Biology subjects

Beckman, M.

Publications and source records attributed to Beckman, M..

3 recordsLinked to original sources

bioRxiv2026

A Comparison and Validation of BIDS Apps for Preprocessing of UCB-J PET data

Background Preprocessing of Positron Emission Tomography (PET) data can be performed in many different ways and often involves manual steps, resulting in reduced comparability across analyses and pipelines. Apps working on PET data organized according to the Brain Imaging Data Structure (BIDS) seek to automate preprocessing, enabling the application of standardized pipelines that increase comparability and reproducibility. In this study, two of these apps were validated against in-house software. Methods Data were acquired in-house from 14 subjects who received placebo in a randomized controlled clinical trial and underwent two PET measurements using the radioligand [11C]UCB-J. Preprocessing was performed with two BIDS Apps, PETPrep and PICNIC, as well as an in-house software. Arterial blood data were processed using Bloodstream, and [11C]UCB-J total distribution volume (VT) values were calculated using a 1-tissue compartment model using kinfitr. Results VT values for all 9 regions of interest were highly consistent across tools with estimates of Intraclass Correlation Coefficients for consistency ranging between 0.94 and >0.99, although bias between tools measured as signed Percentage Difference was present, ranging from 0.1% - 10.2% depending on the region. Tools performed similarly on test-retest metrics. We observed a negative test-retest bias in [11C]UCB-J VT of unknown origin. Conclusion BIDS Apps produce reliable and consistent results when compared both with each other and with an in-house software optimized for processing and analysis of our in-house data. Region-dependant bias between tools warrants caution for direct comparison of VT between tools. The usage of these apps could enable better comparability across publications

neuroscience↗

bioRxiv2023

An intronic copy number variation in Syntaxin 17 determines speed of greying and melanoma incidence in Grey horses

The Greying with age phenotype involves loss of hair pigmentation whereas skin pigmentation is not reduced and a predisposition to melanoma. The causal mutation was initially reported as a duplication of a 4.6 kb intronic sequence in Syntaxin 17. The speed of greying varies considerably among Grey horses. Here we demonstrate the presence of two different Grey alleles, G2 carrying two tandem copies of the duplicated sequence and G3 carrying three. The latter is by far the most common allele, probably due to strong selection for the striking white phenotype. Our results reveal a remarkable dosage effect where the G3 allele is associated with fast greying and high incidence of melanoma whereas G2 is associated with slow greying and low incidence of melanoma. Epigenetic analysis, based on nanopore sequencing of genomic DNA, reveals a drastic reduction in DNA methylation in part of the duplicated sequence harboring MITF binding sites. The copy number expansion transforms a weak enhancer to a strong melanocyte-specific enhancer that underlies hair greying (G2 and G3) and a drastically elevated risk of melanoma (G3 only).

genetics↗

bioRxiv2021

Chronic Seizures Worsen Cognitive Function with Loss of Presenilin 2 Function in a Sex-Related Manner

Patients with early-onset Alzheimers disease (EOAD) are at elevated risk for seizures, including patients with presenilin 2 (PSEN2) variants. Like people with epilepsy, uncontrolled seizures may worsen cognitive function in AD. While the relationship between seizures and amyloid beta accumulation has been more thoroughly investigated, the role of other drivers of seizure susceptibility in EOAD remain relatively understudied. We therefore sought to define the impact of loss of normal PSEN2 function and chronic seizures on cognitive function in the aged brain. Male and female PSEN2 KO and age- and sex-matched wild-type (WT) mice were sham or corneal kindled beginning at 6-months-old. Kindled and sham-kindled mice were then challenged up to 6 weeks later in a battery of cognitive tests: non-habituated open field (OF), T-maze spontaneous alternation (TM), and Barnes maze (BM), followed by immunohistochemistry for markers of neuroinflammation and neuroplasticity. PSEN2 KO mice required significantly more stimulations to kindle (males: p<0.02; females: p<0.02) versus WT. Across a range of behavioral tests, the cognitive performance of kindled female PSEN2 KO mice was most significantly impaired versus age-matched WT females. Male BM performance was generally worsened by seizures (p=0.038), but loss of PSEN2 function did not itself worsen cognitive performance. Conversely, kindled PSEN2 KO females made the most BM errors (p=0.007). Chronic seizures also significantly altered expression of hippocampal neuroinflammation and neuroplasticity markers in a sex-specific manner. Chronic seizures may thus significantly worsen hippocampus-dependent cognitive deficits in aged female, but not male, PSEN2 KO mice. Our work suggests that untreated focal seizures may worsen cognitive burden with loss of normal PSEN2 function in a sex-related manner.

neuroscience↗