Unraveling the universality of chemical fear communication: evidence from behavioral, genetic, and chemical analyses.

Abundant evidence indicates that humans can communicate threat-related information to conspecifics through their body odors. However, prior research has been primarily conducted on Western (WEIRD) samples. In this study, we aimed to investigate whether threat-related information can be transmitted by individuals of East Asian descent who carry a single-nucleotide polymorphism (SNP) 538G → A in the ABCC11 gene, which significantly reduces (noticeable) body odor. To examine this, we recruited 18 self-identified male East Asian AA-homozygotes and 18 self-identified male Western individuals who were carriers of the functional G-allele. We collected samples of their fear-related and neutral body odors. Subsequently, we conducted a double-blind behavioral experiment in which we presented these samples to 69 self-identified female participants of Western Caucasian and East Asian backgrounds. The participants were asked to rate faces that were morphed between expressions of fear and disgust. Notably, despite the "odorless" phenotypical expression of the ABCC11-mutation in East Asians, their fear odor caused a perceptual fear bias in both East Asian and Caucasian receivers. This finding leaves open the possibility of universal fear chemosignaling. Additionally, we conducted exploratory chemical analysis to gain initial insights into the chemical composition of the body odors presented. In a subsequent pre-registered behavioral study (N = 33), we found that exposure to hexadecanoic acid, an abundant compound in the fear and neutral body odor samples, was sufficient to reproduce the observed behavioral effects. While exploratory, these findings provide insight into how specific chemical components can drive chemical fear communication.

Smells like new car or rather like an old carriage? - Resolution of the decay behavior of odorants in vehicle cabins during usage.

The typical new car smell is not only perceived directly after vehicle delivery. Vehicle interiors maintain their characteristic odors for a period of time during use even though the gas composition of the vehicle interior changes due to external influences. To obtain deeper insights into the odorant composition of a passenger cabin, this study aimed at characterizing the gas phase of two vehicle interiors at defined time intervals after vehicle delivery, and use by a customer in a controlled environment using a targeted odorant analysis. Thereby, the decrease in the general emissions in the cars did not coincide with the decay behavior of the odorants due to the chemical characteristics such as polarity of the odorants. Identification of the odorants in the vehicle interior during use revealed three groups of odor contributors exhibiting different decay behaviors: (i) odorants vaporizing rapidly via elevated temperature; (ii) odorants released by continued diffusion from materials; and (iii) fragrance chemicals of the customer. After 23 weeks of vehicle use, octanal, p-chloro-m-cresol, nonanal, p-tert-butylphenol, γ-nonalactone, and unsaturated aldehydes and ketones represented the most important odorants in the vehicle interior constituting the investigated car odor. The results of a descriptive sensory analysis corresponded with the identified odorants.

Follow your nose - Traveling the world of odorants in new cars.

Volatile organic compounds of the vehicle interior are well investigated, but only limited information is available on the odorants of the passenger cabin. To close this gap, we aimed at specifically elucidating the odor, as a general proof of principle, of two new cars with different seat upholstery in a controlled environment using a targeted odorant analysis. In a first step, odor profiles were evaluated by a descriptive sensory analysis. Then, potent odorants of the passenger cabins were characterized by gas chromatography-olfactometry and ranked according to their odor potency via odor extract dilution analysis. Using this approach, 41 potent odorants were detected, and 39 odorants were successfully identified by two-dimensional gas chromatography-mass spectrometry/olfactometry. In a third step, important odorants of the vehicle interior were quantified by means of internal standard addition. The most dominant odorants could be assigned to several specific substance classes comprising esters, saturated and unsaturated aldehydes, unsaturated ketones, rose ketones, phenolic and benzene derivatives, and pyrazines, occurring in a concentration range between 0.05 and 219 ng/L in air. Of these potent odorants, the aldehydes 2-butylhept-2-enal, 2-propyloct-2-enal, and (Z)-2-butyloct-2-enal are reported here for the first time as odorants in the environment of a passenger cabin.

Odorant Metabolism in Humans.

Odorants are relatively small molecules which are easily taken up and distributed in the human body. Despite their relevance in everyday life, however, only a limited amount of evidence about their metabolism, pathways, and bioactivities in the human body exists. With this Review, we aim to encourage future interdisciplinary research on the function and mechanisms of the biotransformation of odorants, involving different disciplines such as nutrition, medicine, biochemistry, chemistry, and sensory sciences. Starting with a general overview of the different ways of odorant uptake and enzymes involved in the metabolism of odorants, a more precise description of biotransformation processes and their function in the oral cavity, the nose, the lower respiratory tract (LRT), and the gastrointestinal tract (GIT) is given together with an overview of the different routes of odorant excretion. Finally, perspectives for future research are discussed.

Sesquiterpenes and sesquiterpenoids harbor modulatory allosteric potential and affect inhibitory GABAA receptor function in vitro.

Naturally occurring compounds such as sesquiterpenes and sesquiterpenoids (SQTs) have been shown to modulate GABAA receptors (GABAA Rs). In this study, the modulatory potential of 11 SQTs at GABAA Rs was analyzed to characterize their potential neurotropic activity. Transfected HEK293 cells and primary hippocampal neurons were functionally investigated using electrophysiological whole-cell recordings. Significantly different effects of ß-caryophyllene and α-humulene, as well as their respective derivatives ß-caryolanol and humulol, were observed in the HEK293 cell system. In neurons, the concomitant presence of phasic and tonic GABAA R configurations accounts for differences in receptor modulation by SQTs. The in vivo presence of the γ2 and δ subunits is important for SQT modulation. While phasic GABAA receptors in hippocampal neurons exhibited significantly altered GABA-evoked current amplitudes in the presence of humulol and guaiol, negative allosteric potential at recombinantly expressed α1 ß2 γ2 receptors was only verified for humolol. Modeling and docking studies provided support for the binding of SQTs to the neurosteroid-binding site of the GABAA R localized between transmembrane segments 1 and 3 at the (+ α)-(- α) interface. In sum, differences in the modulation of GABAA R isoforms between SQTs were identified. Another finding is that our results provide an indication that nutritional digestion affects the neurotropic potential of natural compounds.

Isolation of sesquiterpenoids from Matricaria chamomilla by means of solvent assisted flavor evaporation and centrifugal partition chromatography.

The (semi)volatile fraction of Matricaria chamomilla L., an annual herbal plant from the family of Asteraceae, contains high quantities of sesquiterpenes and sesquiterpenoids. A method was developed to achieve isolation and separation of these compounds, using a combination of solvent assisted flavor evaporation (SAFE) and solid support-free liquid-liquid chromatography. The biphasic liquid solvent system n-heptane/ethyl acetate/methanol/water, 5/2/5/2 v/v/v/v (Arizona S) was elaborated as a suitable solvent system for the simultaneous separation of the target compounds. The lab-scale liquid-liquid chromatography separation performed in a countercurrent chromatography (CCC) column was successfully transferred to a semi-preparative centrifugal partition chromatography (CPC) column, which enabled the isolation of artemisia ketone, artemisia alcohol, α-bisabolone oxide A, and (E)-en-yn-dicycloether. α-Bisabolol oxide A and (Z)-en-yn-dicycloether co-eluted, but were successfully separated by subsequent size-exclusion chromatography (SEC). Similarly, spathulenol and α-bisabolol oxide B were obtained as a mixture, and were separated by means of column chromatography using silica gel as stationary phase. The isolated compounds were characterized by means of nuclear magnetic resonance spectroscopy (NMR) and gas chromatography-mass spectrometry (GC-MS).

Identification of odorants in wood of Calocedrus decurrens (Torr.) Florin by aroma extract dilution analysis and two-dimensional gas chromatography-mass spectrometry/olfactometry.

General emissions of volatile organic compounds from wood are well investigated, but only limited information is available on the odor-active substances contained therein. To close this gap, we aimed at specifically elucidating the odorous constituents of wood from incense cedar [Calocedrus decurrens (Torr.) Florin]; this material is commonly used for the production of a range of products such as pencils and interior accessories. Targeted odorant analysis requires specialized techniques combining modern odorant analytical tools with human-sensory evaluation. Following this concept, the odor profile of the wood sample was first evaluated by human-sensory analyses. Then, the most potent wood odorants were characterized by means of gas chromatography-olfactometry and ranked according to their odor potency via aroma extract dilution analysis. With use of this approach, more than 60 odorous substances were detected, and the 22 most potent odorants were successfully identified by gas chromatography-mass spectrometry/olfactometry and two-dimensional gas chromatography-mass spectrometry/olfactometry. Among the main odorants found were a series of terpenes, several degradation products of fatty acids, and a number of odorants with a phenolic core moiety. Five odorants are reported here for the first time as wood odorants, such as γ-octalactone and 3-phenylpropanoic acid; thymoquinone was demonstrated for the first time to have a pencil-like odor quality.

Responses of Human Neonates to Highly Diluted Odorants from Sweat.

Conjugated forms of odorants contributing to sweat odor occur not only in human sweat but also in amniotic fluid, colostrum, and milk. However, it is unclear whether the released odorants are detected and hedonically discriminated by human newborns. To investigate this issue, we administered highly diluted solutions of (R)/(S)-3-methyl-3-sulfanylhexan-1-ol (MSH), (R)/(S)-3-sulfanylhexan-1-ol (SH), (E)/(Z)-3-methylhex-2-enoic acid (3M2H), and (R)/(S)-3-hydroxy-3-methylhexanoic acid (HMHA) to 3-d-old infants while their respiratory rate and oro-facial movements were recorded. Adult sensitivity to these odorants was assessed via triangle tests. Whereas no neonatal stimulus-specific response was found for respiratory rate, oro-facial reactivity indicated orthonasal detection of MSH and SH by male neonates, and of HMHA by the whole group of neonates. Dependent on the dilution of odorants, newborns evinced neutral responses or longer negative oro-facial expressions compared with the reference stimuli. Finally, newborns appeared to be more sensitive to the target odorants than did adults.

Responsiveness of human neonates to the odor of 5α-androst-16-en-3-one: a behavioral paradox?

The odorous steroid 5α-androst-16-en-3-one (AND) occurs in numerous biological fluids in mammals, including man, where it is believed to play a chemocommunicative role. As AND was recently detected in milk and amniotic fluid, sensitivity and hedonic responses to this substance were assessed in human neonates. To this aim, respiration and facial expressions were recorded in 3-day-old newborns in response to aqueous solutions of AND, ranging from 500ng/mL to 0.5 fg/mL. Although analyses of respiratory rate did not lead to clear-cut results, the newborns changed their facial expressions at concentrations not detected by adults in a triangle test. Newborns displayed negative facial actions of longer duration to AND relative to an odorless control. Thus, AND may be considered to be offensive to newborns, which is a counterintuitive outcome as they are exposed to this compound in the womb (and it should therefore be familiar), in milk, and on the mother's skin surface (and it should therefore be conditioned as positive). Multiple reasons for this perceptual-behavioral paradox are discussed.

Volatile organic compounds in preen oil and feathers - a review.

For a long time birds were assumed to be anosmic or at best microsmatic, with olfaction a poorly understood and seldom investigated part of avian physiology. The full viability of avian olfaction was first discovered through its functions in navigation and foraging. Subsequently, researchers have investigated the role of olfaction in different social and non-social contexts, including reproduction, kin recognition, predator avoidance, navigation and foraging. In parallel to the recognition of the importance of olfaction for avian social behaviour, there have been advances in the techniques and methods available for the sampling and analysis of trace volatiles and odourants, leading to insights into the chemistry underlying chemical communication in birds. This review provides (i) an overview of the current state of knowledge regarding the volatile chemical composition of preen oil and feathers, its phylogenetic coverage, chemical signatures and their potential functions, and (ii) a discussion of current methods used for the isolation and detection of volatiles. Finally, lines for future research are proposed.

Body odor samples from infants and post-pubertal children differ in their volatile profiles.

Body odors change during development, and this change influences the interpersonal communication between parents and their children. The molecular basis for this chemical communication has not been elucidated yet. Here, we show by combining instrumental and sensory analyses that the qualitative odorant composition of body odor samples is similar in infants (0-3 years) and post-pubertal children (14-18 years). The post-pubertal samples are characterized by higher odor dilution factors for carboxylic acids and by the presence of 5α-androst-16-en-3-one and 5α-androst-16-en-3α-ol. In addition to the olfaction-guided approach, the compounds 6-methylhept-5-en-2-one (6MHO), geranyl acetone (GA) and squalene (SQ) were quantified. Both age groups have similar concentrations of 6MHO and GA, whereas post-pubertal children tend to have higher concentration of SQ. In conclusion, sexual maturation coincides with changes to body odor chemical composition. Whether those changes explain differences in parental olfactory perception needs to be determined in future studies with model odors.

Linalool, 1,8-Cineole, and Eugenol Transfer from a Curry Dish into Human Urine.

SCOPE: For most substances, there are several routes of excretion from the human body. This study focuses on urinary excretion of dietary odorants and compares the results with previously obtained results on excretion into milk. METHODS AND RESULTS: Lactating mothers (n = 18) are given a standardized curry dish and donate urine samples before and after the intervention. The odorants 1,8-cineole, linalool, cuminaldehyde, cinnamaldehyde, 4-hydroxy-2,5-dimethyl-3(2H)-furanone, sotolone, eugenol, vanillin, and γ-nonalactone are quantitatively analyzed. A significant transition of up to 6 µg g-1 creatinine into urine is observed for linalool, 1,8-cineole, and eugenol. Maximum concentrations are reached 1.5 h after the intervention for 1,8-cineole and eugenol as well as 2.5 h after the intervention for linalool. Comparison with previous results reveals that the excretion pattern of odorants into urine is divergent from the one into milk. In a second intervention study (n = 6), excretion of phase II metabolites into urine is studied using ß-glucuronidase treatment. Linalool and eugenol concentrations are 23 and 77 times higher after treatment than before treatment with ß-glucuronidase, respectively. CONCLUSION: The study demonstrates transition of linalool, 1,8-cineole, and eugenol from the diet into urine and excretion of glucuronides in the case of linalool, eugenol, and vanillin.

Curry-Odorants and Their Metabolites Transfer into Human Milk and Urine.

SCOPE: The excretion of dietary odorants into urine and milk is evaluated and the impact of possible influencing factors determined. Furthermore, the metabolic relevance of conjugates for the excretion into milk is investigated. METHODS AND RESULTS: Lactating mothers (n = 20) are given a standardized curry dish and donated one milk and urine sample each before and 1, 2, 3, 4.5, 6, and 8 h after the intervention. The concentrations of nine target odorants in these samples are determined. A significant transition is observed for linalool into milk, as well as for linalool, cuminaldehyde, cinnamaldehyde, and eugenol into urine. Maximum concentrations are reached within 1 h after the intervention in the case of milk and within 2-3 h in the case of urine. In addition, the impact of glucuronidase treatment on odorant concentrations is evaluated in a sample subset of twelve mothers. Linalool, eugenol, and vanillin concentrations increased 3-77-fold in milk samples after treatment with ß-glucuronidase. CONCLUSION: The transfer profiles of odorants into milk and urine differ qualitatively, quantitatively, and in temporal aspects. More substances are transferred into urine and the transfer needs a longer period compared with milk. Phase II metabolites are transferred into urine and milk.

Characterization of a Human Respiratory Mucosa Model to Study Odorant Metabolism.

Nasal xenobiotic metabolizing enzymes (XMEs) are important for the sense of smell because they influence odorant availability and quality. Since the major part of the human nasal cavity is lined by a respiratory mucosa, we hypothesized that this tissue contributed to nasal odorant metabolism through XME activity. Thus, we built human respiratory tissue models and characterized the XME profiles using single-cell RNA sequencing. We focused on the XMEs dicarbonyl and l-xylulose reductase, aldehyde dehydrogenase (ALDH) 1A1, and ALDH3A1, which play a role in food odorant metabolism. We demonstrated protein abundance and localization in the tissue models and showed the metabolic activity of the corresponding enzyme families by exposing the models to the odorants 3,4-hexandione and benzaldehyde. Using gas chromatography coupled with mass spectrometry, we observed, for example, a significantly higher formation of the corresponding metabolites 4-hydroxy-3-hexanone (39.03 ± 1.5%, p = 0.0022), benzyl alcohol (10.05 ± 0.88%, p = 0.0008), and benzoic acid (8.49 ± 0.57%, p = 0.0004) in odorant-treated tissue models compared to untreated controls (0 ± 0, 0.12 ± 0.12, and 0.18 ± 0.18%, respectively). This is the first study that reveals the XME profile of tissue-engineered human respiratory mucosa models and demonstrates their suitability to study nasal odorant metabolism.

Recovery rates of selected body odor substances in different textiles applying various work-up and storage conditions measured by gas chromatography-mass spectrometry.

BACKGROUND: Body odor is an important aspect in interpersonal communication. For psychological and chemical research on body odors, suitable procedures for sampling and application, and analysis of body odors are essential. In this study, different textile fabrics (polyester, cotton, and Gazin gauze) were comparatively evaluated in view of their potential suitability for body odor sampling by determining recovery rates of selected body odor substances. In addition, the impact of sample preparation and storage conditions on the recovery rates was determined. RESULTS: The recovery rates of dimethyl disulfide, (E)-non-2-enal, 5α-androst-16-en-3-one, 6-methylhept-5-en-2-one, heptanal and 3-sulfanylhexan-1-ol were determined under different conditions of storage (storage for 30 min at room temperature or storage for 30 min at room temperature followed by freezing at - 80 °C for 4 weeks) and sample work-up (solvent extraction with and without solvent-assisted flavour evaporation, in the following: SAFE). SAFE led to overall lower recovery rates with a significant effect for (E)-non-2-enal and 5α-androst-16-en-3-one. Nevertheless, the results showed that SAFE can be an essential step when working with a complex matrix. When comparing the different fabrics, except for (E)-non-2-enal no difference between the recovery rates obtained for cotton and polyester became evident. Gazin gauze showed lower recovery rates for all compounds. Finally, our results showed that the here investigated target compounds are stable during storage for four weeks at - 80 °C. SIGNIFICANCE AND NOVELTY: The results show on the one hand that the here investigated compounds were stable during storage and that the fiber type had limited influence on overall recovery rates. On the other hand, they highlight the limitations of using textile materials for sampling of volatile substances, especially with regard to low recovery rates for certain substances and the necessity of material pre-treatment or distillation steps for enabling GC-MS analysis after solvent extraction.

Perspectives on Nasal Odorant Metabolism Research.

Olfaction is a multi-step process. At a peripheral level, nasal odorant metabolism contributes to olfaction via signal termination, variation, and regulation. We summarize current techniques used to investigate nasal odorant metabolism and give an outlook on future approaches, such as nasal tissue models and their potential contributions in future research directions.

Past, Present, and Future of Human Chemical Communication Research.

Although chemical signaling is an essential mode of communication in most vertebrates, it has long been viewed as having negligible effects in humans. However, a growing body of evidence shows that the sense of smell affects human behavior in social contexts ranging from affiliation and parenting to disease avoidance and social threat. This article aims to (a) introduce research on human chemical communication in the historical context of the behavioral sciences; (b) provide a balanced overview of recent advances that describe individual differences in the emission of semiochemicals and the neural mechanisms underpinning their perception, that together demonstrate communicative function; and (c) propose directions for future research toward unraveling the molecular principles involved and understanding the variability in the generation, transmission, and reception of chemical signals in increasingly ecologically valid conditions. Achieving these goals will enable us to address some important societal challenges but are within reach only with the aid of genuinely interdisciplinary approaches.

Can you smell my stress? Influence of stress chemosignals on empathy and emotion recognition in depressed individuals and healthy controls.

Human body odors contain chemical signals that play a key role in our non-verbal communication regarding health, genetic identity, immune system, fitness, and emotional state. Studies on human chemosignaling in individuals with psychiatric diseases are scarce but indicate altered smell perception and emotion recognition in depressed individuals. In the present project, we aimed to investigate the influence of chemosensory substances in social stress sweat on emotion recognition, perspective taking, affective responsiveness as well as stress level in healthy and depressed individuals. Therefore, chemosensory stimuli (sweat samples from Trier social stress test (TSST) and friendly-TSST (fTSST)) were obtained from 39 healthy participants (19 females). In a next step, chemosensory stimuli and an odor-free blank (cotton pad) were used to stimulate another group of 40 healthy participants (20 females) and 37 individuals with depression (24 females). Those stimuli were examined regarding their influence on subjective feelings of stress, emotion perception and empathic reactions using an empathy test. Furthermore, physiological data (breathing, heart rate, skin conductance response, stress hormones) of the participants were collected during chemosensory stimulation. Depressed individuals improved their ability of perspective taking and affective responsiveness for the emotion grief when presented with stress chemosignals compared to no chemosignals. Healthy individuals remained unaffected regarding perspective taking and affective responsiveness. Both depressed and healthy individuals showed no increased stress hormone cortisol and α-amylase values during the social stress chemosignals condition, but reduced values for fTSST condition compared to no chemosignals respectively. The results imply that stress chemosignals do not trigger a stress reaction, but for depressed individuals they lead to a better emotion assessment for grief. This research contributes to a deeper understanding of the effects of social stress chemosignals on healthy and depressed individuals. Knowing the impact of human chemosignals on emotional processing is crucial for a better understanding of non-verbal human interaction.

Dietary Linalool is Transferred into the Milk of Nursing Mothers.

SCOPE: Breast milk is repeatedly postulated to shape the first aroma and taste impressions of infants and thus impact their flavor learning. The objective of this study is to assess the transition of aroma compounds from a customary curry dish into milk. METHODS AND RESULTS: The article prepares a standardized curry dish and administers the dish to nursing mothers (n = 18) in an intervention study. The participants donate one milk sample before and three samples after the intervention. Due to their olfactory or quantitative relevance in the curry dish, 1,8-cineole, linalool, cuminaldehyde, cinnamaldehyde, 4-hydroxy-2,5-dimethyl-3(2H)-furanone, sotolone, eugenol, vanillin, and γ-nonalactone are defined as target compounds, and their transition into milk is quantified by gas chromatography-mass spectrometry. A significant transition into the milk is observed for linalool, and its olfactory relevance in this respect is supported by calculated odor activity values. In contrast, no relevant levels are detected for the other eight target compounds. CONCLUSION: Ingestion of a customary curry dish can lead to an alteration of the milk aroma, which might be perceived by the infant during breastfeeding. The current study also demonstrates that the extent of aroma transfer differs between both substances and individuals.

Dietary Piperine is Transferred into the Milk of Nursing Mothers.

INTRODUCTION: The diet of breastfeeding mothers could bring nurslings into contact with flavor compounds putatively contributing to early sensory programming of the infant. The study investigates whether tastants from a customary curry dish consumed by mothers are detectable in their milk afterwards and can be perceived by the infant. METHODS AND RESULTS: Sensory evaluation identifies pungency as the dominating taste impression of the curry dish. Its ingredients of chili, pepper, and ginger suggest the flavor compounds capsaicin, piperine, and 6-gingerol as analytical targets. Breastfeeding mothers are recruited for an intervention trial involving the consumption of the curry dish and subsequent collection of milk samples for flavor compound analysis. Targeted and untargeted mass spectrometric (MS)- investigations identify exclusively piperine as an intervention-derived compound in human milk. However, concentrations are below the human taste threshold. CONCLUSION: Piperine from pepper-containing foods transfers into the mother's milk within 1 h and is delivered to the nursling. Concentrations of 50 and 200 nM of piperine are 70-350 times below the human taste threshold, but TRPV1 (Transient Receptor Potential Vanilloid-1 ion channel) desensitization through frequent exposure to sub-taste-threshold concentrations could contribute to an increased tolerance at a later age.