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Wentz, T.

Publications and source records attributed to Wentz, T..

2 recordsLinked to original sources

A computational neuroimaging account of impulsive premature decision-making

Impulsivity is a multidimensional construct with distinct implications for the pathophysiology and treatment of various neuropsychiatric conditions, including substance use disorders, behavioural addictions, attention deficit hyperactivity disorder, psychosis, and personality disorders. One proposed behavioural subtype, premature responding impulsivity (PRI), appears to be influenced by neuromodulatory pathways frequently implicated in these disorders, in particular dopamine neurotransmission, known for its role in contingency learning. Still, the neurobiological basis of PRI in humans remains insufficiently understood. Here, we theorize that PRI reflects the brains capacity to adapt to environmental uncertainty. To test this hypothesis, twenty-four healthy adults (mean age 22.6 years; 12 females) completed a novel decision-making task featuring alternating stable and volatile probabilistic cue contingencies while undergoing functional magnetic resonance imaging (fMRI). A hierarchical Bayesian model estimated PRI as an urgency-to-respond process, whose parameters were dynamically modulated by volatility. These model-derived indices correlated with established trait impulsivity measures, supporting their construct validity. Model-based fMRI analyses identified a distributed cortico-subcortical network including anterior insula, dorsal anterior cingulate cortex, striatum, and monoaminergic midbrain regions, whose activity tracked within-trial PRI estimates as they evolved over time. Connectivity analyses further showed that high volatility enhanced interactions between subnetworks typically associated with promoting or inhibiting impulsive action. Together, these results outline a neurocomputational account in which environmental uncertainty modulates PRI through interacting brain circuits, offering a principled framework for further probing the transdiagnostic role of impulsivity across neuropsychiatric and neuropsychopharmacological contexts.

neuroscience↗

Identification of divergent botulinum neurotoxin homologs in Paeniclostridium ghonii

Botulinum neurotoxins (BoNTs) are the most potent family of toxins known to science. Bioinformatic studies in recent years have revealed that they are members of a broader toxin family, with an increasing number of divergent homologs identified in genomes of organisms outside of the Clostridium genus. Here, we report the identification of two putative divergent BoNT-like homologs in the genomes of two strains of Paeniclostridium ghonii. We designated them PG-toxin 1 (PGT1) and PG-toxin 2 (PGT2), which share ~54% protein sequence identity. Unlike any other known BoNT homologs, PGT1 and PGT2 are composed of two separate subunits encoded on two neighboring genes: one encoding the protease domain (light chain, LC) with a conserved HExxH motif, and the second encoding the heavy-chain (HC) containing the putative translocation domain and receptor-binding domain. Phylogenetic analysis of both the LC and HC reveal that it is a divergent member of the lineage of BoNT that also includes BoNT/X, BoNT/En and the insecticidal PMP1. The gene clusters harboring PGT1 and PGT2 also include a putative insecticidal delta-endotoxin, Cry8Ea1, as well as putative endolysin and bacteriocin genes that may facilitate lytic toxin secretion, suggesting a possibility that this gene cluster might serve an insecticidal purpose.

bioinformatics↗