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Biology subjects

Roberts, C. J.

Publications and source records attributed to Roberts, C. J..

3 recordsLinked to original sources

An ancient monoaminergic signaling system coordinates contractility in a nerveless sponge

Chemical neurotransmission was a key animal innovation, enabling multicellular coordination of physiology and locomotion. Sponges are early-diverging animals that lack neurons and muscles, yet still coordinate contraction and relaxation of their filter-feeding water canals. Here, we show that Spongilla lacustris synthesizes the monoamines tryptamine, phenethylamine, and tyramine to elicit distinct canal behaviors. We identify previously uncharacterized decarboxylases and vesicular transporters coexpressed in secretory neuroid and metabolic cells. Using phosphoproteomics and label-free 3D imaging, we show that tryptamine activates GPCR signaling and Rho GTPases, remodeling adhesion and actomyosin networks in contractile canal epithelia to drive localized constrictions and whole-body deflations. Together, these findings define an ancestral monoaminergic system linking secretory and contractile cell types that predate neurons and was later elaborated for neuromodulation of synaptic transmission.

evolutionary biology↗

Parabrachial Calca neurons influence aversive and appetitive taste function

The parabrachial (PB) nucleus participates in taste processing and integration with other senses. PB neurons that express the Calca gene support sensory-integrative responses, albeit only limited data have addressed their influence on taste. Here we studied how chemogenetic dampening of PB-Calca neurons impacted mouse orosensory preferences for diverse taste stimuli in brief-access fluid exposure tests, which capture oral sensory/tongue control of licking behavior. Intracranial delivery of Cre-dependent viruses in female and male CalcaCre/+ mice induced expression of the inhibitory designer receptor hM4Di:mCherry (hM4Di mice) or fluorophore mCherry alone (mCherry mice) in PB-Calca neurons. Several weeks later, hM4Di and mCherry mice entered brief-access tests where they could lick taste solutions on discrete seconds-long trials. Stimuli included the behaviorally avoided, but functionally different, bitter taste stimuli quinine (0 [water], 0.1, 0.3, and 1.0 mM) and cycloheximide (0, 0.001, 0.003, and 0.01 mM), and the appetitive sugar sucrose (0, 100, 300, 500, and 1000 mM). Both hM4Di and mCherry mice received the hM4Di ligand clozapine-N-oxide (CNO, 5 mg/kg, i.p.) prior to daily tests performed by blinded experimenters. With CNO, hM4Di mice displayed greater average licking (i.e., less avoidance) of quinine (p < 0.05), but not cycloheximide (p > 0.3), than mCherry mice, implying PB-Calca neurons variably influence orosensory responses across bitter stimuli. Moreover, male hM4Di mice selectively showed reduced mean licking preferences for sucrose under CNO (p < 0.05). These data suggest that PB-Calca neurons participate in both aversive and appetitive taste-guided behaviors, with their role in appetitive taste dependent on sex.

neuroscience↗

Thyroid and androgen receptor signaling are antagonized by CRYM in prostate cancer

Androgen deprivation therapy (ADT) remains a key approach in the treatment of prostate cancer (PCa). However, PCa inevitably relapses and becomes ADT resistant. Besides androgens, there is evidence that thyroid hormone thyroxine (T4) and its active form 3,5,3-triiodo-L-thyronine (T3) are involved in the progression of PCa. Epidemiologic evidence indicates a higher incidence of PCa in men with elevated thyroid hormone levels. The thyroid hormone binding protein -Crystallin (CRYM) mediates intracellular thyroid hormone action by sequestering T3 and blocks its binding to cognate receptors (TRa/TRb) in target tissues. We show in this study that low CRYM expression levels in PCa patient samples are associated with early BCR and poor prognosis. Moreover, we found a disease stage-specific expression of CRYM in PCa. CRYM counteracted thyroid and androgen signaling and blocked intracellular choline uptake. CRYM inversely correlated with [18F]fluoromethylcholine (FMC) levels in PET/MRI imaging of PCa patients. Our data suggest CRYM as a novel antagonist of T3 and androgen-mediated signalling. The role of CRYM could therefore be an essential control mechanism for the prevention of aggressive PCa growth. HighlightsO_LIThyroid and androgen hormone driven pathways in prostate cancer (PCa) are antagonized by - Crystallin (CRYM). C_LIO_LI[18F]fluoromethylcholine uptake and prognostic values in PCa correlate with CRYM protein levels. C_LIO_LIReduced CRYM expression predicts early biochemical recurrence (BCR) in PCa patients. C_LI

cancer biology↗