The characteristics of pre-edge peaks in K-edge x-ray absorption near edge structure (XANES) spectra of 3d transition metals were reviewed from viewpoints of the selection rule, coordination number, number of d-electrons, and symmetry of the coordination sphere. The contribution of the electric dipole and quadrupole transition to the peaks was discussed on the basis of the group theory, polarized spectra, and theoretical calculations. The pre-edge peak intensity for T d symmetry is larger than those for O h symmetry for all 3d elements. The intense pre-edge peak for tetrahedral species of 3d transition metals is not due to 1s-3d transition, but transition to the p component in d-p hybridized orbital. The mixing of metal 4p orbitals with the 3d orbitals depends strongly on the coordination symmetry, and the possibility is predictable by group theory. The transition of 1s electron to d orbitals is electric quadrupole component in any of the symmetries. The d-p hybridization does not occur with regular octahedral symmetry, and the weak pre-edge peak consists of 1s-3d electric quadrupole transition. The pre-edge peak intensity for a compound with a tetrahedral center changes as a function of the number of 3d electrons regardless of the kind of element; it is maximized at d 0 and gradually decreases to zero at d 10 . The features of pre-edge peaks in K-edge XANES spectra for 4d elements and the L 1 -edge for 5d elements are analogous with those for 3d elements, but the pre-edge peak is broadened due to the wide natural width of the core level.It has been recognized since 1940s that features of the pre-edge peak are strongly influenced by the symmetry of the coordination sphere. 3 In 1949, Hanson et al. measured the Mn K-edge x-ray absorption spectra of various manganese compounds with high energy resolution. 4 They observed an intense pre-edge peak for KMnO 4 , and a distinct chemical shift of the absorption edge was observed among XANES spectra of Mn, MnS, MnO 2 , and KMnO 4 . Linear relationships of both energies of the pre-edge peak and the absorption edge against the oxidation number were shown by Wong et al. at the V K-edge. 5 It has been recognized that the pre-edge peak intensity decreases with increase in the coordination number. Figure 1 shows Ti K-edge XANES spectra of Ti 4C species with different coordination numbers summarized by Farges et al. 6,7 Their FEFF calculations of the model TiO x units revealed that the pre-edge peak intensities at the Ti K-edge and the energies for four-coordinated compounds are 2.5 times higher and lower by 2 eV than those for five-coordinated compounds, respectively. 6,7 These characteristic pre-edge features associated with the coordination number of a central atom have been utilized as a powerful fingerprint for the coordination sphere in various samples such as environmental,

Insulin resistance is often associated with obesity and can precipitate type 2 diabetes. To date, most known approaches that improve insulin resistance must be preceded by the amelioration of obesity and hepatosteatosis. Here, we show that this provision is not mandatory; insulin resistance and hyperglycemia are improved by the modification of hepatic fatty acid composition, even in the presence of persistent obesity and hepatosteatosis. Mice deficient for Elovl6, the gene encoding the elongase that catalyzes the conversion of palmitate to stearate, were generated and shown to become obese and develop hepatosteatosis when fed a high-fat diet or mated to leptin-deficient ob/ob mice. However, they showed marked protection from hyperinsulinemia, hyperglycemia and hyperleptinemia. Amelioration of insulin resistance was associated with restoration of hepatic insulin receptor substrate-2 and suppression of hepatic protein kinase C epsilon activity resulting in restoration of Akt phosphorylation. Collectively, these data show that hepatic fatty acid composition is a new determinant for insulin sensitivity that acts independently of cellular energy balance and stress. Inhibition of this elongase could be a new therapeutic approach for ameliorating insulin resistance, diabetes and cardiovascular risks, even in the presence of a continuing state of obesity.

The gene Bcl11b, which encodes zinc finger proteins, and its paralog, Bcl11a, are associated with immune-system malignancies. We have generated Bcl11b-deficient mice that show a block at the CD4-CD8- double-negative stage of thymocyte development without any impairment in cells of B- or gammadelta T cell lineages. The Bcl11b-/- thymocytes showed unsuccessful recombination of V(beta) to D(beta) and lacked the pre-T cell receptor (TCR) complex on the cell surface, owing to the absence of Tcrb mRNA expression. In addition, we saw profound apoptosis in the thymus of neonatal Bcl11b-/- mice. These results suggest that Bcl11b is a key regulator of both differentiation and survival during thymocyte development.

Human atherosclerotic lesions overexpress the lysosomal cysteine protease cathepsin S (Cat S), one of the most potent mammalian elastases known. In contrast, atheromata have low levels of the endogenous Cat S inhibitor cystatin C compared with normal arteries, suggesting involvement of this protease in atherogenesis. The present study tested this hypothesis directly by crossing Cat S-deficient (CatS -/-) mice with LDL receptor-deficient (LDLR -/-) mice that develop atherosclerosis on a high-cholesterol diet. Compared with LDLR -/-mice, double-knockout mice (CatS -/-LDLR -/-) developed significantly less atherosclerosis, as indicated by plaque size (plaque area and intimal thickening) and stage of development. These mice also had markedly reduced content of intimal macrophages, lipids, smooth muscle cells, collagen, CD4 + T lymphocytes, and levels of IFN-γ. CatS -/-LDLR -/-monocytes showed impaired subendothelial basement membrane transmigration, and aortas from CatS -/-LDLR -/-mice had preserved elastic laminae. These findings establish a pivotal role for Cat S in atherogenesis.

Insulin receptor substrate 2 (IRS-2) is the main mediator of insulin signalling in the liver, controlling insulin sensitivity. Sterol regulatory element binding proteins (SREBPs) have been established as transcriptional regulators of lipid synthesis. Here, we show that SREBPs directly repress transcription of IRS-2 and inhibit hepatic insulin signalling. The IRS-2 promoter is activated by forkhead proteins through an insulin response element (IRE). Nuclear SREBPs effectively replace and interfere in the binding of these transactivators, resulting in inhibition of the downstream PI(3)K/Akt pathway, followed by decreased glycogen synthesis. These data suggest a molecular mechanism for the physiological switching from glycogen synthesis to lipogenesis and hepatic insulin resistance that is associated with hepatosteatosis.