A riboside hydrolase that salvages both nucleobases and nicotinamide in the auxotrophic parasite Trichomonas vaginalis.

Pathogenic parasites of the Trichomonas genus are causative agents of sexually transmitted diseases affecting millions of individuals worldwide and whose outcome may include stillbirths and enhanced cancer risks and susceptibility to HIV infection. Trichomonas vaginalis relies on imported purine and pyrimidine nucleosides and nucleobases for survival, since it lacks the enzymatic activities necessary for de novo biosynthesis. Here we show that T. vaginalis additionally lacks homologues of the bacterial or mammalian enzymes required for the synthesis of the nicotinamide ring, a crucial component in the redox cofactors NAD+ and NADP. Moreover, we show that a yet fully uncharacterized T. vaginalis protein homologous to bacterial and protozoan nucleoside hydrolases is active as a pyrimidine nucleosidase but shows the highest specificity toward the NAD+ metabolite nicotinamide riboside. Crystal structures of the trichomonal riboside hydrolase in different states reveals novel intermediates along the nucleoside hydrolase-catalyzed hydrolytic reaction, including an unexpected asymmetry in the homotetrameric assembly. The active site structure explains the broad specificity toward different ribosides and offers precise insights for the engineering of specific inhibitors that may simultaneously target different essential pathways in the parasite.

Trait Versus Task-Induced Emotional Reactivity and Distress Intolerance in Hoarding Disorder: Transdiagnostic Implications.

Evidence from analogue samples suggests that deficits in emotional functioning, namely elevated emotional reactivity and distress intolerance, are implicated in the development and maintenance of hoarding disorder. We aimed to extend previous research in this area by investigating emotional reactivity and distress intolerance in a sample of individuals diagnosed with hoarding disorder (n = 24) in comparison to clinical controls (n = 21) and nonclinical community controls (n = 26) using a combination of self-report, physiological, and behavioral measures. We found that trait distress intolerance was significantly and independently associated with greater hoarding severity. The hoarding and clinical control groups reported more trait emotional reactivity and distress intolerance than the community control group, but did not differ from each other on these traits. The hoarding group reported more subjective distress before beginning a frustrating behavioral task, but did not evidence more physiological arousal. Moreover, the hoarding group experienced similar increases in distress during the task and did not differ from either group in regard to time persisting on this task. The clinical control group, however, terminated the frustrating task significantly faster than the community control group, who tended to persist until the task timed out. Lastly, trait distress intolerance evidenced a small-to-moderate but nonstatistically significant independent relationship with task persistence time. Given the desynchrony between subjective distress and physiological arousal, we encourage researchers to utilize multimodal assessment in the future. We also suggest that clinicians start to use behavioral experiments, as has been done with other psychological disorders, to improve distress intolerance among persons who experience hoarding disorder.