130 research outputs found

    A subset of human plasmacytoid dendritic cells expresses CD8α upon exposure to herpes simplex virus type 1

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    Classical and plasmacytoid dendritic cells (DC) play important roles in the defense against murine and human infections with herpes simplex virus (HSV). So far, CD8α expression has only been reported for murine DC. CD8α+ DC have prominent cross-presenting activities, which are enhanced by murine CD8α+ PDC. The human orthologue of murine CD8α+ DC, the CD141 (BDCA3)+ DC, mainly cross-present after TLR3 ligation. We report here the serendipitous finding that a subset of human PDC upregulates CD8α upon HSV-1 stimulation, as shown by gene array and flow cytometry analyses. CD8α, not CD8ß, was expressed upon exposure. Markers of activation, migration, and costimulation were upregulated on CD8α-expressing human PDC. In these cells, increased cytokine and chemokine levels were detected that enhance development and function of T, B, and NK cells, and recruit immature DC, monocytes, and Th1 cells, respectively. Altogether, human CD8α+ PDC exhibit a highly activated phenotype and appear to recruit other immune cells to the site of inflammation. Further studies will show whether CD8α-expressing PDC contribute to antigen cross-presentation, which may be important for immune defenses against HSV infections in vitro and in vivo

    Chronic Immune Activation in HIV-1 Infection Contributes to Reduced Interferon Alpha Production via Enhanced CD40:CD40 Ligand Interaction

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    Although a signature of increased interferon (IFN-)alpha production is observed in HIV-1 infection, the response of circulating plasmacytoid dendritic cells (PDC) to Toll-like receptor ligand stimulation is substantially impaired. This functional PDC deficit, which we specifically observed in HIV-1 infected individuals with less than 500 CD4+ T cells/µl, is not well understood. We provide evidence that the peripheral IFN-alpha production in HIV-1 infection is actively suppressed by the enhanced interaction of CD40 ligand (CD40L), a member of the tumor necrosis factor family, and its receptor CD40, which are both upregulated upon immune activation. Plasma levels of soluble CD40L were significantly higher in untreated HIV-1 infected individuals (n = 52) than in subjects on long-term antiretroviral therapy (n = 62, p<0.03) and in uninfected control donors (n = 16, p<0.001). Concomitantly, cell-associated CD40L and the expression of the receptor CD40 on the PDC were significantly upregulated in HIV-1 infection (p<0.05). Soluble and cell-associated CD40L inhibited the PDC-derived IFN-alpha production by CpG oligodeoxynucleotides dose-dependently. This suppressive effect was observed at much lower, physiological CD40L concentrations in peripheral blood mononuclear cells (PBMC) of HIV-1 infected individuals compared to controls (p<0.05). The CpG-induced IFN-alpha production in PBMC of HIV-1 infected donors was directly correlated with PDC and CD4+ T cell counts, and inversely correlated with the viral loads (p<0.001). In HIV-1 infected donors with less than 500 CD4+ T cells/µl, the CpG-induced IFN-alpha production was significantly correlated with the percentage of CD40-expressing PDC and the level of CD40 expression on these cells (p<0.05), whereas CD40L plasma levels played a minor role. In addition, low-dose CD40L contributed to the enhanced production of interleukin 6 and 8 in PBMC of HIV-1 infected donors compared to controls. Our data support the conclusion that the chronic immune activation in HIV-1 infection impairs peripheral PDC innate immune responses at least in part via enhanced CD40:CD40L interactions

    NASA GES DISC support of CO2 Data from OCO-2, ACOS, and AIRS

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    NASA Goddard Earth Sciences Data and Information Services Centers (GES DISC) is the data center assigned to archive and distribute current AIRS, ACOS data and data from the upcoming OCO-2 mission. The GES DISC archives and supports data containing information on CO2 as well as other atmospheric composition, atmospheric dynamics, modeling and precipitation. Along with the data stewardship, an important mission of GES DISC is to facilitate access to and enhance the usability of data as well as to broaden the user base. GES DISC strives to promote the awareness of science content and novelty of the data by working with Science Team members and releasing news articles as appropriate. Analysis of events that are of interest to the general public, and that help in understanding the goals of NASA Earth Observing missions, have been among most popular practices.Users have unrestricted access to a user-friendly search interface, Mirador, that allows temporal, spatial, keyword and event searches, as well as an ontology-driven drill down. Variable subsetting, format conversion, quality screening, and quick browse, are among the services available in Mirador. The majority of the GES DISC data are also accessible through OPeNDAP (Open-source Project for a Network Data Access Protocol) and WMS (Web Map Service). These services add more options for specialized subsetting, format conversion, image viewing and contributing to data interoperability

    Erucic acid in feed and food

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    The Panel wishes to thank the members of the Working Group on erucic acid in food and feed: Bruce Cottrill, Eugenia Dogliotti, Juha Laakso, Manfred Metzler, Leonardo Velasco and Christiane Vleminckx for the preparatory work on this scientific output, the hearing expert: Mary Sheppard and EFSA staff members: Katleen Baert, Barbara Dörr, Jose Angel Gomez Ruiz and Enikő Varga for the support provided to this scientific opinion. The Panel acknowledges all European countries and European stakeholder organisations (FEDIOL, SNE and FEFAC) that provided occurrence data on erucic acid in food and feed. The Panel wishes to thank all European countries that supported the collection of consumption data for the Comprehensive European Food Consumption Database.Peer reviewedPublisher PD

    Lock-in thermography as an analytical tool for magnetic nanoparticles: measuring heating power and magnetic fields

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    Magnetic nanoparticles and their ability to convert electromagnetic energy into heat are of explicit interest for various applications. However, precise quantification of their heating efficiency is not always upfront, and several parameters render comparative studies challenging. This paper describes the theory behind lock-in thermography, a new technique for quantifying the heating properties of magnetic nanoparticles. This technique allows the investigation of some of the potential sources of variability: key factors such as magnetic field inhomogeneity and its effects on the heating power are explored in detail. The presented results, obtained from various nanoparticle batches of different origins, highlight the importance of pursuing a standardized and systematic approach when quantifying the heating efficiency of magnetic nanoparticles

    Development of a World Health Organization International Reference Panel for different genotypes of hepatitis E virus for nucleic acid amplification testing.

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    Globally, hepatitis E virus (HEV) is a major cause of acute viral hepatitis. Epidemiology and clinical presentation of hepatitis E vary greatly by location and are affected by the HEV genotype. Nucleic acid amplification technique (NAT)-based assays are important for the detection of acute HEV infection as well for monitoring chronic cases of hepatitis E. The aim of the study was to evaluate a panel of samples containing different genotypes of HEV for use in nucleic NAT-based assays. The panel of samples comprises eleven different members including HEV genotype 1a (2 strains), 1e, 2a, 3b, 3c, 3e, 3f, 4c, 4g as well as a human isolate related to rabbit HEV. Each laboratory assayed the panel members directly against the 1 World Health Organization (WHO) International Standard (IS) for HEV RNA (6329/10) which is based upon a genotype 3 a strain. The samples for evaluation were distributed to 24 laboratories from 14 different countries and assayed on three separate days. Of these, 23 participating laboratories returned a total of 32 sets of data; 17 from quantitative assays and 15 from qualitative assays. The assays used consisted of a mixture of in-house developed and commercially available assays. The results showed that all samples were detected consistently by the majority of participants, although in some cases, some samples were detected less efficiently. Based on the results of the collaborative study the panel (code number 8578/13) was established as the "1st International Reference Panel (IRP) for all HEV genotypes for NAT-based assays" by the WHO Expert Committee on Biological Standardization. This IRP will be important for assay validation and ensuring adequate detection of different genotypes and clinically important sub-genotypes of HEV

    Best Practice in the chemical characterisation of extracts used in pharmacological and toxicological research—The ConPhyMP—Guidelines

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    The Advisory group on Consensus statement on the Phytochemical Characterisation of Medicinal Plant extracts (ConPhyMP) is a consortium of experts on Pharmacognosy and Phytochemistry open access articleBackground: Research onmedicinal plants and extracts derived fromthem differs from studies performed with single compounds. Extracts obtained from plants, algae, fungi, lichens or animals pose some unique challenges: they are multicomponent mixtures of active, partially active and inactive substances, and the activity is often not exerted on a single target. Their composition varies depending on the method of preparation and the plant materials used. This complexity and variability impact the reproducibility and interpretation of pharmacological, toxicological and clinical research. Objectives: This project develops best practice guidelines to ensure reproducibility and accurate interpretations of studies using medicinal plant extracts. The focus is on herbal extracts used in pharmacological, toxicological, and clinical/intervention research. Specifically, the consensus-based statement focuses on defining requirements for: 1) Describing the plant material/herbal substances, herbal extracts and herbal medicinal products used in these studies, and 2) Conducting and reporting the phytochemical analysis of the plant extracts used in these studies in a reproducible and transparent way. The process and methods: We developed the guidelines through the following process: 1) The distinction between the three main types of extracts (extract types A, B, and C), initially conceptualised by the lead author (MH), led the development of the project as such; 2) A survey among researchers of medicinal plants to gather global perspectives, opportunities, and overarching challenges faced in characterising medicinal plant extracts under different laboratory infrastructures. The survey responses were central to developing the guidelines and were reviewed by the core group; 3) A core group of 9 experts met monthly to develop the guidelines through a Delphi process; and. 4) The final draft guidelines, endorsed by the core group, were also distributed for feedback and approval to an extended advisory group of 20 experts, including many journal editors. Outcome: The primary outcome is the “Consensus statement on the Phytochemical Characterisation of Medicinal Plant extracts“ (ConPhyMP) which defines the best practice for reporting the starting plant materials and the chemical methods recommended for defining the chemical compositions of the plant extracts used in such studies. The checklist is intended to be an orientation for authors in medicinal plant research as well as peer reviewers and editors assessing such research for publicatio
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