Discovery of aspirin-triggered eicosanoid-like mediators in a Drosophila metainflammation blood tumor model.

Epidemiologic studies have linked the use of aspirin to a decline in chronic inflammation that underlies many human diseases, including some cancers. Aspirin reduces the levels of cyclooxygenase-mediated pro-inflammatory prostaglandins, promotes the production of pro-resolution molecules, and triggers the production of anti-inflammatory electrophilic mono-oxygenated (EFOX) lipid mediators. We investigated the effects of aspirin in fruit fly models of chronic inflammation. Ectopic Toll/NF-κB and JAK/STAT signaling in mutant D. melanogaster results in overproliferation of hematopoietic blood progenitors resulting in the formation of granuloma-like tumors. Ectopic JAK-STAT signaling also leads to metabolic inflammation. We report that aspirin-treated mutant flies experience reduction in metabolic inflammation, mitosis, ectopic immune signaling, and macrophage infiltration. Moreover, these flies synthesize 13-HODE, and aspirin triggers 13-oxoODE (13-EFOX-L2) production. Providing the precursor of 13-HODE, linoleic acid, or performing targeted knockdown of the transcription factor STAT in inflammatory blood cells, boosts 13-EFOX-L2 levels while decreasing metabolic inflammation. Thus, hematopoietic cells regulate metabolic inflammation in flies, and their effects can be reversed by pharmaceutical or dietary intervention, suggesting deep phylogenetic conservation in the ability of animals to resolve inflammation and repair tissue damage. These findings can help identify novel treatment targets in humans.

Unique Photophysical Behavior of Coumarin-Based Viscosity Probes during Molecular Self-Assembly.

Intermolecular interactions impact self-assembly phenomena having a variety of bio/chemical, physical, and mechanical consequences. Nevertheless, the underlying mechanisms leading to a controlled stereo- and chemo-specific aggregation at the molecular level often remain elusive because of the intrinsically dynamic nature of these processes. Herein, we describe two 3-styryl coumarin molecular rotors capable of probing subtle intermolecular interactions controlling the self-assembly of a small-molecule organogelator. Complementing the characterization of the gel via circular dichroism and atomic force microscopy, thorough spectroscopic investigations on these sensors were carried out to prove their high chemical and spatial affinity toward the 3D supramolecular network. The results were further supported by molecular dynamics simulations to reveal further critical insights into the gelator's dynamic self-assembly mechanism. These sensors could potentially serve as templates to study a variety of soft-supramolecular architectures and the ways in which they assemble.

Different ommochrome pigment mixtures enable sexually dimorphic Batesian mimicry in disjunct populations of the common palmfly butterfly, Elymnias hypermnestra.

With varied, brightly patterned wings, butterflies have been the focus of much work on the evolution and development of phenotypic novelty. However, the chemical structures of wing pigments from few butterfly species have been identified. We characterized the orange wing pigments of female Elymnias hypermnestra butterflies (Lepidoptera: Nymphalidae: Satyrinae) from two Southeast Asian populations. This species is a sexually dimorphic Batesian mimic of several model species. Females are polymorphic: in some populations, females are dark, resemble conspecific males, and mimic Euploea spp. In other populations, females differ from males and mimic orange Danaus spp. Using LC-MS/MS, we identified nine ommochrome pigments: six from a population in Chiang Mai, Thailand, and five compounds from a population in Bali, Indonesia. Two ommochromes were found in both populations, and only two of the nine compounds have been previously reported. The sexually dimorphic Thai and Balinese populations are separated spatially by monomorphic populations in peninsular Malaysia, Singapore, and Sumatra, suggesting independent evolution of mimetic female wing pigments in these disjunct populations. These results indicate that other butterfly wing pigments remain to be discovered.

Energy landscaping in supramolecular materials.

This review details recent developments in the design of supramolecular materials with customizable properties that can be coordinated in space and time. We highlight examples where both kinetic and thermodynamic considerations are incorporated in design, to address three challenges: control of order/disorder in supramolecular assembly; formation of structures with distinct functional domains; formation of out-of-equilibrium structures with controlled lifetimes. The examples that are discussed are based on self-assembling peptide and saccharide-based amphiphiles. These biomolecular amphiphiles are of low complexity and ideally suited to fundamental, systematic studies while they are also considered for applications in environmental remediation, food science, cosmetics and nanomedicine.

Imaging intracellular viscosity by a new molecular rotor suitable for phasor analysis of fluorescence lifetime.

The arsenal of fluorescent probes tailored to functional imaging of cells is rapidly growing and benefits from recent developments in imaging strategies. Here, we present a new molecular rotor, which displays strong absorption in the green region of the spectrum, very little solvatochromism, and strong emission sensitivity to local viscosity. The emission increase is paralleled by an increase in emission lifetime. Owing to its concentration-independent nature, fluorescence lifetime is particularly suitable to image environmental properties, such as viscosity, at the intracellular level. Accordingly, we demonstrate that intracellular viscosity measurements can be efficiently carried out by lifetime imaging with our probe and phasor analysis, an efficient method for measuring lifetime-related properties (e.g., bionalyte concentration or local physicochemical features) in living cells. Notably, we show that it is possible to monitor the partition of our probe into different intracellular regions/organelles and to follow mitochondrial de-energization upon oxidative stress.