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Canines are used by both government agencies and industries for their keen olfactory capability as well as selectivity, reliability, versatility, and speed. Within the last decade, canines have been used for the detection of on-shore crude oil. They were previously shown to find these deposits with high accuracy, providing increased confidence with little risk to oil spill response survey teams. In order to efficiently train canines, it is important to understand the odorants or groups of odorants that such canines use when locating subsurface crude oil deposits, as well as track how the odorant profile changes as the crude oil undergoes degradation. In this study, headspace solid phase microextraction (HS-SPME) was used in combination with gas chromatography-mass spectrometry (GC-MS) to extract and separate odorants from the headspace of various crude oils. After, eluent fractions of the crude oil odor profile were separated and collected onto sorbent materials, which were then used as canine testing probes in a series of trials. These probes, along with negative and positive controls were presented to three previously-trained and operational crude oil detection canines. Three eluent fractions of both fresh and weathered samples were presented, resulting in a 100% response rate from the canines on all three fractions from both the fresh and weathered samples. These results indicated that canines are capable of detecting crude oil from any fraction of the odor profile demonstrating the potential of the canines to generalize across a variety of crude oils and stages of weathering., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Karpinsky et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Multimodal integration is a core neural process with a keen relevance during ecological tasks requiring learning and memory, such as foraging. The benefits of learning multimodal signals imply solving whether the components come from a single event. This challenge presumably depends on the timing and intensity of the stimuli. Here, we used simultaneous and alternate presentations of olfactory and visual stimuli, at low and high intensities, to understand how temporal and intensity variations affect the learning of a bimodal stimulus and its components. We relied on the conditioning of the proboscis extension response (PER) to train honey bees to an appetitive learning task with bimodal stimuli precisely controlled. We trained bees to stimuli with different synchronicity and intensity levels. We found that synchronicity, order of presentation, and intensity significantly impacted the probability of exhibiting conditioned PER responses and the latency of the conditioned responses. At low intensities, synchronous bimodal inputs produced maximal multisensory enhancement, while asynchronous temporal orders led to lower performances. At high intensities, the relative advantage of the synchronous stimulation diminished, and asynchronous stimuli produced similar performances. Memory retention was higher for the olfactory component and bimodal stimuli compared to the visual component, irrespective of the training's temporal configuration. Bees retained the asynchronous bimodal configuration to a lesser extent than the synchronous one, depending on the stimulus intensity. We conclude that time (synchrony), order of presentation, and intensity have interdependent effects on bee learning and memory performance. This suggests caution when assessing the independent effects of each factor., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Gil-Guevara, Riveros. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Animals navigating turbulent odor plumes exhibit a rich variety of behaviors, and employ efficient strategies to locate odor sources. A growing body of literature has started to probe this complex task of localizing airborne odor sources in walking mammals to further our understanding of neural encoding and decoding of naturalistic sensory stimuli. However, correlating the intermittent olfactory information with behavior has remained a long-standing challenge due to the stochastic nature of the odor stimulus. We recently reported a method to record real-time olfactory information available to freely moving mice during odor-guided navigation, hence overcoming that challenge. Here we combine our odor-recording method with head-motion tracking to establish correlations between plume encounters and head movements. We show that mice exhibit robust head-pitch motions in the 5-14Hz range during an odor-guided navigation task, and that these head motions are modulated by plume encounters. Furthermore, mice reduce their angles with respect to the source upon plume contact. Head motions may thus be an important part of the sensorimotor behavioral repertoire during naturalistic odor-source localization., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Tariq et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Detection canines are deployed to detect explosives in a wide range of environmental conditions. These environmental conditions may have negative impacts on canine capabilities as a sensor. This study leveraged an air dilution olfactometer to present controlled odor concentrations of four different energetic materials (double base smokeless powder, Composition C4, ammonium nitrate, and flake Trinitrotoluene) to dogs working in a range of high temperature, standard, and low temperature conditions with high and low humidity conditions. The air dilution olfactometer controlled concentrations independent of environmental condition. Dogs' detection threshold limits were measured using a descending staircase procedure. We measured dogs' threshold twice for each energetic under each environmental condition. Results indicated heterogeneity in effects based on energetic, but all odors were detected at their lowest concentrations under standard conditions. Smokeless powder detection was reduced under all environmental conditions compared to standard and was least detectable under high temperature and humidity conditions. AN detection was poorest under high temperature high and low humidity conditions. C4 in contrast, was least detectable at low temperatures with high humidity. TNT detection was difficult under all conditions, so decrements due to environmental conditions were not statistically detectable. Additional measures were also found to be associated with detection limits. Under high temperature conditions, correlations were observed between canine mean subcutaneous temperature and detection limits, such that dogs experiencing greater temperature increases showed poorer detection limits. In addition, dog's latency to sample the odor port from the onset of a trial was longest in the high temperature conditions. Longer latencies were also predictive of poorer detection performance. Overall, dogs showed deficits in detection sensitivity limits under all environmental conditions for at least one energetic material when the concentration of that energetic material was not directly impacted by the environmental conditions. These results suggest that behavioral factors related to environmental exposure can have important impacts on canine detection sensitivity and should be considered in operational environments., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Fernandez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: More than a year after recovering from COVID-19, a large proportion of individuals, many of whom work in the healthcare sector, still report olfactory dysfunctions. However, olfactory dysfunction was common already before the COVID-19 pandemic, making it necessary to also consider the existing baseline prevalence of olfactory dysfunction. To establish the adjusted prevalence of COVID-19 related olfactory dysfunction, we assessed smell function in healthcare workers who had contracted COVID-19 during the first wave of the pandemic using psychophysical testing., Methods: Participants were continuously tested for SARS-CoV-2 IgG antibodies since the beginning of the pandemic. To assess the baseline rate of olfactory dysfunction in the population and to control for the possibility of skewed recruitment of individuals with prior olfactory dysfunction, consistent SARS-CoV-2 IgG naïve individuals were tested as a control group., Results: Fifteen months after contracting COVID-19, 37% of healthcare workers demonstrated a quantitative reduction in their sense of smell, compared to only 20% of the individuals in the control group. Fifty-one percent of COVID-19-recovered individuals reported qualitative symptoms, compared to only 5% in the control group. In a follow-up study 2.6 years after COVID-19 diagnosis, 24% of all tested recovered individuals still experienced parosmia., Conclusions: In summary, 65% of healthcare workers experienced parosmia/hyposmia 15 months after contracting COVID-19. When compared to a control group, the prevalence of olfactory dysfunction in the population increased by 41 percentage points. Parosmia symptoms were still lingering two-and-a half years later in 24% of SARS-CoV-2 infected individuals. Given the amount of time between infection and testing, it is possible that the olfactory problems may not be fully reversible in a plurality of individuals., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Frasnelli et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Learning an olfactory discrimination task leads to heterogeneous results in honeybees with some bees performing very well and others at low rates. Here we investigated this behavioral heterogeneity and asked whether it was associated with particular gene expression patterns in the bee's brain. Bees were individually conditioned using a sequential conditioning protocol involving several phases of olfactory learning and retention tests. A cumulative score was used to differentiate the tested bees into high and low performers. The rate of CS+ odor learning was found to correlate most strongly with a cumulative performance score extracted from all learning and retention tests. Microarray analysis of gene expression in the mushroom body area of the brains of these bees identified a number of differentially expressed genes between high and low performers. These genes are associated with diverse biological functions, such as neurotransmission, memory formation, cargo trafficking and development., Competing Interests: Authors have declared that no competing interest exists, (Copyright: © 2024 Chakroborty et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aim: To evaluate the effect of olfactory and/or gustatory stimulation interventions on feeding outcomes in preterm infants., Methods: We conducted systematic searches across various academic databases, including PubMed, Embase, Web of Science, the Cochrane Library, the Chinese Biomedical Literature Service System, China National Knowledge Infrastructure, the Wanfang Database, and the Wipu Database. These searches aimed to identify randomized controlled trials investigating the impact of olfactory and/or gustatory stimulation on preterm infants. The search period spanned from the inception of the databases until December 2022. Two independent evaluators autonomously reviewed the literature, extracted pertinent data, assessed the quality of the included studies, and conducted a meta-analysis using RevMan 5.3 software., Results: A total of 7 randomized controlled trials or quasi-experimental studies were included, with a total of 871 participants. Olfactory and gustatory stimulation demonstrated a reduction in the time to full enteral feeds in preterm infants when compared to usual care (MD = -1.60 days; 95% CI = -2.31, -0.89; p<0.0001). No substantial evidence was identified regarding the influence of olfactory and gustatory stimulation on the duration of gastric tube placement, length of hospitalization, incidence of necrotizing enterocolitis, or occurrence of spontaneous bowel perforation in preterm infants., Conclusions: Olfactory and gustatory stimulation show potential benefits for preterm infants. However, due to the low to very low level of certainty associated with the available data, our ability to assess the effects is limited. Further trials and studies are essential to enhance our understanding of the mechanisms and effectiveness of olfactory and gustatory stimulation therapies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Early identification of deficits in our ability to perceive odors is important as many normal (i.e., aging) and pathological (i.e., sinusitis, viral, neurodegeneration) processes can result in diminished olfactory function. To realistically enable population-level measurements of olfaction, validated olfaction tests must be capable of being administered outside the research laboratory and clinical setting., Aim: The purpose of this study was to determine the feasibility of remotely testing olfactory performance using a test that was developed with funding from the National Institutes of Health as part of a ready-to-use, non-proprietary set of measurements useful for epidemiologic studies (NIH Toolbox Odor ID Test)., Materials and Methods: Eligible participants older than 39 years and active (within 6 months) in the Brain Health Registry (BHR), an online cognitive assessment platform which connects participants with researchers, were recruited for this study. Interested participants were mailed the NIH Toolbox Odor ID Test along with instructions on accessing a website to record their responses. Data obtained from subjects who performed the test at home was compared to the normative data collected when the NIH Toolbox Odor ID Test was administered by a tester in a research setting and validated against the Smell Identification Test. The age-range and composition of the population ensured we had the ability to observe both age-related decline and gender-related deficits in olfactory ability, as shown in the experimental setting., Results: We observed that age-associated olfactory decline and gender-associated performance was comparable to performance on the administered test. Self-administration of this test showed the age-related loss in olfactory acuity, F(4, 1156)=14.564, p<.0001 as well as higher accuracy for women compared to men after controlling for participants' age, F(1, 1160) = 22.953, p <.0001. The effect size calculated as Hedge's g, was 0.41., Conclusion: These results indicate that the NIH Toolbox Odor ID Test is an appropriate instrument for self-administered assessment of olfactory performance. The ability to self-administer an inexpensive olfactory test increases its utility for inclusion in longitudinal epidemiological studies and when in-person testing is not feasible., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Jaén et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Working Dogs have shown an extraordinary ability to utilize olfaction for victim recovery efforts. Although instrumental analysis has chemically characterized odor volatiles from various human biospecimens, it remains unclear what perceptually constitutes human scent (HS) for dogs. This may be in part due to the lack of methodology and equipment to train and evaluate HS perception. The aims of this research were 1) to develop an automated human scent olfactometer (AHSO) to present HS to dogs in a controlled setting and 2) use the AHSO to evaluate dogs' response to different scented articles and individual components of HS. A human volunteer was placed in a clear acrylic chamber and using a vacuum pump and computer-controlled valves, the headspace of this chamber was carried to one of three ports in a different room. Dogs were trained to search all three ports of the olfactometer and alert to the one containing HS. In Experiment 1 and 2, the AHSO was validated by testing two dogs naïve to HS (Experiment 1) and five certified Search and Rescue (SAR) teams naïve to the apparatus (Experiment 2). All dogs showed sensitivity and specificity to HS > 95% in the apparatus. In Experiment 3, we used a spontaneous generalization paradigm to evaluate generalization from the HS chamber to different scented articles exposed to the same volunteer and to a breath sample. Dogs' response rate to the different scented articles was < 10% but exceeded 40% for the breath sample. In Experiment 4, we replicated this result by re-testing spontaneous generalization to breath and when the volunteer had breath exhausted/removed from the chamber. Dogs' response rate to breath alone was 88% and only 50% when breath was removed. Altogether, the data indicate that exhaled breath is an important and salient component of HS under these conditions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Many animals display innate preferences for some odors, but the physiological mechanisms underlying these preferences are poorly understood. Here, with behavioral tests, we establish a model system well suited to investigating olfactory mechanisms, the locust Schistocerca americana. We conducted open field tests in an arena designed to provide only olfactory cues to guide navigation choices. We found that newly hatched locusts navigated toward, and spent more time near, the odor of wheat grass than humidified air. In similar tests, we found that hatchlings avoided moderate concentrations of major individual components of the food blend odor, 1-hexanol (1% v/v) and hexanal (0.9% v/v) diluted in mineral oil relative to control presentations of unscented mineral oil. Hatchlings were neither attracted nor repelled by a lower concentration (0.1% v/v) of 1-hexanol but were moderately attracted to a low concentration (0.225% v/v) of hexanal. We quantified the behavior of the animals by tracking their positions with the Argos software toolkit. Our results establish that hatchlings have a strong, innate preference for food odor blend, but the valence of the blend's individual components may be different and may change depending on the concentration. Our results provide a useful entry point for an analysis of physiological mechanisms underlying innate sensory preferences., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Odors are important disease cues, and disgust sensitivity to body odors reflects individual differences in disease avoidance. The body odor disgust sensitivity (BODS) scale provides a rapid and valid assessment of individual differences. Nevertheless, little is known about how individual differences in BODS might correlate with overall odor perception or how it is related to other differences in emotional reactivity (e.g., affect intensity). We investigated how BODS relates to perceptual ratings of pleasant and unpleasant odors. We aggregated data from 4 experiments (total N = 190) that were conducted in our laboratory, and where valence and intensity ratings were collected. Unpleasant odors were body-like (e.g., sweat-like valeric acid), which may provide disease cues. The pleasant odors were, in contrast, often found in soap and cleaning products (e.g., lilac, lemon). Across experiments, we show that individuals with higher BODS levels perceived smells as more highly valenced overall: unpleasant smells were rated as more unpleasant, and pleasant smells were rated as more pleasant. These results suggest that body odor disgust sensitivity is associated with a broader pattern of affect intensity which causes stronger emotional responses to both negative and positive odors. In contrast, BODS levels were not associated with odor intensity perception. Furthermore, disgust sensitivity to odors coming from external sources (e.g., someone else's sweat) was the best predictor of odor valence ratings. The effects were modest in size. The results validate the BODS scale as it is explicitly associated with experimental ratings of odor valence., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Zakrzewska et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Drosophila melanogaster larvae develop on fermenting fruits with increasing ethanol concentrations. To address the relevance of ethanol in the behavioral response of the larvae, we analyzed the function of ethanol in the context of olfactory associative behavior in Canton S and w1118 larvae. The motivation of larvae to move toward or out of an ethanol-containing substrate depends on the ethanol concentration and the genotype. Ethanol in the substrate reduces the attraction to odorant cues in the environment. Relatively short repetitive exposures to ethanol, which are comparable in their duration to reinforcer representation in olfactory associative learning and memory paradigms, result in positive or negative association with the paired odorant or indifference to it. The outcome depends on the order in which the reinforcer is presented during training, the genotype and the presence of the reinforcer during the test. Independent of the order of odorant presentation during training, Canton S and w1118 larvae do not form a positive or negative association with the odorant when ethanol is not present in the test context. When ethanol is present in the test, w1118 larvae show aversion to an odorant paired with a naturally occurring ethanol concentration of 5%. Our results provide insights into the parameters influencing olfactory associative behaviors using ethanol as a reinforcer in Drosophila larvae and indicate that short exposures to ethanol might not uncover the positive rewarding properties of ethanol for developing larvae., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Berger et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Animals are constantly bombarded with stimuli, which presents a fundamental problem of sorting among pervasive uninformative stimuli and novel, possibly meaningful stimuli. We evaluated novelty detection behaviorally in honey bees as they position their antennae differentially in an air stream carrying familiar or novel odors. We then characterized neuronal responses to familiar and novel odors in the first synaptic integration center in the brain-the antennal lobes. We found that the neurons that exhibited stronger initial responses to the odor that was to be familiarized are the same units that later distinguish familiar and novel odors, independently of chemical identities. These units, including both tentative projection neurons and local neurons, showed a decreased response to the familiar odor but an increased response to the novel odor. Our results suggest that the antennal lobe may represent familiarity or novelty to an odor stimulus in addition to its chemical identity code. Therefore, the mechanisms for novelty detection may be present in early sensory processing, either as a result of local synaptic interaction or via feedback from higher brain centers., Competing Interests: The authors have declared that no competing interests exist.

There is an increasing need for rapid, reliable, non-invasive, and inexpensive mass testing methods as the global COVID-19 pandemic continues. Detection dogs could be a possible solution to identify individuals infected with SARS-CoV-2. Previous studies have shown that dogs can detect SARS-CoV-2 on sweat samples. This study aims to establish the dogs' sensitivity (true positive rate) which measures the proportion of people with COVID-19 that are correctly identified, and specificity (true negative rate) which measures the proportion of people without COVID-19 that are correctly identified. Seven search and rescue dogs were tested using a total of 218 axillary sweat samples (62 positive and 156 negative) in olfaction cones following a randomised and double-blind protocol. Sensitivity ranged from 87% to 94%, and specificity ranged from 78% to 92%, with four dogs over 90%. These results were used to calculate the positive predictive value and negative predictive value for each dog for different infection probabilities (how likely it is for an individual to be SARS-CoV-2 positive), ranging from 10-50%. These results were compared with a reference diagnostic tool which has 95% specificity and sensitivity. Negative predictive values for six dogs ranged from ≥98% at 10% infection probability to ≥88% at 50% infection probability compared with the reference tool which ranged from 99% to 95%. Positive predictive values ranged from ≥40% at 10% infection probability to ≥80% at 50% infection probability compared with the reference tool which ranged from 68% to 95%. This study confirms previous results, suggesting that dogs could play an important role in mass-testing situations. Future challenges include optimal training methods and standardisation for large numbers of detection dogs and infrastructure supporting their deployment., Competing Interests: The authors have declared that no competing interests exist.

The degree of attention individuals pay to olfactory cues (called odor awareness) influences the role of odors in everyday life. Particularly, odors produced by the human body (i.e., social odors) are able to carry a wide variety of information and to elicit a broad spectrum of emotional reactions, making them essential in interpersonal relationships. Hence, despite the assessment of awareness toward social odors is crucial, a proper tool is still lacking. Here, we designed and initially validated the Social Odor Scale (SOS), a 12-item scale designed to measure the individual differences in awareness towards different social odors. In Study 1, an exploratory factor analysis (EFA; KMO test: MSA = 0.78; Bartlett's test: χ2(78) = 631.34, p < 0.001; Chi-squared test: χ2(42) = 71.84, p = 0.003) suggests that the three factors structure was the model that best fit with the Italian version of the scale. The confirmatory factor analysis (CFA) supports a second-order model with one higher-order factor representing social odor awareness in general and three lower-order factors representing familiar, romantic partner, and stranger social odors. The final version of the scale presented a good fit (RMSEA = 0.012, SRMR = 0.069, CFI = 0.998, TLI = 0.997). In Study 2, CFA was performed in the German version of the scale confirming the validity of scale structure. Study 3 and 4 revealed that SOS total score and its subscales were positively correlated with other validated olfactory scales, but not with olfactory abilities. Moreover, SOS was found to be related to the gender of the participants: women reported to be more aware to social odors and, specifically, to familiar social odors than men. Overall, the results indicated that SOS is a valid and reliable instrument to assess awareness toward social odors in everyday life., Competing Interests: The authors have declared that no competing interests exist.

Human sweat odor serves as social communication signal for a person's traits and emotional states. This study explored whether body odors can also communicate information about one's self-esteem, and the role of applied fragrance in this relationship. Female participants were asked to rate self-esteem and attractiveness of different male contestants of a dating show, while being exposed to male participant's body odors differing in self-esteem. High self-esteem sweat was rated more pleasant and less intense than low self-esteem sweat. However, there was no difference in perceived self-esteem and attractiveness of male contestants in videos, hence explicit differences in body odor did not transfer to judgments of related person characteristics. When the body odor was fragranced using a fragranced body spray, male contestants were rated as having higher self-esteem and being more attractive. The finding that body odors from male participants differing in self-esteem are rated differently and can be discriminated suggests self-esteem has distinct perceivable olfactory features, but the remaining findings imply that only fragrance affect the psychological impression someone makes. These findings are discussed in the context of the role of body odor and fragrance in human perception and social communication., Competing Interests: The authors have read the journal’s policy and have the following competing interests: Unilever provided financial support for supplies and participant remuneration and material support by supplying fragranced (test product) body sprays in cans free of labels. IG and MS are employees of Unilever. This does not alter the adherence to PLOS ONE policies on sharing data and materials. A Unilever marketed product was used as body spray in the fragranced condition, but without a label or further identification. There are no patents, products in development, or other marketed products associated with this research to declare.

Olfactory loss has been identified as one of the common symptoms related to COVID-19 infection. Although olfactory loss is recognized, our understanding of both the extent of loss and time to olfactory recovery following infection is less well known. Similarly, knowledge of potential impactful patient factors and therapies that influence olfactory recovery is desirable but is not overtly clear in the literature. Our systematic review sought to fill this knowledge gap. We included studies that: involved either an observational or an interventional design that reported data on patients with olfactory dysfunction due to Reverse Transcription Polymerase Chain Reaction (RT-PCR) diagnosed COVID-19 infection; and reported data regarding olfactory recovery measured by an objective olfactory test, Likert scale and/or visual analog scale (VAS). The study methods were determined a priori and registered in PROSPERO (Registration Number CRD42020204354). An information specialist searched Medline, Embase, LitCovid and the Cochrane Register of Controlled Trials up to March 2021, and two reviewers were involved in all aspects of study selection and data collection. After screening 2788 citations, a total of 44 studies of assorted observational designs were included. Patients had undergone objective COVID-19 testing, and most were adult patients with mild to moderate COVID-19. Olfactory recovery was found to occur as early as 7 days, with most patients recovering olfaction within 30 days. Few studies included prolonged follow-up to 6 months or longer duration. Poor olfaction at initial presentation was associated with poor recovery rates. Only a small number of studies assessed olfactory retraining and steroid therapy. Additional trials are underway., Competing Interests: The authors have declared that no competing interests exist.

Olfactory impairment is associated with dementia and is a potential early biomarker of cognitive decline. We developed a novel olfactory threshold test called Sniff Bubble using rose odor-containing beads made with 2-phenylethyl alcohol. We aimed to define cut-off scores for this tool to help identify cognitive decline among elderly people. In total, 162 elderly people (mean age ± SD: 73.04 ± 8.73 years) were administered olfactory threshold and neurocognitive tests. For analyses, we divided the participants into two groups based on cognitive functioning, namely cognitive decline (n = 44) and normal cognition (n = 118) groups. The Sniff Bubble and YSK olfactory function test for olfactory threshold and the Structured Clinical Interview for DSM-5 Disorders-Clinician Version and Korean version of the Consortium to Establish a Registry for Alzheimer's Disease assessment packet for neurocognitive functioning were used. We used K-means cluster analyses and receiver operating characteristic (ROC) analyses to identify the most appropriate cut-off value. We established a positive correlation between the Sniff Bubble and neurocognitive function test scores (r = 0.431, p < 0.001). We defined the cut-off score, using the ROC curve analyses for Sniff Bubble scores, at 3 and higher with an area under the curve of 0.759 (p < 0.001). The Sniff Bubble test can adequately detect cognitive decline in elderly people and may be used clinically as the first step in the screening process., Competing Interests: The authors have declared that no competing interests exist.

Odorant metabolizing enzymes (OMEs) are expressed in the olfactory epithelium (OE) where they play a significant role in the peripheral olfactory process by catalyzing the fast biotransformation of odorants leading either to their elimination or to the synthesis of new odorant stimuli. The large family of OMEs gathers different classes which interact with a myriad of odorants alike and complementary to olfactory receptors. Thus, it is necessary to increase our knowledge on OMEs to better understand their function in the physiological process of olfaction. This study focused on a major olfactory UDP-glucuronosyltransferase (UGT): UGT2A1. Immunohistochemistry and immunogold electronic microscopy allowed to localize its expression in the apical part of the sustentacular cells and originally at the plasma membrane of the olfactory cilia of the olfactory sensory neurons, both locations in close vicinity with olfactory receptors. Moreover, using electroolfactogram, we showed that a treatment of the OE with beta-glucuronidase, an enzyme which counterbalance the UGTs activity, increased the response to eugenol which is a strong odorant UGT substrate. Altogether, the results supported the function of the olfactory UGTs in the vertebrate olfactory perireceptor process., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Healthcare workers (HCW) treating COVID-19 patients are at high risk for infection and may also spread infection through their contact with vulnerable patients. Smell loss has been associated with SARS-CoV-2 infection, but it is unknown whether monitoring for smell loss can be used to identify asymptomatic infection among high risk individuals. In this study we sought to determine if tracking smell sensitivity and loss using an at-home assessment could identify SARS-CoV-2 infection in HCW., Methods and Findings: We performed a prospective cohort study tracking 473 HCW across three months to determine if smell loss could predict SARS-CoV-2 infection in this high-risk group. HCW subjects completed a longitudinal, behavioral at-home assessment of olfaction with household items, as well as detailed symptom surveys that included a parosmia screening questionnaire, and real-time quantitative polymerase chain reaction testing to identify SARS-CoV-2 infection. Our main measures were the prevalence of smell loss in SARS-CoV-2-positive HCW versus SARS-CoV-2-negative HCW, and timing of smell loss relative to SARS-CoV-2 test positivity. SARS-CoV-2 was identified in 17 (3.6%) of 473 HCW. HCW with SARS-CoV-2 infection were more likely to report smell loss than SARS-CoV-2-negative HCW on both the at-home assessment and the screening questionnaire (9/17, 53% vs 105/456, 23%, P < .01). 6/9 (67%) of SARS-CoV-2-positive HCW reporting smell loss reported smell loss prior to having a positive SARS-CoV-2 test, and smell loss was reported a median of two days before testing positive. Neurological symptoms were reported more frequently among SARS-CoV-2-positive HCW who reported smell loss compared to those without smell loss (9/9, 100% vs 3/8, 38%, P < .01)., Conclusions: In this prospective study of HCW, self-reported changes in smell using two different measures were predictive of SARS-CoV-2 infection. Smell loss frequently preceded a positive test and was associated with neurological symptoms., Competing Interests: The authors have declared that no competing interests exist.

Psychosocial chronic stress is a critical risk factor for the development of mood disorders. However, little is known about the consequences of acute stress in the context of chronic stress, and about the related brain responses. In the present study we examined the physio-behavioural effects of a supplementation with a sensory functional food ingredient (FI) containing Citrus sinensis extract (D11399, Phodé, France) in a pig psychosocial chronic stress model. Female pigs underwent a 5- to 6-week stress protocol while receiving daily the FI (FI, n = 10) or a placebo (Sham, n = 10). We performed pharmacological magnetic resonance imaging (phMRI) to study the brain responses to an acute stress (injection of Synacthen®, a synthetic ACTH-related agonist) and to the FI odour with or without previous chronic supplementation. The olfactory stimulation with the ingredient elicited higher brain responses in FI animals, demonstrating memory retrieval and habituation to the odour. Pharmacological stress with Synacthen injection resulted in an increased activity in several brain regions associated with arousal, associative learning (hippocampus) and cognition (cingulate cortex) in chronically stressed animals. This highlighted the specific impact of acute stress on the brain. These responses were alleviated in animals previously supplemented by the FI during the entire chronic stress exposure. As chronic stress establishes upon the accumulation of acute stress events, any attenuation of the brain responses to acute stress can be interpreted as a beneficial effect, suggesting that FI could be a viable treatment to help individuals coping with repeated stressful events and eventually to reduce chronic stress. This study provides additional evidence on the potential benefits of this FI, of which the long-term consequences in terms of behaviour and physiology need to be further investigated., Competing Interests: Authors SM, VN, and PE are employed by Phodé, who provided the functional ingredient and also co-funded the study. All other authors declare no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products to declare.

Background: To introduce new ways to calculate OB volumes, checking their validity and comparing them to already established technique i.e. OB volumetric based on manual segmentation of OB boundaries., Methods: Two approaches were used to calculate OB volumes (1) Manual Segmentation using planimetric manual contouring; (2) Box-frame method, calculating the parameters based on a box placed around the OB., Results: We calculated OB volumes using both techniques and found comparable outcomes. High inter-observer reliability was found for volumes calculated by both observers. For manual segmentation, Cronbach's alpha (α) was 0.91 and 0.93 for right and left OB volume, respectively, whereas for the box-frame method α was 0.94 and 0.90 for right and left OB, respectively., Conclusions: The simple box-frame method of OB volume calculation appears reliable. Its results are comparable to an established technique., Competing Interests: The authors have declared that no competing interests exist.

High-frequency oscillations of the frontal cortex are involved in functions of the brain that fuse processed data from different sensory modules or bind them with elements stored in the memory. These oscillations also provide inhibitory connections to neural circuits that perform lower-level processes. Deficit in the performance of these oscillations has been examined as a marker for Alzheimer's disease (AD). Additionally, the neurodegenerative processes associated with AD, such as the deposition of amyloid-beta plaques, do not occur in a spatially homogeneous fashion and progress more prominently in the medial temporal lobe in the early stages of the disease. This region of the brain contains neural circuitry involved in olfactory perception. Several studies have suggested that olfactory deficit can be used as a marker for early diagnosis of AD. A quantitative assessment of the performance of the olfactory system can hence serve as a potential biomarker for Alzheimer's disease, offering a relatively convenient and inexpensive diagnosis method. This study examines the decline in the perception of olfactory stimuli and the deficit in the performance of high-frequency frontal oscillations in response to olfactory stimulation as markers for AD. Two measurement modalities are employed for assessing the olfactory performance: 1) An interactive smell identification test is used to sample the response to a sizable variety of odorants, and 2) Electroencephalography data are collected in an olfactory perception task with a pair of selected odorants in order to assess the connectivity of frontal cortex regions. Statistical analysis methods are used to assess the significance of selected features extracted from the recorded modalities as Alzheimer's biomarkers. Olfactory decline regressed to age in both healthy and mild AD groups are evaluated, and single- and multi-modal classifiers are also developed. The novel aspects of this study include: 1) Combining EEG response to olfactory stimulation with behavioral assessment of olfactory perception as a marker of AD, 2) Identification of odorants most significantly affected in mild AD patients, 3) Identification of odorants which are still adequately perceived by mild AD patients, 4) Analysis of the decline in the spatial coherence of different oscillatory bands in response to olfactory stimulation, and 5) Being the first study to quantitatively assess the performance of olfactory decline due to aging and AD in the Iranian population., Competing Interests: No - The authors have declared that no competing interests exist.

Objectives: In this study, we aimed to study the clinical presentations, and viral clearance of SARS-COV-2 positive quarantined individuals., Design: Cross-sectional study., Setting: Governmental- designated facility in the eastern province, Saudi Arabia., Participants: 128 laboratory-confirmed COVID-19 quarantined individuals who had a history of travel abroad in the last 14 days before the quarantine or were in direct contact with laboratory-confirmed cases. The study was from March 18th-till April 16th., Primary and Secondary Measures: The clinical presentation, prevalence of asymptomatic carriers among SARS-COV-2 positive quarantined subjects, and the difference between virus clearance among symptomatic and asymptomatic individuals., Results: Sixty-nine of the 128 residents (54%) were completely asymptomatic until the end of the study. The remaining 59 residents (46%) had only mild symptoms. The most common symptom was a sudden loss of smell and taste, accounting for 47.5%. The median time to virus clearance was significantly different between the two groups. Symptomatic residents cleared the virus at a median of 17 days (95% CI, 12.4-21.6) from the first positive PCR vs. 11days (95% CI, 8.7-13.3) in the asymptomatic group (P = 0.011). False-negative test results occurred in 18.8% of the total residents and false-positive results in 3%., Conclusion: The prevalence of asymptomatic carriers among quarantined travelers and those identified by contact tracing is high in our study. Therefore, testing, tracing, and isolating travelers and contacts of laboratory-confirmed cases, regardless of symptoms, were very effective measures for early disease identification and containment. Loss of taste and smell were the most common presentations in our mild symptomatic residents and should be used as a screening tool for COVID-19. The persistent positive PCR beyond 14 days observed in the mild symptomatic residents despite being symptoms free, warrant further studies to determine its implications on disease spread and control., Competing Interests: no competing interest exist.

It is now widely agreed that a positive affective state is a crucial component of animal well-being. The judgment bias test represents a widespread tool used to assess animals' optimistic/pessimistic attitude and to evaluate their emotional state and welfare. Judgment bias tests have been used several times with dogs (Canis familiaris), in most cases using a spatial test with a bowl placed in ambiguous positions located between a relatively positive trained location (P) which contains a baited bowl and a relatively negative trained location (N) which contains an empty bowl. The latency to approach the bowl in the ambiguous locations is an indicator of the dog's expectation of a positive/negative outcome. However, results from such tests are often inconclusive. For the present study, the judgment bias test performance of 51 shelter dogs and 40 pet dogs was thoroughly analysed. A pattern emerged with shelter dogs behaving in a more pessimistic-like way than pet dogs. However, this difference between the two populations was detected only when analysing the raw latencies to reach the locations and not the more commonly applied adjusted score (i.e. average latency values). Furthermore, several methodological caveats were found. First of all, a non-negligible percentage of dogs did not pass the training phase, possibly due to the experimental paradigm not being fully suited for this species. Second, results showed a high intra-dog variability in response to the trained locations, i.e. the dogs' responses were not consistent throughout the test, suggesting that animals may not have fully learned the association between locations and their outcomes. Third, dogs did not always behave differently towards adjacent locations, raising doubts about the animals' ability to discriminate between locations. Finally, a potential influence of the researcher's presence on dogs' performance emerged from analyses. The implications of these findings and potential solutions are discussed., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Taste and smell are important for occupational performance and quality of life. Previous studies suggested that the function of these senses might be influenced by ambient pressure and noise. This knowledge would be helpful for divers, submarine crews, or mine workers. The present study aimed to investigate the effects of noise and hyperbaric pressure on olfactory and gustatory functions., Methods: This prospective controlled study included 16 healthy male divers. Inside a hyperbaric chamber, participants performed olfactory and gustatory function tests at sea level pressure and at 2 bar pressure. The olfaction threshold, and the discrimination and identification of odorants were measured with validated ´Sniffin sticks´. Taste identification and the gustation threshold scores were examined with validated filter paper strips. Tests were performed under two conditions: noise reduction (silence) and white noise stimulation presented at 70 dB sound pressure level., Results: The results showed that normobaric and hyperbaric ambient pressures did not significantly affect olfactory or gustatory function. Moreover, noise had no relevant impact on taste or odor sensation. The odor identification score was not influenced in hyperbaric conditions, and the odor threshold score was not influenced by ambient noise or both barometric conditions. The only taste modality affected by hyperbaric conditions was the sensitivity to salty taste, but it was not significant., Conclusion: We concluded that hyperbaric and noisy environments have no influence on gustatory and olfactory function. From a practical point of view, the influence of pressure in moderate hyperbaric occupations should be negligible., Competing Interests: The authors have declared that no competing interests exist.

Maintaining social relationships depends on the ability to recognize partners or group members against other individuals. This is especially important in animals with relatively stable social groups. The amphisbaenian Trogonophis wiegmanni is a semi blind fossorial reptile that spends its entire life underground where it interacts with mates and social partners. In this environment, visual cues are limited. Chemosensory cues may rather allow conspecific social and partner recognition. We recorded the number of tongue-flick (TF) rates of T. wiegmanni amphisbaenians to scents of both sexes with different pairing social bonds (familiar vs. unfamiliar) presented on cotton swabs to test discrimination of social groups. As seen from a rise in the number of TFs, males discriminated unfamiliar females from unfamiliar males. This suggests that chemical cues may be used by males to locate new mates. In contrast, females detected scent of unfamiliar conspecifics, but did not show sex discrimination. Both males and females discriminated the scent of an individual with which they had formed a pair bond from an unfamiliar individual of the same sex as the partner. Also, males, but not females, were capable of self-recognition, suggesting that scent marks of males in home ranges may provide individual information in intrasexual relationships. We conclude that conspecific discrimination based on chemical cues may allow the maintenance of social relationships and relatively stable pairs in fossorial reptiles inhabiting visually restricted environments., Competing Interests: The authors have declared that no competing interests exist.

Objectives: The aim of the study was to compare olfactory functions between unipolar and bipolar patients according to the thymic states (depressed, euthymic) and determine specific olfactory variations between these different states., Methods: We recruited 176 participants in 5 groups: depressed bipolar (DB), euthymic bipolar (EB), depressed unipolar (DU), euthymic unipolar (EU), and controls (HC). They were assessed using the Sniffin' sticks threshold and identification tests. Odors' pleasantness, intensity, familiarity and emotion were assessed. Clinical evaluation explored dimensions of depression, mania, anxiety, and anhedonia., Results: Smell identification was lower in DU compared to EU patients and controls. Pleasant odors received lower hedonic rating in DU and DB patients compared to EU and EB patients respectively. Negative correlation was found in EB patients between hedonic rating and social anhedonia. In EU patients hedonic rating was negatively correlated with anxiety-state, and anhedonia., Conclusions: Odor identification of pleasant odors is altered in both depressive states. Only unipolar patients would recover a regular identification level in symptomatic remission, while bipolar subjects would keep their deficits. Hedonic rating is lower in bipolar depressed patients compared to unipolar ones, and these deficits improve after remission. Hedonic rating of pleasant odors may distinguish bipolar depression from unipolar depression during periods of decompensation and phases of remission. Olfactory assessment may be useful to screen unipolar and bipolar depression, leading to possible future sensory markers in mood disorders., Competing Interests: The authors have declared that no competing interests exist.

Olfaction plays vital roles in the survival and reproduction of insects. The completion of olfactory recognition requires the participation of various complex protein families. However, little is known about the olfactory-related proteins in Semiothisa cinerearia Bremer et Grey, an important pest of Chinese scholar tree. In this study, we sequenced the antennal transcriptome of S. cinerearia and identified 125 olfactory-related genes, including 25 odorant-binding proteins (OBPs), 15 chemosensory proteins (CSPs), two sensory neuron membrane proteins (SNMPs), 52 odorant receptors (ORs), eight gustatory receptors (GRs) and 23 ionotropic receptors (IRs). BLASTX best hit results and phylogenetic analyses indicated that these genes were most identical to their respective orthologs from Ectropis obliqua. Further quantitative real-time PCR (qRT-PCR) analysis revealed that three ScinOBPs and three ScinORs were highly expressed in male antennae, while seven ScinOBPs and twelve ScinORs were female-specifically expressed. Our study will be useful for the elucidation of olfactory mechanisms in S. cinerearia., Competing Interests: The authors have declared that no competing interests exist.

There have been recent advances in predicting odor characteristics using molecular structure parameters of chemicals. Although the molecular structure parameters are available for each chemical, they cannot be used for chemical mixtures. This study will elucidate a computational method of predicting human odor perception from the mass spectra of chemical mixtures such as essential oils. Furthermore, a method for obtaining similarity among odor descriptors has been proposed although the dataset contains binary values only. When the database indicates a set of odor descriptors for one sample, only binary data are available and the correlation between the similar descriptors disappears. Thus, the prediction performance degrades for not considering the similarity among the odor descriptors. Since mass spectra dataset is highly dimensional, we use auto-encoder to learn the compressed representation from the mass spectra of essential oils in its bottleneck hidden layer and then accomplishes the hierarchical clustering to create odor descriptor groups with similar odor impressions using a matrix of continuous value-based correlation coefficient as well as natural language processing. This work will help to expatiate the process of overcoming binary value problem and find out the similarity among odor descriptors using machine learning with natural language semantic representation of words. To overcome the problem of disproportionate ratio of positive and negative class for both the continuous value-based correlation coefficient and word similarity based models, we use Synthetic Minority Oversampling Technique (SMOTE). This model allows us to predict human odor perception through computer simulations by forming odor descriptors group. Accordingly, this study demonstrates the feasibility of ensembling machine learning with natural language processing and SMOTE approach for predicting odor descriptor group from mass spectra of essential oils., Competing Interests: The authors have declared that no competing interests exist.

Multimodal signaling is nearly ubiquitous across animal taxa. While much research has focused on male signal production contributing to female mate-choice or preferences, females often give their own multimodal signals during intersexual communication events. Multimodal signal components are often classified based on whether they contain redundant information (e.g., the backup hypothesis) or non-redundant information (e.g., the multiple messages hypothesis) from the perspective of the receiver. We investigated the role of two different female vocalizations produced by the female house mouse (Mus musculus): the broadband, relatively low-frequency squeaks (broadband vocalizations or BBVs,), and the higher-frequency ultrasonic vocalizations (USVs). These female vocalizations may convey differently valenced information to the male receivers. We paired these vocalizations with and without female urine to examine the influence of combining information across multiple modalities. We found evidence that female urine and vocalizations act as non-redundant multimodal cues as males responded with different behaviors and vocalization rates depending on the female signal presented. Additionally, male mice responded with greater courtship effort to the multimodal combination of female USVs paired with female urine than any other signal combination. These results suggest that the olfactory information contained in female urine provides the context by which males can then evaluate potentially ambiguous female vocalizations., Competing Interests: The authors have declared that no competing interests exist

As in vertebrates, dopaminergic neural systems are key regulators of motor programs in insects, including the fly Drosophila melanogaster. Dopaminergic systems innervate the Mushroom Bodies (MB), an important association area in the insect brain primarily associated to olfactory learning and memory, but that has been also implicated with the execution of motor programs. The main objectives of this work is to assess the idea that dopaminergic systems contribute to the execution of motor programs in Drosophila larvae, and then, to evaluate the contribution of specific dopaminergic receptors expressed in MB to these programs. Our results show that animals bearing a mutation in the dopamine transporter show reduced locomotion, while mutants for the dopaminergic biosynthetic enzymes or the dopamine receptor Dop1R1 exhibit increased locomotion. Pan-neuronal expression of an RNAi for the Dop1R1 confirmed these results. Further studies show that animals expressing the RNAi for Dop1R1 in the entire MB neuronal population or only in the MB γ-lobe forming neurons, exhibit an increased motor output, as well. Interestingly, our results also suggest that other dopaminergic receptors do not contribute to larval motor behavior. Thus, our data support the proposition that CNS dopamine systems innervating MB neurons modulate larval locomotion and that Dop1R1 mediates this effect., Competing Interests: The authors have declared that no competing interests exist.

Trade-off between vision and olfaction, the fact that investment in one correlates with decreased investment in the other, has been demonstrated by a wealth of comparative studies. However, there is still no empirical evidence suggesting how these two sensory systems coevolve, i.e. simultaneously or alternatively. The "Dark-flies" (Drosophila melanogaster) constitute a unique model to investigate such relation since they have been reared in the dark since 1954, approximately 60 years (~1500 generations). To observe how vision and olfaction evolve, populations of Dark-flies were reared in normal lighting conditions for 1 (DF1G) and 65 (DF65G) generations. We measured the sizes of the visual (optic lobes, OLs) and olfactory (antennal lobes, ALs) primary centres, as well as the rest of the brain, and compared the results with the original and its genetically most similar strain (Oregon flies). We found that, whereas the ALs decreased in size, the OLs (together with the brain) increased in size in the Dark-flies returned back to the light, both in the DF1G and DF65G. These results experimentally show that trade-off between vision and olfaction occurs simultaneously, and suggests that there are possible genetic and epigenetic processes regulating the size of both optic and antennal lobes. Furthermore, although the Dark-flies were able to mate and survive in the dark with a reduced neural investment, individuals being returned to the light seem to have been selected with reinvestment in visual capabilities despite a potential higher energetic cost., Competing Interests: The authors have declared that no competing interests exist.

The ability to modify behavior based on prior experience is essential to an animal's survival. For example, animals may become attracted to a previously neutral odor or reject a previously appetitive food source based on previous encounters. In Drosophila, the mushroom bodies (MBs) are critical for olfactory associative learning and conditioned taste aversion, but how the output of the MBs affects specific behavioral responses is unresolved. In conditioned taste aversion, Drosophila shows a specific behavioral change upon learning: proboscis extension to sugar is reduced after a sugar stimulus is paired with an aversive stimulus. While studies have identified MB output neurons (MBONs) that drive approach or avoidance behavior, whether the same MBONs impact innate proboscis extension behavior is unknown. Here, we tested the role of MB pathways in altering proboscis extension and identified MBONs that synapse onto multiple MB compartments that upon activation significantly decreased proboscis extension to sugar. Activating several of these lines also decreased sugar consumption, revealing that these MBONs have a general role in modifying feeding behavior beyond proboscis extension. The MBONs that decreased proboscis extension and ingestion are different from those that drive avoidance behavior in another context. These studies provide insight into how activation of MB output neurons decreases proboscis extension to taste compounds., Competing Interests: The authors have declared that no competing interests exist.

Olfactory sense remains elusive regarding the primary reception mechanism. Some studies suggest that olfaction is a spectral sense, the olfactory event is triggered by electron transfer (ET) across the odorants at the active sites of odorant receptors (ORs). Herein we present a Donor-Bridge-Acceptor model, proposing that the ET process can be viewed as an electron hopping from the donor molecule to the odorant molecule (Bridge), then hopping off to the acceptor molecule, making the electronic state of the odorant molecule change along with vibrations (vibronic transition). The odorant specific parameter, Huang-Rhys factor can be derived from ab initio calculations, which make the simulation of ET spectra achievable. In this study, we revealed that the emission spectra (after Gaussian convolution) can be acted as odor characteristic spectra. Using the emission spectrum of ET, we were able to reasonably interpret the similar bitter-almond odors among hydrogen cyanide, benzaldehyde and nitrobenzene. In terms of isotope effects, we succeeded in explaining why subjects can easily distinguish cyclopentadecanone from its fully deuterated analogue cyclopentadecanone-d28 but not distinguishing acetophenone from acetophenone-d8., Competing Interests: The authors declare no competing interests.

Many animals display morphological adaptations of the nose that improve their ability to detect and track odors. Bilateral odor sampling improves an animals' ability to navigate using olfaction and increased separation of the nostrils facilitates olfactory source localization. Many bats use odors to find food and mates and bats display an elaborate diversity of facial features. Prior studies have quantified how variations in facial features correlate with echolocation and feeding ecology, but surprisingly none have asked whether bat noses might be adapted for olfactory tracking in flight. We predicted that bat species that rely upon odor cues while foraging would have greater nostril separation in support of olfactory tropotaxis. Using museum specimens, we measured the external nose and cranial morphology of 40 New World bat species. Diet had a significant effect on external nose morphology, but contrary to our predictions, insectivorous bats had the largest relative separation of nostrils, while nectar feeding species had the narrowest nostril widths. Furthermore, nasal echolocating bats had significantly narrower nostrils than oral emitting bats, reflecting a potential trade-off between sonar pulse emission and stereo-olfaction in those species. To our knowledge, this is the first study to evaluate the evolutionary interactions between olfaction and echolocation in shaping the external morphology of a facial feature using modern phylogenetic comparative methods. Future work pairing olfactory morphology with tracking behavior will provide more insight into how animals such as bats integrate olfactory information while foraging., Competing Interests: The authors have declared that no competing interests exist.

Operant conditioning is a crucial tool in neuroscience research for probing brain function. While molecular, anatomical and even physiological techniques have seen radical increases in throughput, efficiency, and reproducibility in recent years, behavioural tools have somewhat lagged behind. Here we present a fully automated, high-throughput system for self-initiated conditioning of up to 25 group-housed, radio-frequency identification (RFID) tagged mice over periods of several months and >106 trials. We validate this "AutonoMouse" system in a series of olfactory behavioural tasks and show that acquired data is comparable to previous semi-manual approaches. Furthermore, we use AutonoMouse to systematically probe the impact of graded olfactory bulb lesions on olfactory behaviour, demonstrating that while odour discrimination in general is robust to even most extensive disruptions, small olfactory bulb lesions already impair odour detection. Discrimination learning of similar mixtures as well as learning speed are in turn reliably impacted by medium lesion sizes. The modular nature and open-source design of AutonoMouse should allow for similar robust and systematic assessments across neuroscience research areas., Competing Interests: The authors have declared that no competing interests exist.

Background: The generation or persistence of sexual arousal may be compromised when inhibitory processes such as negative emotions, outweigh sexual excitation. Disgust particularly, has been proposed as one of the emotions that may counteract sexual arousal. In support of this view, previous research has shown that disgust priming can reduce subsequent sexual arousal. As a crucial next step, this experimental study tested whether disgust (by means of odor) can also diminish sexual arousal in individuals who are already in a state of heightened sexual excitation., Methodology: In this study, participants were all men (N = 78). To elicit sexual arousal, participants watched a pornographic video. Following 4.30 minutes from the start of the video clip, they were exposed to either a highly aversive/disgusting odor (n = 42), or an odorless diluent/solvent (n = 36), that was delivered via an olfactometer, while the pornographic video continued. In both conditions the presentation of the odor lasted 1 second and was repeated 11 times with intervals of 26 seconds. Sexual arousal was indexed by both self-reports and penile circumference., Principal Findings: The disgusting odor (released when the participants were already sexually aroused) resulted in a significant decrease of both subjective and genital sexual arousal compared to the control (odorless) condition., Significance: The finding that the inhibitory effect of disgust was not only expressed in self-report but also expressed on the penile response further strengthens the idea that disgust might hamper behavioral actions motivated by sexual arousal (e.g., poor judgment, coercive sexual behavior). Thus, the current findings indicate that exposure to an aversive odor is sufficiently potent to reduce already present (subjective and) genital sexual arousal. This finding may also have practical relevance for disgust to be used as a tool for self-defence (e.g., Invi Bracelet)., Competing Interests: The authors have declared that no competing interests exist.

Baleen whales face the challenge of finding patchily distributed food in the open ocean. Their relatively well-developed olfactory structures suggest that they could identify the specific odours given off by planktonic prey such as krill aggregations. Like other marine predators, they may also detect dimethyl sulfide (DMS), a chemical released in areas of high marine productivity. However, dedicated behavioural studies still have to be conducted in baleen whales in order to confirm the involvement of chemoreception in their feeding ecology. We implemented 56 behavioural response experiments in humpback whales using two food-related chemical stimuli, krill extract and DMS, as well as their respective controls (orange clay and vegetable oil) in their breeding (Madagascar) and feeding grounds (Iceland and Antarctic Peninsula). The whales approached the stimulus area and stayed longer in the trial zone during krill extract trials compared to control trials, suggesting that they were attracted to the chemical source and spent time exploring its surroundings, probably in search of prey. This response was observed in Iceland, and to a lesser extend in Madagascar, but not in Antarctica. Surface behaviours indicative of sensory exploration, such as diving under the stimulus area and stopping navigation, were also observed more often during krill extract trials than during control trials. Exposure to DMS did not elicit such exploration behaviours in any of the study areas. However, acoustic analyses suggest that DMS and krill extract both modified the whales' acoustic activity in Madagascar. Altogether, these results provide the first behavioural evidence that baleen whales actually perceive prey-derived chemical cues over distances of several hundred metres. Chemoreception, especially olfaction, could thus be used for locating prey aggregations and for navigation at sea, as it has been shown in other marine predators including seabirds., Competing Interests: The authors have declared that no competing interests exist.

Conserving populations of environmentally vulnerable insect species requires a greater understanding of the factors that determine their abundance and distribution, which requires detailed knowledge of their population and community ecology. Chemical ecological tools such as pheromones can be used for non-destructive monitoring of scarab beetle populations, enabling European countries to detect and, in some cases, map the range of some of these species, proving a valuable technique for monitoring elusive saproxylic beetles. In this paper, we investigated the behavioural and chemical ecology of the noble chafer, Gnorimus nobilis L., a model insect species of conservation concern across a Europe-wide distribution, and a red-listed UK Biodiversity Action Plan priority species. We identified a potential pheromone of adult beetles using electrophysiological recordings, behavioural measurements and field trials in the UK. Gnorimus nobilis is highly unusual in that although both sexes produce, at high metabolic cost, the natural product 2-propyl (E)-3-hexenoate, it only attracts males. This pattern of chemical signalling makes the classification of the compound, based on current semiochemical terminology, somewhat problematic, but in our view, it should be termed an aggregation pheromone as a consequence of the production pattern. Since both sexes emit it, but apparently only males respond positively to it, 2-propyl (E)-3-hexenoate may reflect an intermediate evolutionary stage towards developing into a sex-specific signal. From an applied perspective, our study provides a model for the non-invasive surveillance of cryptic vulnerable insect species, without the need for habitat searching or disturbance, and continuous human monitoring., Competing Interests: The authors have declared that no competing interests exist.

Recent studies on machine learning technology have reported successful performances in some visual and auditory recognition tasks, while little has been reported in the field of olfaction. In this paper we report computational methods to predict the odor impression of a chemical from its physicochemical properties. Our predictive model utilizes nonlinear dimensionality reduction on mass spectra data and performs the clustering of descriptors by natural language processing. Sensory evaluation is widely used to measure human impressions to smell or taste by using verbal descriptors, such as "spicy" and "sweet". However, as it requires significant amounts of time and human resources, a large-scale sensory evaluation test is difficult to perform. Our model successfully predicts a group of descriptors for a target chemical through a series of computer simulations. Although the training text data used in the language modeling is not specialized for olfaction, the experimental results show that our method is useful for analyzing sensory datasets. This is the first report to combine machine olfaction with natural language processing for odor character prediction., Competing Interests: The authors have declared that no competing interests exist.

Tourette syndrome is a chronic tic disorder characterized by motor and vocal tics. Comorbidities such as attention deficit hyperactivity disorder and obsessive compulsive disorder can be found. The overlap between neuroanatomical regions and neurotransmitter systems in the olfactory system and the pathophysiology of Tourette syndrome let us hypothesize altered olfactory performance in Tourette syndrome. The main objective of this study was to systematically assess olfactory functioning in subjects with Tourette syndrome and to compare it to healthy controls. We assessed 28 adults with Tourette syndrome (age 33.1±9.4 years, disease duration 23.7±9.7 years) and 28 healthy controls (age 32.9±9.0 years) matched in regard to age, sex, education and smoking habits. The "Sniffin Sticks" test battery was applied to assess odor threshold, discrimination, and identification. Additionally, the combined score of the odor threshold test, the odor discrimination test and the odor identification test of the "Sniffin Sticks" test battery was calculated. Although it was not the primary aim of this study, we assessed whether tics and comorbidity could contribute to olfactory alterations in adults with Tourette syndrome. Therefore, clinical scores were used to assess severity of tics and co-morbidity such as attention deficit hyperactivity disorder, obsessive compulsive disorder, anxiety and depression in subjects with Tourette syndrome. Pathology of the nasal cavities was excluded with rhinoendoscopy. Independent sample t-tests were applied to compare performance in olfactory tests. In the case of statistically significant differences (critical p-value: 0.05), multiple linear regression analysis was carried out to explore whether tic severity, social impairment, co-morbidity or medical treatment had an impact on the differences found. Descriptive values are reported as mean ± standard deviation. Tourette syndrome subjects showed lower combined scores (Tourette syndrome subjects 31.9 ± 5.1 versus healthy controls 35.0 ± 3.1; p = 0.007), odor identification scores (Tourette syndrome subjects 12.4 ± 2.0 versus healthy controls 13.7 ± 1.4; p = 0.008) and odor discrimination scores (Tourette syndrome subjects 12.1 ± 2.1 versus healthy controls 13.2 ± 1.6; p = 0.041) in comparison to healthy subjects, while there was no difference in odor threshold (Tourette syndrome subjects 7.3 ± 2.7 versus healthy controls 8.1 ± 2.2; p = 0.22). Seven out of 28 Tourette syndrome subjects (25%) scored in the range of the age- and sex-dependent combined score for hyposmia, while two of 28 healthy controls (7%) had a similar low combined score. None of the participants were found to have functional anosmia. Multiple linear regression analyses suggest that social impairment may a predictor for low combined score and odor identification score in Tourette syndrome subjects (p = 0.003). Compared to healthy controls, altered olfaction in adults with Tourette syndrome was found in this study. Normal odor threshold level but lower scores at tasks involving supra-threshold odor concentrations point towards a central-nervous alteration in the processing of olfactory information in Tourette syndrome., Competing Interests: The authors have declared that no competing interests exist.

Some components of the neural circuits underlying innate odor-evoked responses have recently been elucidated. Odor information detected by the olfactory receptors is transmitted from the olfactory bulb to the cortical amygdala, where physiological and emotional states such as attraction or avoidance are controlled. Thus, activation of specific olfactory receptors can elicit changes in physiological and/or psychological state. Here, we examined on the odorant Hex-Hex Mix, which has been reported to induce anti-fatigue effects. Fatigue is a prevalent condition that is often related to overwork and psychological stress. Various anti-fatigue treatments have been developed, including supplements and odorants. However, the mechanisms underlying the anti-fatigue effects of these substances are currently unclear. In the present study, we analyzed the involvement of the olfactory system in the mechanisms underlying this effect. We identified the human olfactory receptors activated by Hex-Hex Mix, and evaluated whether activation of these olfactory receptors by a newly developed odorant elicited a similar anti-fatigue effect to Hex-Hex Mix. We assessed anti-fatigue effects with behavioral tests, and 17 healthy males performed the 2-back test as a fatigue-inducing task with or without exposure to the new odorant. Immediately before and after the task, participants performed a cognitive task to evaluate their level of mental fatigue. We found that the difference value of the correct response rate on the cognitive task in the evaluation session was significantly different between in the odorant condition and in the without-odorant condition during the fatigue-inducing session suggesting that the new odorant may improve performance in the fatigue-inducing condition. The results indicated that the new odorant activates the same olfactory receptors as Hex-Hex Mix, which has been reported to induce anti-fatigue effects. Our findings suggest that the olfactory receptors in the olfactory system may be involved in the attenuation of fatigue.

Multidimensional food perception is based mainly on gustatory and olfactory function. Recent research has demonstrated that hypobaric pressure impairs gustatory function and that background noise or distracting auditory stimulation impairs olfactory function. Using a hypobaric chamber, the odor identification, discrimination, and thresholds as well as taste identification and threshold scores were measured in 16 healthy male volunteers under normal and hypobaric (6380 ft) conditions using clinically validated tests. In both conditions, background noise was either canceled out or replaced by white noise presentation (70 dB sound pressure level). Olfactory sensitivity for n-butanol and gustatory sensitivity were impaired in a hypobaric atmosphere. White noise did not influence the odor test results. White noise stimulation impaired sensitivity for sour and sweet but not for bitter or salty tastants. We conclude that hypobaric or noisy environments could impair gustatory and olfactory sensitivity selectively for particular tastants and odorants.

The honeybee olfactory pathway comprises an intriguing pattern of convergence and divergence: ~60.000 olfactory sensory neurons (OSN) convey olfactory information on ~900 projection neurons (PN) in the antennal lobe (AL). To transmit this information reliably, PNs employ relatively high spiking frequencies with complex patterns. PNs project via a dual olfactory pathway to the mushroom bodies (MB). This pathway comprises the medial (m-ALT) and the lateral antennal lobe tract (l-ALT). PNs from both tracts transmit information from a wide range of similar odors, but with distinct differences in coding properties. In the MBs, PNs form synapses with many Kenyon cells (KC) that encode odors in a spatially and temporally sparse way. The transformation from complex information coding to sparse coding is a well-known phenomenon in insect olfactory coding. Intrinsic neuronal properties as well as GABAergic inhibition are thought to contribute to this change in odor representation. In the present study, we identified intrinsic neuronal properties promoting coding differences between PNs and KCs using in-situ patch-clamp recordings in the intact brain. We found very prominent K+ currents in KCs clearly differing from the PN currents. This suggests that odor coding differences between PNs and KCs may be caused by differences in their specific ion channel properties. Comparison of ionic currents of m- and l-ALT PNs did not reveal any differences at a qualitative level.

The meadow spittlebug, Philaenus spumarius L. (Hemiptera, Aphrophoridae) is a commonly found vector of Xylella fastidiosa Wells et al. (1987) strain subspecies pauca associated with the "Olive Quick Decline Syndrome" in Italy. To contribute to the knowledge of the adult P. spumarius chemoreceptivity, electroantennographic (EAG) responses of both sexes to 50 volatile organic compounds (VOCs) including aliphatic aldehydes, alcohols, esters, and ketones, terpenoids, and aromatics were recorded. Measurable EAG responses were elicited by all compounds tested. In both sexes, octanal, 2-octanol, 2-decanone, (E)-2-hexenyl acetate, and vanillin elicited the strongest antennal amplitude within the chemical groups of aliphatic saturated aldehydes, aliphatic alcohols, aliphatic acetates and aromatics, respectively. Male and female EAG responses to sulcatol, (±)linalool, and sulcatone were higher than those to other terpenoinds. In both sexes, the weakest antennal stimulants were phenethyl alcohol and 2-pentanone. Sexual differences in the EAG amplitude were found only for four of test compounds suggesting a general similarity between males and females in antennal sensitivity. The olfactory system of both sexes proved to be sensitive to changes in stimulus concentration, carbon chain length, and compound structure. Compounds with short carbon chain length (C5-C6) elicited lower EAG amplitudes than compounds with higher carbon chain length (C9-C10) in all classes of aliphatic hydrocarbons with different functional groups. The elucidation of the sensitivity profile of P. spumarius to a variety of VOCs provides a basis for future identification of behaviorally-active compounds useful for developing semiochemical-based control strategies of this pest.

Barth syndrome is a rare X-linked disease affecting less than 200 individuals worldwide. Several comorbidities have been associated with the pathology and, among those, cardiac myopathy and neutropenia are the most life threatening. The appropriate nutritive support is important to sustain the everyday life of Barth syndrome patients given the chronic fatigue they experience. Since they often prefer salty and fried food, and avoid vegetables and fruits, their eating habit and food preferences do not always provide the proper amount of vitamins and amino acids. It has been indeed reported that Barth syndrome patients have altered taste sensitivity. As olfaction also contributes to food consumption and flavor perception, we decided to investigate their olfactory abilities using the "Sniffin' sticks' extended test". We found no significant difference in any of the tested olfactory abilities between the group of Barth syndrome patients and the healthy controls. In summary, altered food preference of Barth boys could not be easily explained with an altered olfactory perception.

Objectives: The objective of the present study was to investigate the usefulness of time-frequency analysis (TFA) of olfactory-induced EEG change with a low-cost, portable olfactometer in the clinical investigation of smell function., Materials & Methods: A total of 78 volunteers participated. The study was composed of three parts where olfactory stimuli were presented using a custom-built olfactometer. Part I was designed to optimize the stimulus as well as the recording conditions. In part II EEG-power changes after olfactory/trigeminal stimulation were compared between healthy participants and patients with olfactory impairment. In Part III the test-retest reliability of the method was evaluated in healthy subjects., Results: Part I indicated that the most effective paradigm for stimulus presentation was cued stimulus, with an interstimulus interval of 18-20s at a stimulus duration of 1000ms with each stimulus quality presented 60 times in blocks of 20 stimuli each. In Part II we found that central processing of olfactory stimuli analyzed by TFA differed significantly between healthy controls and patients even when controlling for age. It was possible to reliably distinguish patients with olfactory impairment from healthy individuals at a high degree of accuracy (healthy controls vs anosmic patients: sensitivity 75%; specificity 89%). In addition we could show a good test-retest reliability of TFA of chemosensory induced EEG-power changes in Part III., Conclusions: Central processing of olfactory stimuli analyzed by TFA reliably distinguishes patients with olfactory impairment from healthy individuals at a high degree of accuracy. Importantly this can be achieved with a simple olfactometer.

The molecular receptive range (MRR) of a mammalian odorant receptor (OR) is the set of odorant structures that activate the OR, while the distribution of these odorant structures across odor space is the tuning breadth of the OR. Variation in tuning breadth is thought to be an important property of ORs, with the MRRs of these receptors varying from narrowly to broadly tuned. However, defining the tuning breadth of an OR is a technical challenge. For practical reasons, a screening panel that broadly covers odor space must be limited to sparse coverage of the many potential structures in that space. When screened with such a panel, ORs with different odorant specificities, but equal tuning breadths, might appear to have different tuning breadths due to chance. We hypothesized that ORs would maintain their tuning breadths across distinct odorant panels. We constructed a new screening panel that was broadly distributed across an estimated odor space and contained compounds distinct from previous panels. We used this new screening panel to test several murine ORs that were previously characterized as having different tuning breadths. ORs were expressed in Xenopus laevis oocytes and assayed by two-electrode voltage clamp electrophysiology. MOR256-17, an OR previously characterized as broadly tuned, responded to nine novel compounds from our new screening panel that were structurally diverse and broadly dispersed across an estimated odor space. MOR256-22, an OR previously characterized as narrowly tuned, responded to a single novel compound that was structurally similar to a previously known ligand for this receptor. MOR174-9, a well-characterized receptor with a narrowly tuned MRR, did not respond to any novel compounds in our new panel. These results support the idea that variation in tuning breadth among these three ORs is not an artifact of the screening protocol, but is an intrinsic property of the receptors.

Antenna is the main chemosensory organ in mosquitoes. Characterization of the transcriptional changes after blood meal, especially those related to chemoreception, may help to explain mosquito blood sucking behavior and to identify novel targets for mosquito control. Anopheles sinensis is an Asiatic mosquito species which transmits malaria and lymphatic filariasis. However, studies on chemosensory biology in female An. sinensis are quite lacking. Here we report a transcriptome analysis of An. sinensis female antennae pre- and post- blood meal. We created six An. sinensis antenna RNA-seq libraries, three from females without blood meal and three from females five hours after a blood meal. Illumina sequencing was conducted to analyze the transcriptome differences between the two groups. In total, the sequenced fragments created 21,643 genes, 1,828 of them were novel. 12,861 of these genes were considered to be expressed (FPKM >1.0) in at least one of the two groups, with 12,159 genes expressed in both groups. 548 genes were differentially expressed in the blood-fed group, with 331 genes up-regulated and 217 genes down-regulated. GO enrichment analysis of the differentially expressed genes suggested that there were no statistically over represented GO terms among down-regulated genes in blood-fed mosquitoes, while the enriched GO terms of the up-regulated genes occurred mainly in metabolic process. For the chemosensory gene families, a subtle distinction in the expression levels can be observed according to our statistical analysis. However, the firstly comprehensive identification of these chemosensory gene families in An. sinensis antennae will help to characterize the precise function of these proteins in odor recognition in mosquitoes. This study provides a first global view in the changes of transcript accumulation elicited by blood meal in An. sinensis female antennae.