Biology subjects

Townsend, J.

Publications and source records attributed to Townsend, J..

14 recordsLinked to original sources

bioRxiv2026

Individualized brain-body signatures of positive emotions revealed by large-scale multimodal neurophysiological recording

Using one of the most comprehensive multimodal biosensing datasets in affective research, densely sampled within individuals, we asked how emotions are instantiated in each person's brain and body. Four participants viewed 168 emotion-evoking videos during 128-channel EEG and 28 autonomic, ocular and facial recordings. Cross-validated elastic-net classifiers distinguished each of 15 positive and neutral emotions from baseline in every participant (mean accuracy 87-97%). We found that no emotion was predicted by a single marker and each reflected a multimodal ensemble of cortical and autonomic activity whose composition was largely person-specific. Yet physiology-derived groupings converged selectively with self-report; Interest-Awe-Amusement-Satisfaction and Entrancement-Aesthetic Appreciation recurred across individuals based on physiology. Across emotion groups, frontal and posterior delta, posterior alpha and electrodermal activity formed a shared backbone, plausibly reflecting affective and sensory engagement, whereas cardiovascular and facial signals varied between people. This framework yields individualized, objective neurophysiological indicators of emotion, potentially aiding personalized diagnosis.

neuroscience↗

bioRxiv2026

Complete mitochondrial genomes of Arizona West Nile virus vectors, Culex quinquefasciatus and Culex tarsalis

Here we report a newly developed method utilizing long-range PCR and long-read Pacific Biosciences HiFi sequencing that successfully obtained two full-length and annotated mitochondrial genomes from Culex quinquefasciatus Say, 1823 and Culex tarsalis Coquillett, 1896, both from Maricopa County, Arizona, USA. Given the substantial burden of West Nile virus in Maricopa County over the past decade, and that these vectors are primarily responsible for spillover to human populations in the county, it is critical to better understand their distribution over time and space. This study begins to approach this need by contributing a novel approach that has resulted in the first West Nile virus vector mitochondrial genomes from Arizona. Our circular Cx. quinquefasciatus mitogenome is 15,587 bp in length, making it the first USA-based mitogenome sequenced through the AT-rich control region. The Cx. tarsalis mitochondrial genome is 16,416 bp long, longer than recently published California-based CTarK1 and Texas-based PQ585801 mitogenomes. The increased length of the Cx. tarsalis mitogenome is a result of a 905 bp insertion in the AT-rich control region, not present in the species publicly available mitogenomes. A maximum likelihood-based phylogenetic reconstruction supports the species designation of these newly-sequenced mitogenomes. The newly developed methodology offers a unique approach to study medically-important vector species around the globe, providing a solution to study populations through pooled vector pathogen surveillance programs.

genomics↗

bioRxiv2026

Temporal Variation in Mosquito Vector Population Dynamics in Urban Areas

Locally acquired arboviral infections are an increasing public health concern in the United States. Aedes aegypti and Culex quinquefasciatus, vectors of dengue virus and West Nile virus, respectively, are established in regions where local transmission has been reported. Seasonal variation in mosquito abundance affects vector density, human-vector contact, and arbovirus transmission risk. The aim of this study is to investigate seasonal variations in Ae. aegypti and Cx. quinquefasciatus population dynamics in Miami-Dade County, Florida; Maricopa County, Arizona; and Clark County, Nevada. Monthly relative abundance, average mosquitoes collected per trap-night, normalized abundance ratios, and seasonal-trend decomposition were used to evaluate species- and location-specific seasonal patterns. Mosquito population dynamics differed by species and location. In Miami-Dade County, the two species showed seasonal turnover, with Cx. quinquefasciatus peaking during winter and spring and Ae. aegypti peaking during summer. In Maricopa and Clark counties, both species peaked primarily between August and September. Species dominance also differed by site, with Ae. aegypti more abundant than Cx. quinquefasciatus in Maricopa County and Cx. quinquefasciatus more abundant than Ae. aegypti in Clark and Miami-Dade counties. Seasonal decomposition showed that Ae. aegypti peaked earlier in Miami-Dade County than in Maricopa and Clark counties, whereas Cx. quinquefasciatus showed a spring peak in Miami-Dade County and bimodal seasonal patterns in Maricopa and Clark counties. These results suggest that mosquito population dynamics are species- and location-specific and support the use of local surveillance data to guide the timing of mosquito control and arbovirus preparedness.

ecology↗

bioRxiv2026

Short-term forecasts of Aedes aegypti relative abundance to enhance mosquito control situational awareness

Conventional mosquito surveillance typically relies on contemporaneous data, making it challenging to anticipate future vector surges. To support proactive vector management, this study evaluates a multi-model forecasting framework designed to generate probabilistic 1-to 4-week-ahead forecasts of Aedes aegypti relative abundance per trap night. The framework was validated using multi-year surveillance data across four US jurisdictions spanning varied environments (from subtropical to temperate and arid). We found that an ensemble approach aggregating statistical and machine learning models generally achieved the best performance across all locations and forecast horizons. Relative forecast performance improved as the forecast horizon extended from 1 to 4 weeks ahead. The most challenging data to forecast were primarily restricted to low mosquito activity periods or atypical population peaks with unusual timing or magnitude. While full integration into routine vector management workflows represents a long-term process requiring operational adaptation, this work advances forecasting research and establishes a baseline for translating these approaches into real-time applications for public health authorities, with downstream effects in mitigating the risks of mosquito-borne diseases.

ecology↗

bioRxiv2026

Stepwise Evolution and Epistatic Interaction of Driver Mutations from Endometrial Hyperplasia to Carcinoma

To characterize early oncogenesis, pathologically identified pre-cancerous tissue can be analyzed for the presence of cancer drivers. Here, we argue that in such studies, analyses of the driver status of variants, of the association between step-specific prevalence and progression through tumorigenesis, and of driver co-occurrence and mutual exclusivity should be accompanied by estimates of inherent mutation rate of variants and presented within an evolutionary framework of selective epistasis. To illustrate this point, we examine the transition of endometrial tissue from atypical hyperplasia to carcinoma. We apply a step-specific analysis, demonstrating that the strength of selection on somatic driver mutations promoting cell division and survival differs between hyperplasia to carcinoma. We demonstrate that mutations of PTEN, which are highly prevalent in carcinomas and have been argued to exert substantial driver effects, exhibit an even larger effect of increasing cellular division and survival within developing hyperplasias. A determination of cooccurrence or mutual exclusivity may be a product of genes sharing or differing in underlying sources of mutation, as opposed to a product of biological interaction and selection. By accounting for tumor-specific mutational processes that influence co-occurrence, we calculate epistatic selective intensities between pairs of drivers. Mutations of KRAS and FGFR2 are often mutually exclusive and were indeed found to exhibit significant antagonistic selective epistasis. However, mutations of PIK3CA and PIK3R1, which also have been identified as showing mutual exclusivity, do not demonstrate significant antagonistic selective epistasis. Thus, evidence of mutually exclusivity is insufficient to determine epistasis. Accordingly, the application of quantitative approaches that distinctly analyze mutation and selection on cancer variants has the potential to substantially illuminate the trajectory of tumorigenesis and cancer progression.

Cancer Biology↗

bioRxiv2025

Host usage in Aedes aegypti collected from Houston, Texas and Phoenix, Arizona using whole mosquito third-generation sequencing blood meal analysis

Aedes aegypti is the primary vector of several viruses of international public health concern, including Zika, dengue, yellow fever, and chikungunya. Their synanthropic ecology and establishment in tropical, sub-tropical, and temperate areas make Ae. aegypti one of the most medically relevant mosquito species. While they have been reported to be highly anthropophilic, several studies indicate a broader host range. They are also reported to take multiple blood meals between gonotrophic cycles. Consumption of multiple blood meals makes determination of host usage difficult when using common blood meal analysis methods. In this study, we examined host usage of Ae. aegypti in Harris County, Texas (Houston), and Maricopa County, Arizona (Phoenix), using a Nanopore-based third-generation sequencing protocol to successfully resolve host usage multiplicity and identify a broad range of host usage. Using this method, approximately 80% of samples from each location with evidence of blood feeding resulted in a blood meal species identification, with a single host blood meal in about 80% of samples and approximately 20% containing evidence of multiple blood meals. Overall, we observed a wide host range with human DNA the most prevalent followed by feline and canine. We also identified avian, rodent, ungulate and even ectotherm usage by Ae. aegypti from Maricopa County. The discovery of hosts other than humans expands the understanding of host usage dynamics in Ae. aegypti and their involvement in arbovirus transmission systems in highly urbanized areas such as Harris and Maricopa Counties. SynopsisThe yellow fever mosquito, Aedes aegypti, is a vector of several viral pathogens that frequently cause human disease in tropical and subtropical locations but many of these pathogens are not controlled by vaccination. As such, control of this mosquito is critical to reduce disease transmission and better understanding of the ecology of this species helps to improve the efficacy of operational control. In this study, researchers used a deep sequencing method to define patterns of host usage in two large US metropolitan areas, Houston, TX and Phoenix, AZ, with substantial Ae. aegypti infestations. Results identified frequent multiple blood feeding by individual mosquitoes and that the primary host sources were humans and their pets. Results from Phoenix indicated a broad host usage, including feeding on livestock, birds, and even reptiles. This may provide useful information about Ae. aegypti resting sites and could be used to improve treatment by operational personnel.

ecology↗

bioRxiv2022

Spatiotemporal Distribution of Vector Mosquito Species in Maricopa County, Arizona: The highest West Nile virus disease incidence area in the United States in 2021

Mosquito-borne diseases are a major global public health concern and mosquito surveillance systems are essential for the implementation of effective mosquito control strategies. The objective of our study is to determine the spatiotemporal distribution of vector mosquito species in Maricopa County, AZ from 2011 to 2021, and to identify the hotspot areas for West Nile virus (WNV) and St. Louis Encephalitis virus (SLEV) transmission in 2021. The Maricopa County Mosquito Control surveillance system utilizes BG-Sentinel and EVS-CDC traps throughout the entire urban and suburban areas of the county. We estimated specific mosquito species relative abundance per unit area using the Kernel density estimator in ArcGIS 10.2. We calculated the distance between all traps in the surveillance system and created a 4 km buffer radius around each trap to calculate the extent to which each trap deviated from the mean number of Cx. quinquefasciatus and Cx. tarsalis collected in 2021. Our results show that vector mosquito species are widely distributed and abundant in the urban areas of Maricopa County. A total of 691,170 Culex quinquefasciatus, 542,733 Culex tarsalis, and 292,305 Aedes aegypti were collected from 2011 to 2022. The relative abundance of Ae. aegypti was highly seasonal peaking in the third and fourth quarters of the year. Culex quinquefasciatus, on the other hand, was abundant throughout the year with several regions consistently yielding high numbers of mosquitoes. Culex tarsalis was abundant but it only reached high numbers in well-defined areas bordering natural and rural areas. We also detected high levels of heterogeneity in the risk of WNV and SLEV transmission to humans disregarding traps geographical proximity. The well-defined species-specific spatiotemporal and geographical patterns found in this study can be used to inform vector control operations.

ecology↗

bioRxiv2022

Species Distribution Modeling of Aedes aegypti in Maricopa County, Arizona from 2014-2020

Aedes aegypti mosquitoes, which are of great importance to public health, have recently and rapidly expanded their global range; however, little is understood about the distribution of these mosquitoes in desert environments. Trapping records for Ae. aegypti in Maricopa County, Arizona from 2014-2020 were used to construct species distribution models using Maxent. Satellite imagery and socioeconomic factors were used as predictors. Maps of predicted habitat suitability were converted to binary presence/absence maps, and consensus maps were created that represent "core" habitat for the mosquito over six years of time. Generally, population density was the most important predictor in the models while median income was the least important. This study is the first step toward understanding the distribution of the vector in a desert environment. One-Sentence SummaryThis study uses satellite imagery and socioeconomic factors to identify core habitat over six years in a desert environment.

ecology↗

bioRxiv2021

In-phase and in-antiphase connectivity in EEG

Zero-lag synchrony is generally discarded from functional connectivity studies to eliminate the confounding effect of volume conduction. Demonstrating genuine and significant unlagged synchronization between distant brain regions would indicate that most electroencephalography (EEG) connectivity studies neglect an important mechanism for neuronal communication. We previously demonstrated that local field potentials recorded intracranially tend to synchronize with no lag between homotopic brain regions. This synchrony occurs most frequently in antiphase, potentially supporting corpus callosal inhibition and interhemispheric rivalry. We are now extending our investigation to EEG. By comparing the coherency in a recorded and a surrogate dataset, we confirm the presence of a significant proportion of genuine zero-lag synchrony unlikely to be due to volume conduction or to recording reference artifacts. These results stress the necessity for integrating zero-lag synchrony in our understanding of neural communication and for disentangling volume conduction and zero-lag synchrony when estimating EEG sources and their functional connectivity.

neuroscience↗

bioRxiv2021

Discovery of SARS-CoV-2 papain-like protease inhibitors through a combination of high-throughput screening and FlipGFP-based reporter assay

The papain-like protease (PLpro) of SARS-CoV-2 is a validated antiviral drug target. PLpro is involved in the cleavage of viral polyproteins and antagonizing host innate immune response through its deubiquitinating and deISG15ylating activities, rendering it a high profile antiviral drug target. Through a FRET-based high-throughput screening, several hits were identified as PLpro inhibitors with IC50 values at the single-digit micromolar range. Subsequent lead optimization led to potent inhibitors with IC50 values ranging from 0.56 to 0.90 {micro}M. To help prioritize lead compounds for the cellular antiviral assay against SARS-CoV-2, we developed the cell-based FlipGFP assay that is suitable for quantifying the intracellular enzymatic inhibition potency of PLpro inhibitors in the BSL-2 setting. Two compounds selected from the FlipGFP-PLpro assay, Jun9-53-2 and Jun9-72-2, inhibited SARS-CoV-2 replication in Caco-2 hACE2 cells with EC50 values of 8.89 and 8.32 {micro}M, respectively, which were 3-fold more potent than GRL0617 (EC50 = 25.1 {micro}M). The X-ray crystal structures of PLpro in complex with GRL0617 showed that binding of GRL0617 to SARS-CoV-2 induced a conformational change in the BL2 loop to the more closed conformation. Overall, the PLpro inhibitors identified in this study represent promising starting points for further development as SARS-CoV-2 antivirals, and FlipGFP-PLpro assay might be a suitable surrogate for screening PLpro inhibitors in the BSL-2 setting.

pharmacology and toxicology↗

bioRxiv2020

An expedited approach towards the rationale design of non-covalent SARS-CoV-2 main protease inhibitors with in vitro antiviral activity

The main protease (Mpro) of SARS-CoV-2 is a validated antiviral drug target. Several Mpro inhibitors have been reported with potent enzymatic inhibition and cellular antiviral activity, including GC376, boceprevir, calpain inhibitors II and XII, each containing a reactive warhead that covalently modifies the catalytic Cys145. In this study, we report an expedited drug discovery approach by coupling structure-based design and Ugi four-component (Ugi-4CR) reaction methodology to the design of non-covalent Mpro inhibitors. The most potent compound 23R had cellular antiviral activity similar to covalent inhibitors such as GC376. Our designs were guided by overlaying the structure of SARS-CoV Mpro + ML188 (R), a non-covalent inhibitor derived from Ug-4CR, with the X-ray crystal structures of SARS-CoV-2 Mpro + calpain inhibitor XII/GC376/UAWJ247. Binding site analysis suggests a strategy of extending the P2 and P3 substitutions in ML188 (R) to achieve optimal shape complementary with SARS-CoV-2 Mpro. Lead optimization led to the discovery of 23R, which inhibits SARS-CoV-2 Mpro and SARS-CoV-2 viral replication with an IC50 of 0.31 M and EC50 of 1.27 M, respectively. The binding and specificity of 23R to SARS-CoV-2 Mpro were confirmed in a thermal shift assay and native mass spectrometry assay. The co-crystal structure of SARS-CoV-2 Mpro with 23R revealed the P2 biphenyl fits snuggly into the S2 pocket and the benzyl group in the -methylbenzyl faces towards the core of the enzyme, occupying a previously unexplored binding site located in between the S2 and S4 pockets. Overall, this study revealed the most potent non-covalent SARS-CoV-2 Mpro inhibitors reported to date and a novel binding pocket that can be explored for Mpro inhibitor design.

pharmacology and toxicology↗

bioRxiv2020

Phylogenetic Analysis of St. Louis Encephalitis Virus within Two Southwestern United State Counties: a case for a bulk introduction event into the southwest United States

St. Louis Encephalitis Virus (SLEV) has been seasonally detected within the Culex spp. populations within Maricopa County, Arizona and Coachella Valley, California since an outbreak in Maricopa County in 2015. Previous work revealed that the outbreak was caused by an importation of SLEV genotype III, which had only been detected within Argentina in prior years. However, little is known about when the importation occurred or the population dynamics since its arrival into the southwestern United States. In this study, we wanted to determine if the annual detection of SLEV in Maricopa and Riverside counties is due to enzootic cycling or new importations. To address this question, we analyzed 143 SLEV genomes (138 sequenced as part of this study) using the Bayesian phylogenetic analysis software, BEAST, to estimate the date of arrival into the American Southwest and characterize the underlying population structure of SLEV. Phylogenetic clustering showed that SLEV variants circulating in Arizona and California form two distinct populations with little evidence of transmission among the two populations since the onset of the outbreak. Interestingly, the SLEV variants in Coachella Valley appear to be annually imported from a nearby source, whereas the Arizona population is locally sourced each year. Finally, the earliest representatives of SLEV genotype III in the southwestern US formed a polytomy that includes both California and Arizona samples. We propose that the initial outbreak could have resulted from an introductory population of SLEV, perhaps in one or more bird flocks migrating north in 2013, rather than a single variant introduced by one bird.

bioinformatics↗

bioRxiv2019

Comparison of BOLD and CBV using 3D EPI and 3D GRASE for cortical layer fMRI at 7T.

PurposeFunctional MRI (fMRI) at the mesoscale of cortical layers and columns requires both sensitivity and specificity, which can be compromised if the imaging method is affected by vascular artifacts, particularly cortical draining veins at the pial surface. Recent studies have shown that cerebral blood volume (CBV) imaging is more specific to the actual laminar locus of neural activity than BOLD imaging when using standard gradient-echo (GE) EPI sequences. Gradient and Spin Echo (GRASE) BOLD imaging has also shown greater specificity when compared with GE-BOLD.\n\nMethodsHere we directly compare CBV and BOLD contrasts in high-resolution imaging of the primary motor cortex for laminar fMRI in four combinations of signal labeling, VASO (CBV) and BOLD with 3D GE-EPI and zoomed 3D GRASE image readouts.\n\nResultsWe find that both CBV imaging using EPI-VASO and BOLD imaging using GRASE-BOLD, show similar specificity and sensitivity and are thus useful tools for mesoscopic fMRI in the human cortex.\n\nConclusionThese techniques demonstrate sufficient sensitivity and specificity to allow layer-fMRI to be used by neuroscientists in a wide range of investigations of depth-dependent neural circuitry in the human brain.

neuroscience↗

bioRxiv2017

Phylogenetic analysis of West Nile Virus in Maricopa County, Arizona: Evidence for dynamic behavior of strains in two major lineages in the American Southwest

West Nile Virus (WNV) has been detected annually in Maricopa County, Arizona, since 2003. With this in mind, we sought to determine if contemporary strains are established within the county or are annually imported. As part of this effort, we developed a new protocol for tiled amplicon sequencing of WNV to efficiently attain greater than 99% coverage of 14 WNV genomes collected directly from positive mosquito pools distributed throughout Maricopa County between 2014 and 2017. Bayesian phylogenetic analyses revealed that the contemporary genomes fall within two major lineages, NA/WN02 and SW/WN03. We found that all of the Arizona strains possessed a mutation known to be under positive selection (NS5-K314R), which has arisen independently four times. The SW/WN03 strains exhibited transient behavior, with at least 10 separate introductions into Arizona when considering both historical and contemporary strains. However, NA/WN02 strains are geographically differentiated and appear to be established in Arizona, with likely origins in New York. The clade of New York and Arizona strains looks to be the most ancestral extant lineage of WNV still circulating in the United States. The establishment of WNV strains in Maricopa County provides the first evidence of local overwintering by a WNV strain over the course of several years in Arizona.

evolutionary biology↗