Perinatal granulopoiesis and risk of pediatric asthma.

There are perinatal characteristics, such as gestational age, reproducibly associated with the risk for pediatric asthma. Identification of biologic processes influenced by these characteristics could facilitate risk stratification or new therapeutic targets. We hypothesized that transcriptional changes associated with multiple epidemiologic risk factors would be mediators of pediatric asthma risk. Using publicly available transcriptomic data from cord blood mononuclear cells, transcription of genes involved in myeloid differentiation was observed to be inversely associated with a pediatric asthma risk stratification based on multiple perinatal risk factors. This gene signature was validated in an independent prospective cohort and was specifically associated with genes localizing to neutrophil-specific granules. Further validation demonstrated that umbilical cord blood serum concentration of PGLYRP-1, a specific granule protein, was inversely associated with mid-childhood current asthma and early-teen FEV1/FVCx100. Thus, neutrophil-specific granule abundance at birth predicts risk for pediatric asthma and pulmonary function in adolescence.

Serotonin Transporter Deficiency is Associated with Dysbiosis and Changes in Metabolic Function of the Mouse Intestinal Microbiome.

Serotonin transporter (SERT) plays a critical role in regulating extracellular availability of serotonin (5-HT) in the gut and brain. Mice with deletion of SERT develop metabolic syndrome as they age. Changes in the gut microbiota are being increasingly implicated in Metabolic Syndrome and Diabetes. To investigate the relationship between the gut microbiome and SERT, this study assessed the fecal and cecal microbiome profile of 11 to 12 week-old SERT+/+ and SERT-/- mice. Microbial DNA was isolated, processed for metagenomics shotgun sequencing, and taxonomic and functional profiles were assessed. 34 differentially abundant bacterial species were identified between SERT+/+ and SERT-/-. SERT-/- mice displayed higher abundances of Bacilli species including genera Lactobacillus, Streptococcus, Enterococcus, and Listeria. Furthermore, SERT-/- mice exhibited significantly lower abundances of Bifidobacterium species and Akkermansia muciniphilia. Bacterial community structure was altered in SERT-/- mice. Differential abundance of bacteria was correlated with changes in host gene expression. Bifidobacterium and Bacilli species exhibited significant associations with host genes involved in lipid metabolism pathways. Our results show that SERT deletion is associated with dysbiosis similar to that observed in obesity. This study contributes to the understanding as to how changes in gut microbiota are associated with metabolic phenotype seen in SERT deficiency.

Copper-Catalyzed Formation of α-Alkoxycycloalkenones from N-Tosylhydrazones.

The combination of 20 mol % of copper iodide and lithium tert-butoxide triggers the formation of a broad range of substituted, functionalized α-alkoxy 2H-naphthalenones from readily available N-tosylhydrazones. The data suggests that this transformation occurs through cycloaddition of a copper carbenoid with an ester, followed by a Lewis acid-catalyzed [1,2] alkyl shift of the in situ generated alkoxyepoxide intermediate.