Candidate Tear-Based Uveitis Biomarkers in Children with JIA Based on Arthritis Activity and Topical Corticosteroid Use.

Background: Uveitis is an inflammatory ocular disease secondary to disruption of the retinal pigmented epithelium (RPE) and blood retinal barrier (BRB). Known clinical factors do not accurately predict uveitis risk in Juvenile Idiopathic Arthritis (JIA). Tear fluid is easily obtained for biomarker study.

Mechanistic insight into benzylidene-directed glycosylation reactions using cryogenic infrared spectroscopy.

The stereoselective formation of 1,2- glycosidic linkages is challenging. The currently most widely used strategy for their installation uses 4,6--benzylidene-protected building blocks. The stereoselectivity of this reaction is thought to be driven by a covalent intermediate, which reacts via an S2 mechanism.

Direct Experimental Characterization of a Sialyl Cation.

Sialic acids are monosaccharide residues involved in several biological processes. Controlling the stereoselectivity of sialylation reactions is challenging and mechanistic studies on the structure of its intermediate, the sialyl cation, are scarce. Here it is shown that a sialyl cation can be generated and isolated from an ionized sialic acid precursor.

The impact of side-chain fluorination on proton-bound phenylalanine dimers: a cryogenic infrared spectroscopic study.

The incorporation of fluorine into amino acids is an important strategy to produce tailored building blocks with unique properties for peptide-based materials. Phenylalanine is frequently modified due to its role in cation-π interactions and the formation of amyloid fibres. Previous studies have utilized gas-phase vibrational spectroscopy to study interactions between canonical amino acids.

Evolutionary origins and innovations sculpting the mammalian PRPS enzyme complex.

The phosphoribosyl pyrophosphate synthetase (PRPS) enzyme conducts a chokepoint reaction connecting central carbon metabolism and nucleotide production pathways, making it essential for life. Here, we show that the presence of multiple PRPS-encoding genes is a hallmark trait of eukaryotes, and we trace the evolutionary origins and define the individual functions of each of the five mammalian PRPS homologs - three isozymes (one testis-restricted) and two non-enzymatic associated proteins (APs) - which we demonstrate operate together as a large molecular weight complex capable of attaining a heterogeneous array of functional multimeric configurations. Employing a repertoire of isogenic fibroblast clones in all viable individual or combinatorial assembly states, we define preferential interactions between subunits, and we show that cells lacking PRPS2, PRPSAP1, and PRPSAP2 render PRPS1 into aberrant homo-oligomeric assemblies with diminished metabolic flux and impaired proliferative capacity.