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Zimmerman, D.

Publications and source records attributed to Zimmerman, D..

9 recordsLinked to original sources
bioRxiv2026

Charting neuroimaging-based head circumference and cranial shape across development

Quantitative assessment of head growth supports early detection of neurological disease, yet current clinical practice relies on manual measurements that are variable, anatomically limited, and difficult to scale. Here we introduce a fully automated imaging-native framework (CranioTrace) that transforms routine neuroimaging into standardized, population-referenced markers of cranial development. By integrating topology-constrained segmentation, contour regularization, and geometry-based quality control for automated slice selection, CranioTrace robustly extracts head circumference and cranial morphology from heterogeneous MRI and CT data without manual intervention. The framework enabled construction of sex-specific population growth models across pediatric development in a dataset comprising 9,685 scans spanning birth to early adulthood across 25 cohorts. Imaging-derived head circumference shows strong agreement with tape measurements across independent datasets, high reproducibility (intraclass correlation up to 0.99), and consistent performance across modalities. Beyond conventional head circumference, CranioTrace quantifies cranial shape and asymmetry, capturing developmental dynamics that are not accessible through conventional measurements. Population modeling reveals rapid early-life expansion followed by nonlinear deceleration and stable sex differences. Application to neurogenetic cohorts identifies disease-consistent shifts in growth trajectories: head circumference was higher in neurofibromatosis type 1 and 16p11.2 deletion and lower in 22q11.2 deletion and 16p11.2 duplication. By converting clinical imaging archives into scalable cranial phenotypes linked to probabilistic reference models, CranioTrace provides a foundation for imaging-based growth charting, integrated skull-brain phenotyping, and precise assessment of neurodevelopment.

neuroscience↗
bioRxiv2026

Brain charts for neuroanatomical sex differences across the human lifespan

Population-level sex differences in human neuroanatomy have been highly debated, with prior literature limited by narrow age windows and assumptions about regions scaling with total brain size. Building on recent work charting brain structures across the lifespan, we use magnetic resonance imaging data from over 100,000 individuals (51.7% F) to model normative reference trajectories of 241 structural features capturing age-varying sex effects. Results show replicable age-varying sex differences in nearly all features, and sexs effects survive nonlinear correction for total brain size, with sex biases tending to increase across the lifespan. Notably, models are sensitive to atypicalities in six neuropsychiatric disorders. This work establishes and quantifies population-level sex biases in the largest-to-date study of sex differences in the human brain.

neuroscience↗
bioRxiv2026

An innovative tool for non-invasive contact-free pathogen monitoring in animal saliva

Habitat fragmentation, climate change, poaching, human-wildlife conflicts, and infectious diseases are the main threats to biodiversity conservation. They alter host-pathogen dynamics, reduce viable conservation areas, and promote genetic isolation, resulting in physiological stress among animal populations. Moreover, increased proximity between domestic and wild animals further facilitates disease spillovers exposing naive host species and ecosystems to new pathogens. Of the more than 200 known zoonotic diseases, approximately 60% originate from animals, contributing significantly to the global infectious disease burden. Here, we describe the development of an innovative non-invasive approach for biological sampling that has been validated in mice and shelter cats. Our device consists of a disposable plastic cassette that through odor attractants lures animals to lick a filter paper. This saliva collection approach allowed for the detection of RNA viruses by RTqPCR and third-generation sequencing. RTqPCR oral swab and licked paper results showed that both methods significantly predicted serological status. Our sequencing results revealed the richness of the gene space, demonstrating the potential of this device for discovering rare or unknown species circulating in the saliva donor, enabling this player to be recognized as an environmental sentinel. This study demonstrates the feasibility of deploying this device in sheltered/captive animal settings as well as under laboratory simulations of different environments, providing necessary foundations for future field applications. Our methodology holds great potential for monitoring zoonotic pathogens in both captive and free-ranging animals, to even possibly allow proactive mitigation measures prior to spillover, without interfering with the natural animal behaviour and social structures. Visual abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=141 SRC="FIGDIR/small/705368v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@1325498org.highwire.dtl.DTLVardef@14ff0cdorg.highwire.dtl.DTLVardef@14a4334org.highwire.dtl.DTLVardef@8217e4_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗
bioRxiv2025

Charting structural brain asymmetry across the human lifespan

Lateralization is a fundamental principle of structural brain organization. In vivo imaging of brain asymmetry is essential for deciphering lateralized brain functions and their disruption in neurodevelopmental and neurodegenerative disorders. Here, we present a normative framework for benchmarking brain asymmetry across the lifespan, developed from an aggregated sample of 128 primary neuroimaging studies, including 177,701 scans from 138,231 individuals, jointly spanning the age range from 20 post menstrual weeks to 102 years. This resource includes comprehensive, hemisphere-specific brain growth charts for multiple neuroimaging phenotypes: regional cortical grey matter volume, thickness, surface area, and subcortical volumes. Our findings reveal distinct spatial patterns of asymmetry, with early leftward asymmetry observed in association cortices and late rightward asymmetry in sensory regions. These trajectories support theories of the neuroplasticity of asymmetry and the role of both genetic and environmental factors in shaping brain lateralization. Additionally, we provide tools to generate asymmetry centile scores, which allow the quantification of individual deviations from typical asymmetry throughout the lifespan and can be applied to unseen data or clinical populations. We demonstrate the utility of these models by highlighting group-level differences in asymmetry in autism spectrum disorder, schizophrenia, and Alzheimers disease, and exploring genetic correlations with hemispheric specialization. To facilitate further research, we have made this normative framework freely available as an interactive open-access resource (upon publication), offering an essential tool to advance both basic and clinical neuroscience.

neuroscience↗
bioRxiv2025

Comprehensively Testing the Function of Missense Variation in the STK11 Tumour Suppressor

The tumor suppressor gene STK11 encoding Serine/Threonine Kinase 11 (STK11) is associated with Peutz-Jeghers Syndrome (PJS), a heritable gastrointestinal disease that increases lifetime cancer risk, and with somatic variation that contributes to [~]30% of lung and 20% of cervical cancers. Although identifying pathogenic variants is clinically actionable, over 94% of STK11 missense variants that have been observed clinically lack a definitive classification. We therefore measured the impact of STK11 variants at scale in a mammalian cell-based assay, scoring 6,026 (73% of all possible) amino acid substitutions across the full-length gene. Functional scores--which were consistent with biochemical properties, smaller-scale assays, and pathogenicity annotations--identified a subset of PJS patients with germline STK11 variants diagnosed later in life, as well as somatic STK11 variants found in cancer patients that had comparable overall survival estimates to wild-type STK11. Our scores provided new evidence for 350 annotated VUS STK11 missense variants and [~]80% of missense variants that have not yet been reported clinically, but we might expect to observe in the future. Thus, our effect map provides a proactive resource for gaining sequence-structure-function insights and evidence for actionable interpretation of clinical missense variants.

cancer biology↗
bioRxiv2025

The aging human brain exhibits reduced cerebrospinal fluid flow during sleep due to both neural and vascular factors

Aging reduces the quality and quantity of sleep, and greater sleep loss over the lifespan is predictive of neurodegeneration and cognitive decline. One mechanism by which sleep loss could contribute to impaired brain health is through disruption of cerebrospinal fluid (CSF) circulation. CSF is the primary waste transport system of the brain, and in young adults, CSF waves are largest during NREM sleep. However, whether sleep-dependent brain fluid physiology changes in aging is not known, due to the technical challenges of performing neuroimaging studies during sleep. We collected simultaneous fast fMRI and EEG data to measure large-scale CSF flow in healthy young and older adults and tested whether there were age-related changes to CSF dynamics during nighttime sleep. We found that sleep-dependent CSF flow was reduced in older adults, and this reduction was linked to impaired frontal EEG delta power and global hemodynamic oscillations during sleep. To identify mechanisms underlying reduced CSF flow, we used sensory and vasoactive stimuli to drive CSF flow in daytime task experiments, and found that both neural and cerebrovascular physiological changes contributed to the disruption of CSF flow during sleep. Finally, we found that this reduction in CSF flow was associated with gray matter atrophy in aging. Together, these results demonstrate that the aging human brain has reduced CSF flow during sleep, and identifies underlying neurovascular mechanisms that contribute to this age-related decline, suggesting targets for future interventions.

neuroscience↗
bioRxiv2020

Internal state configures olfactory behavior and early sensory processing in Drosophila larva

Animals exhibit different behavioral responses to the same sensory cue depending on their state at a given moment in time. How and where in the brain are sensory inputs combined with internal state information to select an appropriate behavior? Here we investigate how food deprivation affects olfactory behavior in Drosophila larvae. We find that certain odors reliably repel well-fed animals but attract food-deprived animals. We show that feeding state flexibly alters neural processing in the first olfactory center, the antennal lobe. Food deprivation differentially modulates two separate output pathways that are required for opposing behavioral responses. Uniglomerular projection neurons mediate odor attraction and show elevated odor-evoked activity in the food-deprived state. A multiglomerular projection neuron mediates odor aversion and receives odor-evoked inhibition in the food-deprived state. The switch between these two pathways is regulated by the lone serotonergic neuron in the antennal lobe, CSD. Our findings demonstrate how flexible behaviors can arise from state-dependent circuit dynamics in an early sensory processing center.

neuroscience↗
bioRxiv2018

Enhancement of Transgene Expression by NF-Y and CTCF

If a transgene is effectively delivered to a cell, its expression may still be limited by epigenetic mechanisms that silence the transgene. Indeed, once the transgene reaches the nucleus, it may be bound by histone proteins and condensed into heterochromatin or associated with repressor proteins that block transcription. In this study, we sought to enhance transgene expression by adding binding motifs for several different epigenetic enzymes either upstream or downstream of two promoters (CMV and EF1). Screening these plasmids revealed that luciferase expression was enhanced 10-fold by the addition of a CCAAT box just upstream of the EF1 promoter to recruit nuclear transcription factor Y (NF-Y), while inserting a CCCTC-binding factor (CTCF) motif downstream of the EF1 promoter enhanced expression 14-fold (14.03 {+/-} 6.54). ChIP assays confirmed that NF-Y and CTCF bound to the motifs that were added to each plasmid, but the presence of NF-Y and CTCF did not significantly affect the levels of histone acetylation (H3K9ac). Overall, these result show that transgene expression from the EF1 promoter can be significantly increased with motifs that recruit NF-Y or CTCF.

bioengineering↗