Transcriptomic Profiles in Nasal Epithelium and Asthma Endotypes in Youth.

Importance: T helper 2 (T2) cells and T helper 17 (T17) cells are CD4+ T cell subtypes involved in asthma. Characterizing asthma endotypes based on these cell types in diverse groups is important for developing effective therapies for youths with asthma.

Objective: To identify asthma endotypes in school-aged youths aged 6 to 20 years by examining the distribution and characteristics of transcriptomic profiles in nasal epithelium.

Nasal epithelial gene expression and total IgE in children and adolescents with asthma.

Background: Little is known about nasal epithelial gene expression and total IgE in youth.

Objective: We aimed to identify genes whose nasal epithelial expression differs by total IgE in youth, and group them into modules that could be mapped to airway epithelial cell types.

Methods: We conducted a transcriptome-wide association study of total IgE in 469 Puerto Ricans aged 9 to 20 years who participated in the Epigenetic Variation and Childhood Asthma in Puerto Ricans study, separately in all subjects and in those with asthma.

Intercepted Retro-Nazarov Reaction: Syntheses of Amidino-Rocaglate Derivatives and Their Biological Evaluation as eIF4A Inhibitors.

Rocaglates are a family of natural products isolated from the genus which possess a highly substituted cyclopenta[]benzofuran skeleton and inhibit cap-dependent protein synthesis. Rocaglates are attractive compounds due to their potential for inhibiting tumor cell maintenance by specifically targeting eukaryotic initiation factor 4A (eIF4A) and interfering with recruitment of ribosomes to mRNA. In this paper, we describe an intercepted retro-Nazarov reaction utilizing intramolecular tosyl migration to generate a reactive oxyallyl cation on the rocaglate skeleton.

A photochemical flow reactor for large scale syntheses of aglain and rocaglate natural product analogues.

Herein, we report the development of continuous flow photoreactors for large scale ESIPT-mediated [3+2]-photocycloaddition of 2-(p-methoxyphenyl)-3-hydroxyflavone and cinnamate-derived dipolarophiles. These reactors can be efficiently numbered up to increase throughput two orders of magnitude greater than the corresponding batch reactions.

Identification of Anti-prion Compounds using a Novel Cellular Assay.

Prion diseases are devastating neurodegenerative disorders with no known cure. One strategy for developing therapies for these diseases is to identify compounds that block conversion of the cellular form of the prion protein (PrP) into the infectious isoform (PrP). Most previous efforts to discover such molecules by high-throughput screening methods have utilized, as a read-out, a single kind of cellular assay system: neuroblastoma cells that are persistently infected with scrapie prions.

Development of a Potent and Selective HDAC8 Inhibitor.

A novel, isoform-selective inhibitor of histone deacetylase 8 (HDAC8) has been discovered by the repurposing of a diverse compound collection. Medicinal chemistry optimization led to the identification of a highly potent (0.8 nM) and selective inhibitor of HDAC8.

Obesity and Airway Dysanapsis in Children with and without Asthma.

Rationale: For unclear reasons, obese children with asthma have higher morbidity and reduced response to inhaled corticosteroids.

Objectives: To assess whether childhood obesity is associated with airway dysanapsis (an incongruence between the growth of the lungs and the airways) and whether dysanapsis is associated with asthma morbidity.

Methods: We examined the relationship between obesity and dysanapsis in six cohorts of children with and without asthma, as well as the relationship between dysanapsis and clinical outcomes in children with asthma.

Synthesis and NMR assignment of the two diastereomers of 8,6'-cyclo-2',6'-dideoxyadenosine.

We herein present the first synthesis and characterization of the two C5' diastereomers of 8,6'-cyclo-2',6'-dideoxyadenosine. Starting from commercially available 2'-deoxyadenosine, the target cyclonucleosides were synthesized in 11 linear steps. Following a zinc-mediated cyclization reaction to form the seven-membered ring, the stereochemistry of the newly formed chiral center was established using two-dimensional NOESY NMR experiments.

Synthesis and properties of DNA containing cyclonucleosides.

Here, we present efficient syntheses of the R and S diastereomers of 8,5'-cyclo-2'-deoxyadenosine and 6,5'-cyclo-2'-deoxyuridine. We incorporated these interesting nucleosides into DNA to study how the cyclo linkage affects the stability of duplex formation.

Generation and spectroscopic profiles of stable multiarylaminium radical cations bridged by fluorenes.

A series of arylaminofluorene derivatives (DTFA-1, TTFA-2, TAFB-3, and TAFA-4) were synthesized, and the generation of their corresponding arylaminium cation radicals was readily achieved by Cu(ClO(4))(2) in CH(3)CN. Moreover, the cation radicals were stable at ambient temperature with substantially long life times and exhibited distinct colors. The oxidation mechanism and spectroscopic features of the resulting cation radicals were probed by UV-vis-NIR spectroscopy and electron spin resonance experiments.