73 research outputs found

    Functional analysis of germline <em>VANGL2</em> variants using rescue assays of <em>vangl2</em> knockout zebrafish

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    \ua9 The Author(s) 2023. Published by Oxford University Press. Developmental studies have shown that the evolutionarily conserved Wnt Planar Cell Polarity (PCP) pathway is essential for the development of a diverse range of tissues and organs including the brain, spinal cord, heart and sensory organs, as well as establishment of the left-right body axis. Germline mutations in the highly conserved PCP gene VANGL2 in humans have only been associated with central nervous system malformations, and functional testing to understand variant impact has not been performed. Here we report three new families with missense variants in VANGL2 associated with heterotaxy and congenital heart disease p.(Arg169His), non-syndromic hearing loss p.(Glu465Ala) and congenital heart disease with brain defects p.(Arg135Trp). To test the in vivo impact of these and previously described variants, we have established clinically-relevant assays using mRNA rescue of the vangl2 mutant zebrafish. We show that all variants disrupt Vangl2 function, although to different extents and depending on the developmental process. We also begin to identify that different VANGL2 missense variants may be haploinsufficient and discuss evidence in support of pathogenicity. Together, this study demonstrates that zebrafish present a suitable pipeline to investigate variants of unknown significance and suggests new avenues for investigation of the different developmental contexts of VANGL2 function that are clinically meaningful

    Exploring intersectionality issues in entrepreneurial finance: Policy responses and future research directions

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    Main Message Entrepreneurial finance scholars (and policy-makers) need to adopt an intersectional approach to their analysis (and policy-making) and pay more attention to the interplay between the owner-manager characteristics of ethnicity/race, gender, and social class. Shorter Title of the manuscript Exploring intersectionality issues in entrepreneurial finance Key points Since most literature on entrepreneurial finance treats ethnicity/race, gender, and class separately, an intersectional approach to analysis is complex, whether social (race, gender, social class) or situational characteristics (entrepreneur versus migrant/social or health care worker). Women, ethnic minorities, and working-class people are disadvantaged when seeking finance. We integrate the literature and proposes intersectionality as a framework for policy-makers, since the interplay between these characteristics can be addressed to develop innovative methods of finance

    Closure and the Book of Virgil

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    Gender gaps and reentry into entrepreneurial ecosystems after business failure

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    Despite the significant role played by serial entrepreneurs in the entrepreneurial process, we know little about group differences in reentry decisions after business failure. Using an ecosystems framework and stigma theory, we investigate the variance in gender gaps related to the reentry decisions of 8,171 entrepreneurs from 35 countries who experienced business failures. We find evidence of persisting gender gaps that vary across ecosystem framework conditions of public stigma of business failure and public fear of business failure. Our findings shed new light on ecosystem inefficiencies that arise from multiple interactions between entrepreneurs and institutions
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