No abstract

We conducted a systematic study of top susceptibility variants from a genome-wide association (GWA) study of Bipolar Disorder to gain insight into the functional consequences of genetic variation influencing disease risk. We report here the results of experiments to explore the effects of these susceptibility variants on DNA methylation and mRNA expression in human cerebellum samples. Among the top susceptibility variants, we identified an enrichment of cis regulatory loci on mRNA expression (eQTLs), and a significant excess of quantitative trait loci for DNA CpG methylation, hereafter referred to as mQTLs. Bipolar Disorder susceptibility variants that cis-regulate both cerebellar expression and methylation of the same gene are a very small proportion of Bipolar Disorder susceptibility variants. This finding suggests that mQTLs and eQTLs provide orthogonal ways of functionally annotating genetic variation within the context of studies of pathophysiology in brain. No lymphocyte mQTL enrichment was found, suggesting that mQTL enrichment was specific to the cerebellum, in contrast to eQTLs. Separately, we found that using mQTL information to restrict the number of SNPs studied enhances our ability to detect a significant association. With this restriction a priori informed by the observed functional enrichment, we identified a significant association (rs12618769, Pbonferroni<0.05) from two other GWA studies (TGen+GAIN; 2,191 cases and 1,434 controls) of Bipolar Disorder, which we replicated in an independent GWA study (WTCCC). Collectively, our findings highlight the importance of integrating functional annotation of genetic variants for gene expression and DNA methylation to advance biological understanding of Bipolar Disorder.

No abstract

No abstract

Although 3d transition metal oxides (TMOs) are well-known as promising anodes for Li ion batteries, little is known about the mechanism of electrode process kinetics. In this work, impedance behavior of the flower-like hierarchical CuO electrode is first investigated to understand the kinetics that influences the performances of TMOs toward lithium. The electrochemical impedance spectra are measured at different discharge and charge states during cycling. A modified twoparallel diffusion path model is set up to account for the Nyquist plots. The kinetic parameters in the model that represent the migration of lithium ions through surface-passivating film, charge transfer on active material/electrolyte interfaces, and diffusion of lithium ions in solid material are discussed in detail. On the basis of the analysis of the variation of kinetic parameters, several promising approaches are proposed to improve the electrochemical performances of copper oxides, which can also be applicable to all the 3d transition metal oxides. ' INTRODUCTIONSince Tarascon et al. 1 first reported the excellent electrochemical performance of CoO toward lithium, 3d transition metal oxides (TMOs, where M is Fe, Co, Ni, and Cu) have been widely investigated as promising anodes for lithium ion batteries. [2][3][4][5] The mechanism of Li reactivity in TMOs differs from the classical Li intercalation/deintercalation or Li-alloying process but involves the formation and decomposition of Li 2 O. The electrode reaction of TMOs is shown as followsCompared to the current commercial carbonaceous anodes, TMOs have much higher theoretic capacities and better rate properties, which will hopefully realize the wide application of Li ion batteries in various areas as next-generation electronic devices, electric vehicles, solar energy storage, etc. For instance, the CuO film prepared by spray pyrolysis exhibited high reversible capacity (625 Ah kg -1 ) even over 100 cycles. 6 However, the Coulombic efficiencies and cycling performances of pure TMOs are disappointing. It is commonly attributed to the poor conductivity of active material and incomplete decomposition of Li 2 O during cycling. Thus, surface modification and nanostructure fabrication are developed to improve the electrical conductivity and enhance the electrochemical activity of TMOs. [7][8][9] Although various novel structures and original experiments have been reported, it is still short of theory supports. To effectively overcome the shortcomings of TMOs, it is necessary to understand the kinetics of lithium ion migration through surface film, charge transfer on solid/electrolyte interfaces, and further diffusion in electrode material since these processes indeed govern the polarization and reaction rate of TMOs. It would be desirable to find out what kinetics and relevant properties such as surface resistance, charge transfer resistance, and Li þ diffusion coefficient can improve the electrochemical performances of TMOs.Electrochemical impedance spectroscopy (EIS) is a commonly used technolo...

No abstract

No abstract

No abstract