515 research outputs found
State-of-the-Art Instrumentation Package to Support Model Organism Research in Space
Hardware was developed for the Ames student Fruit-Fly Experiment (AFEx) to support fly growth and analysis during spaceflight. The hardware consists of a 1.5U vented aluminum box that houses an acrylic habitat, video camera, LED lighting, and environmental sensors. Power is provided via two USB connectors, one of which also supports data downlink. While the hardware was designed for use with fruit flies, it will house plants on an upcoming mission and could be adapted for use with other systems
A conceptual model of organochlorine fate from a combined analysis of spatial and mid- to long-term trends of surface and ground water contamination in tropical areas (FWI)
In this study, we investigated the management of long-term
environmental pollution by organic pollutants such as organochlorine
pesticides. We set out to identify conditions that are conducive to reducing
pollution levels for these persistent molecules and then propose a conceptual
model of organochlorine fate in water. Our approach looked at spatio-temporal
changes in pollutant contents in surface water (SW) and groundwater (GW) on a
large scale, in order to decipher the respective roles of soil, geology,
hydrology and past treatment practices. The case of chlordecone (CLD) on the
island of Martinique (1100 km2) was selected given the sampling
campaigns carried out since 2007 over more than 150 sites. CLD, its
metabolite chlordecone-5b-hydro (5bCLD) and the metabolite-to-parent-compound
ratio were compared. As regards the spatial variability of water
contamination, our results showed that banana cropping areas explained the
location of contaminated SW and GW, whereas the combination of soil and
geology factors explained the main spatial variability in the 5bCLD∕CLD
ratio. For temporal variability, these conditions defined a high diversity of
situations in terms of the duration of pollution, highlighting two groups:
water draining old geological formations and ferralsols or vertisols vs.
recent geology and andosols. A conceptual leaching model provided some key
information to help interpret downward trends in CLD and 5bCLD observed in
water. Lastly, a conceptual model of organochlorine fate is proposed to
explain the diversity of the 5bCLD∕CLD ratio in water. Our conclusions
highlight the combined role of soil and groundwater residence time for
differentiating between conditions that are more conducive, or not, to the
disappearance of CLD from the environment. This paper presents a model that
provides an overall perception of organochlorine pesticide fate in the
environment.</p
Interferon-β Pretreatment of Conventional and Plasmacytoid Human Dendritic Cells Enhances Their Activation by Influenza Virus
Influenza virus produces a protein, NS1, that inhibits infected cells from releasing type I interferon (IFN) and blocks maturation of conventional dendritic cells (DCs). As a result, influenza virus is a poor activator of both mouse and human DCs in vitro. However, in vivo a strong immune response to virus infection is generated in both species, suggesting that other factors may contribute to the maturation of DCs in vivo. It is likely that the environment in which a DC encounters a virus would contain multiple pro-inflammatory molecules, including type I IFN. Type I IFN is a critical component of the viral immune response that initiates an antiviral state in cells, primarily by triggering a broad transcriptional program that interferes with the ability of virus to establish infection in the cell. In this study, we have examined the activation profiles of both conventional and plasmacytoid dendritic cells (cDCs and pDCs) in response to an influenza virus infection in the context of a type I IFN-containing environment. We found that both cDCs and pDCs demonstrate a greater activation response to influenza virus when pre-exposed to IFN-β (IFN priming); although, the priming kinetics are different in these two cell types. This strongly suggests that type I IFN functions not only to reduce viral replication in these immune cells, but also to promote greater DC activation during influenza virus infections
Functional Crosstalk between Type I and II Interferon through the Regulated Expression of STAT1
Small "priming" quantities of type I interferon enhance cellular responses to type II interferon by maintaining basal levels of STAT1, explaining the observed crosstalk between these two cytokines
Characterization of a nonvirulent variant of lymphocytic choriomeningitis virus
A cold-adapted, nonvirulent variant of the Armstrong strain of lymphocytic choriomeningitis virus was isolated from infected L929 cells maintained at 25° C. This variant, designated P17, was capable of replicating in the central nervous system of mice without causing disease and conferring immunity to back challenge with the parental strain.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41689/1/705_2005_Article_BF01320786.pd
Simvastatin is associated with a reduced incidence of dementia and Parkinson's disease
<p>Abstract</p> <p>Background</p> <p>Statins are a class of medications that reduce cholesterol by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Whether statins can benefit patients with dementia remains unclear because of conflicting results. We hypothesized that some of the confusion in the literature might arise from differences in efficacy of different statins. We used a large database to compare the action of several different statins to investigate whether some statins might be differentially associated with a reduction in the incidence of dementia and Parkinson's disease.</p> <p>Methods</p> <p>We analyzed data from the decision support system of the US Veterans Affairs database, which contains diagnostic, medication and demographic information on 4.5 million subjects. The association of lovastatin, simvastatin and atorvastatin with dementia was examined with Cox proportional hazard models for subjects taking statins compared with subjects taking cardiovascular medications other than statins, after adjusting for covariates associated with dementia or Parkinson's disease.</p> <p>Results</p> <p>We observed that simvastatin is associated with a significant reduction in the incidence of dementia in subjects ≥65 years, using any of three models. The first model incorporated adjustment for age, the second model included adjusted for three known risk factors for dementia, hypertension, cardiovascular disease or diabetes, and the third model incorporated adjustment for the Charlson index, which is an index that provides a broad assessment of chronic disease. Data were obtained for over 700000 subjects taking simvastatin and over 50000 subjects taking atorvastatin who were aged >64 years. Using model 3, the hazard ratio for incident dementia for simvastatin and atorvastatin are 0.46 (CI 0.44–0.48, <it>p </it>< 0.0001) and 0.91 (CI 0.80–1.02, <it>p </it>= 0.11), respectively. Lovastatin was not associated with a reduction in the incidence of dementia. Simvastatin also exhibited a reduced hazard ratio for newly acquired Parkinson's disease (HR 0.51, CI 0.4–0.55, <it>p </it>< 0.0001).</p> <p>Conclusion</p> <p>Simvastatin is associated with a strong reduction in the incidence of dementia and Parkinson's disease, whereas atorvastatin is associated with a modest reduction in incident dementia and Parkinson's disease, which shows only a trend towards significance.</p
Pharmacogenomics of Interferon-ß Therapy in Multiple Sclerosis: Baseline IFN Signature Determines Pharmacological Differences between Patients
Multiple sclerosis (MS) is a heterogeneous disease. In order to understand the partial responsiveness to IFNbeta in Relapsing Remitting MS (RRMS) we studied the pharmacological effects of IFNbeta therapy. Large scale gene expression profiling was performed on peripheral blood of 16 RRMS patients at baseline and one month after the start of IFNbeta therapy. Differential gene expression was analyzed by Significance Analysis of Microarrays. Subsequent expression analyses on specific genes were performed after three and six months of treatment. Peripheral blood mononuclear cells (PBMC) were isolated and stimulated in vitro with IFNbeta. Genes of interest were measured and validated by quantitative realtime PCR. An independent group of 30 RRMS patients was used for validation. Pharmacogenomics revealed a marked variation in the pharmacological response to IFNbeta between patients. A total of 126 genes were upregulated in a subset of patients whereas in other patients these genes were downregulated or unchanged after one month of IFNbeta therapy. Most interestingly, we observed that the extent of the pharmacological response correlates negatively with the baseline expression of a specific set of 15 IFN response genes (R = -0.7208; p = 0.0016). The negative correlation was maintained after three (R = -0.7363; p = 0.0027) and six (R = -0.8154; p = 0.0004) months of treatment, as determined by gene expression levels of the most significant correlating gene. Similar results were obtained in an independent group of patients (n = 30; R = -0.4719; p = 0.0085). Moreover, the ex vivo results could be confirmed by in vitro stimulation of purified PBMCs at baseline with IFNbeta indicating that differential responsiveness to IFNbeta is an intrinsic feature of peripheral blood cells at baseline. These data imply that the expression levels of IFN response genes in the peripheral blood of MS patients prior to treatment could serve a role as biomarker for the differential clinical response to IFNbet
Lung vasodilatory response to inhaled iloprost in experimental pulmonary hypertension: amplification by different type phosphodiesterase inhibitors
Inhaled prostanoids and phosphodiesterase (PDE) inhibitors have been suggested for treatment of severe pulmonary hypertension. In catheterized rabbits with acute pulmonary hypertension induced by continuous infusion of the stable thromboxane analogue U46619, we asked whether sildenafil (PDE1/5/6 inhibitor), motapizone (PDE3 inhibitor) or 8-Methoxymethyl-IBMX (PDE1 inhibitor) synergize with inhaled iloprost. Inhalation of iloprost caused a transient pulmonary artery pressure decline, levelling off within <20 min, without significant changes in blood gases or systemic hemodynamics. Infusion of 8-Methoxymethyl-IBMX, motapizone and sildenafil caused each a dose-dependent decrease in pulmonary artery pressure, with sildenafil possessing the highest efficacy and at the same time selectivity for the pulmonary circulation. When combining a per se ineffective dose of each PDE inhibitor (200 μg/kg × min 8-Methoxymethyl-IBMX, 1 μg/kg × min sildenafil, 5 μg/kg × min motapizone) with subsequent iloprost nebulization, marked amplification of the prostanoid induced pulmonary vasodilatory response was noted and the area under the curve of P(PA )reduction was nearly threefold increased with all approaches, as compared to sole iloprost administration. Further amplification was achieved with the combination of inhaled iloprost with sildenafil plus motapizone, but not with sildenafil plus 8MM-IBMX. Systemic hemodynamics and gas exchange were not altered for all combinations. We conclude that co-administration of minute systemic doses of selective PDE inhibitors with inhaled iloprost markedly enhances and prolongs the pulmonary vasodilatory response to inhaled iloprost, with maintenance of pulmonary selectivity and ventilation perfusion matching. The prominent effect of sildenafil may be operative via both PDE1 and PDE5, and is further enhanced by co-application of a PDE3 inhibitor
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