Search

Esters are volatile and pleasantly smelling compounds, commonly used as food additives. Using Ti(OBu)[subscript 4]-catalyzed acyl exchange, we demonstrate a scent transmutation experiment, in which two fragrant esters swap their acyl and alkoxy substituents and are, during the course of a reactive distillation, quantitatively converted into two different esters with distinct fragrance properties. We view this simple and appealing experiment as highly suitable for instructional use, since it can be used to teach the concepts of chemical equilibrium, distillation, transesterification, dynamic combinatorial chemistry, and the industrially relevant process of reactive distillation.

The guinea pig is the only small animal model for congenital cytomegalovirus (CMV) but requires species-specific guinea pig cytomegalovirus (GPCMV). Infection of epithelial cells and trophoblasts by GPCMV requires the viral glycoprotein pentamer complex (PC) and endocytic entry because of the absence of platelet-derived growth factor receptor alpha (PDGFRA). Endothelial cells represent an important cell type for infection, dissemination in the host, and disease but have been poorly evaluated for GPCMV. Novel endothelial cell lines were established from animal vascular systems, including aorta (EndoC) and placental umbilical cord vein (GPUVEC). Cell lines were characterized for endothelial cell protein markers (PECAM1, vWF, and FLI1) and evaluated for GPCMV infection. Only PC-positive virus was capable of infecting endothelial cells. Individual knockout mutants for unique PC components (GP129, GP131, and GP133) were unable to infect endothelial cells without impacting fibroblast infection. Ectopic expression of PDGFRA in EndoC cells enabled GPCMV(PC2) infection via direct cell entry independent of the PC. Neutralizing antibodies to the essential viral gB glycoprotein were insufficient to prevent endothelial cell infection, which also required antibodies to gH/gL and the PC. Endothelial cell infection was also dependent upon viral tegument pp65 protein (GP83) to counteract the IFI16/cGAS-STING innate immune pathway, similar to epithelial cell infection. GPCMV endothelial cells were lytically (EndoC) or persistently (GPUVEC) infected dependent on tissue origin. The ability to establish a persistent infection in the umbilical cord could potentially enable sustained and more significant infection of the fetus in utero. Overall, results demonstrate the importance of this translationally relevant model for CMV research. [ABSTRACT FROM AUTHOR]

The guinea pig is the only small animal model for congenital cytomegalovirus (CMV) but requires species-specific guinea pig cytomegalovirus (GPCMV). Tegument protein GP83 is the presumed homolog of HCMV pp65, but gene duplication in the UL82-UL84 homolog locus in various animal CMVs made it unclear if GP83 was a functional homolog. A GP83 null deletion mutant GPCMV (GP83dPC1) generated in the backdrop of glycoprotein pentamer complex (PC)-positive virus, required for nonfibroblast infection, had normal growth kinetics on fibroblasts but was highly impaired on epithelial and trophoblast cells. GP83dPC1 virus was highly sensitive to type I interferon (IFN-I), suggesting that GP83 had an innate immune evasion function. GP83 interacted with cellular DNA sensors guinea pig IFI16 and cGAS, indicating a role in the cGAS/STING pathway. Ectopically expressed GP83 in trophoblast cells restored GP83dPC1 virus growth. Additionally, mutant virus growth was restored in epithelial cells by expression of bovine viral diarrhea virus (BVDV) Npro protein targeting IRF3 as part of the cGAS/STING pathway, or alternatively, by expression of the fibroblast cell receptor platelet-derived growth factor receptor alpha (PDGFRA). HCMV pp65 is a T cell target antigen, and a recombinant adenovirus encoding GP83 was evaluated as a vaccine. In GPCMV challenge studies, vaccinated animals had various levels of protection against wild-type virus, with a protective response against the 22122 prototype strain but little protection against a novel clinical strain of GPCMV (TAMYC), despite 100% identity in GP83 protein sequences. Overall, GP83 is a functional pp65 homolog with novel importance for epithelial cell infection, but a GP83 T cell response provides limited vaccine efficacy. [ABSTRACT FROM AUTHOR]

A series of 11 cross-conjugated cruciform fluorophores based on a benzobisimidazole nucleus has been synthesized and characterized. Like in their previously reported benzobisoxazole counterparts, the HOMOs of these new fluorophores are localized along the vertical bisethynylbenzene axes, while their LUMOs remain relatively delocalized across the molecule, except in cruciforms substituted with electron-withdrawing groups along the vertical axis. Benzobisimidazole cruciforms exhibit a pronounced response to deprotonation in their UV/vis absorption and emission spectra, but their response to protonation is significantly attenuated. [ABSTRACT FROM AUTHOR]

Esters are volatile and pleasantly smelling compounds, commonly used as food additives. Using Ti(OBu)4-catalyzed acyl exchange, we demonstrate a scent transmutation experiment, in which two fragrant esters swap their acyl and alkoxy substituents and are, during the course of a reactive distillation, quantitatively converted into two different esters with distinct fragrance properties. We view this simple and appealing experiment as highly suitable for instructional use, since it can be used to teach the concepts of chemical equilibrium, distillation, transesterification, dynamic combinatorial chemistry, and the industrially relevant process of reactive distulation. [ABSTRACT FROM AUTHOR]