Biology subjects

Huffman, D.

Publications and source records attributed to Huffman, D..

5 recordsLinked to original sources

bioRxiv2024

Characterization of sleep in a mouse model of CLN3 disease revealed sex-specific sleep disturbances

The neuronal ceroid lipofuscinoses (NCLs) are a group of recessively inherited neurodegenerative diseases characterized by lysosomal storage of fluorescent materials. CLN3 disease, or juvenile Batten disease, is the most common NCL that is caused by mutations in the Ceroid Lipofuscinosis, Neuronal 3 (CLN3) gene. Sleep disturbances are among the most common symptoms associated with CLN3 disease, yet this is understudied and has not been delineated in an animal model of the disease. The current study utilized a non-invasive, automated piezoelectric motion sensing system (PiezoSleep) to classify sleep and wakefulness in a Cln3{phi}..ex1-6/{phi}..ex1-6 (Cln3KO) mouse model and age- and sex-matched wild-type (WT) controls. The sleep-wake classification by PiezoSleep was found to be about 90% accurate when validated against simultaneous gold standard polysomnographic recordings including electroencephalography (EEG) and electromyography (EMG) in a small cohort of WT and Cln3KO mice. Our large cohort PiezoSleep study reveals sleep abnormalities during the light period (LP) in male Cln3KO mice compared to WT male, and more subtle differences in Cln3KO female mice throughout the dark period (DP) compared to WT female, recapitulating sleep abnormalities seen in CLN3 disease patients. Our characterization of sleep in a mouse model of CLN3 disease contributes to a better understanding of the sleep disturbances commonly reported for CLN3 disease and other NCLs, which will facilitate the development of new disease treatment and management strategies.

neuroscience↗

bioRxiv2024

Human brain aging heterogeneity observed from multi-region omics data reveals a subtype closely related to Alzheimer's disease

INTRODUCTION: The interconnection between brain aging and Alzheimers disease (AD) remain to be elucidated. METHODS: We investigated multi-omics (transcriptomics and proteomics) data from multiple brain regions (i.e., the hippocampus (HIPP), prefrontal cortex (PFC), and cerebellum (CRBL)) in cognitively normal individuals. RESULTS: We found that brain samples could be divided into ADL (AD-like) and NL (normal) subtypes which were correlated across brain regions. The differentially expressed genes in the ADL samples highly overlapped with AD gene signatures and the changes were consistent across brain regions (PFC and HIPP) in the multi-omics data. Intriguingly, the ADL subtype in PFC showed more differentially expressed genes than other brain regions, which could be explained by the baseline gene expression differences in the PFC NL samples. DISCUSSION: We conclude that brain aging heterogeneity widely exists, and our findings corroborate with the hypothesis that AD-related changes occur decades before the clinical manifestation of cognitive impairment in a sub-population.

neuroscience↗

bioRxiv2021

Goal-oriented predictive representations in the human hippocampus

Recent work in cognitive and systems neuroscience has suggested that the hippocampus might support planning, imagination, and navigation by forming "cognitive maps" that capture the structure of physical spaces, tasks, and situations. Critically, navigation involves planning within a context and disambiguating similar contexts to reach a goal. We examined hippocampal activity patterns in humans during a goal-directed navigation task to examine how contextual and goal information are incorporated in the construction and execution of navigational plans. Results demonstrate that, during planning, the hippocampus carries a context-specific representation of a future goal. Importantly, this effect could not be explained by stimulus or spatial information alone. During navigation, we observed reinstatement of activity patterns in the hippocampus ahead of participants required actions, which was strongest for behaviorally relevant points in the sequence. These results suggest that, rather than simply representing overlapping associations, hippocampal activity patterns are powerfully shaped by context and goals.

neuroscience↗

bioRxiv2019

Genetic and morphological variation is associated with differences in cold-water tolerance and geographic expansion among invasive snails (Melanoides tuberculata) in central Texas

Melanoides tuberculata (Thiaridae) is an old-world freshwater snail that is and now circumtropical. After being introduced in the 1960s via the aquarium trade, populations of M. tuberculata are thriving in spring systems of Texas (USA). Field surveys and experimental investigations of temperature tolerance suggest M. tuberculata is stenothermal, and thus range expansions outside of aquatic habitats with water temperatures between 18{degrees} and 32{degrees}C should be unlikely. However, in 2012 snails were detected in natural aquatic habitats with seasonal temperatures below the experimentally determined lethal thermal minimum. To test whether genetic and phenotypic variation might be associated with cold-water tolerance and range expansion, we sequenced the 16S ribosomal rRNA gene and measured qualitative conch morphology of 170 snails collected at 26 sites in three central Texas rivers. We also conducted phylogenetic analyses of M. tuberculata collected globally and in Texas to determine potential source populations and estimate the number of invasion events. Our results show snails detected in variable temperature habitats are genetically divergent and morphologically distinct from snails collected in habitats with stable temperatures. These data are consistent with at least three introduction events into Texas of M. tuberculata sensu lato that are characterized by distinct habitat preferences, physiological tolerances, and/or adaptive behaviors.

zoology↗

bioRxiv2017

Intestinal crypts recover rapidly from focal damage with coordinated motion of stem cells that is impaired by aging

Despite the continuous renewal and turnover of the small intestinal epithelium, the intestinal stem cell niche maintains a soccer ball-like, alternating pattern of stem and Paneth cells in the crypt. To study the robustness of the niche pattern, we used intravital two-photon microscopy in mice with fluorescently-labeled Lgr5+ intestinal stem cells and precisely perturbed the mosaic pattern with femtosecond laser ablation. Ablation of one to three cells initiated rapid motion of niche cells that restored the alternation in the crypt pattern within about two hours without any cell proliferation. Crypt cells then performed a coordinated dilation of the crypt lumen, which resulted in peristalsis-like motion that forced damaged cells out of the niche. Crypt cell motion was reduced with inhibition of the ROCK pathway and attenuated with old age, and both resulted in incomplete pattern recovery. This suggests that in addition to proliferation and self-renewal, motility of stem cells is critical for maintaining homeostasis. Reduction of this novel behavior of stem cells could contribute to disease and age-related changes.

physiology↗