Brinkman, T. | Search bioRxiv

bioRxiv2026

Neurometabolic correlates of accelerated aging and neurocognitive late effects in long-term survivors of pediatric hodgkin lymphoma and acute lymphoblastic leukemia

Adult survivors of pediatric cancers are at elevated risk for neurocognitive late effects, but how these effects relate to metabolic perturbations in the brain remains unclear. To address this knowledge gap, the present study explored associations between neurometabolite levels and neurocognitive function in adult survivors of Hodgkin lymphoma (HL) and acute lymphocytic leukemia (ALL). Data were collected from a single-center observational study conducted at St. Jude Childrens Research Hospital (SJCRH) between October 2022 and November 2024. Adult survivors of HL (N=11 [5 females]; [≥]5 years post-diagnosis; mean [SD] current age 34 [9.5] years) and ALL (N=24 [16 females]; [≥]5 years post-diagnosis; current age 40 [12.6] years) and community controls (N=35 [17 females]; current age 40 [11] years) completed standardized neurocognitive tests of memory, attention, executive function, and processing speed. Participants also underwent proton magnetic resonance spectroscopy (1H MRS) to quantify neurometabolite levels in the left dorsolateral prefrontal cortex (dlPFC), left hippocampus, and left cerebellum. Analyses used regression models to examine differences in the slope of the relationship between neurometabolite and neurocognitive function or between neurometabolite and age. When comparing HL survivors vs controls, significant interactions were identified for group x age on the ratio of myo-inositol to N-Acetyl aspartic acid (mI/NAA; p=0.007) and group x Gamma-Aminobutyric Acid (GABA) on processing speed (p=0.04) in the left dlPFC. When comparing ALL survivors vs controls, significant interactions were identified for group x myo-inositol on verbal fluency in the left hippocampus (p=0.01) and group x GABA on cognitive flexibility in the left cerebellum (p=0.01). These preliminary findings suggest that neuroinflammation may be a mechanistic underpinning of age-associated neurocognitive impairment in pediatric cancer survivors.

neuroscience↗

bioRxiv2023

Optimization of molecular methods for detection and quantification of specific duckweed-bacteria interactions

Bacterial colonization dynamics of plants can differ between phylogenetically similar bacterial strains as well as in the context of complex bacterial communities. Quantitative studies that can resolve closely related bacteria within complex communities can lead to a better understanding of plant-microbe interactions. However, current methods lack the specificity to differentiate phylogenetically similar bacterial strains. In this study, we describe molecular strategies to study specific duckweed-bacteria interactions. We first systematically optimized a bead-beating protocol to co-isolate nucleic acids simultaneously from duckweed and bacteria. We then developed a generic fingerprinting assay to detect bacteria present in duckweed samples. To detect specific duckweed-bacteria interactions, we developed a genomics-based computational pipeline to generate bacterial strain-specific primers. These strain-specific primers differentiated bacterial strains from the same genus and enabled the detection of specific duckweed-bacteria interactions present in a community context. Moreover, we used these strain-specific primers to quantify the bacterial colonization of duckweed by normalization to a plant reference gene and revealed differences in colonization levels between strains from the same genus. Lastly, confocal microscopy of inoculated duckweed further supported our PCR results and showed bacterial colonization of the duckweed root-frond interface and root interior. The molecular methods introduced in this work should enable the tracking and quantification of specific plant-microbe interactions within plant-microbial communities.

ecology↗