The GLP-1 Receptor Agonist Exenatide Ameliorates Bone Composition and Tissue Material Properties in High Fat Fed Diabetic Mice

Type 2 diabetes mellitus (T2DM) has recently been recognized as a significant risk factor for bone fragility. Careful investigations of bone mechanical properties in human studies suggested possible alterations of bone composition, although this axis has poorly been investigated. The main aim of this study was to evaluate the impact of high fat diet-induced diabetes and therapy using the clinically approved GLP-1 receptor agonist, exenatide, on tissue bone mechanical properties and compositional parameters. Male mice had free access to high fat diet for 16 weeks to induce diabetes prior to commencement of the study. Exenatide was administered twice daily by i.p. injection at a dose of 25 nmol/kg for 52 days. Normal and high fat diet fed (HFD) mice injected with saline were used as controls. Bone mechanical properties was assessed at the organ level by 3-point bending and at the tissue level by nanoindentation. Bone microarchitecture was investigated by microcomputed tomography and bone composition was evaluated by Fourier transform infrared imaging. HFD mice exhibited profound alterations of bone mechanical properties at both the organ and tissue level. Collagen maturity as well as trabecular and cortical bone microarchitectures were abnormal. Administration of exenatide, led to clear ameliorations in bone mechanical properties at the organ and tissue levels by modifications of both cortical microarchitecture and bone compositional parameters (collagen maturity, mineral crystallinity, carbonate/phosphate ratio, acid phosphate content). These results bring new light on the mode of action of exenatide in bone physiology and demonstrate the value of GLP-1 mimetics in the treatment of fragility fractures in diabetes

Export of functional Streptomyces coelicolor alditol oxidase to the periplasm or cell surface of Escherichia coli and its application in whole-cell biocatalysis

Streptomyces coelicolor A3(2) alditol oxidase (AldO) is a soluble monomeric flavoprotein in which the flavin cofactor is covalently linked to the polypeptide chain. AldO displays high reactivity towards different polyols such as xylitol and sorbitol. These characteristics make AldO industrially relevant, but full biotechnological exploitation of this enzyme is at present restricted by laborious and costly purification steps. To eliminate the need for enzyme purification, this study describes a whole-cell AldO biocatalyst system. To this end, we have directed AldO to the periplasm or cell surface of Escherichia coli. For periplasmic export, AldO was fused to endogenous E. coli signal sequences known to direct their passenger proteins into the SecB, signal recognition particle (SRP), or Twin-arginine translocation (Tat) pathway. In addition, AldO was fused to an ice nucleation protein (INP)-based anchoring motif for surface display. The results show that Tat-exported AldO and INP-surface-displayed AldO are active. The Tat-based system was successfully employed in converting xylitol by whole cells, whereas the use of the INP-based system was most likely restricted by lipopolysaccharide LPS in wild-type cells. It is anticipated that these whole-cell systems will be a valuable tool for further biological and industrial exploitation of AldO and other cofactor-containing enzymes.

The gray matter volume of the amygdala is correlated with the perception of melodic intervals: a voxel-based morphometry study

Music is not simply a series of organized pitches, rhythms, and timbres, it is capable of evoking emotions. In the present study, voxel-based morphometry (VBM) was employed to explore the neural basis that may link music to emotion. To do this, we identified the neuroanatomical correlates of the ability to extract pitch interval size in a music segment (i.e., interval perception) in a large population of healthy young adults (N = 264). Behaviorally, we found that interval perception was correlated with daily emotional experiences, indicating the intrinsic link between music and emotion. Neurally, and as expected, we found that interval perception was positively correlated with the gray matter volume (GMV) of the bilateral temporal cortex. More important, a larger GMV of the bilateral amygdala was associated with better interval perception, suggesting that the amygdala, which is the neural substrate of emotional processing, is also involved in music processing. In sum, our study provides one of first neuroanatomical evidence on the association between the amygdala and music, which contributes to our understanding of exactly how music evokes emotional responses

Photodeposition as a facile route to tunable Pt photocatalysts for hydrogen production:on the role of methanol

Photodeposition of H2PtCl6 in the presence of methanol promotes the formation of highly dispersed, metallic Pt nanoparticles over titania, likely via capture of photogenerated holes by the alcohol to produce an excess of surface electrons for substrate-mediated transfer to Pt complexes, resulting in a high density of surface nucleation sites for Pt reduction. Photocatalytic hydrogen production from water is proportional to the surface density of Pt metal co-catalyst, and hence photodeposition in the presence of high methanol concentrations affords a facile route to optimising photocatalyst design and highlights the importance of tuning co-catalyst properties in photocatalysis

Structural Phase Transition at High Temperatures in Solid Molecular Hydrogen and Deuterium

We study the effect of temperature up to 1000K on the structure of dense molecular para-hydrogen and ortho-deuterium, using the path-integral Monte Carlo method. We find a structural phase transition from orientationally disordered hexagonal close packed (hcp) to an orthorhombic structure of Cmca symmetry before melting. The transition is basically induced by thermal fluctuations, but quantum fluctuations of protons (deuterons) are important in determining the transition temperature through effectively hardening the intermolecular interaction. We estimate the phase line between hcp and Cmca phases as well as the melting line of the Cmca solid.Comment: 8 pages, 7 figures; accepted in Phys. Rev.

Counter‐Credit‐Risk Yield Spreads: A Puzzle in China's Corporate Bond Market

yesIn this paper, using China’s risk-free and corporate zero yields together with aggregate credit risk measures and various control variables from 2006 to 2013, we document a puzzle of counter-credit-risk corporate yield spreads. We interpret this puzzle as a symptom of the immaturity of China’s credit bond market, which reveals a distorted pricing mechanism latent in the fundamental of this market. We also find interesting results about relationships between corporate yield spreads and interest rates as well as risk premia and the stock index, and these results are somewhat attributed to this puzzle