831 research outputs found

    Expedition 302 geophysics: integrating past data with new results

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    In preparation for IODP Expedition 302, Arctic Coring Expedition (ACEX), a site survey database comprising geophysical and geological data from the Lomonosov Ridge was compiled. The accumulated database includes data collected from ice islands, icebreakers, and submarines from 1961 to 2001. In addition, seismic reflection profiles were collected during Expedition 302 that complement the existing seismic reflection data and facilitate integration between the acoustic stratigraphy and the Expedition 302 drill cores. An overview of these data is presented in this chapter.It is well recognized that collecting geophysical data in ice-covered seas, in particular the Arctic Ocean, is a challenging endeavor. This is because much of the Arctic Ocean is continuously covered with ice thicknesses that vary from 1 to 6 m. Over the continental shelves, sea ice can be absent during summer months, but it is present year-round in the central basins. This ice cover is the most dominant feature of the Arctic Ocean environment. It circulates in the ocean basin in two main circulation patterns: the Transpolar Drift and the Beaufort Gyre (see the "Expedition 302 summary" chapter; Rudels et al., 1996).Expedition 302 sites are located within the less severe of these two ice circulation systems, the Transpolar Drift, which primarily moves sea ice from the shelves where it is formed (the Laptev and East Siberian Seas) across the basin and exits through the Fram Strait. During late summer, concentrations of Arctic sea ice can be <100% (10/10 ice cover), making it possible for icebreakers to operate. Average ice concentrations in the central Arctic Ocean during summer months can locally vary from partially open water (6/10) to completely ice covered (10/10). This sea-ice cover can move at speeds up to 0.5 kt.Early Arctic Ocean geophysical exploration was performed from ice-drift stations (Weber and Roots, 1990). However, the tracks from these drifting ice stations were controlled "by the whims of nature" (Jackson et al., 1990), preventing detailed, systematic surveys of predetermined target areas. These ice-drift stations were set up on stable icebergs that were trapped in sea ice and moved generally with the large drift patterns, but locally they were erratic, so preselected locations could not be surveyed. In the late 1980s, single icebreakers began to be used for oceanographic survey work in the Arctic Ocean. Between 1991 and 2001, four scientific icebreaker expeditions to the Lomonosov Ridge took place. These cruises all experienced local sea-ice conditions varying between 8/10 and 10/10. During these expeditions, towed geophysical equipment was occasionally damaged or lost, either because of a rapidly closing wake caused by local ice pressure or because ice had cut the air gun array.Conventionally powered icebreakers reached as far as the North Pole for the first time during the 1991 Expedition (Andersen and Carlsonn, 1992; Fütterer, 1992). Geophysical results from this expedition collected two important reflection profiles, AWI-91090 and AWI-91091, that crossed the Lomonosov Ridge between 87° and 88°N. These profiles imaged a ~450 m thick, well-stratified and apparently undisturbed drape of sediments overlying a prominent acoustic unconformity (Jokat et al., 1992) that spawned the idea to conduct a paleoceanographic drilling expedition to this Ridge.The use of US Navy nuclear submarines for geophysical mapping was implemented through the Science Ice Exercise program (SCICEX) (Newton, 2000). The development of the Seafloor Characterization and Mapping Pods (SCAMP), which hold a Chirp subbottom profiler, swath bathymetric profiler, and side scan sonar, was an essential part of the SCICEX program (Chayes et al., 1996). In 1999, the Lomonosov Ridge geophysical database was augmented with acoustic data acquired during the SCICEX program using the SCAMP system mounted on the US nuclear submarine USS Hawkbill (Edwards and Coakley, 2003)

    Non-classical forms of pemphigus: pemphigus herpetiformis, IgA pemphigus, paraneoplastic pemphigus and IgG/IgA pemphigus

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    The pemphigus group comprises the autoimmune intraepidermal blistering diseases classically divided into two major types: pemphigus vulgaris and pemphigus foliaceous. Pemphigus herpetiformis, IgA pemphigus, paraneoplastic pemphigus and IgG/IgA pemphigus are rarer forms that present some clinical, histological and immunopathological characteristics that are different from the classical types. These are reviewed in this article. Future research may help definitively to locate the position of these forms in the pemphigus group, especially with regard to pemphigus herpetiformis and the IgG/ IgA pemphigus.Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM) Dermatology DepartmentUniversidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM) Dermatology and Pathology DepartmentsUNIFESP, EPM, Dermatology DepartmentUNIFESP, EPM, Dermatology and Pathology DepartmentsSciEL

    Attenuation of microglial activation in a mouse model of Alzheimer’s disease via NFAT inhibition

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    BACKGROUND: Amyloid β (Aβ) peptide is hypothesized to stimulate microglia to acquire their characteristic proinflammatory phenotype in Alzheimer’s disease (AD) brains. The specific mechanisms by which Aβ leads to microglial activation remain an area of interest for identifying attractive molecular targets for intervention. Based upon the fact that microglia express the proinflammatory transcription factor, nuclear factor of activated T cells (NFAT), we hypothesized that NFAT activity is required for the Aβ-stimulated microgliosis that occurs during disease. METHODS: Primary murine microglia cultures were stimulated with Aβ in the absence or presence of NFAT inhibitors, FK506 and tat-VIVIT peptide, to quantify secretion of cytokines, neurotoxins, or Aβ phagocytosis. A transgenic mouse model of AD, APP/PS1, was treated subcutaneously via mini-osmotic pumps with FK506 or tat-VIVIT to quantify effects on cytokines, microgliosis, plaque load, and memory. RESULTS: Expression of various NFAT isoforms was verified in primary murine microglia through Western blot analysis. Microglial cultures were stimulated with Aβ fibrils in the absence or presence of the NFAT inhibitors, FK506 and tat-VIVIT, to demonstrate that NFAT activity regulated Aβ phagocytosis, neurotoxin secretion, and cytokine secretion. Delivery of FK506 and tat-VIVIT to transgenic APP/PS1 mice attenuated spleen but not brain cytokine levels. However, FK506 and tat-VIVIT significantly attenuated both microgliosis and Aβ plaque load in treated mice compared to controls. Surprisingly, this did not correlate with changes in memory performance via T-maze testing. CONCLUSIONS: Our findings suggest that development of specific NFAT inhibitors may offer promise as an effective strategy for attenuating the microgliosis and Aβ plaque deposition that occur in AD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-015-0255-2) contains supplementary material, which is available to authorized users

    APP Regulates Microglial Phenotype in a Mouse Model of Alzheimer\u27s Disease

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    Prior work suggests that amyloid precursor protein (APP) can function as a proinflammatory receptor on immune cells, such as monocytes and microglia. Therefore, we hypothesized that APP serves this function in microglia during Alzheimer\u27s disease. Although fibrillar amyloid β (Aβ)-stimulated cytokine secretion from both wild-type and APP knock-out (mAPP−/−) microglial cultures, oligomeric Aβ was unable to stimulate increased secretion from mAPP−/− cells. This was consistent with an ability of oligomeric Aβ to bind APP. Similarly, intracerebroventricular infusions of oligomeric Aβ produced less microgliosis in mAPP−/− mice compared with wild-type mice. The mAPP−/− mice crossed to an APP/PS1 transgenic mouse line demonstrated reduced microgliosis and cytokine levels and improved memory compared with wild-type mice despite robust fibrillar Aβ plaque deposition. These data define a novel function for microglial APP in regulating their ability to acquire a proinflammatory phenotype during disease. SIGNIFICANCE STATEMENT A hallmark of Alzheimer\u27s disease (AD) brains is the accumulation of amyloid β (Aβ) peptide within plaques robustly invested with reactive microglia. This supports the notion that Aβ stimulation of microglial activation is one source of brain inflammatory changes during disease. Aβ is a cleavage product of the ubiquitously expressed amyloid precursor protein (APP) and is able to self-associate into a wide variety of differently sized and structurally distinct multimers. In this study, we demonstrate both in vitro and in vivo that nonfibrillar, oligomeric forms of Aβ are able to interact with the parent APP protein to stimulate microglial activation. This provides a mechanism by which metabolism of APP results in possible autocrine or paracrine Aβ production to drive the microgliosis associated with AD brains

    When is directed deceased donation justified? Practical, ethical, and legal issues

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    This paper explores whether directed deceased organ donation should be permitted, and if so under which conditions. While organ donation and allocation systems must be fair and transparent, might it be “one thought too many” to prevent directed donation within families? We proceed by providing a description of the medical and legal context, followed by identification of the main ethical issues involved in directed donation, and then explore these through a series of hypothetical cases similar to those encountered in practice. Ultimately, we set certain conditions under which directed deceased donation may be ethically acceptable. We restrict our discussion to the allocation of organs to recipients already on the waiting list

    Empowering bioinformatics communities with Nextflow and nf-core

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    Standardized analysis pipelines contribute to making data bioinformatics research compliant with the paradigm of Findability, Accessibility, Interoperability, and Reus-ability (FAIR), and facilitate collaboration. Nextflow and Snakemake, two popular command-line solutions, are increasingly adopted by users, complementing GUI-based platforms such as Galaxy. We report recent developments of the nf-core framework with the new Nextflow Domain-Specific Language (DSL2). An extensive library of modules and subworkflows enables research communities to adopt common standards progressively, as resources and needs allow. We present an overview of some of the research communities built around nf-core and showcase its adoption by six EuroFAANG farmed animal research consortia

    Berberine chloride can ameliorate the spatial memory impairment and increase the expression of interleukin-1beta and inducible nitric oxide synthase in the rat model of Alzheimer's disease

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    BACKGROUND: Berberine is the major alkaloidal component of Rhizoma coptidis, and has multiple pharmacological effects including inhibiting acetylcholinesterase, reducing cholesterol and glucose, lowering mortality in patients with chronic congestive heart failure and anti-inflammation etc. Thus berberine is a promising drug for diabetes, hyperlipemia, coronary artery disease and ischemic stroke etc. The present study was carried out to investigate the effect of berberine chloride on the spatial memory, inflammation factors interleukin-1 beta (IL-1beta) and inducible nitric oxide synthase (iNOS) expression in the rat model of Alzheimer's disease (AD) which was established by injecting Abeta (1–40) (5 microgram) into the rats hippocampuses bilaterally. RESULTS: The rats were given berberine chloride (50 mg/kg) by intragastric administration once daily for 14 days. The spatial memory was assayed by Morris water maze test, IL-1beta and iNOS in the hippocampus were assayed by immunohistochemistry and real time polymerase chain reaction (PCR). Intragastric administration of berberine significantly ameliorated the spatial memory impairment and increased the expression of IL-1beta, iNOS in the rat model of AD. CONCLUSION: Berberine might be beneficial to AD by intragastric administration though it might exaggerate the inflammation reaction
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