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Four 3"-and 4"-deoxy and -fluorogalactosyl ceramides were synthesized, and their ability to stimulate iNKT cells, based on levels of IL-2 production, was assessed in three NKT cell receptor hybridomas. In two of the hybridomas, 1.2 and 2H4, all of the analogs were immunostimulatory, while in the 1.4 hybridoma only the 4"-fluoro analog led to the production of significant levels of IL-2.Cluster of differentiation 1 (CD1) proteins are cell surface glycoproteins distantly related to the class I and II antigen presenting molecules of the major histocompatibility complex (MHC). 1 Unlike the MHC-encoded molecules, which bind and present peptide antigens, CD1 proteins bind a variety of lipids and present them to subsets of lipid-specific T cells. CD1d, a member of the CD1 family, has been shown to present lipid antigens to a specialized subset of lymphocytes known as invariant natural killer T (iNKT) cells. 2-7 Over the past decade CD1d activated iNKT cells have been demonstrated to elicit a range of immune responses with potential implications for treating viral and bacterial infections, cancer and a variety of autoimmune conditions. 8-14 Most studies of the role of iNKT cells have utilized the α-galactosyl ceramide (GalCer), KRN7000 (Figure 1), identified by Kirin Brewery in SAR studies centered around agelasphin-9b, a potent immunostimulatory compound isolated from the Agelus genus of marine sponge. 15 The activity of KRN7000 was found to be mediated by its binding to CD1d and subsequent activation of iNKT cells. 16 Because of the therapeutic potential of iNKT cell stimulation, there has been a growing interest in understanding how the glycolipid structure impacts the immune response. Thus, numerous α-glycosyl ceramides (α-GlyCers) have been synthesized and evaluated for their ability to stimulate iNKT cells.Using KRN7000 as a lead structure the majority of variations have been in the lipid portion. 17-23 Nevertheless, the carbohydrate moiety has been of interest 24-27 because it was assumed and later confirmed that it was this region of the antigen that protruded from the CD1d/ glycolipid complex and interacted with the iNKT T cell receptor (TCR). SAR studies had shown that the C2"-OH (for numbering see Figure 1) was essential for iNKT cell activation and that there was wide tolerance for functional group and size variations on C6". 24,27,28 In Supplementary data Supplementary data associated with this article (experimentals and characterization data) can be found, in the online version, at doi: .Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Autho...

Numerous location-based diet studies have been published describing different aspects of invasive lionfish (Pterois volitans and Pterois miles) feeding ecology, but there has been no synthesis of their diet composition and feeding patterns across regional gradients. 8125 lionfish stomachs collected from 10 locations were analyzed to provide a generalized description of their feeding ecology at a regional scale and to compare their diet among locations. Our regional data indicate lionfish in the western Atlantic are opportunistic generalist carnivores that consume at least 167 vertebrate and invertebrate prey species across multiple trophic guilds, and carnivorous fish and shrimp prey that are not managed fishery species and not considered at risk of extinction by the International Union for Conservation of Nature disproportionately dominate their diet. Correlations between lionfish size and their diet composition indicate lionfish in the western Atlantic

Invasive Indo-Pacific lionfish (Pterois volitans) have rapidly expanded in the Western Atlantic over the past decade and have had a significant negative impact on reef fish biodiversity, habitat, and community structure, with lionfish out-competing native predators for resources. In an effort to reduce this population explosion, lionfish have been promoted for human consumption in the greater Caribbean region. This study examined whether the geographical expansion of the lionfish into a known ciguatera-endemic region can pose a human health threat for ciguatera fish poisoning (CFP). More than 180 lionfish were collected from waters surrounding the US Virgin Islands throughout 2010 and 2011. Ciguatoxin testing included an in vitro neuroblastoma cytotoxicity assay for composite toxicity assessment of sodium-channel toxins combined with confirmatory liquid chromatography tandem mass spectrometry. A 12% prevalence rate of ciguatoxic lionfish exceeding the FDA guidance level of 0.1 µg/kg C-CTX-1 equivalents was identified in fish from the U.S. Virgin Islands, highlighting a potential consumption risk in this region. This study presents the first evidence that the invasive lionfish, pose a direct human health risk for CFP and highlights the need for awareness and research on this food safety hazard in known endemic areas.