To gain insight into how mutant huntingtin (mHtt) CAG repeat length modifies Huntington’s disease (HD) pathogenesis, we profiled mRNA in over 600 brain and peripheral tissue samples from HD knock-in mice with increasing CAG repeat lengths. We find repeat length dependent transcriptional signatures are prominent in the striatum, less so in cortex, and minimal in the liver. Co-expression network analyses reveal 13 striatal and 5 cortical modules that are highly correlated with CAG length and age, and that are preserved in HD models and some in the patients. Top striatal modules implicate mHtt CAG length and age in graded impairment of striatal medium spiny neuron identity gene expression and in dysregulation of cAMP signaling, cell death, and protocadherin genes. Importantly, we used proteomics to confirm 790 genes and 5 striatal modules with CAG length-dependent dysregulation at both RNA and protein levels, and validated 22 striatal module genes as modifiers of mHtt toxicities in vivo.

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Capillary electrophoresis (CE) was used to separate four anionic {arsenite [As()], arsenate [As()], monomethylarsonic acid and dimethylarsinic acid } and two cationic forms (arsenobetaine and arsenocholine) of As in a single run. At sufficiently high concentrations, the determination of these compounds could be accomplished by means of UV detection. The determination of low concentrations (<10 mg l−1) of these compounds of interest was accomplished by coupling CE on-line with inductively coupled plasma mass spectrometry (ICP-MS ). To accomplish this coupling, a microconcentric nebulizer was used. The modifications necessary to make a conventional CE system compatible with ICP-MS, the optimization of the operation parameters and of sample stacking conditions together with the effect of the sheath liquid and of an induced laminar flow are discussed. The analytical figures of merit of the method were assessed and the limit of determination (based on the peak height of a peak for which the signal-to-noise ratio is 1051) was found to be 1-2 mg l−1 As for each species. The recovery for the compounds of interest was determined using a spiked mineral water sample. Samples of mineral water, soil leachate and urine were analyzed with the CE-ICP-MS combination. plasma. Furthermore, since concentric nebulizers are self-

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