Biology subjects

Waller, R.

Publications and source records attributed to Waller, R..

4 recordsLinked to original sources

bioRxiv2026

Neuroanatomical Subtypes of Callous-Unemotional Traits in a Community Sample of Youth

ImportanceCallous Unemotional (CU) traits are associated with significant clinical and neurophysiological heterogeneity that may affect treatment effectiveness. ObjectiveTo uncover neuroanatomical subtypes of CU traits using weakly-supervised machine learning and assess whether emerging subtypes differ on relevant clinical, temperamental, and environmental constructs. Design, Setting, and ParticipantsImaging data was from the longitudinal Adolescent, Brain, Cognitive Development (ABCD) Study. Participants were 9-10 years old at baseline (M=9.925, 69.9% male) and included 222 children with CU traits and 234 typically developing controls matched on age, sex and income. Main Outcomes and MeasuresThe weakly-supervised heterogeneity through discriminative analysis (HYDRA) model was trained on grey matter (GM) volumes from 84 regions of interest (ROIs) and tested for reproducibility using cross-validation and permutation testing. Derived subtypes were compared cross-sectionally and prospectively on relevant clinical, temperamental, and environmental measures and subsequent GM volume at 2-year follow up. ResultsHYDRA revealed an optimal 2-subtype solution within children with CU traits. Subtypes showed comparable levels of aggression that were significantly higher than typically developing controls. At the same time, subtype 1 had larger GM volume, fewer internalizing symptoms, and less adversity exposure, while subtype 2 was characterized by smaller GM volume, more internalizing symptoms, and more adversity exposure. Conclusions and RelevanceThis study provides evidence of neuroanatomically distinct subtypes of CU traits characterized by different clinical and etiological profiles, with implications for diagnosis and treatment.

neuroscience↗

bioRxiv2026

TgmRHel drives unified RNA processing of coxI mRNA generated from a complex mitochondrial genomic context

The mitochondrial genome of Toxoplasma gondii is highly fragmented and recombination-prone, creating a structurally dynamic genetic landscape. How such a genome is used efficiently to produce functional mRNAs remains unclear: it is unknown whether transcription draws from many alternative genomic configurations or a restricted subset, and how any resulting precursor RNAs are processed into mature transcripts. More broadly, mitochondrial RNA processing mechanisms in this system are poorly understood. Here, we show that recombination of the T. gondii mitochondrial genome generates a diverse population of structurally distinct precursor RNAs for the essential cytochrome c oxidase subunit I (coxI) protein. Rather than being derived from a single defined primary transcript, these heterogeneous precursors are unified into a single mature mRNA through a post-transcriptional mechanism dependent on the DEAD-box RNA helicase TgmRHel. TgmRHel is required for 5'-end processing of coxI mRNA and for the accumulation of mitochondrial rRNAs, both of which are essential for Complex IV biogenesis, oxidative phosphorylation, and parasite survival. Loss of TgmRHel leads to the accumulation of diverse coxI precursor RNAs and a failure to generate the mature transcript. Our findings reveal an unexpected genome-transcriptome interface in which extensive genomic variability is not suppressed at the DNA level but instead resolved through RNA helicase-mediated processing. This work establishes a new conceptual framework for how gene expression fidelity can be maintained in the context of highly dynamic, recombining genomes.

molecular biology↗

bioRxiv2025

Comparing Brain-Behavior Relationships Across Dimensional, Tail-Sampled, and Propensity-Matched Models

Large population cohorts are needed to perform brain-wide association studies (BWAS), with evidence that sampling from the tails of a distribution increases effect sizes and improves reproducibility. However, studies rarely compare how variability in sample sociodemographic characteristics relates to imaging or behavioral phenotypes within BWAS. To address this gap, we derived estimates for brain-behavior associations using multivariate regression models, comparing effect sizes for dimensional, tail-sampled, and propensity matched groups. Data were obtained from the Adolescent Brain Cognitive Development (ABCD) Study(R). The independent variables were brain structural imaging phenotypes, with a range of biological and psychological outcomes as dependent variables. We found expected increases in the magnitude of effect sizes moving from full-sample dimensional models to tail-sampled group-based models. However, findings for the propensity-matched group models suggested a non-uniform impact on BWAS (i.e., both increased and decreased effect sizes). Results suggest that sampling from the tails of the distribution of measures of brain structure generally increases effect sizes across biological, clinical, and cognitive outcomes.

neuroscience↗

bioRxiv2018

Effects of in-vitro pH decrease on the gametogenesis of the red tree coral, Primnoa pacifica

Primnoa pacifica is the most ecologically important coral species in the North Pacific Ocean where it provides important habitat for commercially important fish and invertebrates. Ocean acidification (OA) is more rapidly increasing in high-latitude seas because anthropogenic CO2 uptake is greater in these regions. This is due to the solubility of CO2 in cold water and the reduced buffering capacity due to low alkalinity of colder waters. Primnoa pacifica colonies were cultured for six to nine months in either pH 7.55 (predicted 2100 pH levels) or pH 7.75 (control). Oocyte development and fecundity in females, and spermatocyst stages in males were measured to assess the effects of pH on gametogenesis. Oocyte diameters were 13.6% smaller and fecundities were 30.9% lower in the Year 2100 samples, indicating that OA may limit oocyte formation, potentially through lipid limitation. A higher proportion of vitellogenic oocytes (65%) were also reabsorbed (oosorption) in the Year 2100 treatment. Lowered pH appeared to advance the process of spermatogenesis with a higher percentage of later stage sperm compared to control controls. There was a laboratory effect observed in all measurement types, however these only significantly affected the analyses of spermatogenesis. These results indicate that reproduction may not be possible in an acidified ocean, or that if spawning could occur, spawned oocytes would not be sufficiently equipped to support the normal development of larvae.

physiology↗