Modelling the similarity of pitch collections with expectation tensors

Models of the perceived distance between pairs of pitch collections are a core component of broader models of music cognition. Numerous distance measures have been proposed, including voice-leading [1], psychoacoustic [2–4], and pitch and interval class distances [5]; but, so far, there has been no attempt to bind these different measures into a single mathematical or conceptual framework, nor to incorporate the uncertain or probabilistic nature of pitch perception. This paper embeds pitch collections in expectation tensors and shows how metrics between such tensors can model their perceived dissimilarity. Expectation tensors indicate the expected number of tones, ordered pairs of tones, ordered triples of tones, etc., that are heard as having any given pitch, dyad of pitches, triad of pitches, etc.. The pitches can be either absolute or relative (in which case the tensors are invariant with respect to transposition). Examples are given to show how the metrics accord with musical intuition

Understanding the complex genetic architecture connecting rheumatoid arthritis, osteoporosis and inflammation:discovering causal pathways

Rheumatoid arthritis (RA) and osteoporosis (OP) are two comorbid complex inflammatory conditions with evidence of shared genetic background and causal relationships. We aimed to clarify the genetic architecture underlying RA and various OP phenotypes while additionally considering an inflammatory component, C-reactive protein (CRP). Genome-wide association study summary statistics were acquired from the GEnetic Factors for OSteoporosis Consortium, Cohorts for Heart and Aging Research Consortium and UK Biobank. Mendelian randomization (MR) was used to detect the presence of causal relationships. Colocalization analysis was performed to determine shared genetic variants between CRP and OP phenotypes. Analysis of pleiotropy between traits owing to shared causal single nucleotide polymorphisms (SNPs) was performed using PL eiotropic A nalysis under CO mposite null hypothesis (PLACO). MR analysis was suggestive of horizontal pleiotropy between RA and OP traits. RA was a significant causal risk factor for CRP (β = 0.027, 95% confidence interval = 0.016-0.038). There was no evidence of CRP→OP causal relationship, but horizontal pleiotropy was apparent. Colocalization established shared genomic regions between CRP and OP, including GCKR and SERPINA1 genes. Pleiotropy arising from shared causal SNPs revealed through the colocalization analysis was all confirmed by PLACO. These genes were found to be involved in the same molecular function 'protein binding' (GO:0005515) associated with RA, OP and CRP. We identified three major components explaining the epidemiological relationship among RA, OP and inflammation: (1) Pleiotropy explains a portion of the shared genetic relationship between RA and OP, albeit polygenically; (2) RA contributes to CRP elevation and (3) CRP, which is influenced by RA, demonstrated pleiotropy with OP.</p

Pitch perception for mixtures of spectrally overlapping harmonic complex tones

This study measured difference limens for fundamental frequency (DLF0s) for a target harmonic complex in the presence of a simultaneous spectrally overlapping harmonic masker. The resolvability of the target harmonics was manipulated by bandpass filtering the stimuli into a low (800–2400 Hz) or high (1600–3200 Hz) spectral region, using different nominal F0s for the targets (100, 200, and 400 Hz), and different masker F0s (0, +9, or −9 semitones) relative to the target. Three different modes of masker presentation, relative to the target, were tested: ipsilateral, contralateral, and dichotic, with a higher masker level in the contralateral ear. Ipsilateral and dichotic maskers generally caused marked elevations in DLF0s compared to both the unmasked and contralateral masker conditions. Analyses based on excitation patterns revealed that ipsilaterally masked F0 difference limens were small (<2%) only when the excitation patterns evoked by the target-plus-masker mixture contained several salient (>1 dB) peaks at or close to target harmonic frequencies, even though these peaks were rarely produced by the target alone. The findings are discussed in terms of place- or place-time mechanisms of pitch perception

Understanding the complex genetic architecture connecting rheumatoid arthritis, osteoporosis and inflammation: discovering causal pathways

Rheumatoid arthritis (RA) and osteoporosis (OP) are two comorbid complex inflammatory conditions with evidence of shared genetic background and causal relationships. We aimed to clarify the genetic architecture underlying RA and various OP phenotypes while additionally considering an inflammatory component, C-reactive protein (CRP). Genome-wide association study summary statistics were acquired from the GEnetic Factors for OSteoporosis Consortium, Cohorts for Heart and Aging Research Consortium and UK Biobank. Mendelian randomization (MR) was used to detect the presence of causal relationships. Colocalization analysis was performed to determine shared genetic variants between CRP and OP phenotypes. Analysis of pleiotropy between traits owing to shared causal single nucleotide polymorphisms (SNPs) was performed using PL eiotropic A nalysis under CO mposite null hypothesis (PLACO). MR analysis was suggestive of horizontal pleiotropy between RA and OP traits. RA was a significant causal risk factor for CRP (β = 0.027, 95% confidence interval = 0.016-0.038). There was no evidence of CRP→OP causal relationship, but horizontal pleiotropy was apparent. Colocalization established shared genomic regions between CRP and OP, including GCKR and SERPINA1 genes. Pleiotropy arising from shared causal SNPs revealed through the colocalization analysis was all confirmed by PLACO. These genes were found to be involved in the same molecular function 'protein binding' (GO:0005515) associated with RA, OP and CRP. We identified three major components explaining the epidemiological relationship among RA, OP and inflammation: (1) Pleiotropy explains a portion of the shared genetic relationship between RA and OP, albeit polygenically; (2) RA contributes to CRP elevation and (3) CRP, which is influenced by RA, demonstrated pleiotropy with OP

Once and only once: mechanisms of centriole duplication and their deregulation in disease.

Centrioles are conserved microtubule-based organelles that form the core of the centrosome and act as templates for the formation of cilia and flagella. Centrioles have important roles in most microtubule-related processes, including motility, cell division and cell signalling. To coordinate these diverse cellular processes, centriole number must be tightly controlled. In cycling cells, one new centriole is formed next to each pre-existing centriole in every cell cycle. Advances in imaging, proteomics, structural biology and genome editing have revealed new insights into centriole biogenesis, how centriole numbers are controlled and how alterations in these processes contribute to diseases such as cancer and neurodevelopmental disorders. Moreover, recent work has uncovered the existence of surveillance pathways that limit the proliferation of cells with numerical centriole aberrations. Owing to this progress, we now have a better understanding of the molecular mechanisms governing centriole biogenesis, opening up new possibilities for targeting these pathways in the context of human disease