15 research outputs found

    Leveraging Thousands of Contrail Observations from GLOBE Citizen Scientists

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    The GLOBE (Global Learning and Observations to Benefit the Environment) Program is NASA's largest and longest-operating citizen science program contributing Earth observations. Over 800,000 cloud observations have been reported worldwide since YEAR that include reports of short-lived, persistent, and persistent-spreading contrails. While contrails can be challenging to observe with space-borne platforms, humans are adept at spotting contrails from the ground. The NASA GLOBE Clouds team at NASA Langley Research Center in Hampton, Virginia matches cloud observations to multiple satellite platforms for comparison, including: NASA's CERES (Clouds and Earth's Radiant Energy System) instrument onboard Terra and Aqua, CALIPSO (Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation), and geostationary satellites. A pilot project was started with select students in the United States to track airplanes above 25,000 ft and report airplane type, altitude, and report if a contrail was being or was not being produced. The objective of the pilot project was to establish if this is a scalable approach for building an international observational dataset documenting what types of airplanes are creating what types of contrails (short-lived, persistent, spreading) under what atmospheric conditions. Preliminary results of this pilot project will be presented

    Mesenchymal stem cells expressing TRAIL lead to tumour growth inhibition in an experimental lung cancer model

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    AbstractLung cancer is a major public health problem in the western world, and gene therapy strategies to tackle this disease systemically are often impaired by inefficient delivery of the vector to the tumour tissue. Some of the main factors inhibiting systemic delivery are found in the blood stream in the form of red and white blood cells (WBCs) and serum components. Mesenchymal stem cells (MSCs) have been shown to home to tumour sites and could potentially act as a shield and vehicle for a tumouricidal gene therapy vector. Here, we describe the ability of an adenoviral vector expressing TRAIL (Ad.TR) to transduce MSCs and show the apoptosis‐inducing activity of these TRAIL‐carrying MSCs on A549 lung carcinoma cells. Intriguingly, using MSCs transduced with Ad.enhanced‐green‐fluorescent‐protein (EGFP) we could show transfer of viral DNA to cocultured A549 cells resulting in transgenic protein production in these cells, which was not inhibited by exposure of MSCs to human serum containing high levels of adenovirus neutralizing antibodies. Furthermore, Ad.TR‐transduced MSCs were shown not to induce T‐cell proliferation, which may have resulted in cytotoxic T‐cell‐mediated apoptosis induction in the Ad.TR‐transduced MSCs. Apoptosis was also induced in A549 cells by Ad.TR‐transduced MSCs in the presence of physiological concentrations of WBC, erythrocytes and sera from human donors that inhibit or neutralize adenovirus alone. Moreover, we could show tumour growth reduction with TRAIL‐loaded MSCs in an A549 xenograft mouse model. This is the first study that demonstrates the potential therapeutic utility of Ad.TR‐transduced MSCs in cancer cells and the stability of this vector in the context of the blood environment.</jats:p

    Prevalence of Frailty in European Emergency Departments (FEED): an international flash mob study

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    Erratum: Corrigendum: Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution

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    International Chicken Genome Sequencing Consortium. The Original Article was published on 09 December 2004. Nature432, 695–716 (2004). In Table 5 of this Article, the last four values listed in the ‘Copy number’ column were incorrect. These should be: LTR elements, 30,000; DNA transposons, 20,000; simple repeats, 140,000; and satellites, 4,000. These errors do not affect any of the conclusions in our paper. Additional information. The online version of the original article can be found at 10.1038/nature0315

    Mesenchymal stem cells expressing trail lead to tumour growth inhibition in an experimental lung cancer model

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    Lung cancer is a major public health problem in the western world, and gene therapy strategies to tackle this disease systemically are often impaired by inefficient delivery of the vector to the tumour tissue. Some of the main factors inhibiting systemic delivery are found in the blood stream in the form of red and white blood cells (WBCs) and serum components. Mesenchymal stem cells (MSCs) have been shown to home to tumour sites and could potentially act as a shield and vehicle for a tumouricidal gene therapy vector. Here, we describe the ability of an adenoviral vector expressing TRAIL (Ad.TR) to transduce MSCs and show the apoptosis-inducing activity of these TRAIL-carrying MSCs on A549 lung carcinoma cells. Intriguingly, using MSCs transduced with Ad.enhanced-green-fluorescent-protein (EGFP) we could show transfer of viral DNA to cocultured A549 cells resulting in transgenic protein production in these cells, which was not inhibited by exposure of MSCs to human serum containing high levels of adenovirus neutralizing antibodies. Furthermore, Ad.TR-transduced MSCs were shown not to induce T-cell proliferation, which may have resulted in cytotoxic T-cell-mediated apoptosis induction in the Ad.TR-transduced MSCs. Apoptosis was also induced in A549 cells by Ad.TR-transduced MSCs in the presence of physiological concentrations of WBC, erythrocytes and sera from human donors that inhibit or neutralize adenovirus alone. Moreover, we could show tumour growth reduction with TRAIL-loaded MSCs in an A549 xenograft mouse model. This is the first study that demonstrates the potential therapeutic utility of Ad.TR-transduced MSCs in cancer cells and the stability of this vector in the context of the blood environment

    proBDNF Negatively Regulates Neuronal Remodeling, Synaptic Transmission, and Synaptic Plasticity in Hippocampus

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    Experience-dependent plasticity shapes postnatal development of neural circuits, but the mechanisms that refine dendritic arbors, remodel spines, and impair synaptic activity are poorly understood. Mature brain-derived neurotrophic factor (BDNF) modulates neuronal morphology and synaptic plasticity, including long-term potentiation (LTP) via TrkB activation. BDNF is initially translated as proBDNF, which binds p75NTR. In vitro, recombinant proBDNF modulates neuronal structure and alters hippocampal long-term plasticity, but the actions of endogenously expressed proBDNF are unclear. Therefore, we generated a cleavage-resistant probdnf knockin mouse. Our results demonstrate that proBDNF negatively regulates hippocampal dendritic complexity and spine density through p75NTR. Hippocampal slices from probdnf mice exhibit depressed synaptic transmission, impaired LTP, and enhanced long-term depression (LTD) in area CA1. These results suggest that proBDNF acts in vivo as a biologically active factor that regulates hippocampal structure, synaptic transmission, and plasticity, effects that are distinct from those of mature BDNF

    Impact de la durée de stockage au froid des oeufs embryonnés de truite arc-en-ciel

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    International audienceL’objectif gĂ©nĂ©ral du projet EpiCOOL est d’étudier les consĂ©quences du stockage au froid (3°C) des Ɠufs embryonnĂ©s de truite arc-en-ciel, l’espĂšce piscicole majeure de la filiĂšre française. En effet, des Ă©tudes rĂ©centes ont montrĂ© que l’exposition prĂ©coce Ă  des stimuli environnementaux (tels que l’hypoxie ou la tempĂ©rature) pouvait avoir un impact sur la physiologie, la croissance, le mĂ©tabolisme et la nutrition des poissons Ă  plus ou moins long terme. Plusieurs mĂ©canismes peuvent ĂȘtre sous-jacents Ă  cette programmation, parmi eux les modifications des patrons d’expression de gĂšnes et les rĂ©gulations Ă©pigĂ©nĂ©tiques comme par exemple la mĂ©thylation de l’ADN. Dans ce projet, nous testerons donc l’effet d’un passage des Ɠufs au stade oeillĂ© Ă  basse tempĂ©rature (3°C au lieu de 11°C) pendant 15 jours sur plusieurs caractĂšres d’intĂ©rĂȘt aquacole, Ă  savoir les performances zootechniques (survie, croissance et malformations), le mĂ©tabolisme intermĂ©diaire, le dĂ©veloppement du muscle et les qualitĂ©s, ainsi que la rĂ©sistance Ă  des stress ultĂ©rieurs. Nous essaierons Ă©galement de comprendre par quels mĂ©canismes molĂ©culaires l’exposition prĂ©coce au froid peut impacter la physiologie des poissons ultĂ©rieurement, en analysant les patrons d’expression gĂ©nique et la mĂ©thylation de l’ADN (approches LUMA et RRBS). La finalitĂ© est d’utiliser la programmation prĂ©coce comme levier pour mieux maĂźtriser les performances des animaux Ă  long terme. Ce projet se basera sur l’utilisation d’un modĂšle biologique tout Ă  fait pertinent, deux lignĂ©es expĂ©rimentales divergentes pour la teneur en lipides du muscle : lignĂ©e grasse (LG) et lignĂ©e maigre (LM). En effet, elles ont montrĂ© une utilisation diffĂ©rente des aliments et possĂšdent un mĂ©tabolisme intermĂ©diaire et Ă©nergĂ©tique bien diffĂ©renciĂ©. Il est donc possible qu’elles rĂ©agissent diffĂ©remment Ă  l’effet du froid pendant l’incubation. L’utilisation de ces deux lignĂ©es divergentes permettra de tester l’impact du fond gĂ©nĂ©tique sur les rĂ©ponses observĂ©es, et ainsi d’aboutir Ă  une comprĂ©hension plus fine des mĂ©canismes sous-jacents.Financement : FEAMP (Fonds EuropĂ©en pour les Affaires Maritimes et la PĂȘche) – projet EpiCOOL numĂ©ro PFEA470018FA100001

    The problem with reproductive freedom:Procreation beyond procreators’ interests

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    Reproductive freedom plays a pivotal role in debates on the ethics of procreation. This moral principle protects people’s interests in procreative matters and allows them discretion over whether to have children, the number of children they have and, to a certain extent, the type of children they have. Reproductive freedom’s theoretical and political emphasis on people’s autonomy and well-being is grounded in an individual-centred framework for discussing the ethics of procreation. It protects procreators’ interests and significantly reduces the permissible grounds for interference by third parties. In this article I show that procreative decisions have far-reaching effects on the composition and size of the population. The upshot of considering these effects allows for the appreciation of the inadequacy of a framework that solely considers individual (i.e. procreators’) interests to discuss the ethics of procreation. To address such inadequacy, I assess costs and benefits of past and present proposals to reflect on procreation in such a way as to consider its far-reaching effects. I conclude by arguing that reproductive freedom should be defended as an imperfect but instrumentally necessary tool. This framing would enable those participating in debates on the ethics of procreative decisions to work towards an ethical framework that accounts for the cumulative effects of these decisions

    Incidence Rates of Childhood Asthma with Recurrent Exacerbations in the U.S. Environmental influences on Child Health Outcomes (ECHO) Program

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    BACKGROUND: Descriptive epidemiological data on incidence rates (IRs) of asthma with recurrent exacerbations (ARE) are sparse. OBJECTIVE: We hypothesized that IRs for ARE would vary by time, geography, age, race and ethnicity, irrespective of parental asthma history. METHODS: We leveraged data from 17246 children born after 1990 enrolled in 59 U.S. and one Puerto Rican cohort in the Environmental Influences on Child Health Outcomes consortium to estimate IRs for AREs. RESULTS: The overall crude IR for ARE was 6.07/1000 person-years (95% confidence intervals (CI) 5.63, 6.51) and was highest for children age 2-4 years, for Hispanic and non-Hispanic Black children and for those with a parental history of asthma. ARE IRs were higher for 2-4 year olds in each race and ethnicity category and for both sexes. Multi-variable analysis confirmed higher adjusted ARE IRs (aIRR) for children born 2000-2009 compared to 1990-1999 and 2010-2017, 2-4 versus 10-19 years old (aIRR=15.36; CI 12.09, 2.99), and for males versus females (aIRR=1.34; CI 1.16, 1.55). Black children (non-Hispanic and Hispanic) had higher rates than non-Hispanic White children (aIRR=2.51; CI 2.10, 2.99 and aIRR=2.04; CI 1.22, 3.39, respectively). Children born in the Midwest, Northeast and South had higher rates than the West (p\u3c0.01 for each comparison). Children with a parental history of asthma had rates nearly three times higher than those without such history (aIRR=2.90; CI 2.43-3.46). CONCLUSIONS: Factors associated with time, geography, age, race and ethnicity, sex and parental history appear to influence the inception of ARE among children and adolescents
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