Biology subjects

Beckett, A.

Publications and source records attributed to Beckett, A..

6 recordsLinked to original sources

bioRxiv2026

Multiphasic myelination and dendritic growth modulate qMRI signals in human visual cortex.

How does myelin develop in human visual cortex? By combining immunohistochemistry with in vivo and postmortem magnetic resonance imaging of longitudinal relaxation rate (R1), which increases with myelin content, we find that myelin and R1 increase across development but follow distinct trajectories. Immunohistochemistry reveals two phases of myelination: an infant phase of limited oligodendrogenesis, with myelin restricted to deep cortical layers, followed by widespread myelination across all layers during childhood. Cortical R1 also increases across development and correlates with myelin by childhood. However, in infancy, R1 increases outpace myelin growth and instead tracks dendritic arborization, indicating that the microstructural drivers of R1 change across development. We hypothesize that deep layer myelination in infancy contributes to early visual function whereas later myelination of superficial layers enables prolonged cortical plasticity and learning of complex visual behaviors.

neuroscience↗

bioRxiv2025

Functional imaging of hippocampal layers using VASO and BOLD on the Next Generation (NexGen) 7T Scanner

Spatial accuracy and venous biases are a central concern in mesoscale fMRI, with subcortical brain regions facing additional challenges due to lower sensitivity, high physiological noise, and complicated vasculature. Here, we optimized CBV VASO on the NexGen 7T scanner for layer-specific investigations of the human hippocampus. Both VASO and BOLD (from the same acquisition) detected significant hippocampal activation during an established autobiographical memory task. At the macroscale, activation patterns converged, showing pronounced memory task activation in the anterior hippocampus and consistent engagement across the frontoparietal neocortex. At the laminar scale, however, differences in depth-dependent profiles emerged within the subiculum: BOLD exhibited a pronounced bias toward the inner layers, consistent with the known venous drainage pattern in the subfield. Finally, the optimized effective TR of 3.2 s allowed exploratory study of retrieval stages and neocortical functional connectivity, which both supported hippocampal anterior-posterior dissociation using both VASO and BOLD. Thus, hippocampal fMRI allows mapping layer function with high accuracy and can provide deeper insights into a number of neuropsychological phenomena and disorders. Key pointsO_LIOptimized CBV VASO on NexGen 7T for layer-specific hippocampal imaging C_LIO_LIVASO mitigates structural venous bias in subiculum present in BOLD C_LIO_LILong-axis mapping dissociates retrieval stages and neocortical connectivity patterns C_LI

neuroscience↗

bioRxiv2024

Fuzzy ripple artifact in high resolution fMRI: identification, cause, and mitigation

PurposeHigh resolution fMRI is a rapidly growing research field focused on capturing functional signal changes across cortical layers. However, the data acquisition is limited by low spatial frequency EPI artifacts; termed here as Fuzzy Ripples. These artifacts limit the practical applicability of acquisition protocols with higher spatial resolution, faster acquisition speed, and they challenge imaging in lower brain areas. MethodsWe characterize Fuzzy Ripple artifacts across commonly used sequences and distinguish them from conventional EPI Nyquist ghosts, off-resonance effects, and GRAPPA artifacts. To investigate their origin, we employ dual polarity readouts. ResultsOur findings indicate that Fuzzy Ripples are primarily caused by readout-specific imperfections in k-space trajectories, which can be exacerbated by inductive coupling between third-order shims and readout gradients. We also find that these artifacts can be mitigated through complex-valued averaging of dual polarity EPI or by disconnecting the third-order shim coils. ConclusionThe proposed mitigation strategies allow overcoming current limitations in layer-fMRI protocols: O_LIAchieving resolutions beyond 0.8mm is feasible, and even at 3T, we achieved 0.53mm voxel functional connectivity mapping. C_LIO_LISub-millimeter sampling acceleration can be increased to allow sub-second TRs and laminar whole brain protocols with up to GRAPPA 8. C_LIO_LISub-millimeter fMRI is achievable in lower brain areas, including the cerebellum. C_LI

neuroscience↗

bioRxiv2022

Optical photothermal infrared spectroscopy can differentiate equine osteoarthritic plasma extracellular vesicles from healthy controls

BackgroundEquine osteoarthritis is a chronic degenerative disease of the articular joint, characterised by cartilage degradation resulting in pain and reduced mobility and thus is a prominent equine welfare concern. Diagnosis is usually at a late stage through radiographic examination, whilst treatment is symptomatic not curative. Extracellular vesicles are small nanoparticles that are involved in intercellular communication. The objective of this study was to investigate the feasibility of Raman and optical photothermal infrared spectroscopy to detect osteoarthritis using plasma-derived extracellular vesicles. MethodsPlasma samples were derived from thoroughbred racehorses. A total of 14 samples were selected (control; n= 6 and diseased; n=8). Extracellular vesicles were isolated using differential ultracentrifugation and characterised using nanoparticle tracking analysis, transmission electron microscopy, and human tetraspanin chips. Samples were then analysed using Raman and optical photothermal infrared spectroscopy. ResultsInfrared spectra were analysed between 950-1800 cm-1. Raman spectra had bands between the wavelengths of 900-1800 cm-1 analysed. Bands below 900 cm-1. Spectral data for both Raman and optical photothermal infrared spectroscopy was used to obtain a classification model and confusion matrices, characterising the techniques ability to distinguish diseased samples. Optical photothermal infrared spectroscopy could differentiate osteoarthritic extracellular vesicles from healthy with good classification (93.4%) whereas Raman displayed poor classification (64.3%). Plasma-derived extracellular vesicles from osteoarthritic horses contained increased signal for proteins, lipids and nucleic acids. Discussion/ conclusionFor the first time we demonstrated the ability to use optical photothermal infrared spectroscopy to interrogate extracellular vesicles and osteoarthritis-related samples. Optical photothermal infrared spectroscopy was superior to Raman in this study, and could distinguish osteoarthritis samples, suggestive of its potential use diagnostically to identify osteoarthritis in equine patients. This study demonstrates the potential of Raman and optical photothermal infrared spectroscopy to be used as a diagnostic tool in clinical practice, with the capacity to detect changes in extracellular vesicles from clinically derived samples.

molecular biology↗

bioRxiv2021

Isolation and characterisation of bacteriophages with activity against invasive non-typhoidal Salmonella causing bloodstream infection in Malawi

In recent years, novel lineages of invasive non-typhoidal Salmonella (iNTS) serovars Typhimurium and Enteritidis have been identified in patients with bloodstream infection in sub-Saharan Africa. Here, we isolated and characterised 32 phages capable of infecting S. Typhimurium and S. Enteritidis, from water sources in Malawi and the UK. The phages were classified in three major phylogenetic clusters that were geographically distributed. In terms of host range, Cluster 1 phages were able to infect all bacterial hosts tested, whereas Clusters 2 and 3 had a more restricted profile. Cluster 3 contained two sub-clusters, and 3.b contained the most novel isolates. This study represents the first exploration of the potential for phages to target the lineages of Salmonella that are responsible for bloodstream infections in sub-Saharan Africa.

microbiology↗

bioRxiv2020

Structural insights into loss of function of a pore forming toxin and its role in pneumococcal adaptation to an intracellular lifestyle

The opportunistic pathogen Streptococcus pneumoniae has dual lifestyles: one of an asymptomatic colonizer in the human nasopharynx and the other of a deadly pathogen invading sterile host compartments. The latter triggers an overwhelming inflammatory response, partly driven via pore forming activity of the cholesterol dependent cytolysin (CDC), pneumolysin. Although pneumolysin-induced inflammation drives person-to-person transmission from nasopharynx, the primary reservoir for pneumococcus, it also contributes to high mortality rates, creating a bottleneck that hampers widespread bacterial dissemination, thus acting as a double-edged sword. Serotype 1 ST306, a widespread pneumococcal clone, harbours a non-hemolytic variant of pneumolysin (Ply-NH). Performing crystal structure analysis of Ply-NH, we identified Y150H and T172I as key substitutions responsible for loss of its pore forming activity. We uncovered a novel inter-molecular cation-{pi} interaction, governing formation of the transmembrane {beta}-hairpins (TMH) in the pore state of Ply, which can be extended to other CDCs. H150 in Ply-NH disrupts this interaction, while I172 provides structural rigidity to domain-3, through hydrophobic interactions, inhibiting TMH formation. Loss of pore forming activity enabled improved cellular invasion and autophagy evasion, promoting an atypical intracellular lifestyle for pneumococcus, a finding that was corroborated in in vivo infection models. Attenuation of inflammatory responses and tissue damage promoted tolerance of Ply-NH-expressing pneumococcus in the lower respiratory tract. Adoption of this altered lifestyle may be necessary for ST306 due to its limited nasopharyngeal carriage, with loss of pore forming ability of Ply facilitating a benign association of SPN in an alternative, intracellular host niche. AUTHOR SUMMARYStreptococcus pneumoniae, the main causative agent of pneumonia, triggers inflammation and tissue damage by expressing a pore-forming toxin, pneumolysin (Ply). Ply-induced inflammation drives pneumococcal transmission from nasopharynx (its primary reservoir), but also contributes to host mortality, limiting its occupiable habitats. Here, we uncovered the structural basis for loss of pore-forming activity of a Ply variant, present in Serotype 1 ST306, and observed that this enabled adoption of an intracellular lifestyle, attenuating inflammatory responses and prolonging host tolerance of pneumococcus in the lower airways. This commensal-like lifestyle, resembling that of members of the mitis group of Streptococci, might have evolved within ST306 by loss of function ply mutations, compensating for limited nasopharyngeal carriage capacity by facilitating adaptation to an alternate niche.

microbiology↗