40 research outputs found

    Benthic communities in the deep Mediterranean Sea: exploring microbial and meiofaunal patterns in slope and basin ecosystems

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    The long-held perception of the deep sea consisting of monotonous slopes and uniform oceanic basins has over the decades given way to the idea of a complex system with wide habitat heterogeneity. Under the prism of a highly diverse environment, a large dataset was used to describe and compare spatial patterns of the dominant small-size components of deep-sea benthos, metazoan meiofauna and microbes, from Mediterranean basins and slopes. A grid of 73 stations sampled at five geographical areas along the central-eastern Mediterranean Basin (central Mediterranean, northern Aegean Sea, Cretan Sea, Libyan Sea, eastern Levantine) spanning over 4 km in depth revealed a high diversity, irrespective of the benthic group or level of taxonomic analysis. A common decreasing bathymetric trend was detected for meiobenthic abundance, major taxa diversity and nematode genera richness, but no differences were found between the two habitats (basin vs slope). In contrast, microbial richness is significantly higher at the basin ecosystem and tends to increase with depth. Multivariate analyses (ÎČ- and ÎŽ-diversity and ordination analysis) complemented these results and underlined the high within-habitat variability of benthic communities. Meiofaunal communities in particular were found to change gradually and vary more towards the abyss. On the other hand, microbial communities were highly variable, even among samples of the same area, habitat and bathymetry. A significant proportion of the variation of benthic communities and their descriptors was explained by depth and proxies of food availability (sedimentary pigments and organic content), but the combination of predictor variables and the strength of the relationship varied depending on the data set used (based on type of habitat, benthic component, taxonomic level). This, along with the observed high within-habitat variability suggests that other factors, which tend to vary at local scale (hydrodynamics, substrate structure, geochemistry, food quality, etc.), may also relate to the observed benthic patterns. Overall, the results presented here suggest that differences in small-size benthos between the basin and slope habitats are neither strong nor consistent; it appears that within-habitat variability is high, differences among depth ranges are important and further investigation of possible environmental drivers of benthic patterns is needed

    Assessing the suitability of a range of benthic indices in the evaluation of environmental impact of fin and shellfish aquaculture located in sites across Europe

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    The European Union-funded ECASA project (Ecosystem Approach for Sustainable Aquaculture) studied the impacts from aquaculture on ecosystems from northern Norway to Greece. The objectives of this investigation were to identify quantitative indicators of the effects of aquaculture on marine communities, and to assess their applicability over a range of ecosystems and aquaculture production systems. The study included 6 Mediterranean and 4 Atlantic sites, 7 ofwhich produced finfish (seabream, seabass, tuna, salmon and cod), and 2 bivalve molluscs (oysters, mussels, and clams); one site produced both fish and bivalves. Cultivation methods included finfish cages, long-lines and trestles. Similar sampling methodologies were employed at the 10 study sites, obtaining sediment, hydrodynamic, and benthic faunal data. The horizontal impact from organic enrichment extended 50m from the farms, with contradictory responses in several indicators (individual abundance, biomass) and a more consistent response of the Infaunal Trophic Index (ITI) and AZTI'sMarine Biotic Index (AMBI). By means of Partial Redundancy Analysis, it was demonstrated that the environmental variables explained 53.2% of the variability in the macrofaunal variables (individual abundance, species richness, diversity, AMBI and ITI), whilst the explained variance was partialled out within three groups of variables: (i) ‘hydrography’ (depth, distance to farm, average current speed), which explained 11.5% of the variance; (ii) ‘sediment’ (Eh and percentages of silt and total organic matter), which explained 5.4%; and (iii) ‘cages’ (years of production and annual production), which explained 15.2%. The shared variance explained by interactions among these groups was 21.1%. These results, together with multiple regression analysis, provide an accurate assessment of the degree of impact from aquaculture. In conclusion, the use of several benthic indicators, in assessing farm impacts, together with the investigation of dynamics of the studied location, water depth, years of farm activity, and total annual production, must be included when interpreting the response of benthic communities to organic enrichment from aquaculture

    Pre-clinical characterisation of E2814, a high-affinity antibody targeting the microtubule-binding repeat domain of tau for passive immunotherapy in Alzheimer's disease

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    Tau deposition in the brain is a pathological hallmark of many neurodegenerative disorders, including Alzheimer’s disease (AD). During the course of these tauopathies, tau spreads throughout the brain via synaptically-connected pathways. Such propagation of pathology is thought to be mediated by tau species (“seeds”) containing the microtubule binding region (MTBR) composed of either three repeat (3R) or four repeat (4R) isoforms. The tau MTBR also forms the core of the neuropathological filaments identified in AD brain and other tauopathies. Multiple approaches are being taken to limit tau pathology, including immunotherapy with anti-tau antibodies. Given its key structural role within fibrils, specifically targetting the MTBR with a therapeutic antibody to inhibit tau seeding and aggregation may be a promising strategy to provide disease-modifying treatment for AD and other tauopathies. Therefore, a monoclonal antibody generating campaign was initiated with focus on the MTBR. Herein we describe the pre-clinical generation and characterisation of E2814, a humanised, high affinity, IgG1 antibody recognising the tau MTBR. E2814 and its murine precursor, 7G6, as revealed by epitope mapping, are antibodies bi-epitopic for 4R and mono-epitopic for 3R tau isoforms because they bind to sequence motif HVPGG. Functionally, both antibodies inhibited tau aggregation in vitro. They also immunodepleted a variety of MTBR-containing tau protein species. In an in vivo model of tau seeding and transmission, attenuation of deposition of sarkosyl-insoluble tau in brain could also be observed in response to antibody treatment. In AD brain, E2814 bound different types of tau filaments as shown by immunogold labelling and recognised pathological tau structures by immunohistochemical staining. Tau fragments containing HVPGG epitopes were also found to be elevated in AD brain compared to PSP or control. Taken together, the data reported here have led to E2814 being proposed for clinical developmen

    Big conductance calcium-activated potassium channel openers control spasticity without sedation.

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    BACKGROUND AND PURPOSE: Our initial aim was to generate cannabinoid agents that control spasticity, occurring as a consequence of multiple sclerosis (MS), whilst avoiding the sedative side effects associated with cannabis. VSN16R was synthesized as an anandamide (endocannabinoid) analogue in an anti-metabolite approach to identify drugs that target spasticity. EXPERIMENTAL APPROACH: Following the initial chemistry, a variety of biochemical, pharmacological and electrophysiological approaches, using isolated cells, tissue-based assays and in vivo animal models, were used to demonstrate the activity, efficacy, pharmacokinetics and mechanism of action of VSN16R. Toxicological and safety studies were performed in animals and humans. KEY RESULTS: VSN16R had nanomolar activity in tissue-based, functional assays and dose-dependently inhibited spasticity in a mouse experimental encephalomyelitis model of MS. This effect occurred with over 1000-fold therapeutic window, without affecting normal muscle tone. Efficacy was achieved at plasma levels that are feasible and safe in humans. VSN16R did not bind to known CB1 /CB2 /GPPR55 cannabinoid-related receptors in receptor-based assays but acted on a vascular cannabinoid target. This was identified as the major neuronal form of the big conductance, calcium-activated potassium (BKCa ) channel. Drug-induced opening of neuronal BKCa channels induced membrane hyperpolarization, limiting excessive neural-excitability and controlling spasticity. CONCLUSIONS AND IMPLICATIONS: We identified the neuronal form of the BKCa channel as the target for VSN16R and demonstrated that its activation alleviates neuronal excitability and spasticity in an experimental model of MS, revealing a novel mechanism to control spasticity. VSN16R is a potential, safe and selective ligand for controlling neural hyper-excitability in spasticity

    Where Is More Important Than How in Coastal and Marine Ecosystems Restoration

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    Restoration is considered an effective strategy to accelerate the recovery of biological communities at local scale. However, the effects of restoration actions in the marine ecosystems are still unpredictable. We performed a global analysis of published literature to identify the factors increasing the probability of restoration success in coastal and marine systems. Our results confirm that the majority of active restoration initiatives are still concentrated in the northern hemisphere and that most of information gathered from restoration efforts derives from a relatively small subset of species. The analysis also indicates that many studies are still experimental in nature, covering small spatial and temporal scales. Despite the limits of assessing restoration effectiveness in absence of a standardized definition of success, the context (degree of human impact, ecosystem type, habitat) of where the restoration activity is undertaken is of greater relevance to a successful outcome than how (method) the restoration is carried out. Contrary to expectations, we found that restoration is not necessarily more successful closer to protected areas (PA) and in areas of moderate human impact. This result can be motivated by the limits in assessing the success of interventions and by the tendency of selecting areas in more obvious need of restoration, where the potential of actively restoring a degraded site is more evident. Restoration sites prioritization considering human uses and conservation status present in the region is of vital importance to obtain the intended outcomes and galvanize further actions

    Report on identification of keystone species and processes across regional seas. DEVOTES FP7 Project

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    WP6, Deliverable 6.1, DEVOTES ProjectIn managing for marine biodiversity, it is worth recognising that, whilst every species contributes to biodiversity, each contribution is not of equal importance. Some have important effects and interactions, both primary and secondary, on other components in the community and therefore by their presence or absence directly affect the biodiversity of the community as a whole. Keystone species have been defined as species that have a disproportionate effect on their environment relative to their abundance. As such, keystone species might be of particular relevance for the marine biodiversity characterisation within the assessment of Good Environmental Status (GEnS), for the Marine Strategy Framework Directive (MSFD).The DEVOTES Keystone Catalogue and associated deliverable document is a review of potential keystone species of the different European marine habitats. The catalogue has 844 individual entries, which includes 210 distinct species and 19 groups classified by major habitat in the Baltic Sea, North East Atlantic, Mediterranean, Black Sea (EU Regional Seas) and Norwegian Sea (Non-­‐EU Sea). The catalogue and the report make use/cite 164 and 204 sources respectively. The keystones in the catalogue are indicated by models, by use as indicators, by published work (e.g. on traits and interactions with other species), and by expert opinion based on understanding of systems and roles of species/groups. A total of 74 species were considered to act as keystone predators, 79 as keystone engineers, 66 as keystone habitat forming species, while a few were thought of having multiple roles in their marine ecosystems. Benthic invertebrates accounted for 50% of the reported keystone species/groups, while macroalgae contributed 17% and fish12%. Angiosperms were consistently put forward as keystone habitat forming and engineering species in all areas. A significant number of keystones were invasive alien species.Only one keystone, the bivalve Mya arenaria, was common to all four EU regional seas. The Mediterranean Sea had the largest number of potential keystones (56% of the entries) with the least in the Norwegian Sea. There were very few keystones in deep waters (Bathyal-­‐Abyssal, 200+ m), with most reported in sublittoral shallow and shelf seabeds or for pelagic species in marine waters with few in reduced/variable salinity waters. The gaps in coverage and expertise in the catalogue are analysed at the habitat and sea level, within the MSFD biodiversity component groups and in light of knowledge and outputs from ecosystem models (Ecopath with Ecosim).The understanding of keystones is discussed as to when a species may be a dominant or keystone with respect to the definition term concerning ‘disproportionate abundance’, how important are the ‘disproportionate effects’ in relation to habitat formers and engineers, what separates a key predator and key prey for mid-­‐trophic range species and how context dependency makes a species a keystone. Keystone alien invasive species are reviewed and the use of keystone species model outputs investigated. In the penultimate sections of the review the current level of protection on keystone species and the possibilities for a keystone operational metric and their use in management and in GEnS assessments for the MSFD are discussed. The final section highlights the one keystone species and its interactions not covered in the catalogue but with the greatest impact on almost all marine ecosystems, Homo sapiens

    Human activities and resultant pressures on key European marine habitats: An analysis of mapped resources

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    Human activities exert a wide range of pressures on marine ecosystems, often resulting in the loss of species and degradation of habitats. If effective policies and management practices to restore past damage and reduce future impacts to the marine environment are to be developed, knowledge of the extent, duration and severity of activities and pressures is essential, yet often lacking. As part of the EU H2020 project “Marine Ecosystem Restoration in Changing European Seas”, this study uses an exhaustive review of published records, web resources, and grey literature to comprehensively assess the degree to which human activities and pressures are mapped within European seas. The results highlight a number of limitations and gaps, including: (a) limited geographic coverage at both the regional and sub-regional level; (b) insufficient spatial resolution and accuracy in recorded data for the planning of conservation and restoration actions; (c) a lack of access to the background data and metadata upon which maps are based, thus limiting the potential for synthesis of multiple data sources. Based on the findings, several recommendations for future marine research initiatives arise, most importantly the need for coordinated, geographically extended baseline assessments of the distribution and intensity of human activities and pressures, complying with high-level standardization regarding methodological approaches and the treatment of produced data
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