Low sulfated heparins target multiple proteins for central nervous system repair

The lack of endogenous repair following spinal cord injury (SCI) accounts for the frequent permanent deficits for which effective treatments are absent. Previously, we demonstrated that low sulfated modified heparin mimetics (LS‐mHeps) attenuate astrocytosis, suggesting they may represent a novel therapeutic approach. mHeps are glycomolecules with structural similarities to resident heparan sulfates (HS), which modulate cell signaling by both sequestering ligands, and acting as cofactors in the formation of ligand–receptor complexes. To explore whether mHeps can affect the myelination and neurite outgrowth necessary for repair after SCI, we created lesioned or demyelinated neural cell co‐cultures and exposed them with a panel of mHeps with varying degrees and positions of their sulfate moieties. LS‐mHep7 enhanced neurite outgrowth and myelination, whereas highly sulfated mHeps (HS‐mHeps) had attenuating effects. LS‐mHeps had no effects on myelination or neurite extension in developing, uninjured myelinating cultures, suggesting they might exert their proregenerating effects by modulating or sequestering inhibitory factors secreted after injury. To investigate this, we examined conditioned media from cultures using chemokine arrays and conducted an unbiased proteomics approach by applying TMT‐LC/MS to mHep7 affinity purified conditioned media from these cultures. Multiple protein factors reported to play a role in damage or repair mechanisms were identified, including amyloid betaA4. Amyloid beta peptide (1–42) was validated as an important candidate by treating myelination cultures and shown to inhibit myelination. Thus, we propose that LS‐mHeps exert multiple beneficial effects on mechanisms supporting enhanced repair, and represent novel candidates as therapeutics for CNS damage

Fucosylated chondroitin sulfates from the body wall of the sea cucumber <i>Holothuria forskali</i>. Conformation, selectin binding and biological activity

Fucosylated chondroitin sulfate (fCS) extracted from the sea cucumber Holothuria forskali is composed of the following repeating trisaccharide unit: →3)GalNAcβ4,6S(1→4) [FucαX(1→3)]GlcAβ(1→, where X stands for different sulfation patterns of fucose (X = 3,4S (46%), 2,4S (39%), and 4S (15%)). As revealed by NMR and molecular dynamics simulations, the fCS repeating unit adopts a conformation similar to that of the Lex blood group determinant, bringing several sulfate groups into close proximity and creating large negative patches distributed along the helical skeleton of the CS backbone. This may explain the high affinity of fCS oligosaccharides for L- and P-selectins as determined by microarray binding of fCS oligosaccharides prepared by Cu2+-catalyzed Fenton-type and photochemical depolymerization. No binding to E-selectin was observed. fCS poly- and oligosaccharides display low cytotoxicity in vitro, inhibit human neutrophil elastase activity, and inhibit the migration of neutrophils through an endothelial cell layer in vitro. Although the polysaccharide showed some anti-coagulant activity, small oligosaccharide fCS fragments had much reduced anticoagulant properties, with activity mainly via heparin cofactor II. The fCS polysaccharides showed prekallikrein activation comparable with dextran sulfate, whereas the fCS oligosaccharides caused almost no effect. The H. forskali fCS oligosaccharides were also tested in a mouse peritoneal inflammation model, where they caused a reduction in neutrophil infiltration. Overall, the data presented support the action of fCS as an inhibitor of selectin interactions, which play vital roles in inflammation and metastasis progression. Future studies of fCS-selectin interaction using fCS fragments or their mimetics may open new avenues for therapeutic intervention

Antibacterial activity of Thymoquinone, an active principle of Nigella sativa and its potency to prevent bacterial biofilm formation

<p>Abstract</p> <p>Background</p> <p>Thymoquinone is an active principle of <it>Nigella sativa </it>seed known as "Habbah Al-Sauda" in Arabic countries and "Sinouj" in Tunisia. Bacterial biofilms tend to exhibit significant tolerance to antimicrobials drugs during infections.</p> <p>Methods</p> <p>The antibacterial activity of Thymoquinone (TQ) and its biofilm inhibition potencies were investigated on 11 human pathogenic bacteria. The growth and development of the biofilm were assessed using the crystal violet (CV) and the 2, 3-bis [2-methyloxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide (XTT) reduction assay.</p> <p>Results</p> <p>TQ exhibited a significant bactericidal activity against the majority of the tested bacteria (MICs values ranged from 8 to 32 μg/ml) especially Gram positive cocci (<it>Staphylococcus aureus </it>ATCC 25923 and <it>Staphylococcus epidermidis </it>CIP 106510). Crystal violet assay demonstrated that the minimum biofilm inhibition concentration (BIC50) was reached with 22 and 60 μg/ml for <it>Staphylococcus aureus </it>ATCC 25923 and <it>Staphylococcus epidermidis </it>CIP 106510 respectively. In addition our data revealed that cells oxidative activity was influenced by TQ supplementation. In the same way, TQ prevented cell adhesion to glass slides surface.</p> <p>Conclusion</p> <p>The ability of TQ to prevent biofilm formation warrants further investigation to explore its use as bioactive substances with antibiofilm potential.</p

National Government Responses to Marine Stewardship Council (MSC) Fisheries Certification: Insights from Atlantic Canada

Over the last decade, the proliferation of social and environmental certification programmes has attracted the attention of a growing number of political scientists interested in new forms of ‘private’ transnational governance. However, we still lack analyses on the nature and extent of different state responses to and involvement in new private transnational governance arrangements in particular sectors and in different jurisdictions. This paper advances our understanding of the interactions between nation-state and private transnational modes of governance by analysing the role of national government authorities in Marine Stewardship Council (MSC) fisheries certification in Atlantic Canada, known more for the disastrous collapse of Northern cod stocks than good marine stewardship. Focusing on the 2008 certification of Northern shrimp (Pandalus borealis) fisheries off the Province of Newfoundland and Labrador, the analysis finds that the implementation and maintenance of MSC certification in this case depended on significant support from government authorities. The delicate legitimacy of both authorities face a period of uncertainty in this case since some certified shrimp stocks appear to be in decline and perhaps also migrating northward off Newfoundland and Labrador

Collateral damage? Small-scale fisheries in the global fight against IUU fishing

© 2020 The Authors. Fish and Fisheries published by John Wiley & Sons Ltd Concern over illegal, unreported and unregulated (IUU) fishing has led to a number of policy, trade and surveillance measures. While much attention has been given to the impact of IUU regulation on industrial fleets, recognition of the distinct impacts on small-scale fisheries is conspicuously lacking from the policy and research debate. In this paper, we outline three ways in which the application of IUU discourse and regulation undermines small-scale fisheries. First, the mainstream construction of “illegal,” “unreported” and “unregulated” fishing, and also the categorical use of “IUU” in an all-inclusive sense, disregards the diversity, legitimacy and sustainability of small-scale fisheries practices and their governing systems. Second, we explore how the recent trade-related measures to counter IUU fishing mask and reinforce existing inequalities between different sectors and countries, creating an unfair burden on small-scale fisheries and countries who depend on them. Third, as IUU fishing is increasingly approached as “organized crime,” there is a risk of inappropriately targeting small-scale fisheries, at times violently. Reflecting on these three trends, we propose three strategies by which a more sensitive and ultimately more equitable incorporation of small-scale fisheries can be supported in the global fight against IUU fishing

Using Agent-Based Modelling to Inform Policy – What Could Possibly Go Wrong?

© 2019, Springer Nature Switzerland AG. Scientific modelling can make things worse, as in the case of the North Atlantic Cod Fisheries Collapse. Some of these failures have been attributed to the simplicity of the models used compared to what they are trying to model. MultiAgent-Based Simulation (MABS) pushes the boundaries of what can be simulated, prompting many to assume that it can usefully inform policy, even in the face of complexity. That said, MABS also brings with it new difficulties and potential confusions. This paper surveys some of the pitfalls that can arise when MABS analysts try to do this. Researchers who claim (or imply) that MABS can reliably predict are criticised in particular. However, an alternative is suggested – that of using MABS for a kind of uncertainty analysis – identifying some of the possible ways a policy can go wrong (or indeed go right). A fisheries example is given. This alternative may widen, rather than narrow, the range of evidence and possibilities that are considered, which could enrich the policy-making process. We call this Reflexive Possibilistic Modelling

The Paradox of Parkour: Conformity, Resistance and Spatial Exclusion

Drawing upon two years of ethnographic research into the spatially transgressive practice of parkour and freerunning, this chapter attempts to explain and untangle some of the contradictions that surround this popular lifestyle sport and its exclusion from our hyper-regulated cities. While the existing criminological wisdom suggests that these practices are a form of politicised resistance, this chapter positions parkour and freerunning as hyper-conformist to the underlying values of consumer capitalism and explains how late capitalism has created a contradiction for itself in which it must stoke desire for these lifestyle practices whilst also excluding their free practice from central urban spaces. Drawing on the emergent deviant leisure perspective’s interest in issues of infantilisation and adultification, this chapter explores the lifeworlds of young people who are attempting to navigate the challenges and anxieties of early adulthood. For the young people in this study, consumer capitalism’s commodification of rebellious iconography offered unique identities of ‘cool individualism’ and opportunities for flexibilised employment, while the post-industrial ‘creative city’ attempted to harness parkour’s practice, prohibitively if necessary, into approved spatial contexts under the buzzwords of ‘culture’ and ‘creativity’. Therefore, this chapter engages in a critical criminological reappraisal of issues of transgression, deviance and resistance in urban space under consumer capitalism