Biology subjects

Walsh, H.

Publications and source records attributed to Walsh, H..

3 recordsLinked to original sources

bioRxiv2025

Regional and Global Analysis of Cerebrovascular Reactivity Using 4D Flow MRI

Cerebrovascular reactivity (CVR) assessments are promising for diagnostic and prognostic applications related to vascular function and neurodegenerative diseases. Current vascular imaging-based CVR indices have been limited to single-vessel analysis and report conflicting results, for example, whether there are differences in CVR between sexes. Alternative vascular imaging-based indices can be derived from 4D flow MRI, namely intracranial pulse wave velocity and pulsatility transmission, which are based on vascular regions and offer a more comprehensive perspective on vascular function that can also scale to a global level. To date, these types of indices have not been measured with a vascular stimulus. In this work, standard single-vessel and novel regional and global CVR indices were studied in 10 healthy young adults (29 {+/-} 2 years, 5 male, 5 female) in response to hypercapnia. Consistent increases in flow, area and velocity manifested at all levels and were greater in males. Regional pulse wave velocity and pulsatility transmission offered a minimum 40% increase in the dynamic range of CVR magnitudes that may benefit cohort stratification. Notably, pulse wave velocity increased in 50% of the vascular regions (most probably due to vasoconstriction), accompanying an increase in flow; a profound observation given the common expectation of vasorelaxation with hypercapnia. Consistently reduced flow, velocity, area, pulse wave velocity, and transmission index reactivities in females may partially explain the varying pathological outcomes between sexes, evidencing the continued value of 4D flow for the evaluation of CVR in other cohorts. New and NoteworthyCerebrovascular reactivity (CVR) of 4D flow-based intracranial pulse wave velocity and pulsatility transmission were evaluated during hypercapnia for the first time. Remarkably, pulse wave velocity increased in some cases and decreased in others, suggesting that vasorelaxation may not always occur during hypercapnia. These indices also expanded CVR dynamic range by more than 40 % compared to common velocimetry techniques, which could offer improved cohort stratification. Evidence of diminished CVR in females was also observed.

bioengineering↗

bioRxiv2025

Novel Adomaviruses Associated with Blotchy Bass Syndrome in Black Basses (Micropterus spp.)

Black bass (Micropterus spp.) are the most important warmwater game fishes in the United States. They have high socioeconomic and recreational value and support an important aquaculture industry. Since 2008, fisheries managers have been reporting the observation of hyperpigmented melanistic lesions (HPMLs) on smallmouth bass (M. dolomieu) in different ecoregions of the United States. Similar HPMLs have been observed in largemouth bass (M. nigricans) since the 1980s. Here, we report a close association between novel adomaviruses and the hallmark blotchy clinical presentation of hyperpigmented lesions on the skin smallmouth and largemouth black bass and provide evidence that satisfies Rivers postulates. The two adomaviruses are structurally and phylogenetically similar but share only 68.0% identity at aligned nucleotide sites and each has been found in only one host species to date. The manifestation of this skin disease appears to be seasonal in both species, primarily affects adults and is of unknown health consequence. Although the significance of infection to fish health remains unclear, understanding the disease ecology of these can inform biosecurity and the interjurisdictional movement of individuals. Moreover, as hyperpigmentation in other fish species is often idiopathic, our findings reframe perspectives for future investigations into this clinical presentation in other species.

microbiology↗

bioRxiv2023

Genetic, transcriptomic, histological, and biochemical analysis of progressive supranuclear palsy implicates glial activation and novel risk genes

Progressive supranuclear palsy (PSP) is a rare Parkinsonian disorder characterized by problems with movement, balance, cognition, and other symptoms. PSP differs from Alzheimers disease (AD) and other neurodegenerative diseases displaying abnormal forms of the microtubule-associated protein tau ("tauopathies") by the presence of pathology not only in neurons, but also in astrocytes and oligodendrocytes. Genetic contributors may mediate these differences, however much of PSP genetics remains unexplained. Here we conducted the largest genome-wide association study (GWAS) of PSP to date including 2,779 cases (2,595 neuropathologically-confirmed) and 5,584 controls and identified six independent PSP susceptibility loci with genome-wide significant (p < 5x10-8) associations including five known (MAPT, MOBP, STX6, RUNX2, SLCO1A2) and one novel locus (C4A). Integration with cell type-specific epigenomic annotations revealed a unique oligodendrocytic signature that distinguishes PSP from AD and Parkinsons disease. Candidate PSP risk gene prioritization using expression quantitative trait loci (eQTLs) identified oligodendrocyte-specific effects on gene expression in half of the genome-wide significant loci, as well as an association with elevated C4A expression in bulk brain tissue which may be driven by increased C4A copy number in PSP cases. Finally, histological studies demonstrated abnormal tau aggregates in oligodendrocytes that colocalize with C4 (complement) deposition. Integrating GWAS with functional studies including epigenomic and eQTL analyses, we identified potential causal roles for variation in MOBP, STX6, RUNX2, SLCO1A2, and C4A in the pathogenesis of PSP.

neuroscience↗