Human Odor Research Articles

Sorption Kinetic Parameters from Nanomechanical Sensing for Discrimination of 2-Nonenal from Saturated Aldehydes.

Nanomechanical sensors have gained significant attention as promising platforms for artificial olfaction. Since sorption kinetic parameters that can be estimated from the sensing signals of nanomechanical sensors reflect the chemical and physicochemical interactions between the odorant and receptor material, the parameters can be utilized for the direct discrimination of each odorant. In this study, we demonstrated the discrimination of 20 vapors, including hydrocarbons, alcohols, organic acids, ketones, and aldehydes, which are reported as human body odor components, using the parameters extracted in the analytical solution of nanomechanical sensors based on sorption kinetics with viscoelastic behaviors. By using one of the specific nanomechanical sensors─membrane-type surface stress sensor─as a sensing unit, we successfully discriminated trans-2-nonenal known as an aging marker from other saturated aldehydes along with quantifying their concentrations.

Identification of human skin microbiome odorants that manipulate mosquito landing behavior

The resident human skin microbiome is responsible for the production of most of the human scents that are attractive to mosquitoes. Hence, engineering the human skin microbiome to synthesize less of mosquito attractants or produce repellents could potentially reduce bites and prevent the transmission of deadly mosquito-borne pathogens. In order to further characterize the human skin volatilome, we quantified the major volatiles of 39 strains of skin commensals (Staphylococci and Corynebacterium). Importantly, to validate the behavioral activity of these volatiles, we first assessed landing behavior triggered by human skin volatiles. We demonstrated that landing behavior is gated by the presence of carbon dioxide and L-(+)-lactic acid. This is similar to the combinatorial coding triggering mosquito short range attraction. Repellency behavior to selected skin volatiles and terpenes was tested in the presence of carbon dioxide and L-(+)-lactic acid. In a 2-choice landing behavior context, the skin volatiles 2- and 3-methyl butyric acids reduced mosquito landing by 62.0–81.6% and 87.1–99.6%, respectively. Similarly, the terpene geraniol was capable of reducing mosquito landing behavior by 74.9%. We also tested the potential repellency effects of terpenes in mosquitoes at short-range using a 4-port olfactometer. In these assays, geraniol reduced mosquito attraction (69–78%) to a mixture of key human kairomones carbon dioxide, L-(+)-lactic acid, and ammonia. These findings demonstrate that carbon dioxide and L-(+)-lactic acid change the valence of other skin volatiles towards mosquito landing behavior. Moreover, this study offers candidate odorants to be targeted in a novel strategy to reduce attractants or produce repellents by the human skin microbiota that may curtail mosquito bites, and subsequent mosquito-borne disease.

Influence of the human body odor compound HMHA on face perception.

Body odors convey information about the individuals, but the mechanisms are not fully understood yet. As far as human reproduction is concerned, molecules that are produced in sexually dimorphic amounts could be possible chemosignals. 3-hydroxy-3-methylhexanoic acid (HMHA) is one of them-more typical of men. Here, we investigated the possibility that the perception of gender and attractiveness in human faces could be implicitly influenced by this compound. Clearly feminine, ambiguous and clearly masculine faces were primed with an odor of HMHA, a control odor or air. Based on 100-ms face presentation, 40 raters had to identify the face's gender as quickly as possible and provide attractiveness evaluations. 3-hydroxy-3-methylhexanoic acid tended to be perceived as less pleasant and induced lower sniff duration in women compared with men. As to the effects of HMHA on face perception (vs. control conditions), we found that gender identification and the associated response time were unaffected by HMHA. Attractiveness of the faces, however, increased in presence of HMHA, but not in a sex-specific manner and only for unattractive faces with ambiguous gender. In sum, this study found no evidence in favor of a possible role of this sexually dimorphic compound in intrasexual competition nor in intersexual attraction.

A status report on human odorant receptors and their allocated agonists.

Olfactory perception begins when odorous substances interact with specialized receptors located on the surface of dedicated sensory neurons. The recognition of smells depends on a complex mechanism involving a combination of interactions between an odorant and a set of odorant receptors (ORs), where molecules are recognized according to a combinatorial activation code of ORs. Although these interactions have been studied for decades, the rules governing this ligand recognition remain poorly understood, and the complete combinatorial code is only known for a handful of odorants. We have carefully analyzed experimental results regarding the interactions between ORs and molecules to provide a status report on the deorphanization of ORs, i.e. the identification of the first agonist for a given sequence. This meticulous analysis highlights the influence of experimental methodology (cell line or readout) on molecule-receptor association results and shows that 83% of the results are conserved regardless of experimental conditions. The distribution of another key parameter, EC50, indicates that most OR ligand activities are in the micromolar range and that impurities could lead to erroneous conclusions. Focusing on the human ORs, our study shows that 88% of the documented sequences still need to be deorphanized. Finally, we also estimate the size of the ORs' recognition range, or broadness, as the number of odorants activating a given OR. By analogously estimating molecular broadness and combining the two estimates we propose a basic framework that can serve as a comparison point for future machine learning algorithms predicting OR-molecule activity.

Genetic Decoding of the African Malaria Mosquito Olfactory System: New Insights into Responses to Human Odors

Genetic Decoding of the African Malaria Mosquito Olfactory System: New Insights into Responses to Human Odors

Understanding the molecular mechanisms of odorant binding and activation of the human OR52 family

Structural and mechanistic studies on human odorant receptors (ORs), key in olfactory signaling, are challenging because of their low surface expression in heterologous cells. The recent structure of OR51E2 bound to propionate provided molecular insight into odorant recognition, but the lack of an inactive OR structure limited understanding of the activation mechanism of ORs upon odorant binding. Here, we determined the cryo-electron microscopy structures of consensus OR52 (OR52cs), a representative of the OR52 family, in the ligand-free (apo) and octanoate-bound states. The apo structure of OR52cs reveals a large opening between transmembrane helices (TMs) 5 and 6. A comparison between the apo and active structures of OR52cs demonstrates the inward and outward movements of the extracellular and intracellular segments of TM6, respectively. These results, combined with molecular dynamics simulations and signaling assays, shed light on the molecular mechanisms of odorant binding and activation of the OR52 family.

Memory effects of visual and olfactory landmark information in human wayfinding

Non-human animals are exceptionally good at using smell to find their way through the environment. However, the use of olfactory cues for human navigation is often underestimated. Although the sense of smell is well-known for its distinct connection to memory and emotion, memory effects in human navigation using olfactory landmarks have not been studied yet. Therefore, this article compares wayfinding and recognition performance for visual and olfactory landmarks learned by 52 participants in a virtual maze. Furthermore, it is one of the first empirical studies investigating differences in memory effects on human navigation by using two separate test situations 1 month apart. The experimental task was to find the way through a maze-like virtual environment with either olfactory or visual cues at the intersections that served as decision points. Our descriptive results show that performance was above chance level for both conditions (visual and olfactory landmarks). Wayfinding performance did not decrease 1 month later when using olfactory landmarks. In contrast, when using visual landmarks wayfinding performance decreased significantly, while visual landmarks overall lead to better recognition than olfactory landmarks at both times of testing. The results demonstrate the unique character of human odor memory and support the conclusion that olfactory cues may be used in human spatial orientation. Furthermore, the present study expands the research field of human wayfinding by providing a study that investigates memory for landmark knowledge and route decisions for the visual and olfactory modality. However, more studies are required to put this important research strand forward.

Knockout of OR39 reveals redundancy in the olfactory pathway regulating the acquisition of host seeking in Anopheles coluzzii.

The attraction of anthropophilic mosquitoes to human host cues, such as body odour and carbon dioxide, gradually increases during adult maturation. This acquisition of host-seeking behaviour correlates with age-dependent changes in odorant receptor (OR) transcript abundance and sensitivity of olfactory sensory neurons (OSNs). One OR gene of the human malaria vector, Anopheles coluzzii, AcolOR39, is significantly downregulated in mature females, and a cognate ligand of AcolOR39, sulcatone, a major component of human emanations, mediates the observed behavioural inhibition of newly emerged (teneral) females to human body odour. Knockout of AcolOR39, using CRISPR-Cas9 mutagenesis, selectively abolished sulcatone detection in OSNs, housed in trichoid sensilla. However, knockout of AcolOR39 altered neither the response rate nor the flight behaviour of teneral females in a wind tunnel, indicating the involvement of other genes, and thus a redundancy, in regulating the acquisition of host seeking in mosquitoes.

The multi-faceted food odorant 4-methylphenol selectively activates evolutionary conserved receptor OR9Q2.

4-Methylphenol is a food-related odor-active volatile with a high recognition factor, due to its horse stable-like, fecal odor quality. Its ambivalent hedonic impact as key aroma compound, malodor, and semiochemical has spurred the search for its cognate, chemosensory odorant receptors across species. A human odorant receptor for the highly characteristic 4-methylphenol has been elusive. Here, we identified and characterized human receptor OR9Q2 to be tuned to purified 4-methylphenol, but not to its contaminant isomer 3-methylphenol. This highly selective function of OR9Q2 complements an exclusive phenol detection gap in the ancient, most broadly tuned human odorant receptor OR2W1. Moreover, a 4-methylphenol function is evolutionary conserved in phylogenetically related OR9Q2 orthologs from chimpanzee, mouse, and cow. Notably, the cow receptor outperformed human OR9Q2 10-fold in signal strength, consonant with previous reports of 4-methylphenol as a bovine pheromone. Our results suggest OR9Q2 as best sensor for the key food odorant, malodor, and semiochemical 4-methylphenol.

Exploring the visualization of human milk odor profiles: Intuitive characterization and construction of the link between odor compounds and sensory attributes

Studies on odor are not negligible in the human milk (HM) science field because it plays an irreplaceable role in the feeding process of infants. This study aimed to investigate the odor skeleton components (OSCs) in HM and verify and construct an intuitive link between them and the HM odor attributes. A total of 72 odor-active compounds were identified from 32 HMs using the comprehensive two-dimensional gas chromatography–olfactometry-mass spectrometry. Twenty of these compounds were identified as OSCs (average FD ≥ 1 and average OAV ≥ 1), and their actual odor contribution was clarified. Furthermore, the connection of the 20 OSCs with their corresponding eight odor attributes was visualized by constructing a molecular sensory odor wheel. Of them, 2,3-butanedione, (E)-2-decenal, nonanal, (E)-2-nonenal, octanal, 1-octen-3-one, hexanal, methional, and butanoic acid were the most important contributors to dairy-sweet, fishy, dairy-fat, metallic/iron, flour, grassy/green, cooked, and sweaty/rancid odor of HM.

Human Odour Attracts Anopheles and Culex Mosquitoes only Upon Sweating

Human Odour Attracts Anopheles and Culex Mosquitoes only Upon Sweating

A Behavioral Assay to Quantify Odor-Guided Thermotaxis with Anopheles gambiae under Semi-Field Conditions.

The African malaria mosquito Anopheles gambiae is strongly attracted to human body odor and skin temperature. Quantitative behavioral assays suitable for use in semi-field environments with this nocturnal mosquito species are essential to gain improved insights into An. gambiae sensory biology, the mechanistic basis of mosquito attraction to humans, and host preference. In this protocol, we describe steps for engineering equipment for a novel behavioral assay for An. gambiae, which we have termed the odor-guided thermotaxis assay (OGTA). The OGTA uses infrared videography to quantify landings of female An. gambiae on an aluminum platform heated to human skin temperature that can be baited with volatile odorants such as carbon dioxide or human whole body odor. The OGTA facilitates high-content recordings of An. gambiae landing behavior during odor-guided thermotaxis under naturalistic semi-field conditions without the requirement for domestic power.

Behavioral interplay between mosquito and mycolactone produced by Mycobacterium ulcerans and bacterial gene expression induced by mosquito proximity.

Mycolactone is a cytotoxic lipid metabolite produced by Mycobacterium ulcerans, the environmental pathogen responsible for Buruli ulcer, a neglected tropical disease. Mycobacterium ulcerans is prevalent in West Africa, particularly found in lentic environments, where mosquitoes also occur. Researchers hypothesize mosquitoes could serve as a transmission mechanism resulting in infection by M. ulcerans when mosquitoes pierce skin contaminated with M. ulcerans. The interplay between the pathogen, mycolactone, and mosquito is only just beginning to be explored. A triple-choice assay was conducted to determine the host-seeking preference of Aedes aegypti between M. ulcerans wildtype (MU, mycolactone active) and mutant (MUlac-, mycolactone inactive). Both qualitative and quantitative differences in volatile organic compounds' (VOCs) profiles of MU and MUlac- were determined by GC-MS. Additionally, we evaluated the interplay between Ae. aegypti proximity and M. ulcerans mRNA expression. The results showed that mosquito attraction was significantly greater (126.0%) to an artificial host treated with MU than MUlac-. We found that MU and MUlac produced differential profiles of VOCs associated with a wide range of biological importance from quorum sensing (QS) to human odor components. RT-qPCR assays showed that mycolactone upregulation was 24-fold greater for MU exposed to Ae. aegypti in direct proximity. Transcriptome data indicated significant induction of ten chromosomal genes of MU involved in stress responses and membrane protein, compared to MUlac- when directly having access to or in near mosquito proximity. Our study provides evidence of possible interkingdom interactions between unicellular and multicellular species that MU present on human skin is capable of interreacting with unrelated species (i.e., mosquitoes), altering its gene expression when mosquitoes are in direct contact or proximity, potentially impacting the production of its VOCs, and consequently leading to the stronger attraction of mosquitoes toward human hosts. This study elucidates interkingdom interactions between viable M. ulcerans bacteria and Ae. aegypti mosquitoes, which rarely have been explored in the past. Our finding opens new doors for future research in terms of disease ecology, prevalence, and pathogen dispersal outside of the M. ulcerans system.

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.

A mosquito-specific antennal protein is critical for the attraction to human odor in the malaria vector Anopheles gambiae

Mosquitoes rely mainly on the sense of smell to decipher their environment and locate suitable food sources, hosts for blood feeding and oviposition sites. The molecular bases of olfaction involve multigenic families of olfactory proteins that have evolved to interact with a narrow set of odorants that are critical for survival. Understanding the complex interplay between diversified repertoires of olfactory proteins and ecologically-relevant odorant signals, which elicit important behaviors, is fundamental for the design of novel control strategies targeting the sense of smell of disease vector mosquitoes. Previously, large multigene families of odorant receptor and ionotropic receptor proteins, as well as a subset of odorant-binding proteins have been shown to mediate the selectivity and sensitivity of the mosquito olfactory system. In this study, we identify a mosquito-specific antennal protein (MSAP) gene as a novel molecular actor of odorant reception. MSAP is highly conserved across mosquito species and is transcribed at an extremely high level in female antennae. In order to understand its role in the mosquito olfactory system, we generated knockout mutant lines in Anopheles gambiae, and performed comparative analysis of behavioral and physiological responses to human-associated odorants. We found that MSAP promotes female mosquito attraction to human odor and enhances the sensitivity of the antennae to a variety of odorants. These findings suggest that MSAP is an important component of the mosquito olfactory system, which until now has gone completely unnoticed.

Relationship between asymmetric nostril use and human emotional odours in cats

Cat social behaviour and cognition has received a growing interest during the last decades. Recent studies reported that cats efficiently engage in interspecific communication with humans and suggest that cats are sensitive to human emotional visual and auditory cues. To date, there is no evidence on the social and informative role of human emotional odours, which may affect human-cat communication. In this study, we presented cats with human odours collected in different emotional contexts (fear, happiness, physical stress and neutral) and evaluated the animals’ behavioural responses. We found that “fear” odours elicited higher stress levels than “physical stress” and “neutral”, suggesting that cats perceived the valence of the information conveyed by “fear” olfactory signals and regulate their behaviour accordingly. Moreover, the prevalent use of the right nostril (right hemisphere activation) with the increase of stress levels, particularly in response to “fear” odours, provides first evidence of lateralized emotional functions of olfactory pathways in cats.

Multivariate regression modelling for gender prediction using volatile organic compounds from hand odor profiles via HS-SPME-GC-MS.

The efficacy of using human volatile organic compounds (VOCs) as a form of forensic evidence has been well demonstrated with canines for crime scene response, suspect identification, and location checking. Although the use of human scent evidence in the field is well established, the laboratory evaluation of human VOC profiles has been limited. This study used Headspace-Solid Phase Microextraction-Gas Chromatography-Mass Spectrometry (HS-SPME-GC-MS) to analyze human hand odor samples collected from 60 individuals (30 Females and 30 Males). The human volatiles collected from the palm surfaces of each subject were interpreted for classification and prediction of gender. The volatile organic compound (VOC) signatures from subjects' hand odor profiles were evaluated with supervised dimensional reduction techniques: Partial Least Squares-Discriminant Analysis (PLS-DA), Orthogonal-Projections to Latent Structures Discriminant Analysis (OPLS-DA), and Linear Discriminant Analysis (LDA). The PLS-DA 2D model demonstrated clustering amongst male and female subjects. The addition of a third component to the PLS-DA model revealed clustering and minimal separation of male and female subjects in the 3D PLS-DA model. The OPLS-DA model displayed discrimination and clustering amongst gender groups with leave one out cross validation (LOOCV) and 95% confidence regions surrounding clustered groups without overlap. The LDA had a 96.67% accuracy rate for female and male subjects. The culminating knowledge establishes a working model for the prediction of donor class characteristics using human scent hand odor profiles.

Human Olfactory Receptor Sensor for Odor Reconstitution.

Among the five human senses, light, sound, and force perceived by the eye, ear, and skin, respectively are physical phenomena, and therefore can be easily measured and expressed as objective, univocal, and simple digital data with physical quantity. However, as taste and odor molecules perceived by the tongue and nose are chemical phenomena, it has been difficult to express them as objective and univocal digital data, since no reference chemicals can be defined. Therefore, while the recording, saving, transmitting to remote locations, and replaying of human visual, auditory, and tactile information as digital data in digital devices have been realized (this series of data flow is defined as DX (digital transformation) in this review), the DX of human taste and odor information is not yet in the realization stage. Particularly, since there are at least 400,000 types of odor molecules and an infinite number of complex odors that are mixtures of these molecules, it has been considered extremely difficult to realize "human olfactory DX" by converting all odors perceived by human olfaction into digital data. In this review, we discuss the current status and future prospects of the development of "human olfactory DX", which we believe can be realized by utilizing odor sensors that employ the olfactory receptors (ORs) that support human olfaction as sensing molecules (i.e., human OR sensor).

Screening of skatole-degrading bacteria and control of human fecal odor by compound bacteria

PurposeThe biodegradation of skatole was used as a starting point in this study, and existing strains of degrading NH3 and H2S in the laboratory were combined to create a composite deodorant. The deodorization effect of the composite deodorant on human feces was investigated in order to provide a foundation for fecal odor gas treatment.MethodsSkatole-degrading bacteria were identified, degradation conditions were optimized, and skatole metabolites were identified using liquid chromatography-mass spectrometry (LC-MS). The skatole-degrading bacteria were combined with the existing strains of degrading NH3 and H2S in the laboratory to make a compound deodorizer, and the deodorizing effect of the compound deodorizer on fresh human feces and old human feces was compared. Liquid chromatography, specific sensors, and gas chromatography were used to determine the contents of skatole, NH3, H2S, and volatile organic compounds, and the microbial diversity was examined.ResultsMicrobial agents H and Y capable of utilizing skatole were screened out under aerobic and facultative anaerobic conditions, respectively. Within 48 h, the degradation rate of skatole by microbial agent Y was 88.52%. Following condition optimization, the optimum temperature for skatole degradation by microbial agent Y was 33 °C, and the optimum pH was 7. The main functional bacteria were Acinetobacter xiamenensis. The metabolites of skatole were determined by liquid chromatography-mass spectrometry (LC–MS), and six possible metabolites were found, including 3-aldehyde indole, 3-carboxyl indole, 1H-indole-2,3-dione, and 3-methyl indole pyruvate. The skatole-degrading bacteria Lactobacillus rhamnosus and Saccharomyces cerevisiae were then combined in proportion to form a composite deodorant. The 5-day degradation rate of skatole in the old manure group was 88.11%, while the 5-day degradation rate in the fresh manure group was 47.56%.ConclusionsThe compound microbial agent developed in this study has a solid deodorizing effect, particularly in the control of the odor of obsolete feces. The use of composite microbial agents can efficiently degrade skatole in human feces, providing a theoretical foundation for the use of microbial remediation in the actual world.Graphical

Gas-Phase Biosensors (Bio-Sniffers) for Measurement of 2-Nonenal, the Causative Volatile Molecule of Human Aging-Related Body Odor.

The molecule 2-nonenal is renowned as the origin of unpleasant human aging-related body odor that can potentially indicate age-related metabolic changes. Most 2-nonenal measurements rely on chromatographic analytical systems, which pose challenges in terms of daily usage and the ability to track changes in concentration over time. In this study, we have developed liquid- and gas-phase biosensors (bio-sniffers) with the aim of enabling facile and continuous measurement of trans-2-nonenal vapor. Initially, we compared two types of nicotinamide adenine dinucleotide (phosphate) [NAD(P)]-dependent enzymes that have the catalytic ability of trans-2-nonenal: aldehyde dehydrogenase (ALDH) and enone reductase 1 (ER1). The developed sensor quantified the trans-2-nonanal concentration by measuring fluorescence (excitation: 340 nm, emission: 490 nm) emitted from NAD(P)H that was generated or consumed by ALDH or ER1. The ALDH biosensor reacted to a variety of aldehydes including trans-2-nonenal, whereas the ER1 biosensor showed high selectivity. In contrast, the ALDH bio-sniffer showed quantitative characteristics for trans-2-nonenal vapor at a concentration range of 0.4-7.5 ppm (with a theoretical limit of detection (LOD) and limit of quantification (LOQ) of 0.23 and 0.26 ppm, respectively), including a reported concentration (0.85-4.35 ppm), whereas the ER1 bio-sniffer detected only 0.4 and 0.8 ppm. Based on these findings, headspace gas of skin-wiped alcohol-absorbed cotton collected from study participants in their 20s and 50s was measured by the ALDH bio-sniffer. Consequently, age-related differences in signals were observed, suggesting the potential for measuring trans-2-nonenal vapor.