Canadian Automotive Partnership Council

Congenital amusia is a neuro-developmental disorder of music perception and production, with the observed deficits contrasting with the sophisticated music processing reported for the general population. Musical deficits within amusia have been hypothesized to arise from altered pitch processing, with impairments in pitch discrimination and, notably, short-term memory. We here review research investigating its behavioral and neural correlates, in particular the impairments at encoding, retention, and recollection of pitch information, as well as how these impairments extend to the processing of pitch cues in speech and emotion. The impairments have been related to altered brain responses in a distributed fronto-temporal network, which can be observed also at rest. Neuroimaging studies revealed changes in connectivity patterns within this network and beyond, shedding light on the brain dynamics underlying auditory cognition. Interestingly, some studies revealed spared implicit pitch processing in congenital amusia, showing the power of implicit cognition in the music domain. Building on these findings, together with audiovisual integration and other beneficial mechanisms, we outline perspectives for training and rehabilitation and the future directions of this research domain.

One of the major hurdles in the post-genomic era is to understand the function of genes and the interplay of many different cellular proteins. This is especially important for drug development. Capture compound mass spectrometry (CCMS) addresses this challenge by selectively reducing the complexity of the proteome. Capture compounds are trifunctional molecules: a selectivity function reversibly interacts via affinity with proteins; a reactivity function irreversibly forms a covalent bond outside the affinity binding site; and a sorting/pullout function allows the captured protein(s) to be isolated from cellular lysate for mass spectrometric analysis and characterization by database queries. In the present study, we demonstrate the use of a CCMS capture compound with a sulfonamide drug analog as its selectivity function, isolating an expected target protein from cell lysates containing a large excess of other "non-target" proteins. A future application of CCMS is to define or confirm drug target proteins and their mechanisms of drug action, or to discover off-target proteins that cause side effects, enabling subsequent drug structure optimization.