Biology subjects

Cox, E.

Publications and source records attributed to Cox, E..

9 recordsLinked to original sources

bioRxiv2025

Noninvasive detection of bacterial biofilms using an insect olfactory brain-based gas sensor

Bacteria emit volatile organic compounds (VOCs) that can be targeted for disease detection. Biological olfactory systems have keen senses of smell, can detect VOCs at low concentrations, and are naturally adapted to classifying mixtures of VOCs as odors. Here, we employed locust (Schistocerca americana) olfactory neural circuitry to differentiate biofilm and planktonic cultures of Pseudomonas aeruginosa and Staphylococcus aureus using their odors. In vivo extracellular neural recordings were taken from the second-order olfactory processing center (antennal lobe) of locusts. The VOCs from biofilm cultures evoked distinct spiking responses compared to the planktonic cultures for both bacterial species. By analyzing the population neuronal responses, we classified individual bacterial biofilm vs. planktonic odors with up to 96% accuracy. The neural responses were highly discriminatory within the first couple of seconds of odor presentation and our analysis was conducted on less than five seconds of data, highlighting the potential of our biological sensor for real-time biofilm detection.

neuroscience↗

bioRxiv2023

DMS-MapSeq Analysis of Antisense Oligonucleotide Binding to lncRNA PANDA

While various methods exist for examining and visualizing the structure of RNA molecules, dimethyl sulfate-mutational profiling and sequencing (DMS-MaPseq) stands out for its simplicity and versatility. This technique has proven effective for studying RNA structures both in vitro and in complex biological settings. Weve updated the protocol for using DMS-MaPseq, and it can also be employed to identify the binding of antisense oligonucleotides (ASOs) to RNA. By applying this updated protocol, we successfully characterized the structural ensemble of the HIV1 Rev Response Element (RRE), along with its two alternative structures. The findings align with previously published research. Additionally, we resolved the structure of the long non-coding RNA PANDA, which was previously unknown. Moreover, we used PANDA as a basis for designing ASOs and confirmed their binding through a substantial decrease in DMS-reactivities at the anticipated ASO binding locations.

molecular biology↗

bioRxiv2023

Employing a honeybee olfactory neural circuit as a novel gas sensor for the detection of human lung cancer biomarkers

Human breath contains biomarkers (odorants) that can be targeted for early disease detection. It is well known that honeybees have a keen sense of smell and can detect a wide variety of odors at low concentrations. Here, for the first time, we employ honeybee olfactory neuronal circuitry to classify human lung cancer volatile biomarkers and their mixtures at concentration ranges relevant to human breath, parts-per-billion to parts-per-trillion. Different lung cancer biomarkers evoked distinct spiking response dynamics in the honeybee antennal lobe neurons indicating that those neurons encoded biomarker-specific information. By investigating lung cancer biomarker-evoked population neuronal responses from the honeybee antennal lobe, we could classify individual human lung cancer biomarkers successfully (88% success rate). When we mixed six lung cancer biomarkers at different concentrations to create synthetic lung cancer vs. synthetic healthy breath, honeybee population neuronal responses were also able to classify those complex breath mixtures successfully (100% success rate with a leave-one-trial-out method). Finally, we used separate training and testing datasets containing responses to the synthetic lung cancer and healthy breath mixtures. We identified a simple metric, the peak response of the neuronal ensemble, with the ability to distinguish synthetic lung cancer breath from the healthy breath with 86.7% success rate. This study provides proof-of-concept results that a powerful biological gas sensor, the honeybee olfactory system, can be used to detect human lung cancer biomarkers and their complex mixtures at biological concentrations.

bioengineering↗

bioRxiv2022

Bordetella spp. block eosinophil recruitment to suppress lung iBALT formation

A characteristic that differentiates pathogenic and opportunistic bacteria is that pathogens have been selected by their ability to suppress host inflammatory responses allowing colonization and persistence. Bordetella spp. are respiratory pathogens characterized for the arsenal of mechanisms they use to manipulate host immune responses. We have previously characterized a B. bronchiseptica mutant, RB50{Delta}btrS, that is not able to suppress host immune responses, resulting not only in rapid clearance of the infection but also long-term lung sterilizing immunity against reinfection with the three classical Bordetella spp. Interestingly, this strong immune response requires eosinophils. In this work our results indicate that wildtype B. bronchiseptica, RB50, blocks eosinophil pro-inflammatory functions to prevent the rapid recruitment of B and T cells to the lung that results in iBALT formation. Moreover, eosinophils promote a TH17 microenvironment within the iBALT that might be responsible for the long-term robust protective immunity generated by infection with this mutant. Overall, this work provides a novel role for eosinophils as promoters of adaptive immune responses and protective immunity, while also indicating that bacteria actively manipulate those cells to promote long-term persistence and reinfection.

microbiology↗

bioRxiv2022

Outbreak of Highly Pathogenic Avian Influenza H5N1 in New England Seals

The recent incursion of Highly Pathogenic Avian Influenza A (H5N1) virus into North America and subsequent dissemination of virus across the continent, has had significant adverse impacts on domestic poultry, and has led to widespread mortality in many wild bird species. Here we report the recent spillover of H5N1 into marine mammals in the northeastern United States, with associated mortality on a regional scale. This spillover is coincident with a second wave of H5N1 in sympatric wild birds also experiencing regional mortality events. Viral sequences derived from both seal and avian hosts reveal distinct viral genetic differences between the two waves of infection. Spillover into seals was closely related to virus from the second wave, and one of eight seal-derived sequences had the mammalian adaptation PB2 E627K. One-Sentence SummaryAn outbreak of H5N1 in New England seals is the first known population-scale mammalian mortality event associated with the emerging highly pathogenic avian influenza clade 2.3.4.4b.

molecular biology↗

bioRxiv2022

Harnessing insect olfactory neural circuits for noninvasive detection of human cancer

There is overwhelming evidence that metabolic processes are altered in cancer cells and these changes are manifested in the volatile organic compound (VOC) composition of exhaled breath. Here, we take a novel approach of an insect olfactory neural circuit-based VOC sensor for cancer detection. We combined an in vivo antennae-attached insect brain with an electrophysiology platform and employed biological neural computation rules of antennal lobe circuitry for data analysis to achieve our goals. Our results demonstrate that three different human oral cancers can be robustly distinguished from each other and from a non-cancer oral cell line by analyzing individual cell culture VOC composition-evoked olfactory neural responses in the insect antennal lobe. By evaluating cancer vs. non-cancer VOC-evoked population neural responses, we show that olfactory neurons response-based classification of oral cancer is sensitive and reliable. Moreover, this brain-based cancer detection approach is very fast (detection time ~ 250 ms). We also demonstrate that this cancer detection technique is effective across changing chemical environments mimicking natural conditions. Our brain-based cancer detection system comprises a novel VOC sensing methodology that will spur the development of more forward engineering technologies for noninvasive detection of cancer.

bioengineering↗

bioRxiv2021

A Dual-reporter Platform for Screening Tumor-targeted Extracellular Vesicles

Extracellular vesicle (EV)-mediated transfer of biomolecules plays an essential role in intercellular communication and may improve targeted drug delivery. In the past decade, various approaches to EV surface modification for targeting specific cells or tissues have been proposed, including genetic engineering of parental cells or postproduction EV engineering. However, due to technical limitations, targeting moieties of engineered EVs have not been thoroughly characterized. Here, we report the bioluminescence resonance energy transfer (BRET) EV reporter, PalmReNL-based dual-reporter platform for characterizing the cellular uptake of tumor homing peptide (THP)-engineered EVs, targeting PDL1, uPAR, or EGFR proteins expressed in MDA-MB-231 breast cancer cells, simultaneously by bioluminescence measurement and fluorescence microscopy. Bioluminescence analysis of cellular EV uptake revealed the highest binding efficiency of uPAR-targeted EVs, whereas PDL1-targeted EVs showed slower cellular uptake. EVs engineered with two known EGFR-binding peptides via lipid nanoprobes did not increase cellular uptake, indicating that designs of EGFR-binding peptide conjugation to the EV surface are critical for functional EV engineering. Fluorescence analysis of cellular EV uptake allowed us to track individual PalmReNL-EVs bearing THPs in recipient cells. These results demonstrate that the PalmReNL-based EV assay platform can be a foundation for high-throughput screening of tumor-targeted EVs.

bioengineering↗

bioRxiv2021

Spatial proteogenomics reveals distinct and evolutionarily-conserved hepatic macrophage niches

The liver is the largest solid organ in the body, yet it remains incompletely characterized. Here, we present a spatial proteogenomic atlas of the healthy human and murine liver combining single-cell CITE-seq, single-nuclei sequencing, spatial transcriptomics and spatial proteomics. By integrating these multi-omic datasets, we provide validated strategies to reliably discriminate and localize all hepatic cells. We then align this atlas across seven species, revealing the conserved program of bona fide Kupffer cells and bile-duct macrophages. We also uncover the respective spatially-resolved cellular niches of these macrophages and the microenvironmental circuits driving their unique transcriptomic identities. We demonstrate that bile-duct macrophages are induced by local lipid exposure, while Kupffer cells crucially depend on their crosstalk with hepatic stellate cells via the evolutionarily-conserved ALK1-BMP9/10 axis.

immunology↗

bioRxiv2017

Improved Aedes aegypti mosquito reference genome assembly enables biological discovery and vector control

Female Aedes aegypti mosquitoes infect hundreds of millions of people each year with dangerous viral pathogens including dengue, yellow fever, Zika, and chikungunya. Progress in understanding the biology of this insect, and developing tools to fight it, has been slowed by the lack of a high-quality genome assembly. Here we combine diverse genome technologies to produce AaegL5, a dramatically improved and annotated assembly, and demonstrate how it accelerates mosquito science and control. We anchored the physical and cytogenetic maps, resolved the size and composition of the elusive sex-determining \"M locus\", significantly increased the known members of the glutathione-S-transferase genes important for insecticide resistance, and doubled the number of chemosensory ionotropic receptors that guide mosquitoes to human hosts and egg-laying sites. Using high-resolution QTL and population genomic analyses, we mapped new candidates for dengue vector competence and insecticide resistance. We predict that AaegL5 will catalyse new biological insights and intervention strategies to fight this deadly arboviral vector.

genomics↗