Biology subjects

Puckett, H.

Publications and source records attributed to Puckett, H..

3 recordsLinked to original sources

bioRxiv2026

From cognitive abstraction to adaptive behavior: neural bases of concept learning in autistic adolescents

BACKGROUNDLearned knowledge does not consistently generalize to new contexts in autistic individuals, limiting potential for adapting to real-world demands. This challenge is hypothesized to stem from difficulties with forming abstract representations, potentially arising from perceptual processing that favors local details over the gestalt. We tested the prediction that generalization would be primarily based on exemplar-specific representations in autistic youth using computational modelling coupled with neuroimaging. METHODSSixty-four autistic adolescents without intellectual disability (69% males; ages 14-18 years) completed a category generalization task during functional magnetic resonance imaging at two time points. Computational models estimated abstract (prototype-based) and specific (exemplar-based) representations and underlying neural correlates. We further examined associations with adaptive functioning and moderation by autistic traits. RESULTSContrary to predictions, we observed a consistent prototype-dominant majority, a subgroup who generalized without consistent representational reliance, and a small minority who failed to acquire category structure. Prototypes were represented in bilateral ventromedial prefrontal cortex (VMPFC), inferior parietal lobule (IPL), right frontal pole, and right lateral occipital cortex, while exemplars were represented in bilateral cuneus. Better generalization predicted better real-world adaptive functioning. Moreover, greater prototype-related activation in left IPL predicted better adaptive functioning in participants with higher autistic traits. CONCLUSIONSThese findings challenge the prevailing view that concept learning in autism relies primarily on hyper-specific perceptual processing, identify meaningful variability in representational strategies, and reveal neural pathways through which abstract representation may support real-world adaptive behavior.

neuroscience↗

bioRxiv2021

Perfluorooctanoic Acid Induces Liver and Serum Dyslipidemia in Humanized PPARα Mice Fed an American Diet

Per- and polyfluoroalkyl substances (PFAS) are pervasive in the environment resulting in nearly universal detection in people. Human serum PFAS concentrations are strongly associated with increased serum low-density lipoprotein cholesterol (LDL-C), and growing evidence suggests an association with serum triacylglycerides (TG). Here, we tested the hypothesis that perfluorooctanoic acid (PFOA) dysregulates liver and serum triacylglycerides in human peroxisome proliferator activated receptor (hPPAR)-expressing mice fed an American diet. Mice were exposed to PFOA (3.3 mg/l) in drinking water for 6 weeks resulting in a serum concentration of 48 {+/-} 9 g/ml. In male and female hPPAR mice, PFOA increased total liver TG and TG substituted with saturated and monounsaturated fatty acids. Lack of expression of hPPAR alone also increased total liver TG, and PFOA treatment had little effect on liver TG in null mice. In hPPAR mice, PFOA neither significantly increased nor decreased serum TG; however, there was a modest increase in TG associated with very low-density cholesterol particles in both sexes. Across studies, a non-monotonic effect of PFOA on serum TG is evident, with the serum PFOA concentration in this study falling near the "null point" between increasing and decreasing serum TG. Intriguingly, in female PPAR null mice, PFOA significantly increased serum TG, with a similar trend in males. PFOA also modified fatty acid and TG homeostasis-related gene expression in liver, in a hPPAR-dependent manner, but not in adipose. The results reveal the importance of context (serum concentration and genotype) in determining the effect of PFOA on lipid homeostasis.

pharmacology and toxicology↗

bioRxiv2020

Perfluorooctanoic acid activates multiple nuclear receptor pathways and skews expression of genes regulating cholesterol homeostasis in liver of humanized PPARα mice fed an American diet

Humans are exposed to per- and polyfluoroalkyl substances (PFAS) in their drinking water, food, air, dust in their homes, and by direct use of consumer products. Increased concentrations of serum total cholesterol and low density lipoprotein cholesterol are among the endpoints best supported by epidemiology. The objectives of this study were to generate a new model for examining PFAS-induced dyslipidemia and to conduct molecular studies to better define mechanism(s) of action. We tested the hypothesis that PFOA exposure at a human-relevant level dysregulates expression of genes controlling cholesterol homeostasis in livers of mice expressing human PPAR (hPPAR). Female and male hPPAR and PPAR null mice were fed a diet based on the "What we eat in America" analysis and exposed to perfluorooctanoic acid (PFOA) in drinking water (8 {micro}M) for 6 weeks. This resulted in a serum PFOA concentration of 48 g/ml. PFOA increased liver mass, which was associated with histologically-evident lipid accumulation. PFOA induced PPAR and constitutive androstane receptor target gene expression in liver. Expression of genes in four pathways regulating cholesterol homeostasis were also measured. PFOA decreased expression of Hmgcr in a PPAR-dependent manner. PFOA decreased expression of Ldlr and Cyp7a1 in a PPAR-independent manner. Apob expression was not changed. Gene expression in females appeared to be more sensitive to PFOA exposure than in males. This novel study design (hPPAR mice, American diet, long term exposure) generated new insight on the effects of PFOA on cholesterol regulation in the liver and the role of hPPAR.

pharmacology and toxicology↗