Thrombo-Inflammation: A Focus on NTPDase1/CD39

There is increasing evidence for a link between inflammation and thrombosis. Following tissue injury, vascular endothelium becomes activated, losing its antithrombotic properties whereas inflammatory mediators build up a prothrombotic environment. Platelets are the first elements to be activated following endothelial damage; they participate in physiological haemostasis, but also in inflammatory and thrombotic events occurring in an injured tissue. While physiological haemostasis develops rapidly to prevent excessive blood loss in the endothelium activated by inflammation, hypoxia or by altered blood flow, thrombosis develops slowly. Activated platelets release the content of their granules, including ATP and ADP released from their dense granules. Ectonucleoside triphosphate diphosphohydrolase-1 (NTPDase1)/CD39 dephosphorylates ATP to ADP and to AMP, which in turn, is hydrolysed to adenosine by ecto-50 -nucleotidase (CD73). NTPDase1/CD39 has emerged has an important molecule in the vasculature and on platelet surfaces; it limits thrombotic events and contributes to maintain the antithrombotic properties of endothelium. The aim of the present review is to provide an overview of platelets as cellular elements interfacing haemostasis and inflammation, with a particular focus on the emerging role of NTPDase1/CD39 in controlling both processes

Nephrops norvegicus in the Adriatic Sea: Connectivity modeling essential fish habitats and management area network

AbstractKnowledge of connectivity among subpopulations is fundamental in the identification of the appropriate geographical scales for stock status evaluation and management, the identification of areas with greater retention rates, and space‐based fisheries management. Here, an integration of hydrodynamic, biological, and habitat models results is used to assess connectivity and support the definition of essential fish habitats (EFH) in the Adriatic Sea, with reference to Nephrops norvegicus, an important benthic commercial resource, the recruitment of which is strongly related to larval dispersal from spawning to recruitment areas. We explored oceanographic and biological connectivity in the Adriatic Sea under a wide and representative variety of oceanographic conditions (winters 2006–2012) by tracking 3D trajectories of larvae released from different areas. We used a Lagrangian model that features a specific larval behavior module with explicit dependence on environmental parameters (i.e., temperature and sediment type) and that is driven by high‐resolution hydrodynamic and meteorological data. The results were used to partition the area in which Nephrops was observed into 20 homogenous management subareas; to assess the connection between spawning, recruitment, and harvesting grounds; and to identify potential subpopulation boundaries as well as the connectivity among the potential subpopulations. The results suggest the presence of at least three distinct subpopulations, which need to be independently managed and conserved, and confirms that the Jabuka‐Pomo pit is the most important spawning area, but alone it cannot sustain Nephrops populations throughout the Adriatic Sea. The results also show the importance to move from particle‐tracking to approaches based on integrated models

SerpinB3 promotes pro-fibrogenic responses in activated hepatic stellate cells

SerpinB3 is a hypoxia- and hypoxia-inducible factor-2\u3b1-dependent cystein protease inhibitor that is up-regulated in hepatocellular carcinoma and in parenchymal cells during chronic liver diseases (CLD). SerpinB3 up-regulation in CLD patients has been reported to correlate with the extent of liver fibrosis and the production of transforming growth factor-\u3b21, but the actual role of SerpinB3 in hepatic fibrogenesis is still poorly characterized. In the present study we analyzed the pro-fibrogenic action of SerpinB3 in cell cultures and in two different murine models of liver fibrosis. "In vitro" experiments revealed that SerpinB3 addition to either primary cultures of human activated myofibroblast-like hepatic stellate cells (HSC/MFs) or human stellate cell line (LX2 cells) strongly up-regulated the expression of genes involved in fibrogenesis and promoted oriented migration, but not cell proliferation. Chronic liver injury by CCl4 administration or by feeding a methionine/choline deficient diet to transgenic mice over-expressing human SerpinB3 in hepatocytes confirmed that SerpinB3 over-expression significantly increased the mRNA levels of pro-fibrogenic genes, collagen deposition and \u3b1SMA-positive HSC/MFs as compared to wild-type mice, without affecting parenchymal damage. The present study provides for the first time evidence that hepatocyte release of SerpinB3 during CLD can contribute to liver fibrogenesis by acting on HSC/MFs

Lack of Ecto-5'-Nucleotidase Protects Sensitized Mice against Allergen Challenge

Ecto-5'-nucleotidase (CD73), the ectoenzyme that together with CD39 is responsible for extracellular ATP hydrolysis and adenosine accumulation, regulates immune/inflammatory processes by controlling innate and acquired immunity cell functions. We previously demonstrated that CD73 is required for the assessment of a controlled allergic sensitization, in mice. Here, we evaluated the response to aerosolized allergen of female-sensitized mice lacking CD73 in comparison with their wild type counterpart. Results obtained show, in mice lacking CD73, the absence of airway hyperreactivity in response to an allergen challenge, paralleled by reduced airway CD23+B cells and IL4+T cells pulmonary accumulation together with reduced mast cells accumulation and degranulation. Our findings indicate CD73 as a potential therapeutic target for allergic asthma

Korištenje povlačne podvodne kamere za procjene škampa, hlapića i morskog pera u Jadranskom moru

Norway lobster, Nephrops norvegicus, is of great commercial importance throughout the NE Atlantic and Mediterranean, where it lives in burrows within muddy sediments. In several European countries it is assessed by means of towed underwater TV techniques. These are particularly suited to N. norvegicus because, for a number of reasons, the application of common fishery-dependent stock-assessment methods is not thorough for this species. The TV-based methodology relies on the fact that a known surface area of seabed is visually assessed and the number of N. norvegicus burrows, whose features are distinct, can be counted and their inhabitants quantified. It follows that, in theory, the same can be done for other organisms or key ecological features which appear on the footage. This study reports the results of the underwater television surveys (2009 and 2010) carried out jointly by Italy and Croatia in the Pomo/Jabuka pits, an area of the Adriatic Sea important for its N. norvegicus fishery and its hake nursery grounds. The obtained footage allowed quantification of the density of N. norvegicus in the area and the acquisition of estimates of the abundances of the squat lobster, Munida rutllanti and the sea pen Funiculina quadrangularis. The concurrent quantification of trawling activity from the footage has allowed us to place our results in the context of an ecosystem approach to fisheries management.Škamp ( Nephrops norvegicus ) je izuzetno važna gospodarska vrsta koja obitava u rupama u muljevitom sedimentu diljem sjeverno-istočnog Atlantika i Mediterana. Obzirom da uobičajene metode procjene bioloških resursa koje se zasnivaju na ribolovu nisu u potpunosti pogodne za ovu vrstu, nekoliko Europskih zemalja procjene populacije škampa obavlja korištenjem povlačne podvodne kamere. Ova metodologija bazira se na činjenici da škamp u sedimentu iskapa rupe karakterističnog izgleda koje se determiniraju i prebrojavaju vizualnim pregledom snimke dobivene povlačenjem podvodne kamere preko određene površine morskog dna. Teoretski, ova metodologija se može primijeniti i za procjene drugih vrsta ili ekoloških parametara koji su zabilježeni na snimkama. Ova studija iznosi rezultate istraživanja podvodnom kamerom (2009. i 2010. godine) koje su zajednički proveli Italija i Hrvatska na području Jabučke kotline u Jadranskom moru. Ovo područje koje se intenzivno gospodarski iskorištava značajno je kao glavno mrijestilište i rastilište većeg broja pridnenih vrsta, posebno škampa i oslića ( Merluccius merluccius ) Na osnovu dobivenih snimki izrađena je procjena brojnosti i biomase škampa, kao i procjena brojnosti hlapića ( Munida rutllanti ) i morskog pera ( Funiculina quadrangularis ). Istodobna procjena tragova koćarenja zabilježenih na snimkama omogućila nam je da ove rezultate stavimo u kontekst ekosustavnog pristupa gospodarenju bioloških resursa mora

Assessing different causes of crown-of-thorns starfish outbreaks and appropriate responses for management on the Great Barrier Reef

The crown-of-thorns starfish Acanthaster planci (COTS) has contributed greatly to declines in coral cover on Australia's Great Barrier Reef, and remains one of the major acute disturbances on Indo-Pacific coral reefs. Despite uncertainty about the underlying causes of outbreaks and the management responses that might address them, few studies have critically and directly compared competing hypotheses. This study uses qualitative modelling to compare hypotheses relating to outbreak initiation, explicitly considering the potential role of positive feedbacks, elevated nutrients, and removal of starfish predators by fishing. When nutrients and fishing are considered in isolation, the models indicate that a range of alternative hypotheses are capable of explaining outbreak initiation with similar levels of certainty. The models also suggest that outbreaks may be caused by multiple factors operating simultaneously, rather than by single proximal causes. As the complexity and realism of the models increased, the certainty of outcomes decreased, but key areas that require further research to improve the structure of the models were identified. Nutrient additions were likely to result in outbreaks only when COTS larvae alone benefitted from nutrients. Similarly, the effects of fishing on the decline of corals depended on the complexity of interactions among several categories of fishes. Our work suggests that management approaches which seek to be robust to model structure uncertainty should allow for multiple potential causes of outbreaks. Monitoring programs can provide tests of alternative potential causes of outbreaks if they specifically monitor all key taxa at reefs that are exposed to appropriate combinations of potential causal factors

Antigen mimicry as an effective strategy to induce CSPG4-targeted immunity in dogs with oral melanoma: a veterinary trial

BACKGROUND: Melanoma is the most lethal form of skin cancer in humans. Conventional therapies have limited efficacy, and overall response is still unsatisfactory considering that immune checkpoint inhibitors induce lasting clinical responses only in a low percentage of patients. This has prompted us to develop a vaccination strategy employing the tumor antigen chondroitin sulfate proteoglycan (CSPG)4 as a target. METHODS: To overcome the host’s unresponsiveness to the self-antigen CSPG4, we have taken advantage of the conservation of CSPG4 sequence through phylogenetic evolution, so we have used a vaccine, based on a chimeric DNA molecule encompassing both human (Hu) and dog (Do) portions of CSPG4 (HuDo-CSPG4). We have tested its safety and immunogenicity (primary objectives), along with its therapeutic efficacy (secondary outcome), in a prospective, non-randomized, veterinary clinical trial enrolling 80 client-owned dogs with surgically resected, CSPG4-positive, stage II–IV oral melanoma. RESULTS: Vaccinated dogs developed anti-Do-CSPG4 and Hu-CSPG4 immune response. Interestingly, the antibody titer in vaccinated dogs was significantly associated with the overall survival. Our data suggest that there may be a contribution of the HuDo-CSPG4 vaccination to the improvement of survival of vaccinated dogs as compared with controls treated with conventional therapies alone. CONCLUSIONS: HuDo-CSPG4 adjuvant vaccination was safe and immunogenic in dogs with oral melanoma, with potential beneficial effects on the course of the disease. Thanks to the power of naturally occurring canine tumors as predictive models for cancer immunotherapy response, these data may represent a basis for the translation of this approach to the treatment of human patients with CSPG4-positive melanoma subtypes

IMOS national reference stations: A continental-wide physical, chemical and biological coastal observing system

Sustained observations allow for the tracking of change in oceanography and ecosystems, however, these are rare, particularly for the Southern Hemisphere. To address this in part, the Australian Integrated Marine Observing System (IMOS) implemented a network of nine National Reference Stations (NRS). The network builds on one long-term location, where monthly water sampling has been sustained since the 1940s and two others that commenced in the 1950s. In-situ continuously moored sensors and an enhanced monthly water sampling regime now collect more than 50 data streams. Building on sampling for temperature, salinity and nutrients, the network now observes dissolved oxygen, carbon, turbidity, currents, chlorophyll a and both phytoplankton and zooplankton. Additional parameters for studies of ocean acidification and bio-optics are collected at a sub-set of sites and all data is made freely and publically available. Our preliminary results demonstrate increased utility to observe extreme events, such as marine heat waves and coastal flooding; rare events, such as plankton blooms; and have, for the first time, allowed for consistent continental scale sampling and analysis of coastal zooplankton and phytoplankton communities. Independent water sampling allows for cross validation of the deployed sensors for quality control of data that now continuously tracks daily, seasonal and annual variation. The NRS will provide multi-decadal time series, against which more spatially replicated short-term studies can be referenced, models and remote sensing products validated, and improvements made to our understanding of how large-scale, long-term change and variability in the global ocean are affecting Australia's coastal seas and ecosystems. The NRS network provides an example of how a continental scaled observing systems can be developed to collect observations that integrate across physics, chemistry and biology