Urinary VOCs as biomarkers of early stage lung tumour development in mice.

BACKGROUND: Lung cancer is the primary cause of cancer-induced death. In addition to prevention and improved treatment, it has increasingly been established that early detection is critical to successful remission. OBJECTIVE: The aim of this study was to identify volatile organic compounds (VOCs) in urine that could help diagnose mouse lung cancer at an early stage of its development. METHODS: We analysed the VOC composition of urine in a genetically engineered lung adenocarcinoma mouse model with oncogenic EGFR doxycycline-inducible lung-specific expression. We compared the urinary VOCs of 10 cancerous mice and 10 healthy mice (controls) before and after doxycycline induction, every two weeks for 12 weeks, until full-blown carcinomas appeared. We used SPME fibres and gas chromatography - mass spectrometry to detect variations in cancer-related urinary VOCs over time. RESULTS: This study allowed us to identify eight diagnostic biomarkers that help discriminate early stages of cancer tumour development (i.e., before MRI imaging techniques could identify it). CONCLUSION: The analysis of mice urinary VOCs have shown that cancer can induce changes in odour profiles at an early stage of cancer development, opening a promising avenue for early diagnosis of lung cancer in other models.

Masting is uncommon in trees that depend on mutualist dispersers in the context of global climate and fertility gradients.

The benefits of masting (volatile, quasi-synchronous seed production at lagged intervals) include satiation of seed predators, but these benefits come with a cost to mutualist pollen and seed dispersers. If the evolution of masting represents a balance between these benefits and costs, we expect mast avoidance in species that are heavily reliant on mutualist dispersers. These effects play out in the context of variable climate and site fertility among species that vary widely in nutrient demand. Meta-analyses of published data have focused on variation at the population scale, thus omitting periodicity within trees and synchronicity between trees. From raw data on 12 million tree-years worldwide, we quantified three components of masting that have not previously been analysed together: (i) volatility, defined as the frequency-weighted year-to-year variation; (ii) periodicity, representing the lag between high-seed years; and (iii) synchronicity, indicating the tree-to-tree correlation. Results show that mast avoidance (low volatility and low synchronicity) by species dependent on mutualist dispersers explains more variation than any other effect. Nutrient-demanding species have low volatility, and species that are most common on nutrient-rich and warm/wet sites exhibit short periods. The prevalence of masting in cold/dry sites coincides with climatic conditions where dependence on vertebrate dispersers is less common than in the wet tropics. Mutualist dispersers neutralize the benefits of masting for predator satiation, further balancing the effects of climate, site fertility and nutrient demands.

Ability of animals to detect cancer odors.

The olfactory capacity of animals has long been used by humans to help with various activities, e.g., hunting, detecting mines, locating people, and diagnosing diseases. Cancer is among the leading diseases causing death worldwide. Several recent studies have underscored the benefit of using scent to detect cancer, and this paper will review the studies using animals to detect tumor scents. A large variety of animals have been used for this purpose-dogs, rodents, insects, and nematodes-and have shown their capacity to detect cancer, with a success rate close to 90%. Here we discuss these studies, their methodologies, and the animal models used. Finally, we discuss the medical perspectives for cancer diagnosis using odors.

No evidence for long-range male sex pheromones in two malaria mosquitoes.

Cues involved in mate seeking and recognition prevent hybridization and can be involved in speciation processes. In malaria mosquitoes, females of the two sibling species Anopheles gambiae s.s. and An. coluzzii mate in monospecific male swarms and hybrids are rare. Long-range sex pheromones driving this behaviour have been debated in literature but so far, no study has proven their existence or their absence. Here, we attempted to bring to light their existence. To put all the odds in our favour, we used different chemical ecology methods such as behavioural and electrophysiological assays as well chemical analyses, and we worked with mosquitoes at their optimal physiological mating state that is with swarming males during their natural swarming windows. Despite all our efforts, our results support the absence of long-range sex pheromones involved in swarm detection and recognition by females. We briefly discuss the implications of this finding in ecology, evolution and for control strategies.

Limits to reproduction and seed size-number trade-offs that shape forest dominance and future recovery.

The relationships that control seed production in trees are fundamental to understanding the evolution of forest species and their capacity to recover from increasing losses to drought, fire, and harvest. A synthesis of fecundity data from 714 species worldwide allowed us to examine hypotheses that are central to quantifying reproduction, a foundation for assessing fitness in forest trees. Four major findings emerged. First, seed production is not constrained by a strict trade-off between seed size and numbers. Instead, seed numbers vary over ten orders of magnitude, with species that invest in large seeds producing more seeds than expected from the 1:1 trade-off. Second, gymnosperms have lower seed production than angiosperms, potentially due to their extra investments in protective woody cones. Third, nutrient-demanding species, indicated by high foliar phosphorus concentrations, have low seed production. Finally, sensitivity of individual species to soil fertility varies widely, limiting the response of community seed production to fertility gradients. In combination, these findings can inform models of forest response that need to incorporate reproductive potential.

Globally, tree fecundity exceeds productivity gradients.

Lack of tree fecundity data across climatic gradients precludes the analysis of how seed supply contributes to global variation in forest regeneration and biotic interactions responsible for biodiversity. A global synthesis of raw seedproduction data shows a 250-fold increase in seed abundance from cold-dry to warm-wet climates, driven primarily by a 100-fold increase in seed production for a given tree size. The modest (threefold) increase in forest productivity across the same climate gradient cannot explain the magnitudes of these trends. The increase in seeds per tree can arise from adaptive evolution driven by intense species interactions or from the direct effects of a warm, moist climate on tree fecundity. Either way, the massive differences in seed supply ramify through food webs potentially explaining a disproportionate role for species interactions in the wet tropics.

Odours of cancerous mouse congeners: detection and attractiveness.

Chemical communication plays a major role in social interactions. Cancer, by inducing changes in body odours, may alter interactions between individuals. In the framework of research targeting non-invasive methods to detect early stages of cancer development, this study asked whether untrained mice could detect odour changes in cancerous congeners. If yes, were they able to detect cancer at an early developmental stage? Did it influence female preference? Did variations in volatile organic components of the odour source paralleled mice behavioural responses? We used transgenic mice strains developing or not lung cancer upon antibiotic ingestion. We sampled soiled bedding of cancerous mice (CC) and not cancerous mice (NC), at three experimental conditions: before (T0), early stage (T2) and late stage (T12) of cancer development. Habituation/generalisation and two-way preference tests were performed where soiled beddings of CC and NC mice were presented to wild-derived mice. The composition and relative concentration of volatile organic components (VOC) in the two stimuli types were analysed. Females did not show directional preference at any of the experimental conditions, suggesting that cancer did not influence their choice behaviour. Males did not discriminate between CC and NC stimuli at T0 but did so at T2 and T12, indicating that wild-derived mice could detect cancer at an early stage of development. Finally, although the VOC bouquet differed between CC and NC it did not seem to parallel the observed behavioural response suggesting that other types of odorant components might be involved in behavioural discrimination between CC and NC mice.

Odors and cancer: Current status and future directions.

Cancer is the second leading cause of death in the world. Because tumors detected at early stages are easier to treat, the search for biomarkers-especially non-invasive ones-that allow early detection of malignancies remains a central goal to reduce cancer mortality. Cancer, like other pathologies, often alters body odors, and much has been done by scientists over the last few decades to assess the value of volatile organic compounds (VOCs) as signatures of cancers. We present here a quantitative review of 208 studies carried out between 1984 and 2020 that explore VOCs as potential biomarkers of cancers. We analyzed the main findings of these studies, listing and classifying VOCs related to different cancer types while considering both sampling methods and analysis techniques. Considering this synthesis, we discuss several of the challenges and the most promising prospects of this research direction in the war against cancer.

Mosquito Attractants.

Vector control and personal protection against anthropophilic mosquitoes mainly rely on the use of insecticides and repellents. The search for mosquito-attractive semiochemicals has been the subject of intense studies for decades, and new compounds or odor blends are regularly proposed as lures for odor-baited traps. We present a comprehensive and up-to-date review of all the studies that have evaluated the attractiveness of volatiles to mosquitoes, including individual chemical compounds, synthetic blends of compounds, or natural host or plant odors. A total of 388 studies were analysed, and our survey highlights the existence of 105 attractants (77 volatile compounds, 17 organism odors, and 11 synthetic blends) that have been proved effective in attracting one or several mosquito species. The exhaustive list of these attractants is presented in various tables, while the most common mosquito attractants - for which effective attractiveness has been demonstrated in numerous studies - are discussed throughout the text. The increasing knowledge on compounds attractive to mosquitoes may now serve as the basis for complementary vector control strategies, such as those involving lure-and-kill traps, or the development of mass trapping. This review also points out the necessity of further improving the search for new volatile attractants, such as new compound blends in specific ratios, considering that mosquito attraction to odors may vary over the life of the mosquito or among species. Finally, the use of mosquito attractants will undoubtedly have an increasingly important role to play in future integrated vector management programs.

Floral trait differentiation in Anacamptis coriophora: Phenotypic selection on scents, but not on colour.

Current divergent selection may promote floral trait differentiation among conspecific populations in flowering plants. However, whether this applies to complex traits such as colour or scents has been little studied, even though these traits often vary within species. In this study, we compared floral colour and odour as well as selective pressures imposed upon these traits among seven populations belonging to three subspecies of the widespread, generalist orchid Anacamptis coriophora. Colour was characterized using calibrated photographs, and scents were sampled using dynamic headspace extraction and analysed using gas chromatography-mass spectrometry. We then quantified phenotypic selection exerted on these traits by regressing fruit set values on floral trait values. We showed that the three studied subspecies were characterized by different floral colour and odour, with one of the two predominant floral volatiles emitted by each subspecies being taxon-specific. Plant size was positively correlated with fruit set in most populations, whereas we found no apparent link between floral colour and female reproductive success. We detected positive selection on several taxon-specific compounds in A. coriophora subsp. fragrans, whereas no selection was found on floral volatiles of A. coriophora subsp. coriophora and A. coriophora subsp. martrinii. This study is one of the first to document variation in phenotypic selection exerted on floral scents among conspecific populations. Our results suggest that selection could contribute to ongoing chemical divergence among A. coriophora subspecies.

The evolution of resistance and tolerance as cancer defences.

Although there is a plethora of cancer associated-factors that can ultimately culminate in death (cachexia, organ impairment, metastases, opportunistic infections, etc.), the focal element of every terminal malignancy is the failure of our natural defences to control unlimited cell proliferation. The reasons why our defences apparently lack efficiency is a complex question, potentially indicating that, under Darwinian terms, solutions other than preventing cancer progression are also important contributors. In analogy with host-parasite systems, we propose to call this latter option 'tolerance' to cancer. Here, we argue that the ubiquity of oncogenic processes among metazoans is at least partially attributable to both the limitations of resistance mechanisms and to the evolution of tolerance to cancer. Deciphering the ecological contexts of alternative responses to the cancer burden is not a semantic question, but rather a focal point in understanding the evolutionary ecology of host-tumour relationships, the evolution of our defences, as well as why and when certain cancers are likely to be detrimental for survival.

Modulation of feed composition is able to make hens less attractive to the poultry red mite Dermanyssus gallinae.

The poultry red mite (PRM) is an obligatory haematophagous pest that causes substantial economic losses in poultry worldwide. The PRM does not live on the host but in the bird's environment and must find its host remotely. Hence, manipulating chicken odours is of interest. Several crude plant-originating volatile organic compounds (VOCs) have already been shown as repellent to Dermanyssus gallinae. We aimed to test whether these VOCs can interfere with PRM host-seeking behaviour by their oral administration to the poultry. The objectives were to determine (1) if hen odours are modified by supplemented feed ingestion and (2) if such treatment makes hens less attractive to the PRM. Chemical characterization by gas chromatography-mass spectrometry of the hen odour was conducted before and after the hens ingested the supplemented feed. The chromatograms obtained show that hen odour was substantially modified after the hens consumed it. Among the molecules recurrently detected from the supplemented hens, 26% were nearly absent in the unsupplemented hens. Behavioural choice tests to compare the effect of the modified and unmodified-host odours on the PRM show that some of the plant-originating emitted VOCs and the modified whole-hen odours were repellent to the PRM.

Is Perceived Exposure to Mosquitoes Associated with Actual Exposure? Results from Studies in High-Risk and Low-Risk Geographic Areas.

Perceived exposure to mosquitoes plays a fundamental role in the adoption of a range of protective behaviors aiming to prevent and control mosquito-borne disease. However, it is largely unknown in the present literature to what extent perceived exposure is associated with actual exposure. Moreover, the perception of nuisance may depend on the natural environment in which human populations are living, and especially its epidemiological context. In this study, the hypothesis that perceived exposure is driven by mosquito abundance was tested in two different geographic areas. We compared a range of perceived nuisance measures-collected through questionnaires-with egg number measured within ovitraps located in the south of France, which has been recently colonized by an arbovirus vector, and La Martinique island, a tropical French territory, which has a long history of outbreaks of mosquito-borne pathogens. Unexpectedly, only the nuisance due to mosquito noise was correlated with ovitrap activity in southern France. All other perceived exposure measures, both in the south of France and in Martinique, were not correlated with egg number surrounding households investigated. These results suggest the existence of habituation effects that may disturb the engagement in adaptive behaviors in the face of change in the entomological conditions.

Prior contact with permethrin decreases its irritancy at the following exposure among a pyrethroid-resistant malaria vector Anopheles gambiae.

Insecticide-treated nets (ITNs) remain major components for vector control despite the spread of resistance mechanisms among mosquito populations. Multiple exposures to pyrethroids may induce physiological and behavioral changes in mosquitoes, possibly reducing efficacy of control tools. Despite epidemiological relevance, the effects of multiple exposures to pyrethroids on their efficacy against pyrethroid-resistant mosquitoes has received little interest. In the present study, we assessed the effects of a blood-meal successfully obtained upon a permethrin-treated net on the success at taking a second blood-meal in presence of permethrin in Anopheles gambiae, carrying pyrethroid resistance alleles. We also measured the impact of exposure to permethrin on life-history traits to address the delayed efficacy of ITNs. Our results showed that females that successfully blood-fed upon a permethrin-treated net were no longer inhibited by permethrin at the following exposure. Blood-meal inhibition due to permethrin was not affected by female size nor by exposure of mothers when testing the offspring, allowing to discard the effect of genetic or physiological selection. Besides, in our assays, exposure to permethrin did not affect mosquito fecundity, fertility nor survival. These results give insights to understand the long-term efficacy of ITNs, and allow to reevaluate the criteria used when choosing compounds for fighting malaria mosquitoes.

Efficacy of vector control tools against malaria-infected mosquitoes.

Within mosquito vector populations, infectious mosquitoes are the ones completing the transmission of pathogens to susceptible hosts and they are, consequently, of great epidemiological interest. Mosquito infection by malaria parasites has been shown to affect several traits of mosquito physiology and behavior, and could interplay with the efficacy of control tools. In this study, we evaluated, in pyrethroid resistant Anopheles gambiae, the effect of mosquito infection with the human malaria parasite Plasmodium falciparum on the efficacy of nets treated with either the insecticide deltamethrin or the repellent DEET, measuring (i) mosquito success to pass through the net, (ii) blood-feeding on a host and (iii) chemicals-induced mortality. Infection of mosquitoes at non-infectious stage did not affect their success to pass through the net, to blood-feed, nor chemicals-induced mortality. At infectious stage, depending on replicates, infected mosquitoes had higher mortality rates than uninfected mosquitoes, with stronger effect in presence of DEET. This data evidenced a cost of infection on mosquito survival at transmissible stages of infection, which could have significant consequences for both malaria epidemiology and vector control. This stresses the need for understanding the combined effects of insecticide resistance and infection on the efficacy on control tools.

DEET Efficacy Increases With Age in the Vector Mosquitoes Anopheles gambiae s.s. and Aedes albopictus (Diptera: Culicidae).

Old mosquitoes are the most likely to transmit pathogens due to the higher probability that they will be exposed to pathogens, and the time required before a mosquito becomes infectious, the extrinsic incubation period (EIP). However, old mosquitoes are rarely considered in the evaluation of control tools. This study evaluated the effect of mosquito aging on the repellent efficacy of N,N-diethyl-3-methylbenzamide (DEET) in two vector mosquitoes, Anopheles gambiae s.s. (Giles) (Diptera: Culicidae) and Aedes albopictus (Skuse) (Diptera: Culicidae), respective vectors of malaria parasites and arboviruses such as dengue, chikungunya, and Zika viruses. For both mosquito species, DEET-induced inhibition of blood-feeding was assessed in three age classes. Life-history traits related to mosquito fecundity and survival following DEET exposure were also measured. Results showed that, in both species, bloodmeal inhibition induced by DEET was significantly higher in old females (>18 d old) than in younger ones (<13 d old). Life history traits recording showed no combined effects of DEET and aging on mosquito blood engorgement, oviposition rate, number of eggs laid nor survival; however, age effects are reported for all these traits. These results highlight the need for taking into account mosquito age in the evaluation of integrated mosquito management tools. They also suggest that the control of vector-borne pathogens with a long EIP could be improved by targeting old mosquitoes and supports the efficacy of repellents in the fight against mosquito-borne diseases.

Effect of DEET-multiple exposures on behavior and life history traits in the malaria mosquito Anopheles gambiae (s.s.).

BACKGROUND: Vector-borne diseases are major public health concerns, and their control is threatened by the spread of insecticide resistance in vector populations. In this context, the use of repellents is an alternative approach to limit vector-host interactions. However, prior exposure to repellents is suspected to affect mosquito behavior at the subsequent exposure, possibly reducing the efficacy of the compound. Despite this, the effect of mosquito experience on repellent efficacy remains poorly documented. In the present study, we tested whether a first blood meal successfully obtained upon a DEET-treated net would affect the success at taking a second blood meal in spite of DEET in the malaria mosquito Anopheles gambiae (s.s.). The impact of DEET on mosquito life history traits after the first and the second exposure was also measured, in order to assess the long-term consequences of multiple exposures to DEET in vector insects. RESULTS: A first blood meal obtained upon a DEET-treated net did not influence the success of An. gambiae females to take a second blood meal in spite of DEET. However, data showed that a prior exposure to DEET negatively affected all life history traits tested in this study related to fecundity and fertility. DEET pre-exposed females displayed a reduction in blood engorgement at the second exposure, as well as a reduction in the number of eggs laid and in the proportion of offspring that reach adult stage. Also, an increase of mosquito activity was observed during the second blood meal in DEET-pre-exposed females. Taken together, these data suggest an overall impact of DEET exposure on mosquito fitness. CONCLUSIONS: Our results did not evidence any effect of a prior exposure to DEET on its efficacy during the second exposure. However, data show a negative impact of DEET exposure on mosquito fitness. These results give insights to understand the long-term efficacy of the most used mosquito repellent, and highlight that DEET induces deleterious effects on mosquito fitness in addition to repellency, potentially increasing its efficacy for controlling vector-borne diseases.

Influence of pyrethroïd-treated bed net on host seeking behavior of Anopheles gambiae s.s. carrying the kdr allele.

The use of long lasting insecticide nets (LLINs) treated with pyrethroïd is known for its major contribution in malaria control. However, LLINs are suspected to induce behavioral changes in malaria vectors, which may in turn drastically affect their efficacy against Plasmodium sp. transmission. In sub Saharan Africa, where malaria imposes the heaviest burden, the main malaria vectors are widely resistant to pyrethroïds, the insecticide family used on LLINs, which also threatens LLIN efficiency. There is therefore a crucial need for deciphering how insecticide-impregnated materials might affect the host-seeking behavior of malaria vectors in regards to insecticide resistance. In this study, we explored the impact of permethrin-impregnated net on the host attractiveness for Anopheles gambiae mosquitoes, either susceptible to insecticides, or carrying the insecticide resistance conferring allele kdr. Groups of female mosquitoes were released in a dual-choice olfactometer and their movements towards an attractive odor source (a rabbit) protected by insecticide-treated (ITN) or untreated nets (UTN) were monitored. Kdr homozygous mosquitoes, resistant to insecticides, were more attracted by a host behind an ITN than an UTN, while the presence of insecticide on the net did not affect the choice of susceptible mosquitoes. These results suggest that permethrin-impregnated net is detectable by malaria vectors and that the kdr mutation impacts their response to a LLIN protected host. We discuss the implication of these results for malaria vector control.

New methods for field collection of human skin volatiles and perspectives for their application in the chemical ecology of human-pathogen-vector interactions.

Odours emitted by human skin are of great interest to biologists in many fields, with practical applications in forensics, health diagnostic tools and the ecology of blood-sucking insect vectors of human disease. Convenient methods are required for sampling human skin volatiles under field conditions. We experimentally compared four modern methods for sampling skin odours: solvent extraction, headspace solid-phase micro-extraction (SPME), and two new techniques not previously used for the study of mammal volatiles, contact SPME and dynamic headspace with a chromatoprobe design. These methods were tested and compared both on European subjects under laboratory conditions and on young African subjects under field conditions. All four methods permitted effective trapping of skin odours, including the major known human skin volatile compounds. In both laboratory and field experiments, contact SPME, in which the time of collection was restricted to 3 min, provided results very similar to those obtained with classical headspace SPME, a method that requires 45 min of collection. Chromatoprobe sampling also proved to be very sensitive, rapid and convenient for the collection of human-produced volatiles in natural settings. Both contact SPME and chromatoprobe design may considerably facilitate the study of human skin volatiles under field conditions, opening new possibilities for examining the olfactory cues mediating the host-seeking behaviour of mosquito vectors implicated in the transmission of major diseases.

Human skin volatiles: a review.

Odors emitted by human skin are of great interest to biologists in many fields; applications range from forensic studies to diagnostic tools, the design of perfumes and deodorants, and the ecology of blood-sucking insect vectors of human disease. Numerous studies have investigated the chemical composition of skin odors, and various sampling methods have been used for this purpose. The literature shows that the chemical profile of skin volatiles varies greatly among studies, and the use of different sampling procedures is probably responsible for some of these variations. To our knowledge, this is the first review focused on human skin volatile compounds. We detail the different sampling techniques, each with its own set of advantages and disadvantages, which have been used for the collection of skin odors from different parts of the human body. We present the main skin volatile compounds found in these studies, with particular emphasis on the most frequently studied body regions, axillae, hands, and feet. We propose future directions for promising experimental studies on odors from human skin, particularly in relation to the chemical ecology of blood-sucking insects.