Biology subjects

McCoy, R.

Publications and source records attributed to McCoy, R..

3 recordsLinked to original sources

bioRxiv2024

Chromosomal Instability in Human Trophoblast Stem Cells and Placentas

The human placenta, a unique tumor-like organ, is typically thought to exhibit rare aneuploidy associated with adverse pregnancy outcomes. Discrepancies in reported aneuploidy prevalence in placenta likely stem from limitations in modeling and the resolution of detection methods. Here, we used isogenic trophoblast stem cells (TSCs) derived from both naive and primed human pluripotent stem cells (hPSCs) to reveal the spontaneous occurrence of aneuploidy, suggesting chromosomal instability (CIN) as an inherent feature of the trophoblast lineage. We identified potential pathways contributing to the occurrence and tolerance of CIN. These findings were further validated using single cell multiome data from human placentas, where we observed a high prevalence of heterogeneous aneuploidy across trophoblast cells. Despite extensive chromosomal abnormalities, TSCs maintained their proliferative and differentiation capacities, suggesting that CIN is a typical aspect of placental development. Our study challenges the traditional view of aneuploidy in the placenta and provides new insights into the role of CIN in normal placental function.

developmental biology↗

bioRxiv2024

Translating Ethiopian potato seed networks: Identifying strategic intervention points for managing bacterial wilt and other diseases

ContextInformal seed trade can exacerbate crop disease epidemics. Potato production across Ethiopia is threatened by the spread of seedborne pests and pathogens, particularly by bacterial wilt, caused by the Ralstonia solanacearum Species Complex (RSSC). The RSSC is commonly dispersed through informal trade of seed potato, with the potential to move long distances across Ethiopia and among trading countries. Efficient disease testing programs and formal seed systems can reduce the risk of disease expansion in a countrys potato cropping system. ObjectiveIn this study, we characterized networks of potato value chain actors. We also identified candidate locations for disease surveillance and management interventions for improved seed systems, and locations at high risk for bacterial wilt establishment. We propose strategies to reduce the spread of bacterial wilt via infected seed. MethodsWe surveyed seed potato stakeholders to characterize interaction networks of potato value chain actors with a special focus on stakeholders engaged in seed potato quality assurance. We collected data regarding Ethiopias potato seed systems and analyzed the risk of spread of RSSC and other pathogens across the country through expert knowledge elicitation. Network metrics were used to characterize the informal seed trade system across Ethiopia, simulating pathogen spread across a network through scenario analyses. We characterized potato exports and imports to identify the risk of bacterial wilt movement through Ethiopias formal trading partners and neighboring countries where bacterial wilt has not yet been reported. ResultsWare potato farmers and traders were reported to have weak communication with other stakeholders in the potato value chain. In network analyses and simulated epidemics, locations in Agew Awi, Gamo, Gofa, Kembata and Tembaro zones were identified as candidate priorities for national surveillance of pathogen invasion and expansion through management interventions and formal seed system development. Ethiopia has formal trade with Sudan, Southern Sudan, Russia, and other countries where bacterial wilt has not been reported. Ethiopia may be at risk of reintroduction of the RSSC from countries where it is present, like Kenya and India. SignificanceImproving seed systems to manage R. solanacearum and other seedborne pathogens is important for supporting food security and the livelihoods of smallholder farmers in Ethiopia. Implementing surveillance systems and management programs in locations like those identified in Agew Awi, Gamo, Gofa, Kembata, and Tembaro zones, and improving the communication between ware potato traders and other stakeholders, can help to strengthen informal trade of seed potato and mitigate bacterial wilt spread in infected seed.

ecology↗

bioRxiv2022

Multiparametric sensing of outer membrane vesicle-derived supported lipid bilayers demonstrates the specificity of bacteriophage interactions

The use of bacteriophage, viruses that specifically infect bacteria, as antibiotics has become an area of great interest in recent years as the effectiveness of conventional antibiotics recedes. The detection of phage interactions with specific bacteria in a rapid and quantitative way is key for identifying phage of interest for novel antimicrobials. Outer membrane vesicles (OMVs) derived from gram-negative bacteria can be used to make supported lipid bilayers (SLBs) and therefore in vitro membrane models that contain naturally occurring components of the bacterial outer membrane. In this study, we used Escherichia coli OMV derived SLBs and use both fluorescent imaging and surface sensitive techniques to show their interactions with T4 phage. We also integrate these bilayers with microelectrode arrays (MEAs) functionalised with the conducting polymer PEDOT:PSS and show that the pore forming interactions of the phage with the SLBs can be monitored using electrical impedance spectroscopy. To highlight our ability to detect specific phage interactions, we also generate SLBs using OMVs derived from Citrobacter rodentium, which is resistant to T4 phage infection, and identify their lack of interaction with phage. The work presented here shows how interactions occurring between phage and these complex SLB systems can be monitored using a range of experimental techniques. We believe this approach can be used to identify phage against bacterial strains of interest, as well as more generally to monitor any pore forming structure (such as defensins) interacting with bacterial outer membranes, and thus aid in the development of next generation antimicrobials.

bioengineering↗