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Roberts, M. E.

Publications and source records attributed to Roberts, M. E..

3 recordsLinked to original sources

Glacier-induced upwelling shapes microbial communities in Arctic marine systems

The Canadian Arctic Archipelago (CAA) is warming at an unprecedented rate, leading to sea ice loss and glacial retreat. Marine-terminating (tidewater) glaciers can fuel summertime marine productivity by delivering nutrient-rich deep waters via upwelling to the surface ocean. While the impact of glacier-induced upwelling has been well-studied in the context of phytoplankton and primary productivity, its effects on broader marine microbial communities remain poorly understood. We investigated how glacier-driven upwelling shapes marine microbial (bacterial and archaeal) communities across a series of sites in the CAA. At upwelling sites, the upper 50 m of the water column exhibited elevated nutrient concentrations and physical characteristics that resembled deeper waters, which were associated with differences in microbial community composition relative to non-upwelling sites. Our results indicate that upwelling influences microbial communities in surface waters in two ways. It directly introduces typically deeper-water-associated taxa into surface waters and reshapes ecological niches by enhancing nutrient supply and stimulating primary production, indirectly driving changes in microbial communities. The enrichment of Candidatus Nitrosopumilus, a deep water nitrifier, likely affects nitrogen cycling and raises the possibility of active nitrification in surface waters. Likewise, the increased abundance of taxa known to be associated with phytoplankton-derived organic matter in upwelling regions suggests an enhanced capacity to process organic matter generated from elevated primary productivity. Ultimately, as tidewater glaciers continue to retreat, the resulting changes in the glacially-driven upwelling regime will likely shift marine microbial communities towards assemblages adapted to less productive ecosystems, with implications for nutrient cycling in these systems. ImportanceClimate change has a disproportionate impact on the Arctic, with rising temperatures causing increased marine-terminating glacier retreat and changes in the marine water column structure. The consequent loss of the ability of these glaciers to upwell deep water to the surface ocean results in a reduction of nutrient delivery and mixing in these ecosystems. Previous work has highlighted the importance of marine-terminating glaciers in sustaining phytoplankton productivity during the summer season through this delivery of deep-water nutrients to the surface ocean. The impact of glacially-induced upwelling on marine bacterial and archaeal communities, however, remains underexplored. We found that in regions with glacially-driven upwelling, the surface ocean showed enrichment of phytoplankton-associated taxa and nitrifiers commonly associated with deep waters. This work underscores the role of glacially-driven upwelling in structuring both microbial communities and nutrient cycling, suggesting that glacier loss could reshape community composition and biogeochemical processes in a rapidly changing Arctic.

microbiology↗

Systemic and tumor intrinsic expansion of FCRL5 expressing B cells associates with poor response to Bacillus Calmette-Guerin immunotherapy in patients with non-muscle invasive bladder cancer

The majority of patients treated with Bacillus Calmette-Guerin (BCG) immunotherapy, for non-muscle invasive bladder cancer (NMIBC), experience early recurrence due to pre-existing mucosal immune dysfunction. Since B cell are mucosal immune sentinels, we characterized the systemic and local B cell responses in 45 patients with NMIBC. Expansion of circulating atypical B cells (ABCs) following repeated BCG instillation, expanded IgG autoantibody repertoire, progressive IgG reactivity against BCG antigens, and higher tumor IgG deposition, were features of patients who recurred early. Integrated spatial immunophenotyping and single cell spatial transcriptomic analysis of corresponding tumors revealed increased ABCs within tertiary lymphoid structures, and co-localization with PD-1 B cells, regulatory T cells, and CD163 macrophages. Independent validation in two patient cohorts (total n = 409), revealed a significant association between high expression of the ABC specific, FCRL5, and poor outcomes. Our study identifies ABCs as key mediators of poor response to BCG in patients with high-risk NMIBC.

cancer biology↗

From imaging to computational domains for physics-driven molecular biology simulations: Hindered diffusion in platelet masses

When formed in vivo, murine hemostatic thrombi exhibit a heterogeneous architecture comprised of distinct regions of densely and sparsely packed platelets. In this study, we utilize high-resolution electron microscopy alongside machine learning and physics-based simulations to investigate how such clot microstructure impacts molecular diffusivity. We used Serial Block Face - Scanning Electron Microscopy (SBF-SEM) to image select volumes of hemostatic masses formed in a mouse jugular vein, producing large stacks of high-resolution 2D images. Images were segmented using machine learning software (Cellpose), whose training was augmented by manually segmented images. The segmented images were then utilized as a computational domain for Lattice Kinetic Monte-Carlo (LKMC) simulations. This process constitutes a computational pipeline that combines purely data-derived biological domains with physics-driven simulations to estimate how molecular movement is hindered in a hemostatic platelet mass. Using our pipeline, we estimated that the hindered diffusion rates of a globular protein range from 2% to 40% of the unhindered rate, with denser packing regions lending to lower molecular diffusivity. These data suggest that coagulation reactions rates, thrombin generation and activity, as well as platelet releasate activity may be drastically impacted by the internal geometry of a hemostatic thrombus. Author SummaryHemostasis and coagulation are two exquisitely complex, intertwined, and tightly regulated biological processes. Dysregulation of either process may lead to severe health consequences or death. Coagulation reactions have been extensively studied under static laboratory conditions, which are different from in vivo conditions. It is therefore imperative to understand if and how the chemical reactions underlying coagulation are regulated by the environment where they occur. In vivo experimentation enables us to image hemostasis, but not chemical reactions. Physics-driven molecular simulations of chemical reactions can bridge the gap, provided the physical environment is correctly represented computationally. The present work serves as a much-needed foundation for image-to-computation for physics based molecular simulations in biological domains.

systems biology↗