Effects of Passion, Experience, and Cultural Politics on Classical Musicians' Practice During the COVID-19 Pandemic.

The widespread cancelation of cultural events during the early 2020 stages of the COVID-19 pandemic led professional performing musicians across the world to experience an increasing economic fragility that threatened their health and wellbeing. Within this "new normal," developing countries have been at a higher risk due to their vulnerable health systems and cultural policies. Even in such difficult times, the music profession requires musicians to keep up their practicing routines, even if they have no professional commitments. This is because high level technical and expressive skills are crucial to sustaining a music career at a high performance level. However, it could be expected that not all musicians might have had the same engagement with music practice during lockdowns. In this study, we studied the experiences of 309 professional classical musicians based in European and Latin American countries with different levels of performing experience to examine their passionate (or lack thereof) engagement with music practice. Through the mixed methods combination of multigroup invariance and narrative analyses, we identified distinct profiles of musicians who displayed more harmonious or more obsessive passion orientations before and at the peak of the pandemic. We observed that musicians with higher levels of harmonious passion in particular were more capable of sustaining their practice at the peak of the pandemic and that these musicians were mostly located in Latin America-a paradox, considering that cultural politics supporting the careers of professional performing musicians and entrepreneurial education in Latin America are lacking to a great extent, especially in comparison with the European context. We explain this in terms of the "forced" self-management embraced by musicians in Latin American countries who want to engage with music practice both before and during the COVID-19 pandemic even if the music profession does not generate enough revenue for them.

Polygenic risk impacts PDGFRA mutation penetrance in non-syndromic cleft lip and palate.

Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common, severe craniofacial malformation that imposes significant medical, psychosocial and financial burdens. NSCL/P is a multifactorial disorder with genetic and environmental factors playing etiologic roles. Currently, only 25% of the genetic variation underlying NSCL/P has been identified by linkage, candidate gene and genome-wide association studies. In this study, whole-genome sequencing and genome-wide genotyping followed by polygenic risk score (PRS) and linkage analyses were used to identify the genetic etiology of NSCL/P in a large three-generation family. We identified a rare missense variant in PDGFRA (c.C2740T; p.R914W) as potentially etiologic in a gene-based association test using pVAAST (P = 1.78 × 10-4) and showed decreased penetrance. PRS analysis suggested that variant penetrance was likely modified by common NSCL/P risk variants, with lower scores found among unaffected carriers. Linkage analysis provided additional support for PRS-modified penetrance, with a 7.4-fold increase in likelihood after conditioning on PRS. Functional characterization experiments showed that the putatively causal variant was null for signaling activity in vitro; further, perturbation of pdgfra in zebrafish embryos resulted in unilateral orofacial clefting. Our findings show that a rare PDGFRA variant, modified by additional common NSCL/P risk variants, have a profound effect on NSCL/P risk. These data provide compelling evidence for multifactorial inheritance long postulated to underlie NSCL/P and may explain some unusual familial patterns.

mRNA 5' ends targeted by cytoplasmic recapping cluster at CAGE tags and select transcripts are alternatively spliced.

Until cytoplasmic recapping was discovered, decapping was thought to irreversibly destine an mRNA to degradation. Contradicting this idea, we readily observe mRNAs targeted by cytoplasmic capping in uncapped, yet stable forms. 5' rapid amplification of cDNA ends (RACE) shows that nearly all uncapped ends correspond to capped analysis of gene expression tags and that the recapping of ZNF207 mRNA may be restricted to a single splice isoform. Here, a modified RACE approach detected uncapped 5' RNA ends mapping to 46 mRNAs in cells expressing a dominant negative cytoplasmic capping enzyme and in normal cells. Eleven of 46 cloned mRNAs also contained splice isoform-limiting sequences. Collectively, these data reinforce earlier work and suggest that alternative splicing may play a role in targeting transcripts for - and/or determining the position of - cytoplasmic capping.