405 research outputs found

    Asymmetric Synthesis and Biological Screening of Quinoxaline-Containing Synthetic Lipoxin A₄ Mimetics (QNX-sLXms)

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    Failure to resolve inflammation underlies many prevalent pathologies. Recent insights have identified lipid mediators, typified by lipoxins (LXs), as drivers of inflammation resolution, suggesting potential therapeutic benefit. We report the asymmetric preparation of novel quinoxaline-containing synthetic-LXA4-mimetics (QNX-sLXms). Eight novel compounds were screened for their impact on inflammatory responses. Structure–activity relationship (SAR) studies showed that (R)-6 (also referred to as AT-02-CT) was the most efficacious and potent anti-inflammatory compound of those tested. (R)-6 significantly attenuated lipopolysaccharide (LPS)- and tumor-necrosis-factor-α (TNF-α)-induced NF-κB activity in monocytes and vascular smooth muscle cells. The molecular target of (R)-6 was investigated. (R)-6 activated the endogenous LX receptor formyl peptide receptor 2 (ALX/FPR2). The anti-inflammatory properties of (R)-6 were further investigated in vivo in murine models of acute inflammation. Consistent with in vitro observations, (R)-6 attenuated inflammatory responses. These results support the therapeutic potential of the lead QNX-sLXm (R)-6 in the context of novel inflammatory regulators

    Asymmetric Synthesis and Biological Screening of Quinoxaline-Containing Synthetic Lipoxin A4 Mimetics (QNX-sLXms)

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    Failure to resolve inflammation underlies many prevalent pathologies. Recent insights have identified lipid mediators, typified by lipoxins (LXs), as drivers of inflammation resolution, suggesting potential therapeutic benefit. We report the asymmetric preparation of novel quinoxaline-containing syntheticLXA4-mimetics (QNX-sLXms). Eight novel compounds were screened for their impact on inflammatory responses. Structure− activity relationship (SAR) studies showed that (R)-6 (also referred to as AT-02-CT) was the most efficacious and potent anti-inflammatory compound of those tested. (R)-6 significantly attenuated lipopolysaccharide (LPS)- and tumor-necrosis-factor-α (TNF-α)-induced NF-κB activity in monocytes and vascular smooth muscle cells. The molecular target of (R)-6 was investigated. (R)-6 activated the endogenous LX receptor formyl peptide receptor 2 (ALX/FPR2). The anti-inflammatory properties of (R)-6 were further investigated in vivo in murine models of acute inflammation. Consistent with in vitro observations, (R)-6 attenuated inflammatory responses. These results support the therapeutic potential of the lead QNX-sLXm (R)-6 in the context of novel inflammatory regulators

    Nanoscale Mechanical Characterisation of Amyloid Fibrils Discovered in a Natural Adhesive

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    Using the atomic force microscope, we have investigated the nanoscale mechanical response of the attachment adhesive of the terrestrial alga Prasiola linearis (Prasiolales, Chlorophyta). We were able to locate and extend highly ordered mechanical structures directly from the natural adhesive matrix of the living plant. The in vivo mechanical response of the structured biopolymer often displayed the repetitive sawtooth force-extension characteristics of a material exhibiting high mechanical strength at the molecular level. Mechanical and histological evidence leads us to propose a mechanism for mechanical strength in our sample based on amyloid fibrils. These proteinaceous, pleated β-sheet complexes are usually associated with neurodegenerative diseases. However, we now conclude that the amyloid protein quaternary structures detected in our material should be considered as a possible generic mechanism for mechanical strength in natural adhesives

    Marine Invasion in the Mediterranean Sea: The Role of Abiotic Factors When There Is No Biological Resistance

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    The tropical red alga Womersleyella setacea (Rhodomelaceae, Rhodophyta) is causing increasing concern in the Mediterranean Sea because of its invasive behavior. After its introduction it has colonized most Mediterranean areas, but the mechanism underlying its acclimatization and invasion process remains unknown. To understand this process, we decided i) to assess in situ the seasonal biomass and phenological patterns of populations inhabiting the Mediterranean Sea in relation to the main environmental factors, and ii) to experimentally determine if the tolerance of W. setacea to different light and temperature conditions can explain its colonization success, as well as its bathymetric distribution range. The bathymetric distribution, biomass, and phenology of W. setacea were studied at two localities, and related to irradiance and temperature values recorded in situ. Laboratory experiments were set up to study survival, growth and reproduction under contrasting light and temperature conditions in the short, mid, and long term.Results showed that, in the studied area, the bathymetric distribution of W. setacea is restricted to a depth belt between 25 and 40 m deep, reaching maximum biomass values (126 g dw m−2) at 30 m depth. In concordance, although in the short term W. setacea survived and grew in a large range of environmental conditions, its life requirements for the mid and long term were dim light levels and low temperatures. Biomass of Womersleyella setacea did not show any clear seasonal pattern, though minimum values were reported in spring. Reproductive structures were always absent. Bearing in mind that no herbivores feed on Womersleyella setacea and that its thermal preferences are more characteristic of temperate than of tropical seaweeds, low light (50 µmol photon m−2 s−1) and low temperature (12°C) levels are critical for W. setacea survival and growth, thus probably determining its spread and bathymetric distribution across the Mediterranean Sea

    Interpreting ancient food practices:Stable isotope and molecular analyses of visible and absorbed residues from a year-long cooking experiment

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    Chemical analyses of carbonized and absorbed organic residues from archaeological ceramic cooking vessels can provide a unique window into the culinary cultures of ancient people, resource use, and environmental effects by identifying ingredients used in ancient meals. However, it remains uncertain whether recovered organic residues represent only the final foodstuffs prepared or are the accumulation of various cooking events within the same vessel. To assess this, we cooked seven mixtures of C3 and C4 foodstuffs in unglazed pots once per week for one year, then changed recipes between pots for the final cooking events. We conducted bulk stable-isotope analysis and lipid residue analysis on the charred food macro-remains, carbonized thin layer organic patina residues and absorbed lipids over the course of the experiment. Our results indicate that: (1) the composition of charred macro-remains represent the final foodstuffs cooked within vessels, (2) thin-layer patina residues represent a mixture of previous cooking events with bias towards the final product(s) cooked in the pot, and (3) absorbed lipid residues are developed over a number of cooking events and are replaced slowly over time, with little evidence of the final recipe ingredients

    Antioxidant activities of sulfated polysaccharides from brown and red seaweeds

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    The in vitro antioxidant activities of the following six sulfated polysaccharides were investigated: iota, kappa and lambda carrageenans, which are widely used in the food industry, fucoidan (homofucan) from the edible seaweed Fucus vesiculosus and fucans (heterofucans) F0.5 and F1.1 from the seaweed Padina gymnospora. With respect to the inhibition of superoxide radical formation, fucoidan had an IC50 (the half maximal inhibitory concentration) of 0.058 mg·mL−1, while the IC50 for the kappa, iota and lambda carrageenans were 0.112, 0.332 and 0.046 mg·mL−1, respectively. All of the samples had an inhibitory effect on the formation of hydroxyl radicals. The results of peroxidation tests showed that fucoidan had an IC50 of 1.250 mg·mL−1 and that the kappa, iota and lambda carrageenans had an IC50 of 2.753 and 2.338 and 0.323 mg·mL−1, respectively. Fucan fractions showed low antioxidant activity relative to fucoidan. These results clearly indicate the beneficial effect of algal polysaccharides as antioxidants

    Differentiating Salmonid Migratory Ecotypes Through Stable Isotope Analysis of Collagen: Archaeological and Ecological Applications

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    The ability to distinguish between different migratory behaviours (e.g., anadromy and potamodromy) in fish can provide important insights into the ecology, evolution, and conservation of many aquatic species. We present a simple stable carbon isotope (δ13C) approach for distinguishing between sockeye (anadromous ocean migrants) and kokanee (potamodromous freshwater residents), two migratory ecotypes of Oncorhynchus nerka (Salmonidae) that is applicable throughout most of their range across coastal regions of the North Pacific Ocean. Analyses of kokanee (n = 239) and sockeye (n = 417) from 87 sites spanning the North Pacific (Russia to California) show that anadromous and potamodromous ecotypes are broadly distinguishable on the basis of the δ13C values of their scale and bone collagen. We present three case studies demonstrating how this approach can address questions in archaeology, archival, and conservation research. Relative to conventional methods for determining migratory status, which typically apply chemical analyses to otoliths or involve genetic analyses of tissues, the δ13C approach outlined here has the benefit of being non-lethal (when applied to scales), cost-effective, widely available commercially, and should be much more broadly accessible for addressing archaeological questions since the recovery of otoliths at archaeological sites is rare
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