A global transcriptional activator involved in the iron homeostasis in cyanobacteria.

Cyanobacteria use a series of adaptation strategies and a complicated regulatory network to maintain intracellular iron (Fe) homeostasis. Here, a global activator named IutR has been identified through three-dimensional chromosome organization and transcriptome analysis in a model cyanobacterium Synechocystis sp. PCC 6803. Inactivation of all three homologous IutR-encoding genes resulted in an impaired tolerance of Synechocystis to Fe deficiency and loss of the responses of Fe uptake-related genes to Fe-deplete conditions. Protein-promoter interaction assays confirmed the direct binding of IutR with the promoters of genes related to Fe uptake, and chromatin immunoprecipitation sequencing analysis further revealed that in addition to Fe uptake, IutR could regulate many other physiological processes involved in intracellular Fe homeostasis. These results proved that IutR is an important transcriptional activator, which is essential for cyanobacteria to induce Fe-deficiency response genes. This study provides in-depth insights into the complicated Fe-deficient signaling network and the molecular mechanism of cyanobacteria adaptation to Fe-deficient environments.

Diversity and Evolution of Iron Uptake Pathways in Marine Cyanobacteria from the Perspective of the Coastal Strain Synechococcus sp. Strain PCC 7002.

Marine cyanobacteria contribute to approximately half of the ocean primary production, and their biomass is limited by low iron (Fe) bioavailability in many regions of the open seas. The mechanisms by which marine cyanobacteria overcome Fe limitation remain unclear. In this study, multiple Fe uptake pathways have been identified in a coastal strain of Synechococcus sp. strain PCC 7002. A total of 49 mutants were obtained by gene knockout methods, and 10 mutants were found to have significantly decreased growth rates compared to the wild type (WT). The genes related to active Fe transport pathways such as TonB-dependent transporters and the synthesis and secretion of siderophores are found to be essential for the adaptation of Fe limitation in Synechococcus sp. PCC 7002. By comparing the Fe uptake pathways of this coastal strain with other open-ocean cyanobacterial strains, it can be concluded that the Fe uptake strategies from different cyanobacteria have a strong relationship with the Fe bioavailability in their habitats. The evolution and adaptation of cyanobacterial iron acquisition strategies with the change of iron environments from ancient oceans to modern oceans are discussed. This study provides new insights into the diversified strategies of marine cyanobacteria in different habitats from temporal and spatial scales. IMPORTANCE Iron (Fe) is an important limiting factor of marine primary productivity. Cyanobacteria, the oldest photosynthetic oxygen-evolving organisms on the earth, play crucial roles in marine primary productivity, especially in the oligotrophic ocean. How they overcome Fe limitation during the long-term evolution process has not been fully revealed. Fe uptake mechanisms of cyanobacteria have been partially studied in freshwater cyanobacteria but are largely unknown in marine cyanobacterial species. In this paper, the characteristics of Fe uptake mechanisms in a coastal model cyanobacterium, Synechococcus sp. PCC 7002, were studied. Furthermore, the relationship between Fe uptake strategies and Fe environments of cyanobacterial habitats has been revealed from temporal and spatial scales, which provides a good case for marine microorganisms adapting to changes in the marine environment.

Special roles for efflux systems in iron homeostasis of non-siderophore-producing cyanobacteria.

In oligotrophic oceans, low bioavailability of Fe is a key factor limiting primary productivity. However, excessive Fe in cells leads to the Fenton reaction, which is toxic to cells. Cyanobacteria must strictly maintain intracellular Fe homeostasis. Here, we knocked out a series of genes encoding efflux systems in Synechocystis sp. PCC 6803, and found eight genes that are required for high Fe detoxification. Unexpectedly, the HlyBD-TolC efflux system plays an important role in the adaptation of Synechocystis under Fe-deficient conditions. Mutants of HlyD and TolC grew worse than the wild-type strain under low-Fe conditions and showed significantly lower intracellular Fe contents than the wild-type strain. We excluded the possibility that the low Fe sensitivity of the HlyBD-TolC mutants was caused by a loss of the S-layer, the main extracellular protein secreted via this efflux system. Inactivation of the HlyD protein influenced type IV pili formation and direct inactivation of type IV pili related genes affected the adaptation to low-Fe conditions. HlyBD-TolC system is likely involved in the formation of type IV pili and indirectly influenced Fe acquisition. Our findings suggest that efflux system in non-siderophore-producing cyanobacteria can facilitate Fe uptake and help cells adapt to Fe-deficient conditions via novel pathways.

Creating Hierarchical Pores by Controlled Linker Thermolysis in Multivariate Metal-Organic Frameworks.

Sufficient pore size, appropriate stability, and hierarchical porosity are three prerequisites for open frameworks designed for drug delivery, enzyme immobilization, and catalysis involving large molecules. Herein, we report a powerful and general strategy, linker thermolysis, to construct ultrastable hierarchically porous metal-organic frameworks (HP-MOFs) with tunable pore size distribution. Linker instability, usually an undesirable trait of MOFs, was exploited to create mesopores by generating crystal defects throughout a microporous MOF crystal via thermolysis. The crystallinity and stability of HP-MOFs remain after thermolabile linkers are selectively removed from multivariate metal-organic frameworks (MTV-MOFs) through a decarboxylation process. A domain-based linker spatial distribution was found to be critical for creating hierarchical pores inside MTV-MOFs. Furthermore, linker thermolysis promotes the formation of ultrasmall metal oxide nanoparticles immobilized in an open framework that exhibits high catalytic activity for Lewis acid-catalyzed reactions. Most importantly, this work provides fresh insights into the connection between linker apportionment and vacancy distribution, which may shed light on probing the disordered linker apportionment in multivariate systems, a long-standing challenge in the study of MTV-MOFs.

[Effects and potential mechanisms of short-term use of simvastatin on myocardial no-reflow after ischemia-reperfusion in rats].

OBJECTIVE: The main objective of this study is to assess the the effect of simvastatin (sim) on myocardial no-reflow (NR) and explore the possible potential mechanisms. METHODS: Adult male Wistar rats were randomized into sham group (n = 12), I/R (90 min ischemia via coronary ligation/120 min reperfusion, n = 18) and I/R plus sim group (20 mgxkg(-1)xd(-1) sim pretreated via gavage beginning 3 days before I/R, n = 18). After reperfusion, area at risk/area of left ventricular (RA/LVA), area of NR, determined by the area not perfused by thioflavin-S/area at risk (NA/RA) and area of myocardial infarction/area at risk (MIA/RA) were measured. Myocardium homogenate was used to determine the activity of eNOS, iNOS and MPO, and the content of NO and MDA. Myocardial immunohistochemistry was performed to determine the positive index of NF-kappaB p65 in cardiomyocytes and arteriole. RESULTS: The NR and myocardial infarction areas in I/R plus sim group were significantly smaller than those in I/R group (34.10 +/- 7.05 vs. 52.09 +/- 6.89, 78.80 +/- 7.60 vs. 90.13 +/- 5.72, each P < 0.05) while the ischemia area was similar between the 2 groups (P > 0.05). The myocardial activities of iNOS and MPO, the contents of NO and MDA were significantly lower while eNOS activity was significantly higher in I/R plus sim group than those in I/R group (5.02 +/- 1.64 vs. 9.19 +/- 2.89, 586.21 +/- 126.97 vs. 744.49 +/- 137.53, 257.72 +/- 93.43 vs. 384.10 +/- 40.68, 72.10 +/- 18.56 vs. 111.84 +/- 38.58, 7.08 +/- 1.74 vs. 3.72 +/- 0.98, all P < 0.05). The positive index of NF-kappaB p65 in cardiocytes and arteriole at left ventricular wall near the area of myocardial infarction was significantly lower in I/R plus sim group than that in I/R group (21.59 +/- 10.5 vs. 34.32 +/- 9.55, 27.27 +/- 13.19 vs. 44.91 +/- 15.06, each P < 0.05). CONCLUSION: Simvastatin could improve myocardial NR after ischemia-reperfusion by attenuating endothelial dysfunction and inhibiting inflammation and neutrophil activation.