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A large fraction of marine primary production is performed by diverse small protists, and many of these phytoplankton are phagotrophic mixotrophs that vary widely in their capacity to consume bacterial prey. Prior analyses suggest that mixotrophic protists as a group vary in importance across ocean environments, but the mechanisms leading to broad functional diversity among mixotrophs, and the biogeochemical consequences of this, are less clear. Here we use isolates from seven major taxa to demonstrate a tradeoff between phototrophic performance (growth in the absence of prey) and phagotrophic performance (clearance rate when consuming Prochlorococcus ). We then show that trophic strategy along the autotrophy-mixotrophy spectrum correlates strongly with global niche differences, across depths and across gradients of stratification and chlorophyll a . A model of competition shows that community shifts can be explained by greater fitness of faster-grazing mixotrophs when nutrients are scarce and light is plentiful. Our results illustrate how basic physiological constraints and principles of resource competition can organize complexity in the surface ocean ecosystem.

The process of islet transplantation for treating type 1 diabetes has been limited by the high level of graft failure. This may be overcome by locally delivering trophic factors to enhance engraftment. Regenerating islet-derived protein 3α (Reg3α) is a pancreatic secretory protein which functions as an antimicrobial peptide in control of inflammation and cell proliferation. In this study, to investigate whether Reg3α could improve islet engraftment, a marginal mass of syngeneic islets pretransduced with adenoviruses expressing Reg3α or control EGFP were transplanted under the renal capsule of streptozotocin-induced diabetic mice. Mice receiving islets with elevated Reg3α production exhibited significantly lower blood glucose levels (9.057 ± 0.59 mmol/L versus 13.48 ± 0.35 mmol/L, P < 0.05) and improved glucose-stimulated insulin secretion (1.80 ± 0.17 ng/mL versus 1.16 ± 0.16 ng/mL, P < 0.05) compared with the control group. The decline of apoptotic events (0.57% ± 0.15% versus 1.06% ± 0.07%, P < 0.05) and increased β-cell proliferation (0.70% ± 0.10% versus 0.36% ± 0.14%, P < 0.05) were confirmed in islet grafts overexpressing Reg3α by morphometric analysis. Further experiments showed that Reg3α production dramatically protected cultured islets and pancreatic β cells from cytokine-induced apoptosis and the impairment of glucose-stimulated insulin secretion. Moreover, exposure to cytokines led to the activation of MAPKs in pancreatic β cells, which was reversed by Reg3α overexpression in contrast to control group. These results strongly suggest that Reg3α could enhance islet engraftments through its cytoprotective effect and advance the therapeutic efficacy of islet transplantation.

Elevated uric acid causes direct injury to pancreatic β-cells. In this study, we examined the effects of luteolin, an important antioxidant, on uric acid-induced β-cell dysfunction. We first evaluated the effect of luteolin on nitric oxide (NO) formation in uric acid-stimulated Min6 cells using the Griess method. Next, we performed transient transfection and reporter assays to measure transcriptional activity of nuclear factor (NF)-κB. Western blotting assays were also performed to assess the effect of luteolin on the expression of MafA and inducible NO synthase (iNOS) in uric acid-treated cells. Finally, we evaluated the effect of luteolin on uric acid-induced inhibition of glucose-stimulated insulin secretion (GSIS) in Min6 cells and freshly isolated mouse pancreatic islets. We found that luteolin significantly inhibited uric acid-induced NO production, which was well correlated with reduced expression of iNOS mRNA and protein. Furthermore, decreased activity of NF-κB was implicated in inhibition by luteolin of increased iNOS expression induced by uric acid. Besides, luteolin significantly increased MafA expression in Min6 cells exposed to uric acid, which was reversed by overexpression of iNOS. Moreover, luteolin prevented uric acid-induced inhibition of GSIS in both Min6 cells and mouse islets. In conclusion, luteolin protects pancreatic β-cells from uric acid-induced dysfunction and may confer benefit on the protection of pancreatic β-cells in hyperuricemia-associated diabetes.