The peptide hormone ghrelin plays a key role in regulating hunger and energy balance within the body. Ghrelin signaling presents a promising and unexploited target for development of small-molecule therapeutics to treat obesity, diabetes, and other health conditions. Inhibition of ghrelin O-acyltransferase (GOAT), which catalyzes an essential octanoylation step in ghrelin maturation, offers a potential avenue for controlling ghrelin signaling. Through screening a small molecule library, we have identified a class of synthetic triterpenoids that efficiently inhibit ghrelin acylation by the human isoform of GOAT (hGOAT). These compounds function as covalent reversible inhibitors of hGOAT, providing the first evidence for involvement of a nucleophilic cysteine residue in substrate acylation by a MBOAT family acyltransferase. Surprisingly, the mouse form of GOAT does not exhibit susceptibility to cysteine modifying electrophiles revealing an important distinction in the activity and behavior between these closely related GOAT isoforms. This study establishes these compounds as potent small molecule inhibitors of ghrelin acylation and provides a foundation for the development of novel hGOAT inhibitors as therapeutics targeting diabetes and obesity.

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Numerous studies in the past 10 years have reported on the neurocognitive sequalae of pediatric sleep disordered breathing (SDB). Variations in criteria used to define SDB in conjunction with the wide variety of neuropsychological measures selected to evaluate cognitive consequences of SDB have resulted in discrepancies within the literature. This review summarizes the extent literature regarding cognitive effects of pediatric SDB across domains of global intelligence, attention, executive function, memory, language, and visuospatial ability. This review also addresses the proposed etiology underlying neurocognitive consequences of pediatric SDB. The differences in findings across the literature are highlighted and discussed throughout.

Objective Comorbid Autism Spectrum Disorder (ASD) and ADHD are associated with greater symptom severity, including social impairment. Furthering work by Lerner, Pothoff, and Hunter (2015), we sought to identify unique and shared factors that contribute to parent-reported social deficits in children with ADHD, ASD, and ADHD+ASD. We hypothesized attention, hyperactivity, and motor skills would predict social deficits in ADHD, while functional communication and motor skills would predict social deficits in ASD; and additively, all factors would predict social deficits in ADHD+ASD. Method Utilizing a clinical database, we identified 236 participants (4-21 years; Mage = 10.6; 71% male; 28% African American; FSIQ M = 94.31) with diagnoses of ADHD, ASD, and ADHD+ASD. We examined FSIQ from the WISC-4/5, WPPSI-3, or DAS-2, motor skills and social impairment from the SIB-R and attention, hyperactivity, and functional communication from the BASC-2/3. Results Using hierarchical linear regression and controlling for FSIQ, hypotheses were partially supported. FSIQ was controlled for in each group. For ADHD, hyperactivity, functional communication, and motor skills contributed significantly to the model (p < .001), while for ASD, motor skills contributed significantly to the model (p < .001). For ASD + ADHD, functional communication and motor skills contributed significantly to the model (p < .001) Conclusion Results support previous findings that motor deficits and functional communication are associated with social impairment in children with ADHD and ASD, independently and comorbidly. This suggests that targeting motor dysfunction and functional communication concurrently may be effective for improving social interaction skills in children with ADHD +ASD.