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Biology subjects

Williamson, M. R.

Publications and source records attributed to Williamson, M. R..

6 recordsLinked to original sources

Distribution Patterns of rRNA Copy Number Repeats in Prokaryotic Genomes

Unlike tandem repeats in eukaryotes, ribosomal RNA (rRNA) operons across prokaryotic genomes are widely distributed. Here, I examined the distribution of 16S ribosomal RNA gene copies using all entries from the Ribosomal RNA Operon Copy Number Database with a copy number of 2 or greater, using a metric--normalized range--that allows for comparisons between copy number. Normalized range varied across rRNA copy number, with the greatest distribution of rRNA gene copies in prokaryotic accessions with a copy number of 5. There was a significant phylogenetic signal for both bacteria and archaea (p<0.05). Archaea had higher normalized range than bacteria, even when comparing bacteria with comparable copy number (n=2-5) (p<0.05). Normalized range varied across bacterial phyla (p<0.05), with Cyanobacteria having the largest normalized range and Chlamydiae the smallest. Furthermore, normalized range was predicted by copy number, tRNA number, and pseudo-gene number, after correcting for phylum. When restricted to low bacterial copy numbers (n=2-5), normalized range was predicted by genome size, GC content, tRNA number, coding gene number, and pseudo-gene number. For archaea, normalized range was predicted by genome size, GC content, and tRNA number. Comparisons of bacteria and archaea suggest different mechanisms for rRNA copy distribution and maintenance across genomes.

genomics↗

Spaceflight Shifts in Community rRNA Copy Number in the Salivary Microbiome of Astronauts

The oral microbiome is stable, easily sampled, and can indicate disease. Using metagenomic data from GeneLab, I examined the effects of spaceflight on the human salivary microbiome using a composite community measure, average rRNA copy number. A higher copy number is associated with a faster growth rate and primary microbial succession. I found a significant increase in community weighted mean copy number between pre-spaceflight and during-spaceflight samples (p=0.0082). Furthermore, changes in abundance suggest a greater impact on individual species rather than phyla-level changes. Finally, a robustness analysis highlighted the importance of accurate copy number estimates and species-level identification. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=93 SRC="FIGDIR/small/598653v1_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@f079d9org.highwire.dtl.DTLVardef@1cfc53aorg.highwire.dtl.DTLVardef@19d7b5borg.highwire.dtl.DTLVardef@dcda3_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

Microvascular plasticity in stroke recovery: Longitudinal snapshots, network statistical analysis, and dynamics

This research article quantitatively investigates neuro-microvascular network remodeling dynamics following stroke using a novel in vivo two-photon angiography (cubic millimeter volume, weekly snapshots) and high throughput (thousands of connected capillaries) vascular vectorization method. The results suggest distinct temporal patterns of cere-brovascular plasticity, with acute remodeling peaking at one week post-stroke. The network architecture then gradually stabilizes, returning to a new steady state after four weeks. These findings align with previous literature on neuronal plasticity, highlighting the correlation between neuronal and neurovascular remodeling. Quantitative analysis of neurovascular networks using length- and strand-based statistical measures reveals intri-cate changes in network anatomy and topology. The distance and strand-length statistics show significant alterations, with a peak of plasticity observed at one week post-stroke, followed by a gradual return to baseline. The orientation statistic plasticity peaks at two weeks, gradually approaching the (conserved across subjects) stroke signature. The underlying mechanism of the vascular response (angiogenesis vs. tissue deformation), however, is yet unelucidated, requiring network registration advancements. Overall, the combination of two-photon angiography, vectorization, reconstruction/visualization, and statistical analysis enables both qualitative and quantitative assessments of neu-rovascular remodeling dynamics, demonstrating an impactful method for investigating neuro-microvascular network disorders and the therapeutic modes of action thereof. Understanding the timing and nature of neurovascular remodeling allows for optimized interventions, including personalized medicine for stroke rehabilitation. Additionally, the evaluation of pharmaceutical interventions using these tools may facilitate targeted drug development. Furthermore, neurovascular coupling dynamics have implications for neurodegenerative diseases, brain aging, and the field of brain-computer interfaces.

neuroscience↗

Subventricular zone cytogenesis provides trophic support for neural repair

Stroke enhances proliferation of neural precursor cells within the subventricular zone (SVZ) and induces ectopic migration of newborn cells towards the site of injury. Here we characterize the identity of cells arising from the SVZ after stroke and provide insight into their function by uncovering a mechanism through which they facilitate neural repair and functional recovery. Using genetic lineage tracing, we show that SVZ-derived cells that migrate towards stroke- induced cortical lesions in mice are predominantly undifferentiated precursors, suggesting that the main function of post-injury cytogenesis is not cell replacement. We find that SVZ-derived cells are a unique cellular source of trophic factors that instruct neural repair. Chemogenetic ablation of neural precursor cells or conditional knockout of VEGF in the adult neural stem cell lineage impairs neuronal and vascular reparative responses and worsens functional recovery after stroke. In addition, normal aging markedly diminishes the cytogenic response to stroke, resulting in worse functional recovery. Therapeutic replacement of VEGF in peri-infarct cortex is sufficient to induce neural repair and functional recovery in mice with arrested cytogenesis. These findings indicate that the SVZ cytogenic response following brain injury is a source of trophic support that drives neural repair and recovery.

neuroscience↗

Diamond Raman Laser and Yb Fiber Amplifier for In Vivo Multiphoton Fluorescence Microscopy

Here we introduce a fiber amplifier and a diamond Raman laser that output high powers (6.5 W, 1.3 W) at valuable wavelengths (1060 nm, 1250 nm) for multiphoton excitation of red-shifted fluorophores. These custom excitation sources are both simple to construct and cost-efficient in comparison to similar custom and commercial alternatives. Furthermore, they operate at a repetition rate (80 MHz) that allows fast image acquisition using resonant scanners. We demonstrate our systems compatibility with fast resonant scanning, the ability to acquire neuronal images, and the capability to image vasculature at deep locations (>1 mm) within the mouse cerebral cortex.

neuroscience↗

Multimodal mapping of neural activity and cerebral blood flow reveals long-lasting neurovascular dissociations after small-scale strokes

Neurovascular coupling, the close spatial and temporal relationship between neural activity and hemodynamics, is disrupted in pathological brain states. To understand the altered neurovascular relationship in brain disorders, longitudinal, simultaneous mapping of neural activity and hemodynamics is critical yet challenging to achieve. Here, we employ a multimodal neural platform in a mouse model of stroke and realize long-term, spatially-resolved tracking of intracortical neural activity and cerebral blood flow in the same brain regions. We observe a pronounced neurovascular dissociation that occurs immediately after small-scale strokes, becomes the most severe a few days after, lasts into chronic periods, and varies with the level of ischemia. Neuronal deficits extend spatiotemporally whereas restoration of cerebral blood flow occurs sooner and reaches a higher relative value. Our findings reveal the neurovascular impact of mini-strokes and inform the limitation of neuroimaging techniques that infer neural activity from hemodynamic responses.

neuroscience↗