Biology subjects

Compton, A.

Publications and source records attributed to Compton, A..

6 recordsLinked to original sources

bioRxiv2026

Temporal synchrony between human odor rhythms and mosquito olfactory preference shapes host attraction

For anthropophilic mosquitoes such as Aedes aegypti, aligning host-seeking with human availability enhances foraging efficiency and reproductive success. Although time of day modulates mosquito activity and olfactory sensitivity, it remains unknown whether human hosts display rhythmic changes in odor cues and whether mosquitoes adjust their sensory responses accordingly. Here, we combine chemical, behavioral, genetic, and transcriptomic approaches to reveal that both mosquitoes and their human hosts in this interaction are temporally synchronized. Gas chromatography-mass spectrometry showed systematic daily shifts in human body odor composition between morning and evening. Correspondingly, mosquitoes prefer host odors that match their own active phase--a time-specific preference abolished in timeless mutants and under constant darkness. Silencing the timeless gene further induced an aversion for the host scent under light-dark conditions. Transcriptomic analysis of mosquito heads and antennae uncovered rhythmic expression of sensory and neuromodulatory genes, driven by both circadian and light-dark cycles and which peaks during mosquitoes active periods, with rhythmic co-expression networks collapsing in timeless knockouts. Together, these results show that mosquito attraction to humans is temporally tuned by the interplay of host odor rhythms and mosquito sensory rhythms, revealing a previously unrecognized form of interspecific temporal synchronization in vector-host interactions.

animal behavior and cognition↗

bioRxiv2025

Atrophin-1 Antisense Oligonucleotide Provides Robust Protection from Pathology in a Fully Humanized DRPLA Model

Dentatorubral-pallidoluysian atrophy (DRPLA) is a fatal neurodegenerative disease arising from a CAG repeat expansion in the atrophin-1 (ATN1) gene. Because DRPLA, like many repeat expansion disorders (REDs), arises predominantly from toxic gain-of-function mechanisms, we hypothesized that ATN1 knockdown would have therapeutic potential. To test this, we established the first fully-humanized mouse model of a RED, in which one allele of mouse Atn1 is completely replaced by human ATN1, including 112 pure CAG repeats. This novel approach to exploring RED biology provides significant advantages, notably the ability to test sequence-specific therapeutics targeting human sequences, even in introns and untranslated regions of pre-mRNA. We found that our model--the Atn1Q112/+ mouse--recapitulates key features of human DRPLA, including behavioral alterations, reduced brain size and aggregate accumulation. We treated Atn1Q112/+ mice with antisense oligonucleotides (ASOs) targeting mouse Atn1 (to probe for loss of function concerns), human ATN1, or a combination. Treatment with human, but not mouse, ATN1-targeting ASOs provides remarkable protection from a range of disease-related behavioral phenotypes, including aggregation of mutant ATN1 (mATN1), and marked rescue of transcriptional dysregulation in the cerebellum. These results have helped motivate an ongoing human clinical study of ASOs targeting ATN1 for DRPLA.

neuroscience↗

bioRxiv2023

Omicron Spike confers enhanced infectivity and interferon resistance to SARS-CoV-2 in human nasal tissue

Omicron emerged following COVID-19 vaccination campaigns, displaced previous SARS-CoV-2 variants of concern worldwide, and gave rise to lineages that continue to spread. Here, we show that Omicron exhibits increased infectivity in primary adult upper airway tissue relative to Delta. Using recombinant forms of SARS-CoV-2 and nasal epithelial cells cultured at the liquid-air interface, enhanced infectivity maps to the step of cellular entry and evolved recently through mutations unique to Omicron Spike. Unlike earlier variants of SARS-CoV-2, Omicron enters nasal cells independently of serine transmembrane proteases and instead relies upon metalloproteinases to catalyze membrane fusion. This entry pathway unlocked by Omicron Spike enables evasion of constitutive and interferon-induced antiviral factors that restrict SARS-CoV-2 entry following attachment. Therefore, the increased transmissibility exhibited by Omicron in humans may be attributed not only to its evasion of vaccine-elicited adaptive immunity, but also to its superior invasion of nasal epithelia and resistance to the cell-intrinsic barriers present therein.

microbiology↗

bioRxiv2022

Stimulus Whitening Improves the Efficiency of Reverse Correlation

Human perception depends upon internal representations of the environment that help to organize the raw information available from the senses by acting as reference patterns. Internal representations are widely characterized using reverse correlation, a method capable of producing unconstrained estimates of the representation itself, all on the basis of simple responses to random stimuli. Despite its advantages, reverse correlation is often infeasible to apply because the number of stimulus-response trials needed to provide an accurate estimate is typically very large. Prior approaches have aimed to overcome this sampling inefficiency by incorporating prior knowledge of the representation, which biases the estimate and ultimately limits the essential power of reverse correlation. The present approach, however, improves efficiency via stimulus whitening, a statistical procedure that decorrelates stimuli, making them less redundant, and commensurately more favorable for efficient estimation of an arbitrary target. We provide a mathematical justification for whitening, and demonstrate in simulation that whitening provides greater than 85% improvement in efficiency for a given estimation accuracy, and also a two- to five-fold increase in accuracy for a given sample size. Improving the efficiency of reverse correlation may enable a broader scope of investigations into individual variability and potential universality of perceptual mechanisms.

neuroscience↗

bioRxiv2021

Marker-assisted mapping enables effective forward genetic analysis in the arboviral vector Aedes aegypti, a species with vast recombination deserts

Aedes aegypti is a major vector of arboviruses that cause dengue, chikungunya, yellow fever and Zika. Although recent success in reverse genetics has facilitated rapid progress in basic and applied research, integration of forward genetics with modern technologies remains challenging in this important species, as up-to-47% of its chromosome is refractory to genetic mapping due to extremely low rate of recombination. Here we report the development of a marker-assisted-mapping (MAM) strategy to readily screen for and genotype only the rare but informative recombinants, drastically increasing both the resolution and signal-to-noise ratio. Using MAM, we mapped a transgene that was inserted in a >100 Mb recombination desert and a sex-linked spontaneous red-eye (re) mutation just outside the region. We subsequently determined, by CRISPR/Cas9-mediated knockout, that cardinal is the causal gene of re, which is the first forward genetic identification of a causal gene in Ae. aegypti. This study provides the molecular foundation for using gene-editing to develop versatile and stable genetic sexing methods by improving upon the current re-based genetic sexing strains. MAM does not require densely populated markers and can be readily applied throughout the genome to facilitate the mapping of genes responsible for insecticide- and viral-resistance. By enabling effective forward genetic analysis, MAM bridges a significant gap in establishing Ae. aegypti as a model system for research in vector biology. As large regions of suppressed recombination are also common in other plant and animal species including those of economic significance, MAM will have broad applications beyond vector biology.

genetics↗

bioRxiv2020

The beginning of the end: a chromosomal assembly of the New World malaria mosquito ends with a novel telomere

Chromosome level assemblies are accumulating in various taxonomic groups including mosquitoes. However, even in the few reference-quality mosquito assemblies, a significant portion of the heterochromatic regions including telomeres remain unresolved. Here we produce a de novo assembly of the New World malaria mosquito, Anopheles albimanus by integrating Oxford Nanopore sequencing, Illumina, Hi-C and optical mapping. This 172.6 Mbps female assembly, which we call AalbS3, is obtained by scaffolding polished large contigs (contig N50=13.7 Mbps) into three chromosomes. All chromosome arms end with telomeric repeats, which is the first in mosquito assemblies and represents a significant step towards the completion of a genome assembly. These telomeres consist of tandem repeats of a novel 30-32 bp telomeric repeat unit (TRU) and are confirmed by analysing the termini of long reads and through both chromosomal in situ hybridization and a Bal31 sensitivity assay. The AalbS3 assembly included previously uncharacterized centromeric and rDNA clusters and more than doubled the content of transposable elements and other repetitive sequences. This telomere-to-telomere assembly, although still containing gaps, represents a significant step towards resolving biologically important but previously hidden genomic components. The comparison of different scaffolding methods will also inform future efforts to obtain reference-quality genomes for other mosquito species. 100-word Article SummaryWe report AalbS3, a telomere-to-telomere assembly of the Anopheles albimanus genome produced by integrating advancing technologies including Oxford Nanopore and Bionano optical mapping. AalbS3 features much of the difficult-to-assemble genomic dark matters including previously missed transposons, centromeres and rDNA clusters. We describe novel telomeric repeats that are confirmed by analysis of long reads and by telomere hybridization assays. This reference-quality assembly represents a significant step towards completing the genomic puzzle pieces and informs efforts to improve the assembly of other mosquito species. Future research into the relationship between telomere and mosquito life span may have significant implications to disease control.

genomics↗