Thrombosis Is Reduced by Inhibition of COX-1, but Unaffected by Inhibition of COX-2, in an Acute Model of Platelet Activation in the Mouse

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Somatic growth dynamics of West Atlantic hawksbill sea turtles: a spatio-temporal perspective

This is the final version of the article. Available from the publisher via the DOI in this record.Somatic growth dynamics are an integrated response to environmental conditions. Hawksbill sea turtles (Eretmochelys imbricata) are long-lived, major consumers in coral reef habitats that move over broad geographic areas (hundreds to thousands of kilometers). We evaluated spatio-temporal effects on hawksbill growth dynamics over a 33-yr period and 24 study sites throughout the West Atlantic and explored relationships between growth dynamics and climate indices. We compiled the largest ever data set on somatic growth rates for hawksbills – 3541 growth increments from 1980 to 2013. Using generalized additive mixed model analyses, we evaluated 10 covariates, including spatial and temporal variation, that could affect growth rates. Growth rates throughout the region responded similarly over space and time. The lack of a spatial effect or spatio-temporal interaction and the very strong temporal effect reveal that growth rates in West Atlantic hawksbills are likely driven by region-wide forces. Between 1997 and 2013, mean growth rates declined significantly and steadily by 18%. Regional climate indices have significant relationships with annual growth rates with 0- or 1-yr lags: positive with the Multivariate El Niño Southern Oscillation Index (correlation = 0.99) and negative with Caribbean sea surface temperature (correlation = −0.85). Declines in growth rates between 1997 and 2013 throughout the West Atlantic most likely resulted from warming waters through indirect negative effects on foraging resources of hawksbills. These climatic influences are complex. With increasing temperatures, trajectories of decline of coral cover and availability in reef habitats of major prey species of hawksbills are not parallel. Knowledge of how choice of foraging habitats, prey selection, and prey abundance are affected by warming water temperatures is needed to understand how climate change will affect productivity of consumers that live in association with coral reefs

Identifying chondroprotective diet-derived bioactives and investigating their synergism

Osteoarthritis (OA) is a multifactorial disease and nutrition is a modifiable factor that may contribute to disease onset or progression. A detailed understanding of mechanisms through which diet-derived bioactive molecules function and interact in OA is needed. We profiled 96 diet-derived, mainly plant-based bioactives using an in vitro model in chondrocytes, selecting four candidates for further study. We aimed to determine synergistic interactions between bioactives that affected the expression of key genes in OA. Selected bioactives, sulforaphane, apigenin, isoliquiritigenin and luteolin, inhibited one or more interleukin-1-induced metalloproteinases implicated in OA (MMP1, MMP13, ADAMTS4, ADAMTS5). Isoliquiritigenin and luteolin showed reactive oxygen species scavenging activity in chondrocytes whereas sulforaphane had no effect and apigenin showed only a weak trend. Sulforaphane inhibited the IL-1/NFκB and Wnt3a/TCF/Lef pathways and increased TGFβ/Smad2/3 and BMP6/Smad1/5/8 signalling. Apigenin showed potent inhibition of the IL-1/NFκB and TGFβ/Smad2/3 pathways, whereas luteolin showed only weak inhibition of the IL-1/NFκB pathway. All four bioactives inhibited cytokine-induced aggrecan loss from cartilage tissue explants. The combination of sulforaphane and isoliquiritigenin was synergistic for inhibiting MMP13 gene expression in chondrocytes. We conclude that dietary-derived bioactives may be important modulators of cartilage homeostasis and synergistic relationships between bioactives may have an anti-inflammatory and chondroprotective role

Network analysis of sea turtle movements and connectivity: A tool for conservation prioritization

This is the final version. Available on open access from Wiley via the DOI in this recordData availability statement: The data that support the findings of this study are available in the Supplementary Material of this article and Zenodo (https://doi.org/10.5281/zenodo.5898578). Details for all animals included in this study are provided in Appendices S1 and S2. Data used to create the spatial networks are listed in the Appendices S3 and S4. The geospatial files for all networks are available on the Migratory Connectivity in the Ocean Project website (https://mico.eco) and Dryad (https://doi.org/10.5061/dryad.j3tx95xg9). Additional data that support the findings of this study are available from the corresponding author upon reasonable request.Aim Understanding the spatial ecology of animal movements is a critical element in conserving long-lived, highly mobile marine species. Analyzing networks developed from movements of six sea turtle species reveals marine connectivity and can help prioritize conservation efforts. Location Global. Methods We collated telemetry data from 1235 individuals and reviewed the literature to determine our dataset's representativeness. We used the telemetry data to develop spatial networks at different scales to examine areas, connections, and their geographic arrangement. We used graph theory metrics to compare networks across regions and species and to identify the role of important areas and connections. Results Relevant literature and citations for data used in this study had very little overlap. Network analysis showed that sampling effort influenced network structure, and the arrangement of areas and connections for most networks was complex. However, important areas and connections identified by graph theory metrics can be different than areas of high data density. For the global network, marine regions in the Mediterranean had high closeness, while links with high betweenness among marine regions in the South Atlantic were critical for maintaining connectivity. Comparisons among species-specific networks showed that functional connectivity was related to movement ecology, resulting in networks composed of different areas and links. Main conclusions Network analysis identified the structure and functional connectivity of the sea turtles in our sample at multiple scales. These network characteristics could help guide the coordination of management strategies for wide-ranging animals throughout their geographic extent. Most networks had complex structures that can contribute to greater robustness but may be more difficult to manage changes when compared to simpler forms. Area-based conservation measures would benefit sea turtle populations when directed toward areas with high closeness dominating network function. Promoting seascape connectivity of links with high betweenness would decrease network vulnerability.International Climate Initiative (IKI)German Federal Ministry for the Environment, Nature Conservation and Nuclear Safety (BMU

Effect of context exposure after fear learning on memory generalization in mice

BackgroundThe conditions under which memory generalization occurs are not well understood. Although it is believed that fear memory generalization is gradually established after learning, it is not clear whether experiences soon after learning affect generalization.ResultsUsing a contextual fear conditioning paradigm in mice, we found that fear memory generalization occurred when mice were exposed to a familiar, unconditioned context soon after fear learning.ConclusionsOur results suggest that the familiarity of contexts and the timing of their exposure influences memory generalization, which increases our understanding of the mechanisms of generalization

Muc2 Protects against Lethal Infectious Colitis by Disassociating Pathogenic and Commensal Bacteria from the Colonic Mucosa

Despite recent advances in our understanding of the pathogenesis of attaching and effacing (A/E) Escherichia coli infections, the mechanisms by which the host defends against these microbes are unclear. The goal of this study was to determine the role of goblet cell-derived Muc2, the major intestinal secretory mucin and primary component of the mucus layer, in host protection against A/E pathogens. To assess the role of Muc2 during A/E bacterial infections, we inoculated Muc2 deficient (Muc2−/−) mice with Citrobacter rodentium, a murine A/E pathogen related to diarrheagenic A/E E. coli. Unlike wildtype (WT) mice, infected Muc2−/− mice exhibited rapid weight loss and suffered up to 90% mortality. Stool plating demonstrated 10–100 fold greater C. rodentium burdens in Muc2−/− vs. WT mice, most of which were found to be loosely adherent to the colonic mucosa. Histology of Muc2−/− mice revealed ulceration in the colon amid focal bacterial microcolonies. Metabolic labeling of secreted mucins in the large intestine demonstrated that mucin secretion was markedly increased in WT mice during infection compared to uninfected controls, suggesting that the host uses increased mucin release to flush pathogens from the mucosal surface. Muc2 also impacted host-commensal interactions during infection, as FISH analysis revealed C. rodentium microcolonies contained numerous commensal microbes, which was not observed in WT mice. Orally administered FITC-Dextran and FISH staining showed significantly worsened intestinal barrier disruption in Muc2−/− vs. WT mice, with overt pathogen and commensal translocation into the Muc2−/− colonic mucosa. Interestingly, commensal depletion enhanced C. rodentium colonization of Muc2−/− mice, although colonic pathology was not significantly altered. In conclusion, Muc2 production is critical for host protection during A/E bacterial infections, by limiting overall pathogen and commensal numbers associated with the colonic mucosal surface. Such actions limit tissue damage and translocation of pathogenic and commensal bacteria across the epithelium

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Green and hawksbill turtles in the Lesser Antilles demonstrate behavioural plasticity in inter-nesting behaviour and post-nesting migration

Satellite transmitters were deployed on three green turtles, Chelonia mydas, and two hawksbill turtles, Eretmochelys imbricata, nesting in the Lesser Antilles islands, Caribbean, between 2005-2007 to obtain preliminary information about the inter-nesting, migratory and foraging habitats in the region. Despite the extremely small dataset, both year-round residents and migrants were identified; specifically (1) two green turtles used local shallow coastal sites within 50 km of the nesting beach during all of their inter-nesting periods and then settled at these sites on completion of their breeding seasons, (2) one hawksbill turtle travelled 200 km westward before reversing direction and settling within 50 km of the original nesting beach and (3) one green and one hawksbill turtle initially nested at the proximate site, before permanently relocating to an alternative nesting site over 190 km distant. A lack of nesting beach fidelity was supported by flipper tag datasets for the region. Tagging datasets from 2002-2012 supported that some green and hawksbill individuals exhibit low fidelity to nesting beaches, whereas other females exhibited a high degree of fidelity (26 turtles tagged, 40.0km maximum distance recorded from original nesting beach). Individual turtles nesting on St Eustatius and St Maarten appear to exhibit behavioural plasticity in their inter-nesting behaviour and post-nesting migration routes in the Eastern Caribbean. The tracking and tagging data combined indicate that some of the green and hawksbill females that nest in the Lesser Antilles Islands are year-round residents, while others may nest and forage at alternative sites. Thus, continued year-round protection of these islands and implementation of protection programmes in nearby islands could contribute towards safeguarding the green and hawksbill populations of the region

Locus coeruleus and dopaminergic consolidation of everyday memory

Item does not contain fulltextThe retention of episodic-like memory is enhanced, in humans and animals, when something novel happens shortly before or after encoding. Using an everyday memory task in mice, we sought the neurons mediating this dopamine-dependent novelty effect, previously thought to originate exclusively from the tyrosine-hydroxylase-expressing (TH+) neurons in the ventral tegmental area. Here we report that neuronal firing in the locus coeruleus is especially sensitive to environmental novelty, locus coeruleus TH+ neurons project more profusely than ventral tegmental area TH+ neurons to the hippocampus, optogenetic activation of locus coeruleus TH+ neurons mimics the novelty effect, and this novelty-associated memory enhancement is unaffected by ventral tegmental area inactivation. Surprisingly, two effects of locus coeruleus TH+ photoactivation are sensitive to hippocampal D1/D5 receptor blockade and resistant to adrenoceptor blockade: memory enhancement and long-lasting potentiation of synaptic transmission in CA1 ex vivo. Thus, locus coeruleus TH+ neurons can mediate post-encoding memory enhancement in a manner consistent with possible co-release of dopamine in the hippocampus