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The Atlantic Ocean is one of the most important sinks for atmospheric carbon dioxide (CO2), but this sink has been shown to vary substantially in time. Here we use surface ocean CO2 observations to estimate this sink and the temporal variability from 1998 through 2007 in the Atlantic Ocean. We benefit from (i) a continuous improvement of the observations, i.e. the Surface Ocean CO2 Atlas (SOCAT) v1.5 database and (ii) a newly developed technique to interpolate the observations in space and time. In particular, we use a two-step neural network approach to reconstruct basin-wide monthly maps of the sea surface partial pressure of CO2 (pCO2) at a resolution of 1° × 1°. From those, we compute the air–sea CO2 flux maps using a standard gas exchange parameterization and high-resolution wind speeds. The neural networks fit the observed pCO2 data with a root mean square error (RMSE) of about 10 μatm and with almost no bias. A check against independent time-series data and new data from SOCAT v2 reveals a larger RMSE of 22.8 μatm for the entire Atlantic Ocean, which decreases to 16.3 μatm for data south of 40° N. We estimate a decadal mean uptake flux of −0.45 ± 0.15 Pg C yr−1 for the Atlantic between 44° S and 79° N, representing the sum of a strong uptake north of 18° N (−0.39 ± 0.10 Pg C yr−1), outgassing in the tropics (18° S–18° N, 0.11 ± 0.07 Pg C yr−1), and uptake in the subtropical/temperate South Atlantic south of 18° S (−0.16 ± 0.06 Pg C yr−1), consistent with recent studies. The strongest seasonal variability of the CO2 flux occurs in the temperature-driven subtropical North Atlantic, with uptake in winter and outgassing in summer. The seasonal cycle is antiphased in the subpolar latitudes relative to the subtropics largely as a result of the biologically driven winter-to-summer drawdown of CO2. Over the 10 yr analysis period (1998 through 2007), sea surface pCO2 increased faster than that of the atmosphere in large areas poleward of 40° N, while in other regions of the North Atlantic the sea surface pCO2 increased at a slower rate, resulting in a barely changing Atlantic carbon sink north of the Equator (−0.01 ± 0.02 Pg C yr−1 decade−1). Surface ocean pCO2 increased at a slower rate relative to atmospheric CO2 over most of the Atlantic south of the Equator, leading to a substantial trend toward a stronger CO2 sink for the entire South Atlantic (−0.14 ± 0.02 Pg C yr−1 decade−1). In contrast to the 10 yr trends, the Atlantic Ocean carbon sink varies relatively little on inter-annual timescales (±0.04 Pg C yr−1; 1 σ).

Using measurements of the surface-ocean CO2 partial pressure (pCO2) and 14 different pCO2 mapping methods recently collated by the Surface Ocean pCO2 Mapping intercomparison (SOCOM) initiative, variations in regional and global sea–air CO2 fluxes are investigated. Though the available mapping methods use widely different approaches, we find relatively consistent estimates of regional pCO2 seasonality, in line with previous estimates. In terms of interannual variability (IAV), all mapping methods estimate the largest variations to occur in the eastern equatorial Pacific. Despite considerable spread in the detailed variations, mapping methods that fit the data more closely also tend to agree more closely with each other in regional averages. Encouragingly, this includes mapping methods belonging to complementary types – taking variability either directly from the pCO2 data or indirectly from driver data via regression. From a weighted ensemble average, we find an IAV amplitude of the global sea–air CO2 flux of 0.31 PgC yr-1 (standard deviation over 1992–2009), which is larger than simulated by biogeochemical process models. From a decadal perspective, the global ocean CO2 uptake is estimated to have gradually increased since about 2000, with little decadal change prior to that. The weighted mean net global ocean CO2 sink estimated by the SOCOM ensemble is -1.75 PgC yr-1 (1992–2009), consistent within uncertainties with estimates from ocean-interior carbon data or atmospheric oxygen trends.

The Atlantic and Arctic Oceans are critical components of the global carbon cycle. Here we quantify the net sea-air CO2 flux, for the first time, across different methodologies for consistent time and space scales for the Atlantic and Arctic basins. We present the long-term mean, seasonal cycle, interannual variability and trends in sea-air CO2 flux for the period 1990 to 2009, and assign an uncertainty to each. We use regional cuts from global observations and modeling products, specifically a pCO2 -based CO2 flux climatology, flux estimates from the inversion of oceanic and atmospheric data, and results from six ocean biogeochemical models. Additionally, we use basin-wide flux estimates from surface ocean pCO2 observations based on two distinct methodologies. Our estimate of the contemporary sea-air flux of CO2 (sum of anthropogenic and natural components) by the Atlantic between 40° S and 79° N is -0.49 ± 0.05 Pg C yr-1 , and by the Arctic it is -0.12 ± 0.06 Pg C yr-1 , leading to a combined sea-air flux of -0.61 ± 0.06 Pg C yr-1 for the two decades (negative reflects ocean uptake). We do find broad agreement amongst methodologies with respect to the seasonal cycle in the subtropics of both hemispheres, but not elsewhere. Agreement with respect to detailed signals of interannual variability is poor, and correlations to the North Atlantic Oscillation are weaker in the North Atlantic and Arctic than in the equatorial region and southern subtropics. Linear trends for 1995 to 2009 indicate increased uptake and generally correspond between methodologies in the North Atlantic, but there is disagreement amongst methodologies in the equatorial region and southern subtropics.

Liver X receptors (LXRα and -β) are nuclear receptors abundant in the liver where they are regulators of lipid homeostasis. Both LXRs are also expressed in the brain, but their roles in this tissue remain to be clarified. We examined the brains of mice in which the genes of both LXRα and -β have been disrupted and found several severe abnormalities. One of the most striking features is that the lateral ventricles are closed and lined with lipid-laden cells. In addition, there are enlarged brain blood vessels, especially in the pars reticularis of the substantia nigra and in the globus pallidus. Other features of the brains are excessive lipid deposits, proliferation of astrocytes, loss of neurons, and disorganized myelin sheaths. Electron micrographs revealed that, as mice aged, lipid vacuoles accumulated in astrocytes surrounding blood vessels. Comparison of mRNA profiles in LXR knockout mice and wild-type littermates showed that expression of several LXR target genes involved in cholesterol efflux from astrocytes was reduced. These findings show that LXRs have an important function in lipid homeostasis in the brain, and that loss of these receptors results in neurodegenerative diseases. Further characterization of the role of LXRs in the brain could lead to new insights into the etiology and treatment of some neurodegenerative disorders.

In the central Iranian Esfahan-Sirjan and Qom basins sedimentation of the Oligo-/Miocene Qom Formation took place on extensive mixed carbonate–siliciclastic ramps. During this time, both basins were positioned at the Eurasian margin of the Tethyan Seaway, which connected the western and eastern regions of the Tethys Ocean at least until the late Burdigalian. During the so-called Terminal Tethyan Event the Tethyan Seaway was then closed due to the collision of the African/Arabian and Iranian/Eurasian plates. Facies analysis of the sedimentary record of both basins indicates paleoenvironments ranging from terrestrial to open marine settings, including mangrove, restricted inner shelf lagoon, seagrass meadow, reefal, and deeper offshore environments. Recognition of eight depositional sequences and elaboration of an integrated biostratigraphic framework (calcareous nannoplankton, planktic and larger benthic foraminifers, gastropods, and pectinids) allow us to construct a basin-spanning stratigraphy. The assignment of the recognized sea-level lowstands to the Ru 3 to Bur 3 lowstands of the global sea-level curve enables a comparison with time-equivalent sections from the Zagros Basin, which was part of the African/Arabian Plate on the opposing southern margin of the Tethyan Seaway. The so calibrated sections display restrictions of the Tethyan Seaway and interruption of the south Iranian gateways between the Qom Basin and the Proto-Indopacific in relation to ongoing plate collision during the early Burdigalian.

Objective To evaluate the effect of a diet pattern based on Dietary Guidelines for Americans (DGA), in a controlled feeding setting, on plasma markers of inflammation and on cytokine production by peripheral blood mononuclear cells (PBMC). Design Women ( n =  44) with one or more risk factors of metabolic syndrome (and BMI: 25.2-39.8 kg/m 2 ) completed an 8-wk controlled feeding study. They were randomized to either a group following a diet based on DGA 2010 (DGA), or a group given a ‘typical American diet’ (TAD), based largely on a Western diet pattern. By design, women maintained their body weight. Fasting plasma and PBMC were collected at wk. 0 (baseline) and at wk. 8 (post-intervention). Sixteen plasma markers of inflammation and eight PBMC cytokines were measured at both time points, to evaluate if the diet had a significant effect on concentrations of these inflammatory markers. Data were analyzed using ANCOVA, followed by multiple-comparison adjustment using Benjamini-Hochberg method. Results Significant changes observed in Serum Amyloid A (SAA) and Matrix Metalloproteinase 3 (MMP3) in plasma did not retain significance upon multiple comparison adjustment. SAA: p  = 0.044, adj p  = 0.450; DGA mean change [95% CI] = − 12.6[− 32.3 to 7.04]; TAD mean change [95% CI] = − 2.24 [− 9.99 to 5.51]. MMP3: p  = 0.014, adj p  = 0.35; DGA mean change [95% CI] = 2.72[− 4.16 to 9.59]; TAD mean change [95% CI] = − 0.98[− 16.7 to 14.7]). Other inflammation markers were not differently altered by DGA relative to TAD. Effect size of change (Cohens d) indicated a large/medium-large effect of intervention on MMP3 and CRP, and medium effect on IL-6. Conclusions No statistically significant changes were observed in the immune markers examined in this study. The biological roles and magnitude of the non-significant differences seen with two variables, CRP and MMP3, suggest that they be examined in future studies. Trial registration Clinicaltrials.gov identifier NCT02298725.

We present high-resolution autonomous measurements of carbon dioxide partial pressure p(CO2) taken in situ at the Porcupine Abyssal Plain sustained Observatory (PAP-SO) in the northeast Atlantic (49° N, 16.5° W; water depth of 4850 m) for the period 2010–2012. Measurements of p(CO2) made at 30 m depth on a sensor frame are compared with other autonomous biogeochemical measurements at that depth (including chlorophyll a fluorescence and nitrate concentration data) to analyse weekly to seasonal controls on p(CO2) flux in the inter-gyre region of the North Atlantic. Comparisons are also made with in situ regional time series data from a ship of opportunity and mixed layer depth (MLD) measurements from profiling Argo floats. There is a persistent under-saturation of CO2 in surface waters throughout the year which gives rise to a perennial CO2 sink. Comparison with an earlier data set collected at the site (2003–2005) confirms seasonal and inter-annual changes in surface seawater chemistry. There is year-to-year variability in the timing of deep winter mixing and the intensity of the spring bloom. The 2010–2012 period shows an overall increase in p(CO2) values when compared to the 2003–2005 period as would be expected from increases due to anthropogenic CO2 emissions. The surface temperature, wind speed and MLD measurements are similar for both periods of time. Future work should incorporate daily CO2 flux measurements made using CO2 sensors at 1 m depth and the in situ wind speed data now available from the UK Met Office Buoy.

Liver X Receptors Downregulate 11β-Hydroxysteroid Dehydrogenase Type 1 Expression and Activity Thomas M. Stulnig 1 , Udo Oppermann 2 , Knut R. Steffensen 1 , Gertrud U. Schuster 1 and Jan-Åke Gustafsson 1 1 Department of Medical Nutrition and Biosciences, Karolinska Institutet, Huddinge, Sweden 2 Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden Abstract 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) converts inactive corticosteroids into biologically active corticosteroids, thereby regulating the local concentration of active glucocorticoids, such as cortisol. 11β-HSD-1 is particularly expressed in adipocytes and liver and appears to be causally linked to the development of type 2 diabetes and the metabolic syndrome. Liver X receptor (LXR)-α and -β are nuclear oxysterol receptors whose key role in lipid metabolic regulation has recently been established. In this study, we show that treatment of adipocytes derived from 3T3-L1 cells and mouse embryonic fibroblasts in vitro with synthetic or natural LXR agonists decreases mRNA expression of 11β-HSD-1 by ∼50%, paralleled by a significant decline in 11β-HSD-1 enzyme activity. Downregulation of 11β-HSD-1 mRNA by LXRs started after a lag period of 8 h and required ongoing protein synthesis. Moreover, long-term per os treatment with a synthetic LXR agonist downregulated 11β-HSD-1 mRNA levels by ∼50% in brown adipose tissue and liver of wild-type but not of LXRα −/− β −/− mice and was paralleled by downregulation of hepatic PEPCK expression. In conclusion, LXR ligands could mediate beneficial metabolic effects in insulin resistance syndromes including type 2 diabetes by interfering with peripheral glucocorticoid activation. Footnotes Address correspondence and reprint requests to Thomas M. Stulnig, MD, Department of Internal Medicine III, Division of Endocrinology and Metabolism, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria. E-mail: thomas.stulnig{at}akh-wien.ac.at . Received for publication 5 March 2002 and accepted in revised form 20 May 2002. 11β-HSD-1, 11β-hydroxysteroid dehydrogenase type 1; BAT, brown adipose tissue; DMEM, Dulbecco’s modified Eagles medium; FBS, fetal bovine serum; LXR, liver X receptor; MEF, mouse embryonic fibroblast; PPAR, peroxisome proliferator-activated receptor; PPRE, PPAR response element; RXR, retinoid X receptor; SREBP, sterol regulatory element-binding protein; WAT, white adipose tissue. DIABETES

Background. We aimed to define the relative importance of renal and endocrine changes in tenofovir disoproxil fumarate (TDF)–related bone toxicity. Methods. In a study of daily TDF/emtricitabine (FTC) preexposure prophylaxis (PrEP) in human immunodeficiency virus (HIV)–uninfected young men who have sex with men, we measured changes from baseline in blood and urine markers of the parathyroid hormone (PTH)–vitamin D–fibroblast growth factor 23 (FGF23) axis, creatinine, and renal tubular reabsorption of phosphate (TRP). We explored the relationship of those variables to changes in bone mineral density (BMD). Tenofovir-diphosphate (TFV-DP) in red blood cells was used to categorize participants into high and low drug exposure groups. Results. There were 101 participants, median age 20 years (range 15 to 22). Compared with low drug exposure, high-exposure participants showed increase from baseline in PTH and decline in FGF23 by study week 4, with no differences in creatinine, phosphate, or TRP. At 48 weeks, the median (interquartile range) percent decline in total hip BMD was greater in those with high- compared to low- exposure (−1.59 [2.77] vs +1.54 [3.34] %, respectively; P = .001); in high-exposure participants, this correlated with week 4 TFV-DP (inversely; r = −0.60, P = .002) and FGF23 (directly; r = 0.42; P = .039) but not other variables. Conclusions. These findings support the short-term renal safety of TDF/FTC PrEP in HIV-seronegative young men and suggest that endocrine disruption (PTH-FGF23) is a primary contributor to TDF-associated BMD decline in this age group. Clinical Trials Registration. NCT01769469.

Abstract Although the effects of fish oil supplements on airway inflammation in asthma have been studied with varying results, the independent effects of the fish oil components, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), administered separately, are untested. Here, we investigated airway inflammation and hyperresponsiveness using a mouse ovalbumin exposure model of asthma assessing the effects of consuming EPA (1.5% wt/wt), DHA (1.5% wt/wt), EPA plus DHA (0.75% each), or a control diet with no added omega-3 polyunsaturated fatty acids. Consuming these diets for 6 weeks resulted in erythrocyte membrane EPA contents (molar %) of 9.0 (± 0.6), 3.2 (± 0.2), 6.8 (± 0.5), and 0.01 (± 0.0)%; DHA contents were 6.8 (± 0.1), 15.6 (± 0.5), 12.3 (± 0.3), and 3.8 (± 0.2)%, respectively. The DHA group had the highest bronchoalveolar lavage (BAL) fluid eosinophil and IL-6 levels (P < 0.05). Similar trends were seen for macrophages, IL-4, and IL-13, whereas TNF-α was lower in omega-3 polyunsaturated fatty acid groups than the control (P < 0.05). The DHA group also had the highest airway resistance, which differed significantly from the EPA plus DHA group (P < 0.05), which had the lowest. Oxylipins were measured in plasma and BAL fluid, with DHA and EPA suppressing arachidonic acid–derived oxylipin production. DHA-derived oxylipins from the cytochrome P450 and 15-lipoxygenase pathways correlated significantly with BAL eosinophil levels. The proinflammatory effects of DHA suggest that the adverse effects of individual fatty acid formulations should be thoroughly considered before any use as therapeutic agents in asthma.