The contribution of planktonic diazotrophs to the overall N budget is a key unknown in the eastern Indian Ocean. Here we investigated the relationships between dissolved inorganic nutrients, phytoplankton pigment composition, microbial community structure, nitrogen fixation rates and the δ 15 N of fractionated zooplankton samples along the shelf break of Western Australia (32° to 12°S) in September 2012. Bulk nitrogen fixation rates declined from 4.8 nmol l −1 h −1 in the colder and more saline sub-tropical waters at higher latitudes to 1.5 nmol l −1 h −1 in the warmer and fresher Timor Sea at lower latitudes. A regional bloom of Trichodesmium was identified between 13° and 9°S in the Timor Sea. Trichodesmium-specific N 2 fixation rates were 0.05 ± 0.01 nmol colony −1 h −1. Highest dissolved inorganic nitrogen (DIN) concentrations occurred at the highest NH 4 + :NO 3 − ratios, thereby deviating from the paradigm that greater DIN concentrations come primarily from increased NO 3 − through advection, mixing or upwelling. Both the microplankton and nanoflagellate fraction declined significantly in warmer waters, with higher DIN concentrations but decreasing % NO 3 − . A clear increase in the prokaryotic diagnostic pigment zeaxanthin was seen with increasing temperatures from higher to lower latitudes. The microbial community, measured using automated ribosomal intergenic spacer analysis (ARISA), clustered strongly according to the water mass biogeochemistry including temperature, salinity, DIN and phosphate concentrations (p < 0.001). Isotope analysis suggested that injections of low δ 15 N from N 2 fixation lowered the zooplankton δ 15 N signature of animals up to ~500 µm in size and that nearly 47% of the fixed nitrogen was used by zooplankton (≤500 µm fraction) in the Timor Sea.
Combined assessment of glutamine and 2-deoxyglucose accumulation improves the ex vivo identification of macrophage activation states. Combined ex vivo metabolic imaging demonstrates heterogenous and distinct patterns of substrate accumulation in atherosclerotic lesions. Further studies are required to define the in vivo significance of glutamine uptake in atherosclerosis and its potential application in identification of vulnerable plaques.
Diabetes promotes the S-glutathionylation, inactivation and subsequent degradation of mitogen-activated protein kinase phosphatase 1 (MKP-1) in blood monocytes, and hematopoietic MKP-1-deficiency in atherosclerosis-prone mice accelerates atherosclerotic lesion formation, but the underlying mechanisms were not known. Our aim was to determine the mechanisms through which MKP-1 deficiency in monocytes and macrophages promotes atherogenesis. Transplantation of MKP-1-deficient bone marrow into LDL-R−/− (MKP-1LeuKO) mice accelerated high-fat diet (HFD)-induced atherosclerotic lesion formation. After 12 weeks of HFD feeding, MKP-1LeuKO mice showed increased lesion size in both the aortic root (1.2-fold) and the aorta (1.6-fold), despite reduced plasma cholesterol levels. Macrophage content was increased in lesions of MKP-1LeuKO mice compared to mice that received wildtype bone marrow. After only 6 weeks on a HFD, in vivo chemotactic activity of monocytes was already significantly increased in MKP-1LeuKO mice. MKP-1 deficiency in monocytes and macrophages promotes and accelerates atherosclerotic lesion formation by hyper-sensitizing monocytes to chemokine-induced recruitment, predisposing macrophages to M1 polarization, decreased autophagy and oxysterol-induced cell death whereas overexpression of MKP-1 protects macrophages against metabolic stress-induced dysfunction. MKP-1 serves as a master-regulator of macrophage phenotype and function and its dysregulation by metabolic stress may be a major contributor to atherogenesis and the progression of atherosclerotic plaques.
Dietary 23-OHUA reduces weight gain and attenuates atherogenesis in mice by protecting monocytes against metabolic stress-induced priming and dysfunction. Based on its mechanism of action, 23-OHUA may represent a novel therapeutic approach for the prevention and treatment of obesity and atherosclerosis.
Quantifying the different sources of nitrogen (N) within the N cycle is crucial to gain insights in oceanic phytoplankton production. To understand the controls of primary productivity and the associated capture of CO 2 through photosynthesis in the southeastern Indian Ocean, we compiled the physical and biogeochemical data from four voyages conducted in assimilation rates (~530 μmol m À2 h À1 ) relative to NO 3 À assimilation rates (~375 μmol m À2 h À1 ) suggest that the assimilation dynamics of C are primarily regulated by microbial regeneration in our region. N 2 fixation rates did not decline when other source of dissolved inorganic nitrogen were available, although the assimilation of N 2 is a highly energetic process. Our data showed that the diazotrophic community assimilated~2 nmol N L À1 h À1 at relative elevated NH 4 + assimilation rates~12 nmol L À1 h À1 and NO 3 À assimilation rates~6 nmol L À1 h À1 . The small diffusive deep water NO 3 À fluxes could not support the measured NO 3 À assimilation rates and consequently point toward another source of dissolved inorganic NO 3 À . Highest NO 2 À values coincided consistently with shallow lower dissolved O 2 layers (100-200 m; 100-180 μmol L À1 ). These results suggest that nitrification above the pycnocline could be a significant component of the N cycle in the eastern Indian Ocean. In our analysis we provide a conceptual understanding of how NO 3 À in the photic zone could be derived from new N through N 2 fixation. We conclude with the hypothesis that N injected through N 2 fixation can be recycled within the photic zone as NH 4 + and sequentially oxidized to NO 2 À and NO 3 À in shallow lower dissolved oxygen layers.
AimsDietary supplementation with ursolic acid (UA) prevents monocyte dysfunction in diabetic mice and protects mice against atherosclerosis and loss of renal function. The goal of this study was to determine the molecular mechanism by which UA prevents monocyte dysfunction induced by metabolic stress.Methods and resultsMetabolic stress sensitizes or “primes” human THP-1 monocytes and murine peritoneal macrophages to the chemoattractant MCP-1, converting these cells into a hyper-chemotactic phenotype. UA protected THP-1 monocytes and peritoneal macrophages against metabolic priming and prevented their hyper-reactivity to MCP-1. UA blocked the metabolic stress-induced increase in global protein-S-glutathionylation, a measure of cellular thiol oxidative stress, and normalized actin-S-glutathionylation. UA also restored MAPK phosphatase-1 (MKP1) protein expression and phosphatase activity, decreased by metabolic priming, and normalized p38 MAPK activation. Neither metabolic stress nor UA supplementation altered mRNA or protein levels of glutaredoxin-1, the principal enzyme responsible for the reduction of mixed disulfides between glutathione and protein thiols in these cells. However, the induction of Nox4 by metabolic stress, required for metabolic priming, was inhibited by UA in both THP-1 monocytes and peritoneal macrophages.ConclusionUA protects THP-1 monocytes against dysfunction by suppressing metabolic stress-induced Nox4 expression, thereby preventing the Nox4-dependent dysregulation of redox-sensitive processes, including actin turnover and MAPK-signaling, two key processes that control monocyte migration and adhesion. This study provides a novel mechanism for the anti-inflammatory and athero- and renoprotective properties of UA and suggests that dysfunctional blood monocytes may be primary targets of UA and related compounds.
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