Human scent as a first-line defense against disease.

Individuals may have a different body odor, when they are sick compared to healthy. In the non-human animal literature, olfactory cues have been shown to predict avoidance of sick individuals. We tested whether the mere experimental activation of the innate immune system in healthy human individuals can make an individuals' body odor be perceived as more aversive (intense, unpleasant, and disgusting). Following an endotoxin injection (lipopolysaccharide; 0.6 ng/kg) that creates a transient systemic inflammation, individuals smelled more unpleasant compared to a placebo group (saline injection). Behavioral and chemical analyses of the body odor samples suggest that the volatile components of samples from "sick" individuals changed qualitatively rather than quantitatively. Our findings support the hypothesis that odor cues of inflammation in axillary sweat are detectable just a few hours after experimental activation of the innate immune system. As such, they may trigger behavioral avoidance, hence constituting a first line of defense against pathogens of infected conspecifics.

Biodiversity indices and Random Forests reveal the potential for striped skunk (Mephitis mephitis) fecal microbial communities to function as a biomarker for oral rabies vaccination.

Wildlife disease surveillance and monitoring poses unique challenges when assessing rates of population vaccination, immunity, or infection prevalence. Non-invasively detected biomarkers can help reduce risk to both animal and field personnel during wildlife disease management activities. In this study, we investigated the utility of fecal microbiome data collected from captive striped skunks (Mephitis mephitis) in predicting rabies virus vaccination and infection status. We sequenced the hypervariable region 4 (V4) of the bacterial 16S gene and estimated alpha and beta diversity across timepoints in three groups of skunks: vaccination then rabies virus infection, sham vaccination then rabies virus infection, and rabies virus infected without vaccination. Alpha diversity did not differ among treatment groups but beta diversity between treatments was statistically significant. The phyla Firmicutes and Proteobacteria were dominant among all samples. Using Random Forests, we identified operational taxonomic units (OTUs) that greatly influenced classification of fecal samples into treatment groups. Each of these OTUs was correlated with fecal volatile organic compounds detected from the samples for companion treatment groups in another study. This research is the first to highlight striped skunk microbiome biodiversity as a vaccination biomarker which pushes the frontier on alternative methods for surveillance and monitoring of vaccination and disease in wildlife populations.

Strawberry Additive Increases Nicotine Vapor Sampling and Systemic Exposure But Does Not Enhance Pavlovian-Based Nicotine Reward in Mice.

Nicotine is an addictive drug whose popularity has recently increased, particularly among adolescents, because of the availability of electronic nicotine devices (i.e., "vaping") and nicotine e-liquids containing additives with rich chemosensory properties. Some efforts to understand the role of these additives in nicotine reward suggest that they increase nicotine reward and reinforcement, but the sensory contributions of additives, especially in their vapor forms, are largely untested. Here, to better understand how a fruit-flavored (i.e., strawberry) additive influences nicotine reward and aversion, we used a conditioned place preference (CPP) procedure in which nicotine and a strawberry additive were delivered as a vapor to male and female adolescent mice. We found that nicotine vapor alone can lead to a dose-dependent CPP when using a biased design. The strawberry additive did not produce CPP on its own, and we did not observe an effect of the strawberry additive on nicotine vapor-induced reward. Nevertheless, mice exposed to nicotine plus strawberry additive vapor had higher plasma cotinine concentrations, which did not appear to reflect altered nicotine metabolism. Instead, by directly measuring vapor sampling through respiration monitoring, we uncovered an increase in the amount of sniffing toward strawberry-containing nicotine vapor compared with nicotine vapor alone. Together these data indicate that chemosensory-rich e-liquid additives may enhance the perceived sensory profile of nicotine vapors rather than the reward value per se, which leads to overall increased nicotine exposure.

Unique volatile metabolite signature of sinonasal inverted papilloma detectable in plasma and nasal secretions.

BACKGROUND: Sinonasal inverted papilloma (SNIP) is a benign neoplasm with aggressive features, including a high recurrence rate and a propensity for malignant transformation. Accurate diagnosis with complete resection and the need for close long-term surveillance is widely accepted as standard management. In this study, we investigate whether SNIP produces a unique volatile metabolite signature, which may ultimately lead to a novel approach to diagnose and monitor SNIP. METHODS: Whole blood and nasal secretions from patients with SNIP and healthy age-, sex-, and smoking-status-matched controls, were collected. There were 56 blood samples and 42 nasal secretion samples collected. The volatile metabolite signature of SNIP plasma and nasal secretion samples were compared with those of healthy controls using chromatography. RESULTS: Seventy-two volatiles were identified in plasma samples. Multivariate analysis of variance results, even when controlled for smoking status, indicated toluene as a significant univariate result with lower levels of toluene identified in SNIP plasma samples than healthy control plasma samples. A linear discriminant analysis (LDA) model for plasma volatiles correctly classified 23 of 24 SNIP patients and 26 of 27 control patients, with a cross-validation error rate of 6.02%. Sixty-nine volatiles were identified in nasal samples. For nasal secretion samples, no single univariate response was significant. The LDA model correctly classified 21 of 21 SNIP patients and 11 of 12 control patients, with a cross-validation error rate of 6.55%. CONCLUSION: This study suggests that SNIP produces a unique, detectable volatile metabolite signature. With further investigation, this can have dramatic clinical implications for diagnosis and monitoring. Although most volatile metabolite studies have investigated solid-organ malignancy, this novel study addresses a benign sinonasal neoplasm by using nasal secretions and plasma as an analysis medium, representing the first such study.

Training the domestic ferret to discriminate odors associated with wildlife disease.

Recent avian influenza infection outbreaks have resulted in global biosecurity and economic concerns. Mallards are asymptomatic for the disease and can potentially spread AI along migratory bird flyways. In a previous study, trained mice correctly discriminated the health status of individual ducks on the basis of fecal odors when feces from post-infection periods were paired with feces from pre-infection periods. Chemical analyses indicated that avian influenza infection was associated with a marked increase of acetoin (3-hydroxy-2-butanone) in feces. In the current study, domesticated male ferrets (Mustela putorius furo) were trained to display a specific conditioned response (i.e. active scratch alert) in response to a marked increase of acetoin in a presentation of an acetoin:1-octen-3-ol solution. Ferrets rapidly generalized this learned response to the odor of irradiated feces from avian influenza infected mallards. These results suggest that a trained mammalian biosensor could be employed in an avian influenza surveillance program.

Differing Alterations of Odor Volatiles Among Pathogenic Stimuli.

Alterations of the volatile metabolome (the collection of volatiles present in secretions and other emanations) that occur in response to inflammation can be detected by conspecifics and chemometric analyses. Using a model system where mouse urinary metabolites are altered by treatment with lipopolysaccharide (found in the outer cell membrane of gram-negative bacteria), we hypothesized that alteration of body odor volatiles will vary according to the pathogen responsible for inducing the inflammation. We tested this hypothesis by treating mice with different immunogens that engage different immune signaling pathways. Results suggest that alterations of body odor volatiles resulting from inflammation do contain detailed information about the type of pathogen that instigated the inflammation and these differences are not merely dependent on the severity of the inflammatory event. These results are encouraging for the future of differential medical diagnosis of febrile diseases by analysis of the volatile metabolome. In particular, our data support the possibility that bacterial infections can be differentiated from viral infections such that antibiotic drug stewardship could be drastically improved by reducing unneeded treatments with antibiotics.

Exposure to fruit-flavoring during adolescence increases nicotine consumption and promotes dose escalation.

The rise of e-cigarette popularity has sparked interest in the role of palatable flavors on nicotine use. Despite growing evidence that sweet flavorants enhance nicotine reward, their influence on nicotine consumption has not been studied extensively. In addition, the impact that flavored nicotine use in adolescence could have on nicotine reward and dependence in adulthood remains unclear. This study examined the role of flavored nicotine access on nicotine preference and consumption longitudinally, from adolescence to adulthood. Male and female adolescent mice preferred a fruit-flavored nicotine solution over an unflavored nicotine solution. However, only adolescent female mice with access to flavored nicotine consumed higher doses. Furthermore, while adolescent male mice escalated consumption of both flavored and unflavored nicotine, female mice only escalated nicotine consumption when given access to flavored nicotine. As mice matured into adulthood, there was no evidence that a history of flavored-nicotine access altered preference for unflavored nicotine compared to a nicotine-free control in a classic two-bottle choice design. However, when the nicotine concentration was progressively reduced, mice that had consumed strawberry-flavored nicotine in adolescence maintained baseline nicotine consumption levels longer than mice that initiated nicotine use without flavor in adolescence. Finally, addition of fruit-flavorants into the nicotine solution during adulthood led to nicotine preference and increased levels of nicotine consumption, regardless of previous flavored-nicotine access or of familiarity with the selected flavorant. These results indicate that flavorants increase nicotine consumption independent of life stage, possibly posing a disproportionate risk to adolescent females. Our results also point to an effect of adolescent flavored-nicotine use on nicotine dose maintenance in adulthood, which could have implications for the success of future quit attempts.

Biodetection of a specific odor signature in mallard feces associated with infection by low pathogenic avian influenza A virus.

Outbreaks of avian influenza virus (AIV) infection included the spread of highly pathogenic AIV in commercial poultry and backyard flocks in the spring of 2015. This resulted in estimated losses of more than $8.5 million from federal government expenditures, $1.6 billion from direct losses to produces arising from destroyed turkey and chicken egg production, and economy-wide indirect costs of $3.3 billion from impacts on retailers and the food service industries. Additionally, these outbreaks resulted in the death or depopulation of nearly 50 million domestic birds. Domesticated male ferrets (Mustela putorius furo) were trained to display a specific conditioned behavior (i.e. active scratch alert) in response to feces from AIV-infected mallards in comparison to feces from healthy ducks. In order to establish that ferrets were identifying samples based on odors associated with infection, additional experiments controlled for potentially confounding effects, such as: individual duck identity, housing and feed, inoculation concentration, and day of sample collection (post-infection). A final experiment revealed that trained ferrets could detect AIV infection status even in the presence of samples from mallards inoculated with Newcastle disease virus or infectious laryngotracheitis virus. These results indicate that mammalian biodetectors are capable of discriminating the specific odors emitted from the feces of non-infected versus AIV infected mallards, suggesting that the health status of waterfowl can be evaluated non-invasively for AIV infection via monitoring of volatile fecal metabolites. Furthermore, in situ monitoring using trained biodetectors may be an effective tool for assessing population health.

Olfactory Communication of Sickness Cues in Respiratory Infection.

Animals detect sick conspecifics by way of body odor that enables the receiver to avoid potential infectious transmission. Human observational studies also indicate that different types of disease are associated with more or less aversive smells. In addition, body odors from otherwise healthy human individuals smell more aversive as a function of experimentally induced systemic inflammation. To investigate if naturally occurring immune activation also gives rise to perceivable olfactory changes, we collected body odor samples during two nights from individuals with a respiratory infection as well as when they were healthy. We hypothesized that independent raters would rate the body odor originating from sick individuals as smelling more aversive than when the same individuals were healthy. Even though body odor samples from sick individuals nominally smelled more intense, more disgusting, and less pleasant and healthy than the body odor from the same individuals when healthy, these effects were not statistically significant. Moreover, raters filled out three questionnaires, Perceived Vulnerability to Disease, Disgust Scale, and Health Anxiety, to assess potential associations between sickness-related personality traits and body odor perception. No such association was found. Since experimentally induced inflammation have made body odors more aversive in previous studies, we discuss whether this difference between studies is due to the level of sickness or to the type of trigger of the sickness response.

People expressing olfactory and visual cues of disease are less liked.

For humans, like other social animals, behaviour acts as a first line of defence against pathogens. A key component is the ability to detect subtle perceptual cues of sick conspecifics. The present study assessed the effects of endotoxin-induced olfactory and visual sickness cues on liking, as well as potential involved mechanisms. Seventy-seven participants were exposed to sick and healthy facial pictures and body odours from the same individual in a 2 × 2 factorial design while disgust-related facial electromyography (EMG) was recorded. Following exposure, participants rated their liking of the person presented. In another session, participants also answered questionnaires on perceived vulnerability to disease, disgust sensitivity and health anxiety. Lower ratings of liking were linked to both facial and body odour disease cues as main effects. Disgust, as measured by EMG, did not seem to be the mediating mechanism, but participants who perceived themselves as more prone to disgust, and as more vulnerable to disease, liked presented persons less irrespectively of their health status. Concluding, olfactory and visual sickness cues that appear already a few hours after the experimental induction of systemic inflammation have implications for human sociality and may as such be a part of a behavioural defence against disease. This article is part of the Theo Murphy meeting issue 'Olfactory communication in humans'.

Narrowing uncertainties in the effects of elevated CO2 on crops.

Plant responses to rising atmospheric carbon dioxide (CO2) concentrations, together with projected variations in temperature and precipitation will determine future agricultural production. Estimates of the impacts of climate change on agriculture provide essential information to design effective adaptation strategies, and develop sustainable food systems. Here, we review the current experimental evidence and crop models on the effects of elevated CO2 concentrations. Recent concerted efforts have narrowed the uncertainties in CO2-induced crop responses so that climate change impact simulations omitting CO2 can now be eliminated. To address remaining knowledge gaps and uncertainties in estimating the effects of elevated CO2 and climate change on crops, future research should expand experiments on more crop species under a wider range of growing conditions, improve the representation of responses to climate extremes in crop models, and simulate additional crop physiological processes related to nutritional quality.

Volatile metabolomic signatures of rabies immunization in two mesocarnivore species.

Rabies is a zoonotic disease caused by infection with rabies virus, which circulates naturally in several wild carnivore and bat reservoirs in the United States (US). The most important reservoir in the US from an animal and public health perspective is the raccoon (Procyon lotor). To prevent the westward expansion of a significant raccoon rabies epizootic along the eastern seaboard, an operational control program implementing oral rabies vaccination (ORV) has existed in the US since the 1990s. Recently, two vaccine efficacy studies conducted with raccoons and striped skunks (Mephitis mephitis) provided the opportunity to determine if volatile fecal metabolites might be used to non-invasively monitor ORV programs and/or predict virus protection for these species. The volatile metabolome is a rich source of information that may significantly contribute to our understanding of disease and infection. Fecal samples were collected at multiple time points from raccoons and striped skunks subjected to oral treatment with rabies vaccine (or sham). Intramuscular challenge with a lethal dose of rabies virus was used to determine protection status at six (raccoons) and 11 (skunks) months post-vaccination. In addition to fecal samples, blood was collected at various time points to permit quantitative assessment of rabies antibody responses arising from immunization. Feces were analyzed by headspace gas chromatography with mass spectrometric detection and the chromatographic responses were grouped according to cluster analysis. Cluster scores were subjected to multivariate analyses of variance (MANOVA) to determine if fecal volatiles may hold a signal of immunization status. Multiple regression was then used to build models of the measured immune responses based on the metabolomic data. MANOVA results identified one cluster associated with protective status of skunks and one cluster associated with protective status of raccoons. Regression models demonstrated considerably greater success in predicting rabies antibody responses in both species. This is the first study to link volatile compounds with measures of adaptive immunity and provides further evidence that the volatile metabolome holds great promise for contributing to our understanding of disease and infections. The volatile metabolome may be an important resource for monitoring rabies immunization in raccoons and striped skunks.

Controlled infrared heating of an artic meadow: challenge in the vegetation establishment stage.

BACKGROUND: Global warming is going to affect both agricultural production and carbon storage in soil worldwide. Given the complexity of the soil-plant-atmosphere continuum, in situ experiments of climate warming are necessary to predict responses of plants and emissions of greenhouse gases (GHG) from soils. Arrays of infrared (IR) heaters have been successfully applied in temperate and tropical agro-ecosystems to produce uniform and large increases in canopy surface temperature across research plots. Because this method had not yet been tested in the Arctic where consequences of global warming on GHG emission are expected to be largest, the objective of this work was to test hexagonal arrays of IR heaters to simulate a homogenous 3 °C warming of the surface, i.e. canopy and visible bare soil, of five 10.5-m2 plots in an Arctic meadow of northern Norway. RESULTS: Our results show that the IR warming setup was able to simulate quite accurately the target + 3 °C, thereby enabling us to simulate the extension of the growing season. Meadow yield increased under warming but only through the lengthening of the growing season. Our research also suggests that, when investigating agricultural systems on the Arctic, it is important to start the warming after the vegetation is established,. Indeed, differential emergence of meadow plants impaired the homogeneity of the warming with patches of bare soil being up to 9.5 °C warmer than patches of vegetation. This created a pattern of soil crusting, which further induced spatial heterogeneity of the vegetation. However, in the Arctic these conditions are rather rare as the soil exposed by snow melt is often covered by a layer of senescent vegetation which shelters the soil from direct radiation. CONCLUSIONS: Consistent continuous warming can be obtained on average with IR systems in an Arctic meadow, but homogenous spatial distribution requires that the warming must start after canopy closure.

Detection of Inflammation via Volatile Cues in Human Urine.

Contagious disease is a major threat to survival, and the cost of relying on the immune system to defeat pathogens is high; therefore, behavioral avoidance of contagious individuals is arguably an adaptive strategy. Animal findings demonstrate the ability to detect and avoid sick individuals by the aid of olfactory cues, and a recent study indicated that human axillary odor also becomes more aversive as a function of immune activation. By injecting healthy human participants with lipopolysaccharide (0.6 ng/kg body weight) to experimentally induce inflammation, this study demonstrates that natural daily rhythms of urine odor-its perceived dimensions and volatile profile-are altered within hours of inflammation onset. Whereas healthy human urine decreases in averseness over the course of a single day, inflammation interrupts this process and results in an increased urine odor averseness and an altered volatile composition. These results support the notion that subtle and early cues of sickness may be detected and avoided, thereby complementing the immune system in its role of keeping us alive and healthy.

Sharing an environment with sick conspecifics alters odors of healthy animals.

Body odors change with health status and the odors of sick animals can induce avoidance behaviors in healthy conspecifics. Exposure to sickness odors might also alter the physiology of healthy conspecifics and modify the odors they produce. We hypothesized that exposure to odors of sick (but non-infectious) animals would alter the odors of healthy cagemates. To induce sickness, we injected mice with a bacterial endotoxin, lipopolysaccharide. We used behavioral odor discrimination assays and analytical chemistry techniques followed by predictive classification modeling to ask about differences in volatile odorants produced by two types of healthy mice: those cohoused with healthy conspecifics and those cohoused with sick conspecifics. Mice trained in Y-maze behavioral assays to discriminate between the odors of healthy versus sick mice also discriminated between the odors of healthy mice cohoused with sick conspecifics and odors of healthy mice cohoused with healthy conspecifics. Chemical analyses paired with statistical modeling revealed a parallel phenomenon. Urine volatiles of healthy mice cohoused with sick partners were more likely to be classified as those of sick rather than healthy mice based on discriminant model predictions. Sickness-related odors could have cascading effects on neuroendocrine or immune responses of healthy conspecifics, and could affect individual behaviors, social dynamics, and pathogen spread.

Feminization of Male Brown Treesnake Methyl Ketone Expression via Steroid Hormone Manipulation.

Pheromones are useful tools for the management of invasive invertebrates, but have proven less successful in field applications for invasive vertebrates. The brown treesnake, Boiga irregularis, is an invasive predator that has fundamentally altered the ecology of Guam. The development of control tools to manage Boiga remains ongoing. Skin-based, lipophilic pheromone components facilitate mating in brown treesnakes, with females producing the same long-chain, saturated and monounsaturated (ketomonoene) methyl ketones known to function as pheromones in garter snakes, Thamnophis sirtalis. Boiga also express novel, diunsaturated methyl ketones (ketodienes) with a purported function as a sex pheromone. In our study, we implanted 17 ß-estradiol in adult male brown treesnakes in order to manipulate methyl ketone expression as sex attractants, an effect that would mirror findings with garter snakes. Specifically, estrogen promoted production of two ketomonoenes, pentatriaconten-2-one and hexatriaconten-2-one, and suppressed production of one ketodiene, heptatriacontadien-2-one. In bioassays, estrogen-implanted males elicited tongue-flicking and chin rubbing behavior from unmanipulated males, though the responses were weaker than those elicited by females. On Guam, wild males exhibited greatest responses to whole female skin lipid extracts and only weak responses to the methyl ketone fractions from females and implanted males. Our results suggest that sex identity in brown treesnakes may be conferred by the ratio of ketomonoenes (female) to ketodienes (male) from skin lipids and may be augmented by a sex-specific endocrine signal (estradiol). However, a blend of long-chain methyl ketones alone is not sufficient to elicit maximal reproductive behaviors in male Boiga.

Infrared heater system for warming tropical forest understory plants and soils.

The response of tropical forests to global warming is one of the largest uncertainties in predicting the future carbon balance of Earth. To determine the likely effects of elevated temperatures on tropical forest understory plants and soils, as well as other ecosystems, an infrared (IR) heater system was developed to provide in situ warming for the Tropical Responses to Altered Climate Experiment (TRACE) in the Luquillo Experimental Forest in Puerto Rico. Three replicate heated 4-m-diameter plots were warmed to maintain a 4°C increase in understory vegetation compared to three unheated control plots, as sensed by IR thermometers. The equipment was larger than any used previously and was subjected to challenges different from those of many temperate ecosystem warming systems, including frequent power surges and outages, high humidity, heavy rains, hurricanes, saturated clayey soils, and steep slopes. The system was able to maintain the target 4.0°C increase in hourly average vegetation temperatures to within ± 0.1°C. The vegetation was heterogeneous and on a 21° slope, which decreased uniformity of the warming treatment on the plots; yet, the green leaves were fairly uniformly warmed, and there was little difference among 0-10 cm depth soil temperatures at the plot centers, edges, and midway between. Soil temperatures at the 40-50 cm depth increased about 3°C compared to the controls after a month of warming. As expected, the soil in the heated plots dried faster than that of the control plots, but the average soil moisture remained adequate for the plants. The TRACE heating system produced an adequately uniform warming precisely controlled down to at least 50-cm soil depth, thereby creating a treatment that allows for assessing mechanistic responses of tropical plants and soil to warming, with applicability to other ecosystems. No physical obstacles to scaling the approach to taller vegetation (i.e., trees) and larger plots were observed.

Chemical composition of glandular secretions from a pair-living monogamous primate: Sex, age, and gland differences in captive and wild owl monkeys (Aotus spp.).

Broadening our knowledge of olfactory communication in strictly monogamous systems can inform our understanding of how chemosignals may facilitate social and reproductive behavior between the sexes. Compared to other social and mating systems, relatively little is known about olfactory communication in strictly monogamous non-human primates. Furthermore, platyrrhines are not well represented in chemical analyses of glandular secretions. We conducted semi-quantitative headspace gas chromatography with mass spectrometry to investigate the chemical components of glandular secretions from the subcaudal and pectoral glands of a strictly pair-living platyrrhine, the owl monkey (Aotus spp.). In this study, the first chemical analysis of a wild platyrrhine population, our goals were to (1) conduct a robust analysis of glandular secretions from both captive and wild owl monkey populations and (2) identify whether biologically relevant traits are present in glandular secretions. We also compared and contrasted the results between two Aotus species in different environmental contexts: wild Aotus azarae (N = 33) and captive A. nancymaae (N = 104). Our findings indicate that secretions from both populations encode sex, gland of origin, and possibly individual identity. These consistent patterns across species and contexts suggest that secretions may function as chemosignals. Our data also show that wild A. azarae individuals are chemically discriminated by age (adult or subadult). Among the captive A. nanycmaae, we found chemical differences associated with location, possibly caused by dietary differences. However, there was no noticeable effect of contraception on the chemical profiles of females, nor evidence that closely related individuals exhibit more similar chemical profiles in A. nancymaae. Overall, our data suggest that glandular secretions of both wild and captive Aotus convey specific information. Future studies should use behavioral bioassays to evaluate the ability of owl monkeys to detect signals, and consider whether odor may ultimately facilitate social and sexual relationships between male and female owl monkeys.

Cytokine contributions to alterations of the volatile metabolome induced by inflammation.

Several studies demonstrate that inflammation affects body odor. Volatile signals associated with inflammation induced by pyrogens like LPS are detectable both by conspecifics and chemical analyses. However, little is known about the mechanisms which translate detection of a foreign molecule or pathogen into a unique body odor, or even how unique that odor may be. Here, we utilized C57BL/6J trained mice to identify the odor of LPS-treated conspecifics to investigate potential pathways between LPS-induced inflammation and changes in body odor, as represented by changes in urine odor. We hypothesized that the change in volatile metabolites could be caused directly by the pro-inflammatory cytokine response mediated by TNF or IL-1ß, or by the compensatory anti-inflammatory response mediated by IL-10. We found that trained biosensors generalized learned LPS-associated odors to TNF-induced odors, but not to IL-1ß or IL-10-induced odors. Analyses of urine volatiles using headspace gas chromatography revealed distinct profiles of volatile compounds for each treatment. Instrumental discrimination relied on a mixture of compounds, including 2-sec-butyl-4,5-dihydrothiazole, cedrol, nonanal, benzaldehyde, acetic acid, 2-ethyl-1-hexanol, and dehydro-exo-brevicomin. Although interpretation of LDA modeling differed from behavioral testing, it does suggest that treatment with TNF, IL-1ß, and LPS can be distinguished by their resultant volatile profiles. These findings indicate there is information found in body odors on the presence of specific cytokines. This result is encouraging for the future of disease diagnosis via analysis of volatiles.

Author Correction: The uncertainty of crop yield projections is reduced by improved temperature response functions.

Nature Plants 3, 17102 (2017); published online 17 July 2017; corrected online 27 September 2017.