Biology subjects

Johnson, P. D.

Publications and source records attributed to Johnson, P. D..

3 recordsLinked to original sources

bioRxiv2021

A novel imaging ligand as a biomarker for mutant huntingtin-lowering in Huntington's disease

Huntingtons disease (HD) is a dominantly inherited neurodegenerative disorder caused by a CAG trinucleotide expansion in the huntingtin (HTT) gene that encodes the pathologic mutant HTT (mHTT) protein with an expanded polyglutamine (PolyQ) tract. While several therapeutic programs targeting mHTT expression have advanced to clinical evaluation, no method is currently available to visualize mHTT levels in the living brain. Here we demonstrate the development of a positron emission tomography (PET) imaging radioligand with high affinity and selectivity for mHTT aggregates. This small molecule radiolabeled with 11C ([11C]CHDI-180R) enables non-invasive monitoring of mHTT pathology in the brain and can track region-and time-dependent suppression of mHTT in response to therapeutic interventions targeting mHTT expression. We further show that therapeutic agents that lower mHTT in the striatum have a functional restorative effect that can be measured by preservation of striatal imaging markers, enabling a translational path to assess the functional effect of mHTT lowering.

neuroscience↗

bioRxiv2020

Range reduction of the Oblong Rocksnail, Leptoxis compacta, shapes riverscape genetic patterns

Many freshwater gastropod species face extinction, including 79% of species in the family Pleuroceridae. The Oblong Rocksnail, Leptoxis compacta, is a narrow range endemic pleurocerid from the Cahaba River basin in central Alabama that has seen rapid range contraction in the last 100 years. Such a decline is expected to negatively affect genetic diversity in the species. However, precise patterns of genetic variation and gene flow across the restricted range of L. compacta are unknown. This lack of information limits our understanding of human impacts on the Cahaba River system and Pleuroceridae. Here, we show that L. compacta has likely seen a species-wide decline in genetic diversity, but remaining populations have relatively high genetic diversity. We also report a contemporary range extension compared to the last published survey. Leptoxis compacta does not display an isolation by distance pattern, contrasting patterns seen in many riverine taxa. Our findings also indicate that historical range contraction has resulted in the absence of common genetic patterns seen in many riverine taxa like isolation by distance as the small distribution of L. compacta allows for relatively unrestricted gene flow across its remaining range despite limited dispersal abilities. Two collection sites had higher genetic diversity than others, and broodstock sites for future captive propagation and reintroduction efforts should utilize sites identified here as having the highest genetic diversity. Broadly, our results support the hypothesis that range contraction will result in the reduction of species-wide genetic diversity, and common riverscape genetic patterns cannot be assumed to be present in species facing extinction risk.

zoology↗

bioRxiv2020

Conservation genomics reveals low genetic diversity and multiple parentage in the threatened freshwater mussel, Margaritifera hembeli

Margaritifera hembeli is a federally threatened freshwater mussel species restricted to three central Louisiana drainages. Currently, management efforts are being formulated without an understanding of population-level genetic patterns, which could result in sub-optimal conservation outcomes. In particular, information about riverscape genetic patterns is needed to design effective propagation and reintroduction plans. We apply a genomic approach (RADseq) to assess genetic diversity and structure among four wild populations sampled from across the species range. We also assess the genetic diversity of a captively reared cohort produced from a single female. We recovered population differentiation between individuals sampled to the north and south of the Red River. All sites had similarly low levels of heterogeneity and other measures of genetic diversity. The captive cohort displayed higher levels of genetic diversity than expected and likely represents a case of multiple paternity. Future propagation efforts will likely be able to produce genetically diverse cohorts from a small number of wild-caught females, and we recommend future reintroduction efforts utilize brooders within the sub-drainage closest to the reintroduction effort.

genomics↗