Biology subjects

Hooker, J. M.

Publications and source records attributed to Hooker, J. M..

3 recordsLinked to original sources

bioRxiv2026

MeFluHyA: a novel fluorescent screening tool for high-throughput identification of HDAC6-selective inhibitors

The cytosolic histone deacetylase 6 (HDAC6) plays a key role not only in cancer but also in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) peripheral neuropathies. Pharmacological inhibition as well as genetic silencing of HDAC6 is able to rescue several defects. Therefore, developing pharmacological compounds targeting this enzyme is of crucial interest. Here, we report the design, synthesis, and characterization of Methyl Fluorescent Hydroxamic Acid (MeFluHyA), a novel fluorescent HDAC6-selective probe designed for cell imaging. By integrating a Cy5 fluorophore into a phenyl hydroxamic acid scaffold, MeFluHyA shows binding to the catalytically active CD2 domain of HDAC6 without significantly inhibiting its deacetylating function in the sub-micromolar range. Biochemical enzymatic activity assays confirmed its selectivity over other HDAC isoforms. Fluorescent imaging studies in HeLa cells demonstrated strong colocalization with HDAC6-eGFP and a commercial HDAC6 antibody. Competitive binding assays revealed that MeFluHyA effectively identifies known HDAC6 inhibitors, with reduced probe-binding serving as a readout for successful target engagement. MeFluHyA is a cell-permeable, fast and easy to use probe that can be added organism-independent, and its red-shifted fluorophore makes it compatible with multiplex, live and fixed imaging. Overall, we provide a novel tool for screening platforms aimed at identifying novel HDAC6-targeting inhibitors.

biochemistry↗

bioRxiv2026

Energetic implications of fMRI-based nodal complex network metrics: a complex picture unfolds across diverse brain states

Functional MRI-based graph theory has provided profound insights into the brains functional organization, yet the neuroenergetic meaning of widely used graph-theoretical metrics remains poorly understood. Although resting-state research suggests a positive coupling between network topology and glucose metabolism, it remains unclear whether this relationship reflects a general principle of brain organization or a state-specific phenomenon. Here, we test the neuroenergetic interpretability of nodal graph-theoretical metrics by linking complex network topology to cerebral glucose consumption across diverse brain states. Leveraging simultaneous functional PET-MRI, we directly compare state-dependent fluctuations in glucose consumption and network topology during sensory, cognitive, and arousal conditions. We further assess metabolic-topological couplings in disease through a meta-analysis of resting-state FDG-PET and fMRI studies involving Alzheimers disease, Parkinsons disease, major depressive disorder, and schizophrenia. Our results show that nodal graph-theoretical metrics exhibit state- and network-dependent metabolic associations, with coupling patterns diverging across experimental and disease contexts. Notably, frontoparietal and attentional networks show more conserved metabolic-topological coupling than other large-scale networks across states. These findings underscore a dynamic, complex interplay between metabolic demand and complex network organization, highlighting the need for a nuanced interpretation of the energetic underpinnings of nodal graph-theoretical metrics in health and disease.

neuroscience↗

bioRxiv2025

Age-Related Changes in Curiosity: The Influence of Locus Coeruleus on Information-Seeking Behavior

Curiosity enhances learning and memory and has been linked to the locus coeruleus (LC), which undergoes age-related decline. To examine how aging affects curiosity and information-seeking, we developed the Photographic Art Storytelling Task. Participants (sixty-eight young and sixty-five older adults) viewed photographs, rated their curiosity, and later read stories associated with selected images. The stories were deliberately constructed to be either interesting or boring, functioning as rewards that elicited prediction errors. Participants reappraised their curiosity, allowing us to separate intrinsic motivation from story-driven reward influences. Associations between performance and both pupil diameter and MRI measures of LC integrity supported a role of LC in curiosity regulation. Aging was associated with greater reliance on novelty-driven (initial) curiosity and a shift away from prediction error-related information-seeking. Both age groups showed curiosity-driven memory enhancement, with older adults exhibiting youth-like effects, suggesting a role for intrinsic motivation in preserving cognitive function in aging.

neuroscience↗