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A spin-1/2 triangular-lattice Heisenberg antiferromagnet (TLHAF) is a prototypical frustrated quantum magnet, which exhibits remarkable quantum many-body effects that arise from the synergy between spin frustration and quantum fluctuation. The ground-state properties of a spin-1/2 TLHAF are theoretically well understood. However, the theoretical consensus regarding the magnetic excitations is limited. The experimental study of the magnetic excitations in spin-1/2 TLHAFs has also been limited. Here we show the structure of magnetic excitations in the spin-1/2 TLHAF Ba3CoSb2O9 investigated by inelastic neutron scattering. Significantly different from theoretical expectations, the excitation spectrum has a three-stage energy structure. The lowest-energy first stage is composed of dispersion branches of single-magnon excitations. The second and third stages are dispersive continua accompanied by a columnar continuum extending above 10 meV, which is six times larger than the exchange interaction J = 1.67 meV. Our results indicate the shortcomings of the current theoretical framework.

Extracellular superoxide dismutase (SOD3), a secretory copper enzyme, plays an important role in atherosclerosis and hypertension by modulating the levels of extracellular superoxide anion (O 2 •-) in the vasculature. Little is known about the mechanisms by which SOD3 obtains its catalytic copper cofactor. Menkes ATPase (MNK) has been shown to transport cytosolic copper to the secretory pathway in nonvascular cells. We performed the present study to determine whether MNK is required for the activation of SOD3 in the vasculature. Here we show that MNK was highly expressed in the various vascular tissues and cells. Aortas and cultured fibroblasts from MNK mutant (MNK mut ) mice showed a marked decrease in specific activity of SOD3, but not SOD1 (cytosolic form), which was partially restored by copper addition. Copper treatment in wild-type cells promoted the direct interaction and colocalization of SOD3 with MNK in the trans-Golgi network (TGN), suggesting that MNK transports copper to SOD3 in the TGN. Aortas of MNK mut mice revealed a decrease in activity of SOD3, but not SOD1, in association with a robust increase in O 2 •-levels. Finally, both MNK and SOD3 proteins were highly expressed in the intimal lesions of atherosclerotic vessels. In conclusion, vascular MNK plays an essential role in full activity of SOD3 through transporting copper to SOD3 in the TGN, thereby regulating O 2 •-levels in the vasculature. These studies provide a novel insight into vascular MNK as a critical modulator of "superoxide" stress, which may contribute to cardiovascular disease.Key words: SOD1 • SOD3 • atherosclerosis • copper • MNK ascular superoxide anion (O 2 •-) production contributes to the pathogenesis of many cardiovascular diseases, including atherosclerosis, hypertension, and diabetes (1, 2). The major cellular defense against O 2 •-is a group of oxidoreductases known as superoxide dismutases (SODs). In mammalian tissue, three isoforms of SODs exist: the cytoplasmic Cu/Zn SOD (SOD1), the mitochondrial Mn SOD (SOD2), and the extracellular SOD (SOD3). SOD3 is highly expressed in the vasculature, which is synthesized by vascular smooth muscle cells and fibroblasts, and is the major SOD in the extracellular space (3). It is secreted and V Page 1 of 21 (page number not for citation purposes)anchored to the extracellular matrix and endothelial cell surface through binding to the heparan sulfate proteoglycan, collagen, and fibulin-5 (3-5). Because of its extracellular location, SOD3 plays an important role in regulating blood pressure and endothelial function by modulating the levels of extracellular O 2 •-and nitric oxide bioactivity in the vasculature (3,6,7). Recently, the R213G polymorphism in the SOD3 gene, which reduces binding to endothelial surface and increases serum SOD3 levels, has been linked to an increase in cardiovascular risk (8).SOD3 is a secretory copper-containing enzyme with a similar active site to that of the SOD1. It has been shown that the SOD activity of both wild-type SOD1 and SOD3 depends criti...

Extracellular superoxide dismutase (SOD3), a secretory copper-containing antioxidant enzyme, plays an important role in various oxidative stress-dependent cardiovascular diseases. Although cofactor copper is required for SOD3 activity, it remains unknown whether it can regulate SOD3 transcription. We previously demonstrated that SOD3 activity requires the copper chaperone Antioxidant-1 (Atox1) involved in copper delivery to SOD3 at the trans-Golgi network (TGN). Here we show that copper treatment in mouse fibroblasts significantly increases mRNA and protein levels of SOD3, but not SOD1, which is abolished in Atox1-deficient cells. Copper promotes Atox1 translocation to the nucleus. Promoter deletion analysis identifies copper- and Atox1-response element (RE) at the SOD3 promoter. Gel shift and ChIP assays reveal that Atox1 directly binds to the Atox1-RE in a copper-dependent manner in vitro and in vivo. Adenovirus-mediated re-expression in Atox1-/- cells with nucleus-targeted Atox1 (Atox1-NLS), but not TGN-targeted Atox1 (Atox1-TGN), increases SOD3 transcription without affecting SOD3 activity. Importantly, re-expression of both Atox1-NLS and Atox1-TGN together, but not either alone, in Atox1-/- cells increases SOD3 activity. SOD3 transcription is positively regulated by copper through transcription factor function of Atox1, while full activity of SOD3 requires both copper chaperone and transcription factor function of Atox1. Thus, Atox1 is a potential therapeutic target for oxidant stress-dependent cardiovascular disease.

The long-term survival of patients with Kawasaki disease complicated by giant coronary aneurysms is moderately good with multiple catheter and surgical interventions. Further research should focus on the prevention of coronary vascular remodeling and on the indications for and effectiveness of percutaneous and surgical coronary interventions.