Biology subjects

Davis, A. A.

Publications and source records attributed to Davis, A. A..

3 recordsLinked to original sources

bioRxiv2021

VCP protects neurons from proteopathic seeding

Uptake and spread of proteopathic seeds, such as S, Tau, and TDP-43, contribute to neurodegeneration. The cellular machinery necessary for this process is poorly understood. Using a genome-wide CRISPR-Cas9 screen, we identified Valosin Containing Protein (VCP) as a suppressor of S seeding. Dominant mutations in VCP cause multisystem proteinopathy (MSP) with muscle and neuronal degeneration. VCP inhibition or disease mutations increase S seeding in cells and neurons. This is not associated with an increase in seed uptake and is similar to treatment with the lysosomal damaging agent, LLoME. Intrastriatal injection of S seeds into VCP disease mice enhances seeding efficiency compared with controls. This is not specific to S since VCP inhibition or disease mutations increased TDP-43 seeding in neurons. These data support that VCP protects against proteopathic spread of pathogenic aggregates. The spread of distinct aggregate species may dictate pleiotropic phenotypes and pathologies in VCP associated MSP.

neuroscience↗

bioRxiv2021

Lack of Host Reproductive Trade-offs Associated with Fecundity Compensation Response to Parasitic Castration

Host-parasite coevolution may result in life-history changes in hosts that can limit the detrimental effects of parasitism. Fecundity compensation is one such life-history response, occurring when hosts increase their current reproductive output to make up for expected losses in future reproduction due to parasitic infection. However, the potential trade-offs between quantity and quality of offspring produced during fecundity compensation are relatively unexplored. This study uses the trematode, Schistosoma mansoni, and its snail intermediate host, Biomphalaria glabrata, to better understand the impacts of this host life-history response. Measures of host reproductive output as well as offspring hatching success and survival were collected to assess the reproductive consequences of infection. Infected snails exhibited fecundity compensation (increase in the number of eggs laid compared to controls) and had a higher probability of laying any eggs at all. Infection status did not play a significant role in hatching or offspring survival to maturity. However, the age of the parental snail had a significant impact on hatching success, as offspring from older parents demonstrated a higher hatching success rate. Overall, the lack of an apparent trade-off between quantity and quality of offspring suggests that infected parental snails invest more resources towards reproduction in order to maintain the fitness of their offspring, possibly at the expense of their own longevity.

evolutionary biology↗

bioRxiv2019

Overlapping Genetic Architecture between Parkinson Disease and Melanoma

Epidemiologic studies have reported inconsistent results regarding an association between Parkinson disease (PD) and cutaneous melanoma (melanoma). Identifying shared genetic architecture between these diseases can support epidemiologic findings and identify common risk genes and biological pathways. Here we apply polygenic, linkage disequilibrium-informed methods to the largest available case-control, genome-wide association study summary statistic data for melanoma and PD. We identify positive and significant genetic correlation (correlation: 0.17, 95% CI 0.10 to 0.24; P = 4.09 x 10-06) between melanoma and PD. We further demonstrate melanoma and PD-inferred gene expression to overlap across tissues (correlation: 0.14, 95% CI 0.06 to 0.22; P = 7.87 x 10-04), and highlight seven genes including PIEZO1, TRAPPC2L, and SOX6 as potential mediators of the genetic correlation between melanoma and PD. These findings demonstrate specific, shared genetic architecture between PD and melanoma that manifests at the level of gene expression.

genetics↗