Micra Transcatheter Pacing System Post-Approval Registry ClinicalTrials.gov identifier: NCT02536118; Micra Transcatheter Pacing Study ClinicalTrials.gov identifier: NCT02004873.

This study investigated whether congenital amusia, a neuro-developmental disorder of musical perception, also has implications for speech intonation processing. In total, 16 British amusics and 16 matched controls completed five intonation perception tasks and two pitch threshold tasks. Compared with controls, amusics showed impaired performance on discrimination, identification and imitation of statements and questions that were characterized primarily by pitch direction differences in the final word. This intonation-processing deficit in amusia was largely associated with a psychophysical pitch direction discrimination deficit. These findings suggest that amusia impacts upon one's language abilities in subtle ways, and support previous evidence that pitch processing in language and music involves shared mechanisms.

Despite much research, disagreements abound regarding the detailed charac-teristicsof question intonation in different languages or even in the same language.The present study investigates question intonation in Mandarin by also consideringthe role of focus that is frequently ignored in previous research. In experiment 1,native speakers of Mandarin produced statements, yes/no questions, particle ques-tions,wh-questions, rhetorical questions and confirmation questions with narrowfocus on the initial, medial or final word of the sentence, or on none of the words.Detailed F0 contour analyses showed that focus generated the same pitch rangemodification in questions as in statements, i.e., expanding the pitch range of thefocused word, suppressing (compressing and lowering) that of the post-focuswords, but leaving that of the pre-focus words largely unaffected. When the effects offocus (as well as other functions also potentially present) were controlled by sub-tractingstatement F0 contours from those of the corresponding yes/no questions,the resulting difference curves resembled exponential or even double-exponentialfunctions. Further F0 analyses also revealed an interaction between focus andinterrogative meaning in the form of a boost to the pitch raising by the question start-ingfrom the focused word. Finally, subtle differences in the amount of pitch raisingwere also observed among different types of questions, especially at the sentence-finalposition. Experiment 2 investigated whether listeners could detect both focusand question in the same utterance. Results showed that listeners could identifyboth in most cases, indicating that F0 variations related to the two functions could besimultaneously transmitted. Meanwhile, the lowest identification rates were foundfor neutral focus in questions and for statements with final focus. In both cases, theconfusions seemed to arise from the competing F0 adjustments by interrogativemeaning and focus at the sentence-final position. These findings are consistent withthe functional view of intonation, according to which components of intonation aredefined and organized by individual communicative functions that are independentof each other but are encoded in parallel.

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Tone language experience benefits pitch processing in music and speech for typically developing individuals. No known studies have examined pitch processing in individuals with autism who speak a tone language. This study investigated discrimination and identification of melodic contour and speech intonation in a group of Mandarin-speaking individuals with high-functioning autism. Individuals with autism showed superior melodic contour identification but comparable contour discrimination relative to controls. In contrast, these individuals performed worse than controls on both discrimination and identification of speech intonation. These findings provide the first evidence for differential pitch processing in music and speech in tone language speakers with autism, suggesting that tone language experience may not compensate for speech intonation perception deficits in individuals with autism.

Congenital amusia is a neuro-developmental disorder of pitch perception that causes severe problems with music processing but only subtle difficulties in speech processing. This study investigated speech processing in a group of Mandarin speakers with congenital amusia. Thirteen Mandarin amusics and thirteen matched controls participated in a set of tone and intonation perception tasks and two pitch threshold tasks. Compared with controls, amusics showed impaired performance on word discrimination in natural speech and their gliding tone analogs. They also performed worse than controls on discriminating gliding tone sequences derived from statements and questions, and showed elevated thresholds for pitch change detection and pitch direction discrimination. However, they performed as well as controls on word identification, and on statement-question identification and discrimination in natural speech. Overall, tasks that involved multiple acoustic cues to communicative meaning were not impacted by amusia. Only when the tasks relied mainly on pitch sensitivity did amusics show impaired performance compared to controls. These findings help explain why amusia only affects speech processing in subtle ways. Further studies on a larger sample of Mandarin amusics and on amusics of other language backgrounds are needed to consolidate these results.

Oxidative rearrangements play key roles in introducing structural complexity and biological activities of natural products biosynthesized by type II polyketide synthases (PKSs). Chartreusin (1) is a potent antitumor polyketide that contains a unique rearranged pentacyclic aromatic bilactone aglycone derived from a type II PKS. Herein, we report an unprecedented dioxygenase, ChaP, that catalyzes the final α-pyrone ring formation in 1 biosynthesis using flavin-activated oxygen as an oxidant. The X-ray crystal structures of ChaP and two homologues, docking studies, and site-directed mutagenesis provided insights into the molecular basis of the oxidative rearrangement that involves two successive C-C bond cleavage steps followed by lactonization. ChaP is the first example of a dioxygenase that requires a flavin-activated oxygen as a substrate despite lacking flavin binding sites, and represents a new class in the vicinal oxygen chelate enzyme superfamily.

In this study, we investigated the impact of congenital amusia, a disorder of musical processing, on speech and song imitation in speakers of a tone language, Mandarin. A group of 13 Mandarin-speaking individuals with congenital amusia and 13 matched controls were recorded while imitating a set of speech and two sets of song stimuli with varying pitch and rhythm patterns. The results indicated that individuals with congenital amusia were worse than controls in both speech and song imitation, in terms of both pitch matching (absolute and relative) and rhythm matching (relative time and number of time errors). Like the controls, individuals with congenital amusia achieved better absolute and relative pitch matching and made fewer pitch interval and contour errors in song than in speech imitation. These findings point toward domain-general pitch (and time) production deficits in congenital amusia, suggesting the presence of shared pitch production mechanisms but distinct requirements for pitch-matching accuracy in language and music processing.