Proteins with expanded polyQ repeats are associated with at least nine neurodegenerative disorders including ataxins 1 and 3, Kennedy's disease, and Huntington's disease (HD) 1,2 . These diseases are dominantly inherited and although the polyQ-containing proteins are expressed widely in the brain, they result in selective neuronal death. There is a significant and striking correlation between the length of the polyQ repeat and pathology; longer repeats result in earlier onset and more severe symptoms with the threshold of approximately 40 glutamine residues. In the case of HD, for example, expanded polyQ in huntingtin (htt) protein causes disease 3,4 . A characteristic of the polyQ diseases is the appearance of neuronal inclusions that are formed by aggregation of the polyQ proteins with other cellular proteins 5,6 . This has led to the "toxic gain-of-function" hypothesis that essential proteins can be sequestered, which 3 over time leads to cellular dysgenesis. The expression of polyQ can cause other metastable proteins to lose functionality, and in turn these proteins amplify the toxicity of polyQ by enhancing overall aggregation 7 . Self-aggregation of polyQ proteins has been proposed to be mediated by association of parallel β-sheet structures 8 . However, the intrinsic in vivo events leading to the aggregation of polyQ proteins remain poorly understood.Protein misfolding is a natural consequence of protein biogenesis. To combat cytotoxicity that results from the accumulation of misfolded proteins, all cells express molecular chaperones that are essential for the productive folding of proteins 9,10 . Molecular chaperones are of several classes; for example, Hsp70/J-domain proteins interact with unfolded or partially folded proteins in concert with co-chaperones, while the chaperone machines of the chaperonin (Hsp60) family form cage-like structures that sequester non-native states of proteins 11 . The chaperonin containing t-complex polypeptide 1 (CCT)/t-complex polypeptide 1 ring complex (TRiC) is a member of chaperonin family 12 that facilitates the folding of proteins in the eukaryotic cytosol upon ATP hydrolysis 13,14 . CCT shows a weak but significant homology to E. coli GroEL and forms a hexadecamer double-troidal complex composed of eight different subunits 15,16 . Substrate proteins are captured in the cavity, and released after folding is completed 17 . Approximately 10% of newly-synthesized proteins have been proposed to be recognized by CCT.Recently, in a genome-wide screen to identify modifier genes for polyQ aggregation in C. elegans, approximately 200 genes were found to be required for the prevention of polyQ aggregation 18 . This included the genes encoding two Hsp70s, one J-protein, and six CCT subunits. These observations suggested a 4 role of CCT in preventing polyQ aggregation. We show here in mammalian cells that CCT has a key protective role against the toxicity of htt/polyQ and affects aggregation process at the soluble stage. In the context of our recent in vitro data showing that ...

The valley splitting, which lifts the degeneracy of the lowest two valley states in a SiO(2)/Si(100)/SiO(2) quantum well, is examined through transport measurements. We demonstrate that the valley splitting can be observed directly as a step in the conductance defining a boundary between valley-unpolarized and -polarized regions. This persists to well above liquid helium temperature and shows no dependence on magnetic field, indicating that single-particle valley splitting and valley polarization exist in (100) silicon even at zero magnetic field.

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