Biomechanics and control of vocalization in a non-songbird

The neuromuscular control of vocalization in birds requires complicated and precisely coordinated motor control of the vocal organ (i.e. the syrinx), the respiratory system and upper vocal tract. The biomechanics of the syrinx is very complex and not well understood. In this paper, we aim to unravel the contribution of different control parameters in the coo of the ring dove (Streptopelia risoria) at the syrinx level. We designed and implemented a quantitative biomechanical syrinx model that is driven by physiological control parameters and includes a muscle model. Our simple nonlinear model reproduces the coo, including the inspiratory note, with remarkable accuracy and suggests that harmonic content of song can be controlled by the geometry and rest position of the syrinx. Furthermore, by systematically switching off the control parameters, we demonstrate how they affect amplitude and frequency modulations and generate new experimentally testable hypotheses. Our model suggests that independent control of amplitude and frequency seems not to be possible with the simple syringeal morphology of the ring dove. We speculate that songbirds evolved a syrinx design that uncouples the control of different sound parameters and allows for independent control. This evolutionary key innovation provides an additional explanation for the rapid diversification and speciation of the songbirds

Genetically distinct subsets within ANCA-associated vasculitis

BACKGROUND Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a severe condition encompassing two major syndromes: granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis) and microscopic polyangiitis. Its cause is unknown, and there is debate about whether it is a single disease entity and what role ANCA plays in its pathogenesis. We investigated its genetic basis. METHODS A genomewide association study was performed in a discovery cohort of 1233 U. K. patients with ANCA-associated vasculitis and 5884 controls and was replicated in 1454 Northern European case patients and 1666 controls. Quality control, population stratification, and statistical analyses were performed according to standard criteria. RESULTS We found both major-histocompatibility-complex (MHC) and non-MHC associations with ANCA-associated vasculitis and also that granulomatosis with polyangiitis and microscopic polyangiitis were genetically distinct. The strongest genetic associations were with the antigenic specificity of ANCA, not with the clinical syndrome. Anti-proteinase 3 ANCA was associated with HLA-DP and the genes encoding alpha(1)-antitrypsin (SERPINA1) and proteinase 3 (PRTN3) (P = 6.2x10(-89), P = 5.6x10(-12), and P = 2.6x10(-7), respectively). Anti-myeloperoxidase ANCA was associated with HLA-DQ (P = 2.1x10(-8)). CONCLUSIONS This study confirms that the pathogenesis of ANCA-associated vasculitis has a genetic component, shows genetic distinctions between granulomatosis with polyangiitis and microscopic polyangiitis that are associated with ANCA specificity, and suggests that the response against the autoantigen proteinase 3 is a central pathogenic feature of proteinase 3 ANCA-associated vasculitis. These data provide preliminary support for the concept that proteinase 3 ANCA-associated vasculitis and myeloperoxidase ANCA-associated vasculitis are distinct autoimmune syndromes. (Funded by the British Heart Foundation and others.