of Influential Spreading during Contagion Dynamics through the Air Transportation Network

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    The spread of infectious diseases at the global scale is mediated by long-range human travel. Our ability to predict the impact of an outbreak on human health requires understanding the spatiotemporal signature of early-time spreading from a specific location. Here, we show that network topology, geography, traffic structure and individual mobility patterns are all essential for accurate predictions of disease spreading. Specifically, we study contagion dynamics through the air transportation network by means of a stochastic agent-tracking model that accounts for the spatial distribution of airports, detailed air traffic and the correlated nature of mobility patterns and waiting-time distributions of individual agents. From the simulation results and the empirical air-travel data, we formulate a metric of influential spreading––the geographic spreading centrality––which accounts for spatial organization and the hierarchical structure of the network traffic, and provides an accurate measure of the early-time spreading power of individual nodes

    Characterization of Cholinesterases in Plasma of Three Portuguese Native Bird Species: Application to Biomonitoring

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    Over the last decades the inhibition of plasma cholinesterase (ChE) activity has been widely used as a biomarker to diagnose organophosphate and carbamate exposure. Plasma ChE activity is a useful and non-invasive method to monitor bird exposure to anticholinesterase compounds; nonetheless several studies had shown that the ChE form(s) present in avian plasma may vary greatly among species. In order to support further biomonitoring studies and provide reference data for wildlife risk-assessment, plasma cholinesterase of the northern gannet (Morus bassanus), the white stork (Ciconia ciconia) and the grey heron (Ardea cinerea) were characterized using three substrates (acetylthiocholine iodide, propionylthiocholine iodide, and S-butyrylthiocholine iodide) and three ChE inhibitors (eserine sulphate, BW284C51, and iso-OMPA). Additionally, the range of ChE activity that may be considered as basal levels for non-exposed individuals was determined. The results suggest that in the plasma of the three species studied the main cholinesterase form present is butyrylcholinesterase (BChE). Plasma BChE activity in non-exposed individuals was 0.48±0.11 SD U/ml, 0.39±0.12 SD U/ml, 0.15±0.04 SD U/ml in the northern gannet, white stork and grey heron, respectively. These results are crucial for the further use of plasma BChE activity in these bird species as a contamination bioindicator of anti-cholinesterase agents in both wetland and marine environments. Our findings also underscore the importance of plasma ChE characterization before its use as a biomarker in biomonitoring studies with birds

    Parental investment by skin feeding in a caecilian amphibian

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    Although the initial growth and development of most multicellular animals depends on the provision of yolk, there are many varied contrivances by which animals provide additional or alternative investment in their offspring(1). Providing offspring with additional nutrition should be favoured by natural selection when the consequent increased fitness of the young offsets any corresponding reduction in fecundity(2). Alternative forms of nutrition may allow parents to delay and potentially redirect their investment. Here we report a remarkable form of parental care and mechanism of parent-offspring nutrient transfer in a caecilian amphibian. Boulengerula taitanus is a direct-developing, oviparous caecilian(3), the skin of which is transformed in brooding females to provide a rich supply of nutrients for the developing offspring. Young animals are equipped with a specialized dentition, which they use to peel and eat the outer layer of their mother's modified skin. This new form of parental care provides a plausible intermediate stage in the evolution of viviparity in caecilians. At independence, offspring of viviparous and of oviparous dermatotrophic caecilians are relatively large despite being provided with relatively little yolk. The specialized dentition of skin-feeding (dermatophagous) caecilians may constitute a pre-adaptation to the fetal feeding on the oviduct lining of viviparous caecilians.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62957/1/nature04403.pd

    Superior Neuroprotective Efficacy of LAU-0901, a Novel Platelet-Activating Factor Antagonist, in Experimental Stroke

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    Platelet-activating factor (PAF) accumulates during cerebral ischemia, and inhibition of this process plays a critical role in neuronal survival. Recently, we demonstrated that LAU-0901, a novel PAF receptor antagonist, is neuroprotective in experimental stroke. We used magnetic resonance imaging in conjunction with behavior and immunohistopathology to expand our understanding of this novel therapeutic approach. Sprague–Dawley rats received 2 h middle cerebral artery occlusion (MCAo) and were treated with LAU-0901 (60 mg/kg) or vehicle 2 h from MCAo onset. Behavioral function, T2-weighted imaging (T2WI), and apparent diffusion coefficients were performed on days 1, 3, and 7 after MCAo. Infarct volume and number of GFAP, ED-1, and NeuN-positive cells were conducted on day 7. Behavioral deficit was significantly improved by LAU-0901 treatment compared to vehicle on days 1, 3, and 7. Total lesion volumes computed from T2WI were significantly reduced by LAU-0901 on days 1, 3, and 7 (by 83%, 90%, and 96%, respectively), which was consistent with decreased edema formation. Histopathology revealed that LAU-0901 treatment resulted in significant reduction of cortical and subcortical infarct volumes, attenuated microglial infiltration, and promoted astrocytic and neuronal survival. These findings suggest LAU-0901 is a promising neuroprotectant and provide the basis for future therapeutics in patients suffering ischemic stroke

    Evaluation of behavioural and antioxidant activity of Cytisus scoparius Link in rats exposed to chronic unpredictable mild stress

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    <p>Abstract</p> <p>Background</p> <p>Various human diseases have oxidative stress as one of their component. Many herbs have been reported to exhibit properties that combat oxidative stress through their active constituents such as flavonoids, tannins, phenolic compounds etc. <it>Cytisus scoparius </it>(CS) Link, (Family: Leguminosae), also called <it>Sarothamnus scoparius</it>, has been shown in <it>invitro </it>experiments to be endowed with anti-diabetic, hypnotic and sedative and antioxidant activity. Therefore this study was carried out to evaluate CS for its anxiolytic, antidepressant and anti-oxidant activity in stressed rats.</p> <p>Methods</p> <p>60% methanolic extract of CS was quantified for phenolic content by Folin-Ciocalteau's method. Chronic unpredictable mild stress (CMS) was employed to induce stress in rats. CS (125 and 250 mg/kg, p.o) and diazepam (DZM) (2 mg/kg, p.o) was administered during the 21 day stress exposure period. Anxiolytic and antidepressant activities of CS were assessed in open field exploratory and behavioural despair paradigms, respectively. Plasma glucose and total lipids; endogenous antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT); non-enzymic-ascorbic acid and thiobarbituric acid reactive substances (TBARS) levels were measured in brain, kidneys and adrenals using standard protocols to assess the effect of CS.</p> <p>Results</p> <p>Total phenolic content of CS was found to be 8.54 ± 0.16% w/w. CMS produced anxiogenic and depressive behaviour in experimental rats with metabolic disturbance. Significant decrease in SOD, CAT levels and increase in lipid peroxidation level was observed in stressed rats. CS administration for 21 days during stress exposure significantly increased the ambulatory behaviour and decreased the freezing time in open field behaviour. In behavioural despair test no significant alteration in the immobility period was observed. CS also improved SOD, CAT, and ascorbic acid level and controlled the lipid peroxidation in different tissues.</p> <p>Conclusion</p> <p>CS possesses anti-stress and moderate anxiolytic activity which may be due, in part, to its antioxidant effect that might warrant further studies.</p
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