Biology subjects

Dobson, S.

Publications and source records attributed to Dobson, S..

4 recordsLinked to original sources

bioRxiv2024

Detection of airborne Coccidioides spores using lightweight portable air samplers affixed to uncrewed aircraft systems in California's Central Valley

Coccidioidomycosis is an emerging fungal infection caused by inhalation of Coccidioides spp. spores. While airborne dispersal is critical to Coccidioides transmission, limited recovery of the pathogen from air has hindered understanding of the aerosolization and transport of spores. Here, we examine uncrewed aircraft systems (UAS) with portable, active air samplers as a novel means of capturing aerosolized Coccidioides and characterizing emissions and exposure risk. We sampled in September 2023 in eastern San Luis Obispo County, California, in an area with confirmed Coccidioides immitis in soils. We completed 41 20-minute flights across 14 sites using UAS equipped with an 8 L/min bioaerosol sampler and a low-cost particulate matter sensor. We sampled source soils and air under ambient conditions using one UAS at 1-10 m above ground level, and under a simulated high-dust event using two UAS, one at <2 m height and one at 5-12 m. We detected Coccidioides DNA in two of 41 air samples (4.9%), both under ambient conditions at 8 m above ground level, representing the highest known height of airborne Coccidioides detection. Spatially explicit UAS-based sampling could enhance understanding of Coccidioides aerobiology and enable detection in hard-to-reach or hazardous air masses, including dust storms and wildfire smoke. SynopsisUAS-based air sampling for bioaerosols, including pathogenic Coccidioides spp., opens new possibilities for characterizing the aerosolization and transport of fungal spores and other airborne pathogens.

ecology↗

bioRxiv2022

Development of Enterovirus anti-viral agents that target the viral 2C protein

The enterovirus (EV) genus includes a number of important human and animal pathogens. EV-A71, EV-D68, poliovirus (PV), and coxsackievirus (CV) outbreaks have affected millions worldwide causing a range of upper respiratory, skin, neuromuscular diseases, including acute flaccid myelitis, and hand-foot-and-mouth disease. There are no FDA-approved anti-viral therapeutics for these enteroviruses. In this study, we describe novel broad spectrum anti-viral compounds targeting the conserved non-structural viral protein 2C that have low micro-molar to nanomolar IC50 values. The selection of resistant mutants resulted in amino acid substitutions in the viral capsid protein, implying a role for 2C in capsid assembly, as has been seen in PV. The assembly and encapsidation stages of the viral life cycle are not fully understood and the inhibitors reported here could be useful probes in understanding these processes.

pharmacology and toxicology↗

bioRxiv2021

Identifying locations susceptible to micro-anatomical reentry using a spatial network representation of atrial fibre maps

Micro-anatomical reentry has been identified as a potential driver of atrial fibrillation (AF). In this paper, we introduce a novel computational method which aims to identify which atrial regions are most susceptible to micro-reentry. The approach, which considers the structural basis for micro-reentry only, is based on the premise that the accumulation of electrically insulating interstitial fibrosis can be modelled by simulating percolation-like phenomena on spatial networks. Our results suggest that at high coupling, where micro-reentry is rare, the micro-reentrant substrate is highly clustered in areas where the atrial walls are thin and have convex wall morphology. However, as transverse connections between fibres are removed, mimicking the accumulation of interstitial fibrosis, the substrate becomes less spatially clustered, and the bias to forming in thin, convex regions of the atria is reduced. Comparing our algorithm on image-based models with and without atrial fibre structure, we find that strong longitudinal fibre coupling can suppress the micro-reentrant substrate, whereas regions with disordered fibre orientations have an enhanced risk of micro-reentry. We suggest that with further development, these methods may have future potential for patient-specific risk stratification, taking a longitudinal view of the development of the micro-reentrant substrate. Author summaryAtrial fibrillation (AF) is the most common abnormal heart rhythm, yet, despite extensive research, treatment success rates remain poor. In part, this is because there is an incomplete understanding of the mechanistic origin of AF. In this paper, we investigate one proposed mechanism of AF, the formation of "micro-reentrant circuits", which can be thought of as a "short circuit", forming when electrically insulating fibrosis (structural repair tissue) infiltrates the space between heart muscle cells. Previously, such circuits have been found in experimental hearts, but identifying these circuits clinically is difficult. Here, we aim to take a small step towards developing computational methods for identifying where in the atria these circuits are most likely to form, drawing on techniques from network science. Our approach indicates that a number of factors are key to determining where circuits form, most notably the thickness of the heart muscle, and the alignment of muscle fibres.

physiology↗

bioRxiv2019

Modelling the effects of environmental heterogeneity within the lung on the tuberculosis life-cycle

Progress in shortening the duration of tuberculosis (TB) treatment is hampered by the lack of a predictive model that accurately reflects the diverse environment within the lung. This is important as TB has been shown to produce distinct localisations to different areas of the lung during different disease stages, with the environmental heterogeneity within the lung of factors such as air ventilation, blood perfusion and oxygen tension believed to contribute to the apical localisation witnessed during the post-primary form of the disease. Building upon our previous model of environmental lung heterogeneity, we present a networked metapopulation model that simulates TB across the whole lung, incorporating these notions of environmental heterogeneity across the whole TB life-cycle to show how different stages of the disease are influenced by different environmental and immunological factors. The alveolar tissue in the lung is divided into distinct patches, with each patch representing a portion of the total tissue and containing environmental attributes that reflect the internal conditions at that location. We include populations of bacteria and immune cells in various states, and events are included which determine how the members of the model interact with each other and the environment. By allowing some of these events to be dependent on environmental attributes, we create a set of heterogeneous dynamics, whereby the location of the tissue within the lung determines the disease pathological events that occur there. Our results show that the environmental heterogeneity within the lung is a plausible driving force behind the apical localisation during post-primary disease. After initial infection, bacterial levels will grow in the initial infection location at the base of the lung until an adaptive immune response is initiated. During this period, bacteria are able to disseminate and create new lesions throughout the lung. During the latent stage, the lesions that are situated towards the apex are the largest in size, and once a post-primary immune-suppressing event occurs, it is the uppermost lesions that reach the highest levels of bacterial proliferation. Our sensitivity analysis also shows that it is the differential in blood perfusion, causing reduced immune activity towards the apex, which has the biggest influence of disease outputs.

systems biology↗