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Biology subjects

Wolf, J. M.

Publications and source records attributed to Wolf, J. M..

4 recordsLinked to original sources

Synaptic density imaging associates with performance but not self-report in autism

Autism is a common neurodevelopmental condition with considerable between-person variability and unknown biological etiology. Diagnosis of autism in adults relies on measurement of performance (e.g., clinician rating of social behavior, standardized assessment of cognition) and self-report of autism features. Our prior work revealed a strong relationship between clinician ratings of social function in autism and in vivo measures of synaptic density as measured by [11C]UCB-J PET (Matuskey et al., 2025). However, it is not understood how the measured aspects of the autism phenotype index underlying biology. Here, in a sample of 12 autistic adults, we address this question by relating synaptic density imaging to a range of performance measures, such as cognition and face recognition, in contrast to self-report measures. Our results identify a dissociation between these measurement types in that synaptic density correlates strongly with measures of performance but shows virtually no relationship with self-report. These findings suggest that, while self-report and performance measures share variance in characterizing phenotypes in autism, they diverge when mapping onto the underlying biology. Results suggest that higher synaptic density may index a general mechanism that facilitates social and cognitive performance across a range of tasks. These data also indicate that performance and self-report measures are not interchangeable in capturing brain-behavior correspondences in autism, a finding that can guide measure selection in future biomarker studies and clinical research.

neuroscience↗

Peroxisomes regulate virulence and cell density sensing in Cryptococcus neoformans

Cryptococcus neoformans, a ubiquitous environmental fungus that causes cryptococcosis, survives in diverse environments including human hosts due to metabolic flexibility. Consequently, identifying how C. neoformans connects diverse metabolic pathways and virulence factor expression is important for understanding fungal pathogenesis. Peroxisomes play an essential role in metabolic homeostasis and regulation of carbon and lipid metabolism. In this article, we report a link between nickel exposure, a known hypoxia-mimetic and mitochondrial respiration inhibitor in yeast, and peroxisomal {beta}-oxidation. Loss of the last two genes involved in the peroxisomal {beta}-oxidation pathway, MFE2 (CNAG_05721) and POT1 (CNAG_00490), resulted in cell density-dependent virulence factor defects and growth inhibition attributed to a metabolic state involving large peroxisomes. We found that increasing cell density rescued virulence factor phenotypes and growth. Our results implicate mitochondrial retrograde signaling (RTG), a previously uncharacterized pathway in C. neoformans, in cell density sensing, peroxisomal {beta}-oxidation pathway expression, and virulence, thus highlighting a critical role for metabolism in cryptococcal virulence.

microbiology↗

Bull Trout passage at beaver dams in two Montana streams

Beaver (Castor canadensis) translocation and mimicry is an increasingly popular tool for process-based restoration of degraded streams. Processes influenced by beaver restoration include stream-floodplain connectivity, multi-threaded channel formation, enhanced riparian condition and fire resiliency, and streamflow attenuation. Beaver activity can also be a nuisance in agricultural settings, increase invasive species abundance, and create in-stream barriers to fish. Previous studies indicate that spring-spawning salmonid species can pass beaver dams in higher proportions than fall-spawning species. Thus, restoration or mimicry of beavers in streams containing fall-spawning, threatened Bull Trout (Salvelinus confluentus) is of concern to many biologists. We evaluated Bull Trout passage at beaver dams in two Montana streams: Meadow Creek (East Fork Bitterroot River drainage) in summer 2020 and Morrison Creek (Middle Fork Flathead River drainage) from 1997 to 2011. In Meadow Creek, 16% of PIT-tagged Bull Trout which entered a large beaver dam complex were detected upstream of some dams, but no fish moved through the entire 1 km complex. In Morrison Creek, redds were more likely than random to be located below dams, but two or more redds were found upstream of at least one dam in 6 of 9 years dams were present. These results suggest that beaver dams can affect the movement of Bull Trout, but that passage depends on the characteristics of individual dams and reach geomorphology. Our methods cannot distinguish between inhibition of fish movement and selection of beaver-created habitats by fish. Therefore, we suggest future research on beaver restoration in streams with Bull trout.

ecology↗

Using summary statistics to evaluate the genetic architecture of multiplicative combinations of initially analyzed phenotypes with a flexible choice of covariates

While the promise of electronic medical record and biobank data is large, major questions remain about patient privacy, computational hurdles, and data access. One promising area of recent development is pre-computing non-individually identifiable summary statistics to be made publicly available for exploration and downstream analysis. In this manuscript we demonstrate how to utilize pre-computed linear association statistics between individual genetic variants and phenotypes to infer genetic relationships between products of phenotypes (e.g., ratios; logical combinations of binary phenotypes using and and or) with customized covariate choices. We propose a method to approximate covariate adjusted linear models for products and logical combinations of phenotypes using only pre-computed summary statistics. We evaluate our methods accuracy through several simulation studies and an application modeling various fatty acid ratios using data from the Framingham Heart Study. These studies show consistent ability to recapitulate analysis results performed on individual level data including maintenance of the Type I error rate, power, and effect size estimates. An implementation of this proposed method is available in the publicly available R package pcsstools.

genetics↗