Biology subjects

Hamilton, L.

Publications and source records attributed to Hamilton, L..

3 recordsLinked to original sources

bioRxiv2024

Mapping the peripheral immune landscape of Parkinson's disease patients with single-cell sequencing

Parkinsons Disease (PD) is most recognized for its impact on the central nervous system. However, recent breakthroughs underscore the crucial role of interactions between central and peripheral systems in PDs pathogenesis. The spotlight is now shifting as we explore beyond the central nervous system, discovering that peripheral changes such as inflammatory dysfunctions may predict the rate of disease progression and severity. Despite more than 200 years of research on PD, reliable diagnostic or progression biomarkers and effective disease-modifying treatments are still lacking. Additionally, the cellular mechanisms that drive changes in immunity are largely unknown. Thus, understanding peripheral immune signatures could lead to earlier diagnosis and more effective treatments for PD. Here, we sought to define the transcriptomic alterations of the complete peripheral immune cell compartment by single-cell RNA- and T-cell receptor-sequencing with hopes of uncovering PD signatures and potential peripheral blood biomarkers. Following transcriptional profiling of 78 876 cells from 10 healthy controls and 14 PD donors, we observed five major classes of immune cell types; myeloid (monocytes, dendritic cells) and lymphoid (T, B, natural killer) cells from which we identified 38 cellular subtypes following bioinformatic re-clustering. Comparing immune cell subtypes and phenotypes between PD patients and healthy controls revealed notable features of PD: 1) a significant shift of classical CD14+ monocytes towards an activated CD14+/CD83+ state, 2) changes in lymphocyte subtype abundance, including a significant decrease in CD4+ naive and mucosal-associated invariant T-cells subtypes, along with an increase in CD56+ natural killer cells, 3) the identification by T-cell receptor sequencing of several PD specific T-cell clones shared between multiple patients, suggesting the implication of common epitopes in PD pathogenesis, 4) a notable increase in the expression of activation signature genes, including the AP-1 stress-response transcription factor complex, across all PD cell types. This signal was not present in atypical parkinsonism patients with multiple systems atrophy or progressive supranuclear palsy. Overall, we present a comprehensive atlas of peripheral blood mononuclear cells from control and PD patients which should serve as a tool to improve our understanding of the role the immune cell landscape plays in PD pathogenesis.

genetics↗

bioRxiv2023

Microhabitat acclimatization shifts physiological baselines and thermal tolerance of the symbiotic anemone, Anthopleura elegantissima

Contemporary organisms in extreme environments can give insight into how species will respond to environmental change. The intertidal forms an environmental gradient where stress increases with tidal height. Here, we explore the contribution of fixed genotypic and plastic environmental effects on thermal tolerance of the intertidal anemone Anthopleura elegantissima and its algal symbionts using a laboratory-based tank experiment. High intertidal anemones had lower baseline symbiont-to-host cell ratios under control conditions, but their symbionts had higher baseline maximum quantum yield compared to low intertidal anemone symbionts, despite identical symbiont communities. High intertidal anemones maintained greater maximum quantum yield and symbiont-to-host cell ratios under heat stress compared to low intertidal anemones, suggesting that high intertidal holobionts have greater thermal tolerance. However, thermal tolerance of clonal anemones acclimatized to different zones was not explained by tidal height alone, indicating emersion duration is not the sole environmental driver of physiological variation. Fixed genotypic effects also influenced physiological baselines, but did not modulate thermal tolerance, demonstrating thermal tolerance is largely driven by environmental history. These results indicate that this symbiosis is highly plastic and may be able to rapidly acclimatize to climate change, defying the convention that symbiotic organisms are more susceptible to environmental stress.

ecology↗

bioRxiv2021

Quantification and uncertainty of root growth stimulation by elevated CO2 in mature temperate deciduous forest

Increasing CO2 levels are a major global challenge, and the extent to which increasing anthropogenic CO2 emissions can be mitigated by natural carbon sinks remains poorly understood. The uptake of elevated CO2 (eCO2) by the terrestrial biosphere, and subsequent sequestration as biomass in ecosystems, may act as a negative feedback in the carbon budget, but remains hard to quantify in natural ecosystems. Here, we combine large-scale field observations of fine root stocks and flows, derived from belowground imaging and soil cores, with image analysis, stochastic modelling, and statistical inference, to elucidate belowground root dynamics in a mature temperate deciduous forest under free-air CO2 enrichment to 150ppm above ambient levels. Using over 67k frames of belowground observation, we observe that eCO2 leads to relatively faster root production (a peak volume fold change of 4.52 {+/-} 0.44 eCO2 versus 2.58 {+/-} 0.21 control). We identify an increase in existing root elongation relative to root mass decay as the likely causal mechanism for this acceleration. Direct physical analysis of biomass and width measurements from 552 root systems recovered from soil cores support this picture, with lengths and widths of fine roots significantly increasing under eCO2. We use dynamic measurements to estimate fine root contributions to net primary productivity, finding an increase under eCO2, with an estimated mean annual 204 {+/-} 93 g dw m-2yr-1 eCO2 versus 140 {+/-} 60 g dw m-2 yr-1 control. We also quantify and discuss the uncertainties in such productivity measurements. This multi-faceted approach thus sheds quantitative light on the challenging characterisation of the eCO2 response of root biomass in mature temperate forests.

plant biology↗