The power and scope of disease modeling can be markedly enhanced through the incorporation of broad genetic diversity. The introduction of pathogenic mutations into a single inbred mouse strain sometimes fails to mimic human disease. We describe a cross-species precision disease modeling platform that exploits mouse genetic diversity to bridge cell-based modeling with whole organism analysis. We developed a universal protocol that permitted robust and reproducible neural differentiation of genetically diverse human and mouse pluripotent stem cell lines and then carried out a proof-of-concept study of the neurodevelopmental gene
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DYRK1A . Results in vitro reliably predicted the effects of genetic background onDyrk1a loss-of-function phenotypes in vivo. Transcriptomic comparison of responsive and unresponsive strains identified molecular pathways conferring sensitivity or resilience toDyrk1a1A loss and highlighted differential messenger RNA isoform usage as an important determinant of response. This cross-species strategy provides a powerful tool in the functional analysis of candidate disease variants identified through human genetic studies.Free, publicly-accessible full text available April 5, 2025 -
Abstract Plant collections held by botanic gardens and arboreta are key components of ex situ conservation. Maintaining genetic diversity in such collections allows them to be used as resources for supplementing wild populations. However, most recommended minimum sample sizes for sufficient ex situ genetic diversity are based on microsatellite markers, and it remains unknown whether these sample sizes remain valid in light of more recently developed next‐generation sequencing (NGS) approaches. To address this knowledge gap, we examine how ex situ conservation status and sampling recommendations differ when derived from microsatellites and single nucleotide polymorphisms (SNPs) in garden and wild samples of two threatened oak species. For
Quercus acerifolia , SNPs show lower ex situ representation of wild allelic diversity and slightly lower minimum sample size estimates than microsatellites, while results for each marker are largely similar forQ. boyntonii . The application of missing data filters tends to lead to higher ex situ representation, while the impact of different SNP calling approaches is dependent on the species being analyzed. Measures of population differentiation within species are broadly similar between markers, but larger numbers of SNP loci allow for greater resolution of population structure and clearer assignment of ex situ individuals to wild source populations. Our results offer guidance for future ex situ conservation assessments utilizing SNP data, such as the application of missing data filters and the usage of a reference genome, and illustrate that both microsatellites and SNPs remain viable options for botanic gardens and arboreta seeking to ensure the genetic diversity of their collections. -
The impact of relative humidity (RH) on organic new particle formation (NPF) from ozonolysis of monoterpenes remains an area of active debate. Previous reports provide contradictory results indicating both depression and enhancement of NPF under conditions of moderate RH, while others do not indicate a potential impact. Only several reports have suggested that the effect may depend on absolute mixing ratio of the precursor volatile organic compound (VOC, ppbv). Herein we report on the impact of RH on NPF from dark ozonolysis of α- and β-pinene at mixing ratios ranging from 0.2 to 80 ppbv. We show that RH enhances NPF (by a factor of eight) at the lowest α-pinene mixing ratio, with a very strong dependence on α-pinene mixing ratio from 4 to 22 ppbv. At higher mixing ratios, the effect of RH plateaus, with resulting modest decreases in NPF. In the case of α- and β-pinene, NPF is enhanced at low mixing ratios due to a combination of chemistry, accelerated kinetics, and reduced partitioning of semi-volatile oxidation products to the particulate phase. Reduced partitioning would limit particle growth, permitting increased gas-phase concentrations of semi- and low-volatility products, which could favor NPF.more » « less
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This preliminary study explored how many representations of standard videos, animations/comics, and 360 videos are being used in mathematics methods courses to teach future teachers. Drawing on knowledge from prior studies on standard videos, this study aimed to address the gaps in literature to encompass other representations that are being utilized and obtained. Analyses show that standard videos are the primary medium being used to teach future teachers in math methods, followed by animations/comics, and then 360 videos. Findings suggest that teacher educators are more likely to use a medium that they are more familiar with than a medium with greater perceived usefulness. Further, findings indicate that teacher educators perceived usefulness and frequency of use as not related to their level of familiarity with all representation types, suggesting more factors are at play.more » « less