Natural Product Phenolic Diglycosides Created from Wildfires, Defining Their Impact on California and Oregon Grapes and Wines.

Forest fires produce malodorous phenols, bioaccumulated in grapes as odorless phenol glycosides (mono- to tri-), and produce unpleasant smoke tainted wines when these complexes are transformed by glycosidases in saliva. Metabolomic analyses were used to further understand smoke taint by quantitating marker phenolic diglycosides via UHPLC separations and MS/MS multiple reaction monitoring. A collection of grapes and wines provided data to forecast wine quality of grapes subjected to wildfire smoke infestations; the analytics used a panel of reference compounds (1-6). Overall, eight different Vitis vinifera varietals were examined from 2017-2021 vintages involving >218 distinct samples (wines and/or grapes) from 21 different American Viticulture Areas. Results acquired allowed correlation of phenolic diglycoside levels as a function of grape cultivar, varietal clones, and intensity of wildfire smoke. Baseline data were tabulated for nonsmoked samples (especially, Cabernet Sauvignon having a sum 1-6 of <6 µg/L) and then compared to those exposed to six other levels of smoke. Outcomes established that (1) analyzing paired samples (bottled wines versus smoke-exposed grapes) can provide diagnostic metabolomic data, (2) phenolic diglycosides are stable in wines aged for >2.5 years, and (3) major gaps exist in our current understanding of this pool of metabolites.

Compromised External Validity: Federally Produced Cannabis Does Not Reflect Legal Markets.

As the most widely used illicit drug worldwide, and as a source of numerous under-studied pharmacologically-active compounds, a precise understanding of variability in psychological and physiological effects of Cannabis varieties is essential. The National Institute on Drug Abuse (NIDA) is designated as the sole legal producer of Cannabis for use in US research studies. We sought to compare the chemical profiles of Cannabis varieties that are available to consumers in states that have state-legalized use versus what is available to researchers interested in studying the plant and its effects. Our results demonstrate that the federally-produced Cannabis has significantly less variety and lower concentrations of cannabinoids than are observed in state-legal U.S. dispensaries. Most dramatically, NIDA's varieties contain only 27% of the THC levels and as much as 11-23 times the Cannabinol (CBN) content compared to what is available in the state-legal markets. Research restricted to using the current range of federally-produced Cannabis thus may yield limited insights into the chemical, biological and pharmacological properties, and medical potential of material that is available in the state markets. Investigation is urgently needed on the full diversity of Cannabis chemotypes known to be available to the public.

A kinetic model for beta-amyloid adsorption at the air/solution interface and its implication to the beta-amyloid aggregation process.

At the air/buffer solution interface the kinetics of adsorption of amyloid beta peptide, Abeta(1-42), whose bulk concentration (submicromolar) is more than 2 orders of magnitude lower than that typically used in other in vitro aggregation studies, has been studied using a Langmuir-Blodgett trough. The pressure-time curves exhibit a lag phase, wherein the surface pressure essentially remains at zero, and a rising phase, corresponding to the Abeta adsorption at the interface. The duration of the lag phase was found to be highly dependent on both the Abeta bulk concentration and the solution temperature. A large activation energy (62.2 +/- 4.1 KJ/mol) was determined and the apparent adsorption rate constant was found to be linearly dependent on the Abeta bulk concentration. Attenuated total reflection-IR spectra of the adsorbed Abeta transferred to a solid substrate and circular dichroism measurements of Abeta in the solution layer near the interface reveal that the natively unstructured Abeta in the bulk undergo a conformation change (folding) to mainly the alpha-helical structure. The results suggest that, prior to the adsorption step, an equilibrium between Abeta conformations is established within the subsurface. The kinetic equation derived from this model confirms that the overall Abeta adsorption is kinetically controlled and the apparent rate constant is proportional to the Abeta bulk concentration. This model also indicates that interfaces such as cell membranes and lipid bilayers may facilitate Abeta aggregation/ fibrillation by providing a thin hydrophobic layer adjacent to the interface for the initial A/beta conformation change (misfolding) and accumulation. Such a preconcentration effect offers a plausible explanation of the fact that Abeta fibrillation occurs in vivo at nanomolar concentrations. Another important biological implication from our work is that Abeta misfolding may occur before its adsorption onto a cell membrane. This general kinetic model should also find applications in adsorption studies of other types of biomolecules whose overall kinetics exhibits a lag phase that is dependent on the bulk concentration of the adsorbate.