ornl.gov/ftp/oceans/LDEO_Database/Version_2009/). Using these raw observations we can re-construct the representation of pCO2 data at our model grid. By sub-sampling the model by the data locations, we can remove the mismatches due to data scaling, and produce a less biased,

one-to-one comparison. We use these to compare with co-located, coincident estimates of pCO2 from the MERRA model forcing version to understand the effects of gridding and sampling on the global gridded representations of pCO2. Carbon flux estimates are not available in the ungridded data from LDEO, but we can estimate them from pCO2 and climatological ocean and atmospheric variables using the OCMIP protocols, similar to the way FCO2 is computed by the model. The required variables are wind speed, sea level pressure, and atmospheric pCO2. While all of these are derived from www.selleckchem.com/mTOR.html or force the model in the model derivation of FCO2, we use data climatologies here to estimate FCO2 I-BET-762 in vivo from the LDEO pCO2 point measurement data. The data are taken

from LDEO to retain as much consistency as possible. Results are evaluated globally and regionally in 12 major oceanographic basins (Fig. 4) from the forcing by each of the four reanalysis products. Comparisons are statistical, including differences between model global and regional means and correlation analysis. Our emphasis is on large temporal and spatial scale results, using annual area-weighted means and correlation analysis across the basins (N = 12, with 10 degrees of freedom). We additionally compare model pCO2 and FCO2 from one Interleukin-3 receptor of the reanalyses, MERRA, against in situ data sub-regionally to estimate the influences of inherent model biases on the results shown in the intercomparison of reanalysis products. Global annual mean FCO2 from the model forced by the four different reanalysis products show considerable spatial similarity (Fig. 5). The difference between the lowest estimate, NCEP2 (−0.276 mol C m−2 y−1) and the highest, ECMWF (−0.402 mol C m−2 y−1) is about 0.13 mol C m−2 y−1,

or about 45%. MERRA forcing is closest to in situ estimates (within 0.008 mol C m−2 y−1, or 2%), with NCEP1 only slightly more distant (by 0.024 mol C m−2 y−1, or 7.0%). Correlations with in situ estimates across basins are positive and statistically significant (P < 0.05) for all forcing, with correlation coefficient ranging from 0.73 (MERRA and ECMWF) to 0.80 (NCEP1). There are, however, substantial differences in basin-scale estimates of FCO2 among the various reanalysis forcings, especially in the high latitudes and tropics (Fig. 5). In the high latitudes (>±40° latitude), all the forcings produce strong sinks in the oceans, in accordance with the in situ estimates, but all are weaker than the data. The NCEP2 sink in the Antarctic is the lowest (−0.97 mol C m−2 y−1), representing only about a third the magnitude of the next smallest sink (ECMWF).

3% Triton X-100 and 10% skimmed milk) or a polyclonal anti-FG raised in rabbit (Bioscience Research Reagents, Temecula, CA; diluted 1:10,000 in PB containing 0.3% Triton X-100 and 10% skimmed milk) for 24–48 h at 4 °C. After several rinses, they were transferred to a biotinylated anti-rabbit secondary antibody raised in goat (Vector, Burlingame, CA; 1:200 dilution) for 2 h at room temperature, rinsed again and exposed to the ABC mixture (Vectastain, Elite ABC Kit, Vector Laboratories; 1:200 dilution) for 2 h at room temperature. The peroxidase reaction product

was visualized by using SCH772984 in vivo the glucose-oxidase procedure (Itoh et al., 1979) and the metal-free 3,3′-diaminobenzidine tetrahydrochloride (DAB) as the chromogen. The sections were mounted on gelatinized slides, air-dried, and dipped in a 0.05% learn more aqueous solution of osmium tetroxide for 20 s to enhance the visibility of the labeling, dehydrated, transferred into xylene and coverslipped with DPX. An adjacent series was stained with thionin. The brain sections were analyzed with a microscope under brightfield and darkfield illumination. The PHA-L and FG injection sites and the distribution of anterograde labeling of representative cases were mapped

by the aid of a computer drawing program (AutoCad, Release 13) combined with a microscope (Leitz, Diaplan, Leica Microsystems, Wetzlar, Germany) and camera lucida aimed at a flat-screen computer monitor. Photomicrographs

were taken with a Spot 2 digital camera. The low power photomicrographs are montages of four fields captured with a ×10 objective. The digitized images were converted to gray scale and contrast and brightness adjusted by using Photoshop software (version 5.5; Adobe Systems, Mountain View, CA, USA). Unless, otherwise specified, the nomenclature and cytoarchitectonic parceling adhere to the rat brain atlas of Paxinos and Watson (2007). We thank Dr. Phospholipase D1 Martin A. Metzger and Dr. Newton S. Canteras for critical reading of a previous version of the manuscript and valuable suggestions, and Ana Maria Peraçoli Campos for expert technical assistance. We are also grateful to Dr. Newton S. Canteras for allowing us full access to his collection of cases with PHA-L injection in the medial amygdaloid nucleus. This work was supported by FAPESP grant 2008/52907-1 (to S.J.S.L) and FAPESP fellowship 2008/50445-0 (to L.S.N). “
“Page 52, column 1, last line and column 2, lines 1-5 should read as follows: [In 1922, Forbes raised the possibility of fiber group rotation during fatiguing contractions but emphasized that it required testing. As described by Bawa and coworkers (2006), motor unit rotation can be characterized as follows: “A motor unit of similar threshold is now recruited, while the fatigued unit cannot continue to discharge. After some minutes, this second motor unit falls silent, and the originally discharging unit resumes tonic discharge”.

,

2000), Osimertinib supplier PLA2 clone A85/9-4 (Kanashiro et al., 2002), and hemorrhagin (Zn-metalloproteinase) clone 59/2-E4 (Barros et al., 1998) of B. atrox snake venom were cultured with DMEN-F12 medium, supplemented with 10% FCS and 10 μg/mL gentamicin. Each culture was expanded and 1 × 106 cells were inoculated i.p. in adult BALB/c mice previously i.p. injected with 400 μl mineral oil. After ten days, mice were euthanized by CO2 inhalation, and the ascitic fluid was collected by abdominal puncture. Monoclonal antibodies were purified with caprylic acid followed by ammonium sulfate precipitation (Steinbuch et al., 1970). Briefly, ascitic fluid was diluted 1:3 in 60 mM sodium acetate buffer, pH 4.0, and 0.4 mL caprylic acid was added under agitation for 30 min at room temperature for each 10 mL of ascitic fluid. The mixture was centrifuged at BMN-673 5000× g for 1 h and the supernatant was collected. After centrifugation, the pH of supernatant was adjusted to 7.0 and ammonium sulfate was added under agitation to achieve a 45% concentration (w/v), and the mixture allowed to stand at 4 °C overnight. Precipitates were recovered by centrifugation at 5000× g for 30 min, redissolved

and dialyzed against saline 0.9%, and immunochemically analyzed by SDS-PAGE and Western blot. Samples of dialyzed mAbs were subjected to 12% polyacrylamide gel electrophoresis (SDS-PAGE), according to the method described by Laemmli (1970) with modifications. The samples were dissolved in sample buffer (0.5 M Tris–HCl buffer, pH 6.8 plus 10% SDS, 10% 2-β-mercaptoethanol, and 0.5% bromophenol blue dye), boiled at 100 °C, loaded on 12% polyacrylamide gel, and run at 150 v. Protein bands were stained with Coomassie brilliant blue and subjected to computerized densitometric analysis (Bozzo and Retamal, 1991). Western blot was performed, according to a previously described method (Towbin et al., 1979).

Binding ability of the purified mAbs to the respective antigen was evaluated by ELISA test, according to the methodology described by Almeida et al. (1998). Briefly, B. atrox venom (10 μg/mL) or enriched fraction Farnesyltransferase of thrombin-like toxin (10 μg/mL) was diluted in 0.1 M carbonate/bicarbonate buffer (pH 9.6) and adsorbed to the ELISA plate. After a blocking step with gelatin, mAbs were diluted and added to wells. ELISA plates were incubated at 37 °C for 45 min followed by the addition of secondary antibody. The reaction was developed with o-phenylenediamine plus hydrogen peroxide, and color development was stopped with 50 μL 3 N H2SO4. Plates were read spectrophotometrically at 490 nm. Forty micrograms of myotoxic PLA2 from B. atrox venom, purified according to the method described by Kanashiro et al. (2002), were preincubated with 140 μg A85/9-4 mAb, and then aliquots of the mixtures were injected into the gastrocnemius muscle of five Swiss mice.

To analyze relative expression of different stage mRNAs, the amount of cDNA was normalized based on the signals from ubiquitously expressed β-actin mRNA (beta-actin5, 5′-GACCTGACAGACTACCTGAT-3′, and beta-actin3, 5′-AGACAGCACTGTGTTGGCAT-3′). To GW3965 provide negative controls and exclude

contamination by genomic DNA, the reverse transcriptase was omitted in the cDNA synthesis step, and the samples were subjected to the PCR reaction in the same manner with the same primer sets as indicated above for RT-PCR (−). PCR products were separated by electrophoresis in agarose or polyacrylamide gels, and the bands were visualized with ethidium bromide on an Alphaimager (Alpha Innotech). The identity of all the PCR products was confirmed by

sequencing. All obtained sequences were analyzed with the Genetyx software version 7.0 (GENETYX CORPORATION).The sequence was submitted to GenBank (Accession number; AB698464, GSK1120212 clinical trial AB698465, AB698466). In situ hybridization of zebrafish was performed as described previously ( Makino et al., 2005). Briefly, samples were fixed overnight at 4 °C in 4% paraformaldehyde in phosphate-buffered saline (PBS), washed briefly in two changes of PBS-0.1% Tween 20 (PBT), and transferred to 100% methanol for storage at − 20 °C. The samples were rehydrated stepwise through methanol in PBT and then washed Selleck Regorafenib in four changes of PBT. Subsequently,

samples were incubated with 10 μg/ml proteinase K in PBT for 15–60 min and rinsed twice in PBT before a 20-min refixation. After washes in five changes of PBT, samples were prehybridized at 65 °C for 1 h in buffer consisting of 100% formamide, 20x SSC, 0.1% Tween 20, 10 mg/ml heparin, 9 mM citric acid, and 50 mg/ml yeast RNA and then hybridized overnight in hybridization buffer containing 0.5 mg/ml digoxigenin-labeled RNA probes with the sense or anti-sense sequence. Labeling of the RNA probe was performed with a labeling kit (Roche) using the pGEM-T-Easy vector cloned zMai1 sequence, which is common to all splice variants of zMsi1, and the probe was confirmed by sequencing. Samples were then washed at 65 °C for 10 min each in 75% hybridization buffer/25% 20x SSC, 50% hybridization buffer/50% 20 × SSC, and 25% hybridization buffer/75% 20 × SSC, followed by two washes for 30 min each in 0.2 × SSC at 65 °C. Further washes for 5 min each were conducted at room temperature in 75% 0.2 × SSC/25% PBT, 50% 0.2 × SSC/50% PBT, and 25% 0.2 × SSC/75% PBT. After a 1-h incubation period in PBT containing 2 mg/ml bovine serum albumin, samples were incubated for 2 h in the same solution with a 1:2000 dilution of sample-preabsorbed anti-digoxigenin antibody.

LPS also increased the expression of pro-inflammatory genes such as chemokines, chemokine ligands, cytokines, prostaglandins and transcription factors. The most highly up-regulated genes were C–C motif chemokines (CCL) 11 and

7, chemokine (C–X–C motif) ligand (CXCL) 3 and 5, IL11, IL1B, and prostaglandin-endoperoxide synthase 2 (PTGS2). LPS also induced the expression of structural proteins (collagen types III, IV, V, and VI), proteoglycans (laminin), glycoproteins (fibronectin) and enzymes involved in ECM remodeling (matrix metalloproteinase (MMP) 3 and 10, tissue inhibitor of metalloproteinases (TIMP) 2. The expression of a set of pro-fibrotic factors such as transforming growth factor beta selleck inhibitor receptor III (TGFBR3), platelet-derived growth factor D (PDGFD), platelet derived growth factor receptor alpha polypeptide (PDGFRA), fibroblast growth factor (FGF) 2 and 7

was also higher upon LPS treatment. The inflammatory response elicited by LPS Luminespib was reduced by co-incubation with the anti-inflammatory agent dexamethasone, which significantly repressed the expression of most pro-inflammatory and ECM components as well as pro-fibrotic factor genes (Table 2). The presence of different cell types in the human 3D liver model was assessed by immunohistochemistry (Fig. 3A). Hepatocytes and HSC were detected by albumin and vimentin immunostaining, respectively. The presence of Kupffer and endothelial cells was confirmed by the expression of two markers transmembrane glucoprotein F4/80 (Iwaisako et al., 2012) and ICAM-1 respectively (Fig. 3A). The data show the presence of these four main cell types Protein kinase N1 of the liver in 30-day-old

human 3D liver cultures. In addition, we demonstrated that the nylon scaffold allowed formation of bile canaliculli-like stuctures between hepatocytes as shown by the distinct expression of DPPIV in bile canalicular plasma membrane (Fig. 3B). 3D liver co-cultures were created by seeding proportions of cells on a 3D nylon scaffold similar to native liver such as 60% hepatocytes and 40% NPC (Dash et al., 2009 and Naughton et al., 1994). To reveal whether the proportion between PC and NPC in the human 3D liver model is preserved during long term cultivation of cells, FACS analysis of 30-day-old culture was performed. Albumin positive cells revealed 60% presence of hepatocytes after 30 days in culture, concordant with the originally seeded proportion (Fig. 3C). Functional Kupffer cells were detected by uptake of fluorescent-labeled latex beads and accounted for 12.5% of total cells (Fig. 3C). As 3D liver cultures have preserved hepatic function for up to 3 months (Fig. 1, Fig. 2 and Supplementary Fig. 1A), this allows the performance of not only single, but also repeated drug-treatment studies.

Note that contrary to the original formula we express ERS with positive and ERD with negative values. As a reference period, the time period

between −700 and −200 ms relative to stimulus onset was used. Five different repeated measures ANOVAs were calculated, four with theta and alpha ERS/ERD as dependent measures and one with delta ERS. Three ANOVAs tested for effects in the active condition and focused on alpha, delta and theta ERS/ERD as dependent variables, respectively: CONDITION (target, non-target), TIME (t1, t2, t3, t4; t1=0–200 ms, t2=200–400 ms, t3=400–600 and t4=600–800 ms see more post-stimulus), ELECTRODES (Fz, Cz, Pz). For elimination of multiple comparisons error the false discovery rate (FDR) correction according to Benjamini and Hochberg (2000) was used. Two ANOVAs were performed in order to test the effect of familiar and unfamiliar voices on stimulus processing in the passive condition: NAME (SON vs. UN), VOICE (FV vs. UV), ELECTRODES (Fz, Cz and Pz) and TIME (t1, t2, t3; t1=0–200 ms, t2=200–400 ms, t3=400–600 ms post-stimulus). Additional ANOVAs

selleck chemical were performed post-hoc in order to specify hemispheric asymmetries apparent in the passive listening and active counting condition. For post-hoc tests we only focus on effects of interest, that is interactions

with factor TARGET for the active condition and factors VOICE and NAME for the passive. ERPs results for all conditions are also reported in supplementary materials as well as individual ERS/ERD values, tested against zero, C59 in vivo for the active condition. All the mentioned analyses were conducted on a sample of 14 healthy volunteers except the ANOVA to test specific hemispheric asymmetry in the processing of target, which was calculated with 13 subjects due to an outlier (power exceeding M±2 SD on C3 and C4). We would like to thank Daniel Koerner for his help with data acquisition. This study was supported by the Doctoral College “Imaging the Mind” (FWF; W1233) (R. del Giudice J. Lechinger and D. P. J. Heib). D.P.J. Heib and M. Wislowska were financially supported by the FWF project I-934-B23. “
“In this paper, we failed to cite appropriate references in several places. Revised text in the Discussion is as follows: 1) Among the causes of hydrocephalus are the overproduction of CSF by the choroid plexus and failure to drain the CSF at the subarachnoid space. Furthermore, blockage of CSF flow through the narrow Sylvian aqueduct is believed to be the primary cause of congenital hydrocephalus (Pérez-Fígares et al., 2001; Huh et al., 2009).

In Fig. 2C, the membrane intact cells make up approximately 82% of total cells and also match the cell population in R1 (Fig. 1A), whereas membrane compromised cells make up approximately 18% of the total cells and match the cell population in R2 (Fig. 1A), further indicating that R1 and R2 are comprised of healthy and damaged cells respectively. It is noted that there is a proportion of cells (red events, Fig. 2C) that are present in region R3 (Fig. 1). These red fluorescent events are an indication that damaged cells with low light scatter properties may be present in R3. Alternatively,

these events may be due to the presence of cell particulate Selleckchem Torin 1 or microparticles from microvesiculation of cells, an occurrence that is observed during long-term storage of red blood cells [3], [7] and [12]. Fig. 3 shows

the events registered by the flow cytometer that have been identified as cells when using either a light scatter, or a fluorescence threshold. The multiparameter capability of the flow cytometer allows for direct comparison of the light scatter and fluorescence properties of each recorded event. A comparison of the two gating strategies for HUVEC controls shows a similar number of healthy cells gated by either light scatter or fluorescence. Using fluorescence gates, an increase was observed in the number of damaged cells (EB) in plunged samples compared to controls. see more However, the light scatter threshold excludes many damaged cells from both control and plunged samples. The total number of cells observed using light

scatter gates was approximately 60% less than the total number observed using fluorescence gates, indicating that light scatter thresholds are ineffective at detecting damaged cells in both control and plunged samples whereas fluorescence gating allows for detection of most cells in the suspension. JC-1 was used as an indicator of mitochondrial polarization to identify healthy and cryoinjured cells all from debris. Fig. 4A and B show JC-1 green fluorescence of HUVEC control samples. Fig. 4A shows a fluorescence histogram separating low intensity events (low green), from high intensity events (high green). High intensity events correspond to the cell population, whereas low intensity events represent debris in suspension, elucidated by the action of the JC-1 assay, a membrane potential dependent stain that requires a negatively charged intracellular environment in order for its monomers to concentrate.

For this last reason, the energy efficiencies of these processes (RH and rH) are always greater than the corresponding quantum yields (ΦH and qH), that is, normally RH > ΦH and rH > qH. To calculate the energy efficiencies of heat production (RH and rH), we used the efficiencies, calculated earlier,

of the other two accompanying processes, i.e. chlorophyll a fluorescence (Rfl and rfl) and photosynthesis (Rph and rph) and the budget (13), (14), (15) and (16) given in the Introduction. In order to characterize the different quantum yields and energy efficiencies of all three processes in which the excited states of phytoplankton pigment molecules are deactivated, the

vertical profiles of these yields/efficiencies were modelled in sea waters of 11 trophic types (see Annex 2), in three climatic SCH727965 zones (tropical, temperate, polar) and in two seasons of the year (June – summer in the northern hemisphere and January – winter in the northern hemisphere). The model calculations of these yields/efficiencies were limited to oceanic Case 1 waters, according to the optical classification of Morel & Prieur (1977), which applies to more than 90% of the volume of the World Ocean. The three climatic zones of the ocean were represented by buy PD173074 waters adjoining the relevant latitudes in the northern hemisphere: tropical (0–10°N), temperate Sitaxentan (ca 40°N) and polar (ca 60°N). The input data for these

model calculations made for different depths in the sea z (representing the fundamental variable) were: • surface concentration of chlorophyll a Ca(0), expressed in [mg chla m− 3], The surface layer temperatures temp and surface irradiances PAR(0) were based on the geographical distributions and seasonal variations of these parameters, as given by Timofeyev (1983) and Gershanovich & Muromtsev (1982). The surface irradiances PAR(0), expressed as the surface density of a stream of light quanta in [μEin m− 2 s− 1], were calculated from the overall daily doses, given by those authors, of the energy of downward solar irradiance at the sea surface < ηday > month and the day length td  2. The specifications of these data are given in Table 2. The values of the optical depth in the sea τ(z) [dimensionless], which were used directly to calculate the PAR(z) irradiance and the yields/efficiencies of the three processes, were determined on the basis of the algorithm presented in Woźniak et al. (2003). They were worked out from a statistical model of the vertical distributions of chlorophyll a concentrations at particular depths in the sea Ca(z) in stratified oceanic basins ( Woźniak et al. 1992).

1% patients without specific treatment (spontaneous recanalization), 46.2% patients treated with IVT, 63.2% patients treated with IAT, 67.5% of patients treated with combined IVT–IAT and in up to 83.6% patients treated with mechanical methods [5]. Nevertheless, the use of these methods only in specialized centers represents the main limitation.

Sono-lysis is one of the methods used for the acceleration of recanalization of the occluded intracranial artery. Although the complex effect of ultrasound on the acceleration of thrombus lysis is not yet fully understood, it is assumed that the ultrasonic waves accelerate enzymatic fibrinolysis by primarily non-thermal mechanisms – increasing the transport of fibrinolytic agents into the thrombus by mechanical disruption of its structure [14], direct activation of fibrinolytic selleck enzymes, either mechanical breaking of the complex molecules, in which fibrinolytic enzymes are inactivated by binding to their inhibitors, or irritation of the endothelium with increased production of fibrinolytic enzymes [15] and [16],

transient peripheral (capillary) vasodilatation caused probably by increased production of nitrite oxide in the endothelium [17] and [18]. Radiation force and acoustic cavitation are the next possible and discussed mechanical effects of ultrasound [19]. Different frequencies (20 kHz to 3.4 MHz) and intensities of ultrasound with different effects have Anti-infection Compound high throughput screening been used in various in vitro studies [20] and [21]. Low frequency (about 20 kHz) and high intensity ultrasound lead to a rapid and efficient lysis of thrombi into microscopic fragments primarily by direct mechanical effect although the signs of activation of fibrinolytic lysis were also observed. These studies even demonstrated the ability of ultrasound to disrupt both fibrous and calcified atherosclerotic plaques [15], [22], [23], [24], [25] and [26]. Unfortunately thermal impairment and perforation of vascular walls were observed as side effects. Unlike low-frequency

ultrasonic waves, the high frequency ultrasound (0.5–3.4 MHz) with ultrasound intensities Y-27632 2HCl higher than 1 W/cm2 led primarily to the increase of fibrinolytic-induced fibrinolysis [27], [28], [29], [30], [31] and [32]. Sono-lysis in these studies accelerated lysis of thrombus in the presence of a fibrinolytic. Without the presence of fibrinolytics, neither lysis nor mechanical thrombus fragmentation were observed. Similar results were found also in in vivo studies with animal models [25], [26], [33] and [34]. Sono-lysis using ultrasound with low frequencies and high intensities in dog models of femoral and coronary artery resulted to recanalization of thrombosis without the use of fibrinolytic agents. However, histological signs of damage to the vascular wall were found in some models.

Due to the long life of hydrocarbons in certain shoreline types, it is imperative that severe measures are taken to address the problem early in the accident(s), at national and international levels, so the impact on marine ecosystems and shoreline populations is mitigated or prevented. Post-spill monitoring of key environmental parameters is therefore crucial to monitor the normal shoreline recovery procedures (Doerffer, 1992, De La Huz et al., Selleck Bafilomycin A1 2005 and Kirby and Law, 2010). The main conclusion of this work is that the three-step method proposed in this paper allows the definition of regions

of higher susceptibility and hazard in case on an oil spill in confined marine basins. The three-step method can be summarised as follows: (1) Step 1 – bathymetric,

geomorphological, geological and oceanographic parameters from the region surrounding the oil spill should be considered as BLZ945 cost key parameters controlling the dispersion of oil slicks. The compilation of oil spill hazard maps is important to a successful response to oil spill accidents in their early stage. This is because areas of intense urbanization, or environmentally sensitive zones, require an accurate management from civil protection authorities in the very first hours after an oil spill. In the case of an oil spill in deep offshore areas, real-time oceanographic and meteorological data will be paramount to model the Aldol condensation path and dispersion rates of oil slicks. As a corollary of this work, the two scenarios modelled show that sea bottom irregularities controlled by the geological structure, as well as coastline morphology and geology, have important impacts on oil spill spreading and dispersion in confined marine basins. In all models, a final factor to consider is the coupling between the direction of shallow sea currents, wind and wave during rough weather conditions. Changing wind conditions can be an important factor and should

be taken into account in oil spill models, as they can allow the movement of oil slicks without affecting the shoreline. Similarly, the effect of the Stoke drift when of rough sea state conditions has to be taken into account, especially close to the shoreline. This work has been co-financed by the EU Humanitarian Aid and Civil Protection under Grant Agreement No. 638494/2012/ECHO/A5/SUB – Project “Embracing Innovation for Preparedness in Civil Protection & Marine Pollution”. The authors thank MPB’s editor and an anonymous reviewer for their constructive comments. “
“With nearly half the world’s population now living within 100 km of the coast it is no wonder that the coastal ocean is heavily impacted by human activities on land, along the coast and on the sea. The continental margins are home to some of the most productive and diverse ecosystems in the world, which are of very high value to us – not least in an economic sense, providing a wide range of valuable ecosystem services.