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Biology subjects

Hillhouse, A.

Publications and source records attributed to Hillhouse, A..

3 recordsLinked to original sources

Bloodmeal metabarcoding of the argasid tick (Ornithodoros turicata Duges) reveals extensive vector-host associations

Molecular methods to understand host feeding patterns of arthropod vectors are critical to assess exposure risk to vector-borne disease and unveil complex ecological interactions. We build on our prior work discovering the utility of PCR-Sanger sequencing bloodmeal analysis that work remarkably well for soft ticks (Acari: Argasidae), unlike for hard ticks (Acari: Ixodidae), thanks to their unique physiology that retains vertebrate DNA from prior bloodmeals viable for years. Here, we capitalize on this feature and apply bloodmeal metabarcoding using amplicon deep sequencing to identify multiple host species in individual Ornithodoros turicata soft ticks collected from two natural areas in Texas, United States. Of 788 collected O. turicata, 394 were evaluated for bloodmeal source via metabarcoding, revealing 27 different vertebrate host species (17 mammals, 5 birds, 1 reptile, and 4 amphibians) fed upon by 274 soft ticks. Information on multiple hosts for individual O. turicata was derived from 168 of these (61%). Metabarcoding revealed more mixed vertebrate bloodmeals in O. turicata previously processed using Sanger sequencing. These data reveal wide host range of O. turicata and demonstrate the value of bloodmeal metabarcoding for understanding the ecology for known and potential tick-borne pathogens circulating among humans, domestic animals and wildlife such as relapsing fever caused by Borrelia turicatae. Our results also document, for the first time an off-host soft tick collected to have evidence of prior feeding on wild pig which is a critical observation in the context of the threat of enzootic transmission of African swine fever virus if it were introduced to the US. This research enhances our understanding of vector-host associations and offers a promising perspective for biodiversity monitoring and disease control strategies.

ecology↗

Development of an ASO therapy for Angelman syndrome by targeting an evolutionarily conserved region at the start of the UBE3A-AS transcript

Angelman syndrome is a devastating neurogenetic disorder for which there is currently no effective treatment. It is caused by mutations or epimutations affecting the expression or function of the maternally inherited allele of the ubiquitin-protein ligase E3A (UBE3A) gene. The paternal UBE3A allele is imprinted in neurons of the central nervous system (CNS) by the UBE3A antisense (UBE3A-AS) transcript, which represents the distal end of the SNHG14 transcription unit. Reactivating the expression of the paternal UBE3A allele in the CNS has long been pursued as a therapeutic option for Angelman syndrome. Here, we designed and optimized antisense oligonucleotides (ASO) targeting an evolutionarily conserved region demarcating the start of the human UBE3A-AS transcript and show that ASOs targeting this region can reverse imprinting of UBE3A in cultured Angelman syndrome neurons and throughout the CNS of a non-human primate model. Findings from this study advanced the first investigational molecular therapy for Angelman syndrome into clinical development (ClinicalTrials.gov, NCT04259281). SUMMARYHere, we describe the preclinical studies supporting the first investigational molecular therapy for Angelman syndrome to advance into clinical development (ClinicalTrials.gov, NCT04259281).

genetics↗

Rapid genomic expansion and purging associated with habitat transitions in a clade of beach crustaceans (Haustoriidae: Amphipoda)

Genome sizes vary by orders of magnitude across the Tree of Life and lack any correlation with organismal complexity. Some crustacean orders, such as amphipods, have genome sizes that correlate with body size, temperature, and water depth, indicating that natural selection may constrain genome sizes due to physiological pressures. In this study, we examine the relationship between genome size, repetitive content, and environmental variables on a clade of sand-burrowing amphipods (Haustoriidae) that are distributed across the Gulf of Mexico and the North Atlantic. We uncover a 6-fold genome size variation within a clade that is less than 7 million years old. Unlike previous studies, we find no correlation between genome size and latitude, but do uncover a significant relationship between genome size and body length. Further, we find that the proportion of repetitive content predicts genome size, and that the largest genomes appear to be driven by expansions of LINE elements. Finally, we find evidence of genomic purging and body size reduction in two lineages that have independently colonized warm brackish waters, possibly indicating a strong physiological constraint of transitioning from surf-swept beaches to protected bays. Significance StatementThe evolution of genome size has been a long-standing puzzle in biology. In this work, we find that genome sizes may be driven by different selection regimes following shifts to a new habitat. Dramatic genome size changes can occur rapidly, in only a few million years. Data Availability StatementRaw data sheets have been deposited on Dryad: SUBMITTED. Raw sequence reads are available at from NCBI under Bioproject SUBMITTED.

evolutionary biology↗