Forazoline A: Marine‐Derived Polyketide with Antifungal In Vivo Efficacy

Forazoline A, a novel antifungal polyketide with in vivo efficacy against Candida albicans, was discovered using LCMS‐based metabolomics to investigate marine‐invertebrate‐associated bacteria. Forazoline A had a highly unusual and unprecedented skeleton. Acquisition of ¹³C–¹³C gCOSY and ¹³C–¹⁵N HMQC NMR data provided the direct carbon–carbon and carbon–nitrogen connectivity, respectively. This approach represents the first example of determining direct ¹³C–¹⁵N connectivity for a natural product. Using yeast chemical genomics, we propose that forazoline A operated through a new mechanism of action with a phenotypic outcome of disrupting membrane integrity.     

Partial-wave analysis of the π+π+π− system through the region of the A3 meson

A recent spin-parity analysis of the π⁺π⁺π^? system formed opposite a proton and a coherent deuteron by incident 13 GeV/c²π⁺ mesons, is extended to a three-pion mass of 1.9 GeV/c. Relative proportions of the contributing partial waves are presented, from threshold, and the A₃ region is discussed in detail. Contrary to results with the (3π)^? system, a change in phase is noted for the 2^? amplitude decaying to f⁰π⁺via am S-wave.The method employs the University of Illinois three-body partial-wave-analysis program.     

A preliminary study of ππ scattering in the reaction πp→(ππ)Δ at 13 GeV/c

Aphase shift analysis of π⁺π⁻ scattering in the mass range 0.6→1.4 GeV confirms the rapid rise of the I=0 s-wave through the KK? threshold.     

Characterization of Retinal Pigment Epithelial Melanin and Degraded Synthetic Melanin Using Mass Spectrometry and In Vitro Biochemical Diagnostics

With increasing age, there is an observable loss of melanin in retinal pigment epithelial (RPE) cells. It is possible that degradation of the pigment contributes to the pathogenesis of retinal disease, as the cellular antioxidant material is depleted. Functionally, intact melanin maintains protective qualities, while oxidative degradation of melanin promotes reactive oxygen species (ROS) generation and formation of metabolic byproducts, such as melanolipofuscin. Understanding the structural and functional changes to RPE melanin with increasing age may contribute to a better understanding of disease progression and risk factors for conditions such as age‐related macular degeneration (AMD). In this study, human donor RPE melanin is characterized using MALDI mass spectrometry to follow melanin degradation trends. In vitro models using ARPE‐19 cells are used to assess photo‐reactivity in repigmented cells. Significant protection against intracellular ROS produced by blue light is observed in calf melanin‐pigmented cells versus unpigmented and black latex bead controls (P < 0.0001). UV‐B exposure to aged human melanin‐pigmented cells results in a significant increase in nitric oxide production versus control cells (P < 0.001). Peroxide‐treated synthetic melanin is characterized to elucidate degradation products that may contribute to RPE cell damage.