White adipose tissue (WAT) is a complex organ with both metabolic and endocrine functions. Dysregulation of all of these functions of WAT, together with low-grade inflammation of the tissue in obese individuals, contributes to the development of insulin resistance and type 2 diabetes. n-3 polyunsaturated fatty acids (PUFAs) of marine origin play an important role in the resolution of inflammation and exert beneficial metabolic effects. Using experiments in mice and overweight/obese patients with type 2 diabetes, we elucidated the structures of novel members of fatty acid esters of hydroxy fatty acids—lipokines derived from docosahexaenoic acid (DHA) and linoleic acid, which were present in serum and WAT after n-3 PUFA supplementation. These compounds contained DHA esterified to 9- and 13-hydroxyoctadecadienoic acid (HLA) or 14-hydroxydocosahexaenoic acid (HDHA), termed 9-DHAHLA, 13-DHAHLA, and 14-DHAHDHA, and were synthesized by adipocytes at concentrations comparable to those of protectins and resolvins derived from DHA in WAT. 13-DHAHLA exerted anti-inflammatory and proresolving properties while reducing macrophage activation by lipopolysaccharides and enhancing the phagocytosis of zymosan particles. Our results document the existence of novel lipid mediators, which are involved in the beneficial anti-inflammatory effects attributed to n-3 PUFAs, in both mice and humans.

Salinomycin has found renewed interest as an agent for prevention of cancer recurrence through selectively targeting cancer stem cells. Strategies for generation of improved salinomycin analogs by individual modification of its hydroxyl groups are presented. An evaluation of the dose-response effects of the resulting library on breast cancer cell lines shows that acylation of the C20 hydroxyl can be used to improve IC50 values down to one fifth that of salinomycin.

KAR(1) and glyceronitrile, chemicals in smoke-water that are known to stimulate germination in other species, did not promote the germination of G. racemiger. This suggests that other chemical(s) which promote germination are present in smoke, and may be derived from burning cellulose alone.

SummarySmoke-derived compounds provide a strong chemical signal to seeds in the soil seed bank, allowing them to take advantage of the germination niche created by the occurrence of fire. The germination stimulatory activity of smoke can largely be attributed to karrikinolide (KAR 1 ), while a related compound, trimethylbutenolide (TMB), has been shown to have an inhibitory effect on germination. The aim of this study was to characterize the interaction of these potent firegenerated compounds.Dose-response analysis, leaching tests and a detailed transcriptome study were performed using highly KAR 1 -sensitive lettuce (Lactuca sativa cv 'Grand Rapids') achenes.Dose-response analysis demonstrated that the compounds are not competitors and TMB modulates germination in a concentration-dependent manner. The transcriptome analysis revealed a contrasting expression pattern induced by the compounds. KAR 1 suppressed, while TMB up-regulated ABA, seed maturation and dormancy-related transcripts. The effect of TMB was reversed by leaching the compound, while the KAR 1 effect was only reversible by leaching within the first 2 h of KAR 1 treatment.Our findings suggest that the compounds may act in concert for germination-related signaling. After the occurrence of fire, sufficient rainfall would contribute to post-germination seedling recruitment by reducing the concentration of the inhibitory compound.

Many species in fire-prone environments germinate after fire including most taxa in the genus Anigozanthos Labill. Following preliminary studies with Anigozanthos manglesii D.Don subsp. manglesii, the response of several Anigozanthos taxa to germination stimulants relating to the post-fire environment including smoke, karrikinolide (KAR1, 3-methyl-2H-furo[2,3-c]pyran-2-one) and nitrate were compared in seed when freshly collected and after a period of burial. Following after-ripening, the response of seed to water, smoke-water, KAR1 and glyceronitrile (2,3-dihydroxypropanenitrile) was examined. Seed of 16 Anigozanthos taxa, and the related monotypic genus Blancoa Lindl., were highly dormant at maturity. Investigations of eight Anigozanthos taxa and B. canescens indicated that these taxa had morphophysiological dormancy. Following a period of either 3- to 4 months or 1 year of burial and exhumation in autumn, many taxa remained dormant. However, dormancy was alleviated and smoke-water stimulated some germination of A. manglesii subsp. manglesii, A. flavidus DC., A. viridis Endl. subsp. viridis, and A. viridis Endl. subsp. Cataby (S.D. Hopper 1786). Nitrate also stimulated germination of A. flavidus in the light. Following 3–3.5 years of laboratory after-ripening, 13 of the 17 Anigozanthos taxa examined were smoke-responsive. When testing individual smoke-derived compounds these taxa germinated in response to glyceronitrile and not KAR1. In contrast, smoke-responsive B. canescens seed responded to KAR1 and not glyceronitrile. These findings suggest a phylogenetic link between responsiveness to different chemicals in smoke in this family that may shed light on the evolutionary development of these smoke responses.