Chemical SensesPub Date : 2025-10-08DOI: 10.1093/chemse/bjaf042
Joshua S Danoff, Kaitao Zhao, Kevin Monahan
{"title":"Determinants of odorant receptor transcription and gene choice.","authors":"Joshua S Danoff, Kaitao Zhao, Kevin Monahan","doi":"10.1093/chemse/bjaf042","DOIUrl":"https://doi.org/10.1093/chemse/bjaf042","url":null,"abstract":"<p><p>The mammalian olfactory system enables the detection of a wide variety of chemical compounds via the expression of a repertoire of olfactory receptors comprising the largest gene family in the mammalian genome. Olfactory sensory neurons each express only one odorant receptor (OR) gene. In mice, this requires activation of one OR gene and repression of over 1400 other OR genes. In this review, we describe the mechanisms that support the transcription of OR genes and how these mechanisms impact which OR is expressed in each neuron. First, we discuss what is currently known about the role of transcription in OR choice. We then describe the role of specific features of OR genes and enhancers in the regulation of OR transcription. Finally, we discuss characteristics of olfactory sensory neurons which specify transcription of some OR genes while restricting the transcription of others.</p>","PeriodicalId":9771,"journal":{"name":"Chemical Senses","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemical SensesPub Date : 2025-10-08DOI: 10.1093/chemse/bjaf044
Stephen P Wooding
{"title":"Diverse approaches to diverse receptors: a multidimensional study of caffeine perception.","authors":"Stephen P Wooding","doi":"10.1093/chemse/bjaf044","DOIUrl":"https://doi.org/10.1093/chemse/bjaf044","url":null,"abstract":"","PeriodicalId":9771,"journal":{"name":"Chemical Senses","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemical SensesPub Date : 2025-09-30DOI: 10.1093/chemse/bjaf041
Claire A de March, Patrick Breheny, William B Titlow, Hiroaki Matsunami, Timothy S McClintock
{"title":"Distinct Odorant Receptor Response Patterns to Aliphatic Odorants in Freely Behaving Mice.","authors":"Claire A de March, Patrick Breheny, William B Titlow, Hiroaki Matsunami, Timothy S McClintock","doi":"10.1093/chemse/bjaf041","DOIUrl":"https://doi.org/10.1093/chemse/bjaf041","url":null,"abstract":"<p><p>In mammals, odors are encoded by a combinatorial code determined by the pattern of responses across hundreds of odorant receptors expressed monogenically and monoallelically in olfactory sensory neurons. The compositions of these receptor response patterns are largely unknown and overlap between them has yet to be explored. Activity-dependent reporter gene expression in freely behaving S100a5-tauGFP mice allowed capture of activated olfactory sensory neurons and identified 168 receptors responsive to moderate concentrations of one or more of 12 aliphatic (5-8 carbons) ketones, alcohols, and carboxylic acids. These 12 response patterns are remarkably different, with only 19% of the receptors responding to more than 1 of these odorants. This distinctiveness corresponds with the ease of discrimination of these odorants and may help maintain perceptual constancy in the face of response pattern variability, such as across odorant concentrations. This set of 168 receptors is not specific to aliphatic odorants but instead has 16% overlap with the receptors responsive to seven odors tested previously in vivo, consistent with a receptor repertoire evolved to produce combinatorial codes. Aliphatic odorant response pattern similarity depends more upon odorant functional group than carbon chain length but the impact of chain length increases with the number of carbons. The response patterns to these aliphatic odorants are mostly composed of unrelated receptors, except some patterns contain minor subsets of closely related receptors. These findings argue that the major selective forces driving OR evolution are expansion of the odorant receptor gene family and the production of distinct response patterns.</p>","PeriodicalId":9771,"journal":{"name":"Chemical Senses","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemical SensesPub Date : 2025-09-26DOI: 10.1093/chemse/bjaf040
Kolbe M Sussman, Thomas G Mast, Joseph M Breza
{"title":"Aging Decreases Preferences for Salts, but not for Sucrose and Alters Morphology of Fungiform Taste Pores in Mice.","authors":"Kolbe M Sussman, Thomas G Mast, Joseph M Breza","doi":"10.1093/chemse/bjaf040","DOIUrl":"https://doi.org/10.1093/chemse/bjaf040","url":null,"abstract":"<p><p>Mice are commonly used for laboratory research, due in large part to the widespread advancement in the genetic toolbox, such as reporters, knock-in, and knockout mice. The effects of aging on the taste system in mice has been largely unstudied. The aim of this study was to examine whether taste preferences to sucrose, NaCl, and NH4Cl were associated with aging and changes in ultrastructural characteristics of fungiform taste pores using scanning electron microscopy. Thirty-minute two-bottle preference tests in wild-type mice indicated that preferences for NaCl and NH4Cl, but not sucrose, were significantly different in aged mice (16-17 months old) relative to young mice (5 months old). In the same animals, we found that the percentage of fungiform papilla with taste pores present was significantly reduced in the aged group. These findings are consistent with our recent study in rats, where aging had a significant impact on chorda tympani nerve responses to salt and ultrastructural characteristics of fungiform taste pores. Collectively, these data suggest that aging significantly affects fungiform taste pore morphology and has a significant impact on taste processing. Future studies investigating the factors that form and maintain taste pores are of critical importance as the pore is necessary for taste stimuli access to taste bud cells.</p>","PeriodicalId":9771,"journal":{"name":"Chemical Senses","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemical SensesPub Date : 2025-09-24DOI: 10.1093/chemse/bjaf039
Camille Pennaneach, Andrew Costanzo, Caterina Dinnella, Sara Spinelli, Erminio Monteleone, Russell Keast
{"title":"Post-oral receptors and alimentary taste: implications for energy intake and appetite.","authors":"Camille Pennaneach, Andrew Costanzo, Caterina Dinnella, Sara Spinelli, Erminio Monteleone, Russell Keast","doi":"10.1093/chemse/bjaf039","DOIUrl":"https://doi.org/10.1093/chemse/bjaf039","url":null,"abstract":"<p><p>Eating behaviour is shaped by genetic, psychological, and physiological factors, with nutrient sensing playing a central role in modulating intake. The tongue, as the primary gustatory organ, initiates this process by influencing hedonic preferences, food choices, and feeding behaviour. Recent sensory research has highlighted the potential role of an emerging class of taste modalities known as alimentary tastes. This concept refers to the gustatory detection of compounds that produce weak or subtle taste perceptions but elicit strong post-oral effects. While most studies have focused on umami and fat taste in that category, growing interest surrounds newly characterised modalities such as kokumi and complex carbohydrate-associated tastes. Basic and alimentary taste stimulus influence behaviour and physiological processes both pre and post ingestion. Their receptors, present in enteroendocrine cells, detect specific nutrients and regulate gut feedback mechanisms. Emerging research is investigating not only their involvement in metabolic disorders and conditions such as malnutrition, but also their potential as therapeutic targets for modulating appetite, nutrient absorption, and endocrine responses. This narrative review aims to identify and characterise the functions of these post-oral receptors along the gastrointestinal tract in the regulation of food intake and to evaluate their therapeutic potential in metabolic conditions such as obesity and type 2 diabetes.</p>","PeriodicalId":9771,"journal":{"name":"Chemical Senses","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemical SensesPub Date : 2025-09-19DOI: 10.1093/chemse/bjaf035
Jacqueline Guillemin, Grace Davis, Kayla Audette, Tucker Avonda, Ella Freed, Ava Vitters, Jessica Cerniglia, Braden Woods, Erinn Wagner, Lauren T Schwartz, Ian Orsmond, Beckett Hampp, Megan Burdick, Peter Gause, Sascha Taylor, Brenna Asaro, Alice Sperber, Kaitlyn A Zoller, Molly Stanley
{"title":"Amino acids activate parallel chemosensory pathways in Drosophila.","authors":"Jacqueline Guillemin, Grace Davis, Kayla Audette, Tucker Avonda, Ella Freed, Ava Vitters, Jessica Cerniglia, Braden Woods, Erinn Wagner, Lauren T Schwartz, Ian Orsmond, Beckett Hampp, Megan Burdick, Peter Gause, Sascha Taylor, Brenna Asaro, Alice Sperber, Kaitlyn A Zoller, Molly Stanley","doi":"10.1093/chemse/bjaf035","DOIUrl":"https://doi.org/10.1093/chemse/bjaf035","url":null,"abstract":"<p><p>Amino acids (AAs) are essential dietary macronutrients that impact an organism's fitness in a concentration-dependent manner, but the mechanisms mediating AA detection to drive consumption are less clear. In Drosophila, we identified the repertoire of taste cells and receptors that are salient for feeding initiation when flies encounter a glutamate-rich AA peptide mixture, tryptone, using in vivo calcium imaging and the proboscis extension response (PER). We found that tryptone attraction occurs through sweet cells, whereas feeding aversion is mediated through Ionotropic Receptor 94e (IR94e) cells and bitter cells, dependent on concentration. Further, our results corroborate previous findings that IR76b, IR51b, and IR94e detect AAs in specific cell types, even when exposed to a more complex peptide mixture. Additionally, we describe a new role for the appetitive IR56d receptor and bitter Gustatory Receptors (GRs) in sensing tryptone. This work establishes a cellular and molecular framework salient for AA and peptide feeding initiation and highlights redundancy in aversive pathways that regulate AA feeding.</p>","PeriodicalId":9771,"journal":{"name":"Chemical Senses","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemical SensesPub Date : 2025-01-22DOI: 10.1093/chemse/bjaf020
Jingjing Xia, Yaqun Yuan, Chenxi Li, Anna Kucharska-Newton, Qu Tian, Jayant M Pinto, Jiantao Ma, Eleanor M Simonsick, Honglei Chen
{"title":"Olfaction and diabetes among older adults.","authors":"Jingjing Xia, Yaqun Yuan, Chenxi Li, Anna Kucharska-Newton, Qu Tian, Jayant M Pinto, Jiantao Ma, Eleanor M Simonsick, Honglei Chen","doi":"10.1093/chemse/bjaf020","DOIUrl":"10.1093/chemse/bjaf020","url":null,"abstract":"<p><p>Both poor olfaction and diabetes are common in older adults. It is biologically plausible that they may be related and interact to affect the health of older adults. We examined the association between poor olfaction and diabetes and their joint associations with mortality among 2,416 older adults from the Health, Aging, and Body Composition Study. Olfaction was assessed at year 3 (1999 to 2000) using the Brief Smell Identification Test (B-SIT). We used year 4 (2000 to 2001) as the study baseline and followed participants to year 11 (2007 to 2008) to identify incident diabetes and year 14 (2010 to 2011) to assess mortality. We used logistic regression to analyze the association of poor olfaction with prevalent diabetes and Cox proportional hazard models to assess its relationship to incident diabetes and its joint association with diabetes on mortality. Of the 2,416 participants, 611 (25.3%) had diabetes at baseline and 138 (7.6%) developed incident diabetes during 6.4 ± 1.7 yr of follow-up. Compared to those with good olfaction, the odds ratio of prevalent diabetes was 1.11 (95% confidence interval/CI: 0.87 to 1.42) for those with poor olfaction, and the corresponding hazard ratio (HR) for incident diabetes was 1.01 (95%CI: 0.66 to 1.57). During 8.2 ± 2.8 yr of follow-up, 1007 (41.7%) participants died. Compared with participants without poor olfaction and diabetes, those with both were twice likely to die during the follow-up (HR = 2.16, 95%CI: 1.71 to 2.73). However, we found no evidence for synergistic interaction (P = 0.97). In conclusion, poor olfaction is not associated with the risk of diabetes, and these two conditions independently predict mortality in older adults.</p>","PeriodicalId":9771,"journal":{"name":"Chemical Senses","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12228038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemical SensesPub Date : 2025-01-22DOI: 10.1093/chemse/bjaf028
Eitan Yisraeli, Yifat Elizera, Yoram Ben-Shaul
{"title":"Regularity, variability, and individuality: urine marking patterns of male mice toward stimuli representing varying degrees of kinship.","authors":"Eitan Yisraeli, Yifat Elizera, Yoram Ben-Shaul","doi":"10.1093/chemse/bjaf028","DOIUrl":"https://doi.org/10.1093/chemse/bjaf028","url":null,"abstract":"<p><p>Successful social interactions require the identification of conspecifics and their traits. Often, individuals do not directly interact with conspecifics, but rather with their secretions. Among bodily secretions, urine plays a primary role in social communication across species. Urine provides a wealth of social information, and accordingly, several species, including mice, use it to advertise and mark territories. Here, we asked if kinship relations are reflected by the subject's marking patterns. Specifically, we studied counter-marking patterns of outbred ICR male mice following presentation of urinary cues from conspecifics with varying degrees of kinship. Examination of more than 1000 individual marking patterns from 10 mice reveals a high degree of variability. Variability is apparent across different mice and across single marking bouts of any given individual. Yet, we identify consistent effects of stimulus kinship, and, somewhat unexpectedly, even more robust differences among individuals. Individual-specific marking patterns are also evident in an empty arena, prior to the introduction of an external stimulus. Stimulus presentation gives rise to further changes in marking patterns, reflecting the relationship between the subject and donor mice. Notably, while stimuli representing highly distinct kinship relations induce robust differences at the population level, finer distinctions, including discrimination of same-strain conspecifics and self-urine, are only displayed by a subset of mice. Thus, while counter marking patterns are determined by a variety of factors, some of which cannot be easily controlled or measured, they ultimately reflect the identity of the marker and the kinship relation with the stimulus donor.</p>","PeriodicalId":9771,"journal":{"name":"Chemical Senses","volume":"50 ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12375953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemical SensesPub Date : 2025-01-22DOI: 10.1093/chemse/bjaf021
Jennifer N Wei, Carlos Ruiz, Marnix Vlot, Benjamin Sanchez-Lengeling, Brian K Lee, Luuk Berning, Martijn W Vos, Rob W M Henderson, Wesley W Qian, Jacob N Sanders, D Michael Ando, Kurt M Groetsch, Richard C Gerkin, Alexander B Wiltschko, Jeffrey A Riffell, Koen J Dechering
{"title":"A deep learning and digital archaeology approach for mosquito repellent discovery.","authors":"Jennifer N Wei, Carlos Ruiz, Marnix Vlot, Benjamin Sanchez-Lengeling, Brian K Lee, Luuk Berning, Martijn W Vos, Rob W M Henderson, Wesley W Qian, Jacob N Sanders, D Michael Ando, Kurt M Groetsch, Richard C Gerkin, Alexander B Wiltschko, Jeffrey A Riffell, Koen J Dechering","doi":"10.1093/chemse/bjaf021","DOIUrl":"10.1093/chemse/bjaf021","url":null,"abstract":"<p><p>Insect-borne diseases kill > 0.5 million people annually. Currently available repellents for personal or household protection are limited in their efficacy, applicability, and safety profile. Here, we describe a machine-learning-driven high-throughput method for the discovery of novel repellent molecules. To achieve this, we digitized a large, historic dataset containing ~19,000 mosquito repellency measurements. We then trained a graph neural network (GNN) to map molecular structure and repellency. We applied this model to select 317 candidate molecules to test in parallelizable behavioral assays, quantifying repellency in multiple insect vectors of the pathogens of disease and in follow-up trials with human volunteers. The GNN approach outperformed a chemoinformatic model and produced a hit rate that increased with training data size, suggesting that both model innovation and novel data collection were integral to predictive accuracy. We identified > 10 molecules with repellency similar to or greater than the most widely used repellents. We analyzed the neural responses from the mosquito antennal (olfactory) lobe to selected repellents and found strong responses to many of the tested compounds, including those predicted to be strong repellents. Results from the antennal lobe recordings also demonstrated a correlation between the evoked responses to strong repellents and our GNN representation. This approach enables computational screening of billions of possible molecules to identify empirically tractable numbers of candidate repellents, leading to accelerated progress towards solving a global health challenge.</p>","PeriodicalId":9771,"journal":{"name":"Chemical Senses","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12342189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemical SensesPub Date : 2025-01-22DOI: 10.1093/chemse/bjaf003
Ha Nguyen, Cailu Lin, Katherine Bell, Amy Huang, Mackenzie Hannum, Vicente Ramirez, Carol Christensen, Nancy E Rawson, Lauren Colquitt, Paul Domanico, Ivona Sasimovich, Riley Herriman, Paule Joseph, Oghogho Braimah, Danielle R Reed
{"title":"Worldwide study of the taste of bitter medicines and their modifiers.","authors":"Ha Nguyen, Cailu Lin, Katherine Bell, Amy Huang, Mackenzie Hannum, Vicente Ramirez, Carol Christensen, Nancy E Rawson, Lauren Colquitt, Paul Domanico, Ivona Sasimovich, Riley Herriman, Paule Joseph, Oghogho Braimah, Danielle R Reed","doi":"10.1093/chemse/bjaf003","DOIUrl":"10.1093/chemse/bjaf003","url":null,"abstract":"<p><p>The bitter taste of medicines hinders patient compliance, but not everyone experiences these difficulties because people worldwide differ in their bitterness perception. To better understand how people from diverse ancestries perceive medicines and taste modifiers, 338 adults, European and recent US and Canadian immigrants from Asia, South Asia, and Africa, rated the bitterness intensity of taste solutions on a 100-point generalized visual analog scale and provided a saliva sample for genotyping. The taste solutions were 5 medicines, tenofovir alafenamide (TAF), moxifloxacin, praziquantel, amodiaquine, and propylthiouracil (PROP), and 4 other solutions, TAF mixed with sucralose (sweet, reduces bitterness) or 6-methylflavone (tasteless, reduces bitterness), sucralose alone, and sodium chloride alone. Bitterness ratings differed by ancestry for 2 of the 5 drugs (amodiaquine and PROP) and for TAF mixed with sucralose. Genetic analysis showed that people with variants in 1 bitter receptor variant gene (TAS2R38) reported PROP was more bitter than did those with a different variant (P = 7.6e-19) and that people with either an RIMS2 or a THSD4 genotype found sucralose more bitter than did others (P = 2.6e-8, P = 7.9e-11, respectively). Our findings may help guide the formulation of bad-tasting medicines to meet the needs of those most sensitive to them.</p>","PeriodicalId":9771,"journal":{"name":"Chemical Senses","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12010088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}