Leptin acts via its receptor (LepRb) to modulate gene expression in hypothalamic LepRb-expressing neurons, thereby controlling energy balance and glucose homeostasis. Despite the importance of the control of gene expression in hypothalamic LepRb neurons for leptin action, the transcriptional targets of LepRb signaling have remained undefined because LepRb cells contribute a small fraction to the aggregate transcriptome of the brain regions in which they reside. We thus employed translating ribosome affinity purification followed by RNA sequencing to isolate and analyze mRNA from the hypothalamic LepRb neurons of wild-type or leptin-deficient ( mice treated with vehicle or exogenous leptin. Although the expression of most of the genes encoding the neuropeptides commonly considered to represent the main targets of leptin action were altered only following chronic leptin deprivation, our analysis revealed other transcripts that were coordinately regulated by leptin under multiple treatment conditions. Among these, acute leptin treatment increased expression of the transcription factor in LepRb neurons. Furthermore, ablation of from LepRb neurons (Atf3KO mice) decreased leptin efficacy and promoted positive energy balance in mice. Thus, this analysis revealed the gene targets of leptin action, including , which represents a cellular mediator of leptin action.
Newborn congenital cytomegalovirus (cCMV) screening programs have been found to increase the rates of early diagnosis and treatment. In North America, newborn cCMV screening programs have not been widely implemented, leaving healthcare providers to rely on clinical suspicion alone to prompt testing. This study sought to examine healthcare providers’ cCMV testing practices at a quaternary children’s hospital. A retrospective review of the electronic health record was completed for eligible infants over a six-year period. Bivariate calculations and analyses were performed. Between 2014 and 2019, a total of 40,091 infants were cared for at the study institution, of which 178 were tested for cCMV and 10 infants were diagnosed with cCMV. Isolated small-for-gestational age was the most common indication (53/178) to prompt testing. Overall, the cCMV testing rate was 4.5 tests per 1000 infants, with a resulting diagnostic prevalence of 0.2 cases per 1000 infants, which is 15-fold lower than the expected prevalence. Providers relying on clinical suspicion alone are infrequently testing infants for cCMV, resulting in missed diagnoses and missed opportunities for treatment. Systematic cCMV screening practices may improve diagnosis, treatment, and childhood outcomes.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.