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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.

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