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Concept: Chemical compound


Whisky is distilled to around 70% alcohol by volume (vol-%) then diluted to about 40 vol-%, and often drunk after further slight dilution to enhance its taste. The taste of whisky is primarily associated with amphipathic molecules, such as guaiacol, but why and how dilution enhances the taste is not well understood. We carried out computer simulations of water-ethanol mixtures in the presence of guaiacol, providing atomistic details on the structure of the liquid mixture. We found that guaiacol is preferentially associated with ethanol, and, therefore, primarily found at the liquid-air interface in mixtures that contain up to 45 vol-% of ethanol. At ethanol concentrations of 59 vol-% or higher, guaiacol is increasingly surrounded by ethanol molecules and is driven to the bulk. This indicates that the taste of guaiacol in the whisky would be enhanced upon dilution prior to bottling. Our findings may apply to other flavour-giving amphipathic molecules and could contribute to optimising the production of spirits for desired tastes. Furthermore, it sheds light on the molecular structure of water-alcohol mixtures that contain small solutes, and reveals that interactions with the water may be negligible already at 89 vol-% of ethanol.

Concepts: Oxygen, Water, Molecule, Ethanol, Chemical substance, Chemical compound, Vodka, Brandy


Indoor dust is a reservoir for commercial consumer product chemicals, including many compounds with known or suspected health effects. However, most dust exposure studies measure few chemicals in small samples. We systematically searched the U.S. indoor dust literature on phthalates, replacement flame retardants (RFRs), perfluoroalkyl substances (PFASs), synthetic fragrances, and environmental phenols and estimated pooled geometric means (GMs) and 95% confidence intervals for 45 chemicals measured in ≥3 data sets. In order to rank and contextualize these results, we used the pooled GMs to calculate residential intake from dust ingestion, inhalation, and dermal uptake from air, and then identified hazard traits from the Safer Consumer Products Candidate Chemical List. Our results indicate that U.S. indoor dust consistently contains chemicals from multiple classes. Phthalates occurred in the highest concentrations, followed by phenols, RFRs, fragrance, and PFASs. Several phthalates and RFRs had the highest residential intakes. We also found that many chemicals in dust share hazard traits such as reproductive and endocrine toxicity. We offer recommendations to maximize comparability of studies and advance indoor exposure science. This information is critical in shaping future exposure and health studies, especially related to cumulative exposures, and in providing evidence for intervention development and public policy.

Concepts: Mathematics, Measurement, Chemistry, Fire retardant, Chemical compound, Dust, Intake, Aroma compound


Plastic debris litters aquatic habitats globally, the majority of which is microscopic (< 1 mm), and is ingested by a large range of species. Risks associated with such small fragments come from the material itself and from chemical pollutants that sorb to it from surrounding water. Hazards associated with the complex mixture of plastic and accumulated pollutants are largely unknown. Here, we show that fish, exposed to a mixture of polyethylene with chemical pollutants sorbed from the marine environment, bioaccumulate these chemical pollutants and suffer liver toxicity and pathology. Fish fed virgin polyethylene fragments also show signs of stress, although less severe than fish fed marine polyethylene fragments. We provide baseline information regarding the bioaccumulation of chemicals and associated health effects from plastic ingestion in fish and demonstrate that future assessments should consider the complex mixture of the plastic material and their associated chemical pollutants.

Concepts: Chemical substance, Mixture, Toxicology, Pollution, Plastic, Chemical compound, Material, Ocean


Human beings continuously emit chemicals into the air by breath and through the skin. In order to determine whether these emissions vary predictably in response to audiovisual stimuli, we have continuously monitored carbon dioxide and over one hundred volatile organic compounds in a cinema. It was found that many airborne chemicals in cinema air varied distinctively and reproducibly with time for a particular film, even in different screenings to different audiences. Application of scene labels and advanced data mining methods revealed that specific film events, namely “suspense” or “comedy” caused audiences to change their emission of specific chemicals. These event-type synchronous, broadcasted human chemosignals open the possibility for objective and non-invasive assessment of a human group response to stimuli by continuous measurement of chemicals in air. Such methods can be applied to research fields such as psychology and biology, and be valuable to industries such as film making and advertising.

Concepts: Oxygen, Carbon dioxide, Species, Carbon, Chemical compound, Volatile organic compound, Film, Film director


TRPV4 ion channels represent osmo-mechano-TRP channels with pleiotropic function and wide-spread expression. One of the critical functions of TRPV4 in this spectrum is its involvement in pain and inflammation. However, few small-molecule inhibitors of TRPV4 are available. Here we developed TRPV4-inhibitory molecules based on modifications of a known TRPV4-selective tool-compound, GSK205. We not only increased TRPV4-inhibitory potency, but surprisingly also generated two compounds that potently co-inhibit TRPA1, known to function as chemical sensor of noxious and irritant signaling. We demonstrate TRPV4 inhibition by these compounds in primary cells with known TRPV4 expression - articular chondrocytes and astrocytes. Importantly, our novel compounds attenuate pain behavior in a trigeminal irritant pain model that is known to rely on TRPV4 and TRPA1. Furthermore, our novel dual-channel blocker inhibited inflammation and pain-associated behavior in a model of acute pancreatitis - known to also rely on TRPV4 and TRPA1. Our results illustrate proof of a novel concept inherent in our prototype compounds of a drug that targets two functionally-related TRP channels, and thus can be used to combat isoforms of pain and inflammation in-vivo that involve more than one TRP channel. This approach could provide a novel paradigm for treating other relevant health conditions.

Concepts: Protein, Molecule, Chemistry, Enzyme inhibitor, Chemical compound, Ion channels, Transient receptor potential channel, TRPV


This paper describes the design of a new instrumental technique, Gas Chromatography Recomposition-Olfactometry (GC-R), that adapts the reconstitution technique used in flavor chemistry studies by extracting volatiles from a sample by headspace solid-phase microextraction (SPME), separating the extract on a capillary GC column, and recombining individual compounds selectively as they elute off of the column into a mixture for sensory analysis (Figure 1). Using the chromatogram of a mixture as a map, the GC-R instrument allows the operator to “cut apart” and recombine the components of the mixture at will, selecting compounds, peaks, or sections based on retention time to include or exclude in a reconstitution for sensory analysis. Selective recombination is accomplished with the installation of a Deans Switch directly in-line with the column, which directs compounds either to waste or to a cryotrap at the operator’s discretion. This enables the creation of, for example, aroma reconstitutions incorporating all of the volatiles in a sample, including instrumentally undetectable compounds as well those present at concentrations below sensory thresholds, thus correcting for the “reconstitution discrepancy” sometimes noted in flavor chemistry studies. Using only flowering lavender (Lavandula angustifola ‘Hidcote Blue’) as a source for volatiles, we used the instrument to build mixtures of subsets of lavender volatiles in-instrument and characterized their aroma qualities with a sensory panel. We showed evidence of additive, masking, and synergistic effects in these mixtures and of “lavender' aroma character as an emergent property of specific mixtures. This was accomplished without the need for chemical standards, reductive aroma models, or calculation of Odor Activity Values, and is broadly applicable to any aroma or flavor.

Concepts: Mixture, Chromatography, High performance liquid chromatography, Analytical chemistry, Gas chromatography, Chemical compound, Solid phase microextraction, Separation process


Polymethylmethacrylate bone cement cannot provide an adhesive chemical bonding to form a stable cement-bone interface. Bioactive bone cements show bone bonding ability, but their clinical application is limited because bone resorption is observed after implantation. Porous polymethylmethacrylate can be achieved with the addition of carboxymethylcellulose, alginate and gelatin microparticles to promote bone ingrowth, but the mechanical properties are too low to be used in orthopedic applications. Bone ingrowth into cement could decrease the possibility of bone resorption and promote the formation of a stable interface. However, scarce literature is reported on bioactive bone cements that allow bone ingrowth. In this paper, we reported a porous surface modified bioactive bone cement with desired mechanical properties, which could allow for bone ingrowth.

Concepts: Bone, Hydrogen, Molecule, Orthopedic surgery, Chemical compound, Portland cement, Cement


BACKGROUND: Successful delivery of compounds to the brain and retina is a challenge in the development of therapeutic drugs and imaging agents. This challenge arises because internalization of compounds into the brain and retina is restricted by the blood–brain barrier (BBB) and blood-retinal barrier (BRB), respectively. Simple and reliable in vivo assays are necessary to identify compounds that can easily cross the BBB and BRB. METHODS: We developed six fluorescent indoline derivatives (IDs) and examined their ability to cross the BBB and BRB in zebrafish by in vivo fluorescence imaging. These fluorescent IDs were administered to live zebrafish by immersing the zebrafish larvae at 7–8 days post fertilization in medium containing the ID, or by intracardiac injection. We also examined the effect of multidrug resistance proteins (MRPs) on the permeability of the BBB and BRB to the ID using MK571, a selective inhibitor of MRPs. RESULTS: The permeability of these barriers to fluorescent IDs administered by simple immersion was comparable to when administered by intracardiac injection. Thus, this finding supports the validity of drug administration by simple immersion for the assessment of BBB and BRB permeability to fluorescent IDs. Using this zebrafish model, we demonstrated that the length of the methylene chain in these fluorescent IDs significantly affected their ability to cross the BBB and BRB via MRPs. CONCLUSIONS: We demonstrated that in vivo assessment of the permeability of the BBB and BRB to fluorescent IDs could be simply and reliably performed using zebrafish. The structure of fluorescent IDs can be flexibly modified and, thus, the permeability of the BBB and BRB to a large number of IDs can be assessed using this zebrafish-based assay. The large amount of data acquired might be useful for in silico analysis to elucidate the precise mechanisms underlying the interactions between chemical structure and the efflux transporters at the BBB and BRB. In turn, understanding these mechanisms may lead to the efficient design of compounds targeting the brain and retina.

Concepts: Fluorescence, Brain, In vivo, Retina, Chemical compound, Zebrafish, Injection, Intracardiac injection


ABSTRACT Soils host diverse microbial communities that include filamentous actinobacteria (actinomycetes). These bacteria have been a rich source of useful metabolites, including antimicrobials, antifungals, anticancer agents, siderophores, and immunosuppressants. While humans have long exploited these compounds for therapeutic purposes, the role these natural products may play in mediating interactions between actinomycetes has been difficult to ascertain. As an initial step toward understanding these chemical interactions at a systems level, we employed the emerging techniques of nanospray desorption electrospray ionization (NanoDESI) and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) imaging mass spectrometry to gain a global chemical view of the model bacterium Streptomyces coelicolor interacting with five other actinomycetes. In each interaction, the majority of secreted compounds associated with S. coelicolor colonies were unique, suggesting an idiosyncratic response from S. coelicolor. Spectral networking revealed a family of unknown compounds produced by S. coelicolor during several interactions. These compounds constitute an extended suite of at least 12 different desferrioxamines with acyl side chains of various lengths; their production was triggered by siderophores made by neighboring strains. Taken together, these results illustrate that chemical interactions between actinomycete bacteria exhibit high complexity and specificity and can drive differential secondary metabolite production. IMPORTANCE Actinomycetes, filamentous actinobacteria from the soil, are the deepest natural source of useful medicinal compounds, including antibiotics, antifungals, and anticancer agents. There is great interest in developing new strategies that increase the diversity of metabolites secreted by actinomycetes in the laboratory. Here we used several metabolomic approaches to examine the chemicals made by these bacteria when grown in pairwise coculture. We found that these interspecies interactions stimulated production of numerous chemical compounds that were not made when they grew alone. Among these compounds were at least 12 different versions of a molecule called desferrioxamine, a siderophore used by the bacteria to gather iron. Many other compounds of unknown identity were also observed, and the pattern of compound production varied greatly among the interaction sets. These findings suggest that chemical interactions between actinomycetes are surprisingly complex and that coculture may be a promising strategy for finding new molecules from actinomycetes.

Concepts: Bacteria, Metabolism, Mass spectrometry, Molecule, Chemical compound, Electrospray ionization, Streptomyces, Actinobacteria


Human African Trypanosomiasis is a vector-borne disease of sub-Saharan Africa that causes significant morbidity and mortality. Current therapies have many drawbacks, and there is an urgent need for new, better medicines. Ideally such new treatments should be fast-acting cidal agents that cure the disease in as few doses as possible. Screening assays used for hit-discovery campaigns often do not distinguish cytocidal from cytostatic compounds and further detailed follow-up experiments are required. Such studies usually do not have the throughput required to test the large numbers of hits produced in a primary high-throughput screen. Here, we present a 384-well assay that is compatible with high-throughput screening and provides an initial indication of the cidal nature of a compound. The assay produces growth curves at ten compound concentrations by assessing trypanosome counts at 4, 24 and 48 hours after compound addition. A reduction in trypanosome counts over time is used as a marker for cidal activity. The lowest concentration at which cell killing is seen is a quantitative measure for the cidal activity of the compound. We show that the assay can identify compounds that have trypanostatic activity rather than cidal activity, and importantly, that results from primary high-throughput assays can overestimate the potency of compounds significantly. This is due to biphasic growth inhibition, which remains hidden at low starting cell densities and is revealed in our static-cidal assay. The assay presented here provides an important tool to follow-up hits from high-throughput screening campaigns and avoid progression of compounds that have poor prospects due to lack of cidal activity or overestimated potency.

Concepts: Pharmacology, Drug discovery, Chemical compound, Trypanosoma brucei, African trypanosomiasis, Euglenozoa, Trypanosome, High-throughput screening