Biology subjects

Walton, T.

Publications and source records attributed to Walton, T..

4 recordsLinked to original sources

bioRxiv2026

Seafloor topography structures subseafloor microbial communities in the Puerto Rico Trench

The influence of seafloor topography on subseafloor microbial communities is poorly understood. In this study, we systematically sampled subseafloor sedimentary microbial communities and pore-water geochemistry at bathyal, abyssal, and hadal water depths of the Puerto Rico Trench. The Puerto Rico Trench exhibits vertical relief of over 8 km with seafloor topography shaped by active plate tectonics and characterized by a very steep southern wall and active mass wasting. Sampling across these features, we find that subseafloor microbial communities are influenced by topography in the following two ways. First, subseafloor sediment in the deepest part of the trench is anoxic, enriched in organic matter due to mass transport of sediment from shallower water depths, and contains an anaerobic subseafloor community that is quite distinct from the anaerobic subseafloor community in anoxic sediment at bathyal depths. The difference between these bathyal and hadal subseafloor anaerobic communities is consistent with influence of water-depth-related physical properties on subseafloor community composition. Second, subseafloor sediment remains oxygenated for meters below seafloor on steep slopes within the bathyal zone, an abyssal topographic high within the trench, and the abyssal plain seaward of the trench subseafloor, likely due to limited sediment accumulation, which selects for the presence of aerobic microbial communities. The difference between these bathyal and abyssal aerobic subseafloor communities and the anaerobic communities at bathyal and hadal depths reflects the role of seafloor topography in structuring subseafloor availability of redox reactants, which in turn drives the activities and composition of subseafloor microbial communities.

microbiology↗

bioRxiv2026

Kainate receptors coordinate primitive hematopoiesis and hemogenic niche organization to promote hematopoietic stem cell development

The adult hematopoietic system is established during embryogenesis through the generation of hematopoietic stem and progenitor cells (HSPCs) within specialized transient niches, yet the signaling mechanisms that coordinate this process remain poorly understood. Here, we identify a developmental role for kainate receptors (KARs), glutamate-gated ion channels classically associated with excitatory neurotransmission, in coordinating primitive hematopoiesis and hemogenic niche formation in zebrafish. Loss of the KAR subunits encoded by grik1b or grik5 depletes primitive blood cells and disrupts hemogenic niche organization. These defects are accompanied by endothelial oxidative stress and impaired Notch signaling, which together reduce HSPC emergence and limit the clonal diversity of the adult hematopoietic stem cell pool. Shifting primitive hematopoietic output away from erythropoiesis and toward myelopoiesis restored macrophage niche colonization, endothelial Notch activity, and HSPC formation in KAR-deficient embryos. Moreover, hemogenic cell-specific Notch reactivation rescued HSPC production, demonstrating that KAR-dependent primitive hematopoiesis regulates this process through endothelial Notch signaling. Lastly, conserved KAR expression in endothelial and hematopoietic populations across zebrafish, mouse, and human suggests that these receptors may regulate blood development across multiple cellular components. Together, these findings reveal that glutamate receptor signaling extends beyond its well-established functions in neuronal transmission to coordinate the developmental processes that establish the blood system.

developmental biology↗

bioRxiv2022

In vivo 18F-DOPA PET imaging identifies a dopaminergic deficit in a rat model with a G51D α-synuclein mutation

Parkinsons disease (PD) is a neurodegenerative condition with several major hallmarks, including loss of substantia nigra neurons, reduction in striatal dopaminergic function, and formation of -synuclein-rich Lewy bodies. Mutations in SNCA, encoding for -synuclein, are a known cause of familial PD, and the G51D mutation causes a particularly aggressive form of the condition. CRISPR/Cas9 technology was used to introduce the G51D mutation into the endogenous rat SNCA gene. SNCAG51D/+ and SNCAG51D/G51D rats were born in Mendelian ratios and did not exhibit any severe behavourial defects. L-3,4-dihydroxy-6-18F-fluorophenylalanine (18F-DOPA) positron emission tomography (PET) imaging was used to investigate this novel rat model. Wild-type (WT), SNCAG51D/+ and SNCAG51D/G51D rats were characterised over the course of ageing (5, 11, and 16 months old) using 18F-DOPA PET imaging and kinetic modelling. We measured the influx rate constant (Ki) and effective distribution volume ratio (EDVR) of 18F-DOPA in the striatum relative to the cerebellum in WT, SNCAG51D/+ and SNCAG51D/G51D rats. A significant reduction in EDVR was observed in SNCAG51D/G51D rats at 16 months of age indicative of increased dopamine turnover. Furthermore, we observed a significant asymmetry in EDVR between the left and right striatum in aged SNCAG51D/G51D rats. The increased and asymmetric dopamine turnover observed in the striatum of aged SNCAG51D/G51D rats is similar to prodromal PD, which suggests the presence of compensatory mechanisms. SNCAG51D rats represent a novel genetic model of PD, and kinetic modelling of 18F-DOPA PET data has identified a highly relevant early disease phenotype.

neuroscience↗

bioRxiv2018

Crystallographic observation of nonenzymatic RNA primer extension

The importance of genome replication has inspired detailed crystallographic studies of enzymatic DNA/RNA polymerization. In contrast, the mechanism of nonenzymatic polymerization is less well understood, despite its critical role in the origin of life. Here we report the direct observation of nonenzymatic RNA primer extension through time-resolved crystallography. We soaked crystals of an RNA primer-template-dGMP complex with guanosine-5'-phosphoro-2-aminoimidazolide for increasing times. At early times we see the activated ribonucleotides bound to the template, followed by formation of the imidazolium-bridged dinucleotide intermediate. At later times, we see a new phosphodiester bond forming between the primer and the incoming nucleotide. The intermediate is pre-organized because of the constraints of base-pairing with the template and hydrogen bonding between the imidazole amino group and both flanking phosphates. Our results provide atomic-resolution insight into the mechanism of nonenzymatic primer extension, and set the stage for further structural dissection and optimization of the RNA copying process.

biochemistry↗