These moths smell with their wings and their noses

Amazing stuff! I wish I could smell with my finger tips. Just kidding!

"Like most insects, the wings of tobacco hawk moths (Manduca sexta) are covered in tiny hairs. These microscopic strands help insects taste and stay stable in flight. But the tobacco hawk moth’s wing hairs do something researchers haven’t documented in any other insect: they help the animal smell ..."

From the abstract:

"In addition to their primary olfactory organs, the antennae, insects can smell using other parts of their bodies.

In this study, we examined the olfactory capabilities of the wings of the tobacco hawkmoth, Manduca sexta (Lepidoptera: Sphingidae). Using scanning electron microscopy, we identified an average of 21–32 sensory bristles along the margins of each wing. In addition to raised sockets that indicate mechanosensory function, we observed a subapical pore and numerous wall pores.

These pores are signs of chemosensory function, suggesting that the wings can detect chemicals upon contact or in gaseous form.

Gene expression analysis revealed the presence of genes encoding chemosensory receptors, such as gustatory receptors (GRs) and ionotropic receptors (IRs), including IR76b, the co-receptor of amine-sensing IRs, and IR8a, the co-receptor of acid-sensing IRs.

Genes encoding several odorant receptors (ORs) were also expressed in the wings; however, expression of the gene encoding ORCo, the obligatory OR co-receptor, was not detected.

Electrophysiological recordings revealed that only the volatile amines pyrrolidine and piperidine elicited responses from the wings.

Protein modeling and molecular docking simulations identified members of the Lepidoptera-specific IR7d clade as encoding candidate receptors for these compounds. These are characteristic alkaloids found in solanaceous plants, which tobacco hawkmoths prefer for laying eggs.

Together, these findings demonstrate that the wings of M. sexta function as accessory olfactory organs that may influence oviposition choice."

These moths smell with their wings | Science | AAAS

Noses on the wing: the olfactory capacity of hawkmoth wings (open access)

Fig. 1 Sensilla on the wing margins of Manduca sexta.

Scientists Create First-Ever map of smell receptors in the nose

Amazing stuff!

"At a glance

• Scientists have created the first detailed map of smell receptors in the nose, catching up with similar achievements in sight, hearing, and touch.
• The map reveals that smell receptors are highly organized into tight bands based on type.
• The findings provide foundational knowledge needed to develop better therapies for loss of smell.

...

Yet from a scientific perspective, “olfaction is super-mysterious,” ... with basic biological understanding lagging behind that of vision, hearing, and touch. ...

Working in mice, ... team have now created the first detailed map of how the thousand-plus types of smell receptors in the nose are organized.

They discovered that unlike what scientists had long believed, the neurons expressing these receptors have a high degree of spatial organization: They form horizontal stripes based on receptor type from the top of the nose to the bottom. ..."

From the highlights and abstract:

"Highlights

• ∼1,100 olfactory receptors adopt stereotyped spatial distributions in the epithelium

• Epithelial space coherently regulates the graded expression of ∼250 genes

• Precursor spatial identities bias olfactory receptor choice

• Receptor positions in the nose are aligned with their axonal targets in the brain

Summary

Although topographical maps organize many peripheral sensory systems, mouse olfactory sensory neurons (OSNs) are thought to randomly choose which one of ∼1,100 possible olfactory receptors (ORs) to express, with spatial organization in the olfactory epithelium limited to a handful of broad anatomical “zones” that modestly restrict OR choice.

Here, we reveal that each OR is instead expressed at a unique mean dorsoventral position, thereby instantiating a stereotyped receptor map in the olfactory epithelium.

OSN dorsoventral identities are encoded by a coherent gene expression program, which includes key transcription factors and axon guidance molecules; use of this program reflects a dorsoventral gradient in retinoic acid signaling, translates each physical location into a spatially appropriate distribution of potential OR choices, and aligns receptor maps in the nose and brain.

Spatial order in the olfactory system, therefore, arises from a continuously varying transcriptional code that precisely organizes the many discrete channels responsible for smell."

Scientists Create First-Ever ‘Smell Map’ | Harvard Medical School "A detailed diagram of smell receptors in the nose fills in missing details of how olfaction works"

A spatial code governs olfactory receptor choice and aligns sensory maps in the nose and brain (open access)

Graphical abstract

Figure 2 Each OSN subtype occupies a unique region of the epithelium

Gut bacteria influence mice social behavior through smell

Amazing stuff! Why do humans use perfume and deodorants?

When one metabolite molecule regulates aggressiveness of individuals!

"In a new study, Northwestern University neurobiologists discovered that gut bacteria and the nose work together to shape social behavior in mice, including who fights and who backs down. Using a combination of genetic and behavioral experiments, the scientists found gut microbes produce a pungent odor that other animals can smell. When detected, these scents trigger aggression and shape social hierarchies. The discovery reveals a previously unknown way the microbiome influences social interactions. ...

"Over the past 20 years, there's been a growing realization that microbes in the gut have profound influences on behavior and physiology," ... "They produce bioactive chemicals that affect the function of many organ systems, including the immune system, and can even cross the blood-brain barrier to affect behavior. These chemicals can also affect social behaviors through the sense of smell. While species use microbiome-derived chemicals for social communication, our study is the first to uncover the underlying mechanism." ...

In the new study, ... team focused on trimethylamine (TMA), a molecule produced in the gut that smells like dead, rotten fish. When gut bacteria break down choline-rich foods, such as eggs and meat, they generate TMA as a byproduct. The body's liver then converts TMA into an odorless metabolite. But in adult male mice, testosterone suppresses the liver enzyme that typically neutralizes TMA, allowing it to accumulate in urine.

"It seemed like mice use TMA as a male-specific odor," ...

To better understand why adult male mice produce this odor, ... team imaged the olfactory bulb within the brain to see which neurons respond to TMA. They specifically focused on trace amine-associated receptors (TAARs), a small family of odor detectors that are especially sensitive to strong-smelling molecules. Among the 14 TAARs in mice, the team found that TAAR5 is the most sensitive receptor to TMA and plays a central role in detecting the odor. ...

From scent to social hierarchy

When mice detect this scent, it changes how they behave. Dominant animals initiate fights, while subordinate mice adopt defensive postures—patterns that quickly establish a social hierarchy. 

But when ... team disabled TAAR5 in mice, those distinctions blurred. Mice still interacted with one another, but their behavior became more evenly matched. Without this signal, it took longer for clear dominant-subordinate relationships to emerge. ..."

From the highlights and abstract:

"Highlights

• TAAR5 deletion alters aggression and social dominance in male mice

• The effect of TAAR5 on social behavior occurs via the main olfactory pathway

• Blocking production of the TAAR5 ligand TMA by gut microbes reduces aggression

• A microbiome-derived chemical cue shapes mammalian social behavior via olfaction

Summary

Many species use microbiome-derived metabolites as chemosensory cues, yet the chemicals involved and the sensory pathways that detect and process them remain poorly understood.

Trimethylamine (TMA) is a volatile metabolite that is produced by the gut microbiome and selectively accumulated in the urine of sexually mature male mice.

Here, we show that TMA regulates inter-male aggression and social dominance by activating trace amine-associated receptor 5 (TAAR5) in the main olfactory system.

In wild-type mice, early aggressive behavior during male-male encounters strongly predicts eventual social status: dominant males initiate more attacks, whereas subordinate males display more defensive behaviors.

Deletion of TAAR5 eliminated this asymmetry, with dominant and subordinate mice showing similar levels of aggressive and defensive behaviors.

Strikingly, restoring TAAR5 expression in olfactory sensory neurons (OSNs) rescued the behavioral asymmetry, indicating that this effect is mediated by the main olfactory system and arguing against contributions from proposed TAAR5 expression in the brain.

Finally, pharmacological suppression of microbial TMA production reduced inter-male aggression, and this effect was reversed by painting treated males with TMA, showing that microbiome-derived TMA is the key volatile ligand for TAAR5 in this context.

Taken together, our findings identify TMA as a critical olfactory cue that signals the presence of sexually mature males and facilitates social hierarchy formation. More broadly, our results demonstrate that a microbiome-derived metabolite can shape mammalian social interactions through the main olfactory system and uncover a previously unrecognized role for the TAAR family in regulating social behavior."

Gut bacteria may influence social behavior through smell

A microbiome-derived olfactory signal regulates inter-male aggression and social dominance in mice (open access)

Graphical abstract

Two Women can find friendship at first whiff. Really!

Wearing the same perfume/deodorant at the same place? It has the appeal of junk science.

They have used only heterosexual women for this study? In this day and age of LGBTQ mania? Just kidding!

Notice Cornell University also appears to use the ideological driven "person" instead of woman.

"... Yet two women meeting for the first time can judge within minutes whether they have potential to be friends – guided as much by smell as any other sense, according to new Cornell psychology research. ...

“... But scent, which people are registering at some level, though probably not consciously, forecasts whether you end up liking this person,” ...

In a study of heterosexual women, ... found that personal, idiosyncratic preferences based on a person’s [???] everyday scent, captured on a T-shirt, predicted how much women liked their interaction partner following four-minute chats across a table in a crowded room. These face-to-face conversations, in turn, influenced how participants later judged the T-shirt scent alone. ..."

From the abstract:

"Who we choose to befriend is highly personal, driven by idiosyncratic preferences about other individuals, including sensory cues. How does a person’s unique sensory evaluation of others’ body odor affect friendship formation? Female participants took part in a speed-friending event where they made judgments of friendship potential (FP) following a 4-minute live interaction. Prior to and following the speed-friending event, participants judged the FP of these women based solely on diplomatic odor (including daily perfume/hygiene products) presented on worn t-shirts. Participants also judged FP based on facial appearance (a 100-ms presentation of portrait photographs).

Judgments based solely on diplomatic odor predicted FP judgments following in-person interactions, beyond the predictive ability of photograph-based judgments.

Moreover, judgments based on the live interaction predicted changes in the second round of diplomatic odor judgments, suggesting that the quality of the live interaction modified olfactory perception.

Results were driven more strongly by idiosyncratic preferences than by global perceiver or target effects. Findings highlight the dynamic role of ecologically relevant social olfactory cues in informing friendship judgments, as well as the involvement of odor-based associative learning during the early stages of friendship formation."

Finding friendship at first whiff | Cornell Chronicle

The interactive role of odor associations in friendship preferences (open access)

Fig. 1 Schematic Representation of Study Procedures and Key Measures

Engineered commensal Nose bacteria can sneak drugs into the brain to reduce body weight/obesity by regulating the appetite

Amazing stuff! How about sniffing out obesity one sniff at a time! 😊

"Bacteria that colonize the nose have been engineered to ferry drugs to the brains of mice. Researchers examined bacteria in the nasal microbiome and identified the species Lactobacillus plantarum as both safe to use in treatment and able to bind to a molecule found on a nose membrane connected to the brain. They then engineered L. plantarum to produce and secrete three appetite-suppressing hormones. Obese mice that received a dose of the bacteria in their nose each day for eight weeks ate less and lost weight during the treatment period."

"... On 5 February, scientists reported in Cell that they have used nasal bacteria to deliver appetite-suppressing hormones to obese mice, which subsequently lost weight. Although the approach is still a long way from being used in humans, it is one of the latest examples of widespread efforts to harness bacteria to deliver drugs to where they are needed in the body more effectively. Another study, published today in Cell Systems, uses a different bacterial species to deliver a protective enzyme to skin cells. ..."

From the highlights and abstract:

"Highlights

• Intranasal Lactobacillus plantarum (Lp) targets the mouse olfactory epithelium (OE)

• Intranasal Lp releases payloads in the OE, facilitating transport to the brain

• Intranasal Lp-secreted appetite-regulating hormones reduce obesity in mice

• Lp-secreted Leptin shows sustained effects over pure Leptin when delivered intranasally

Summary

Intranasal administration through the olfactory epithelium (OE) presents a direct pathway for brain-targeted therapeutic delivery, although its feasibility is hampered by the anatomical and absorptive limitations of the OE.

In this study, we identified Lactobacillus plantarum WCFS1 (Lp), a commensal strain with a natural affinity for the OE and engineered it to function as a vector for cerebral drug delivery.

Upon intranasal administration, Lp released specific payload molecules within the OE, with subsequent transport and accumulation in the brain. The therapeutic efficacy of Lp was further validated by the recombinant production and secretion of appetite-regulating hormones. When administered intranasally in a murine model of obesity prevention, the engineered Lp significantly alleviated obesity-related symptoms. This was evidenced by decreased appetite, reduced body weight gain, and improved glucose metabolism and fat mass deposition. Our study demonstrates the capability of Lp as an intranasal delivery vehicle, emphasizing its potential for brain-targeted therapeutic applications."

Nature Briefing: Translational Research

Engineered nose bacteria sneak drugs into the brain "Microbes that reside peaceably in the nasal passageways and on the skin can be harnessed for taking drugs to target cells."

Engineered commensals for targeted nose-to-brain drug delivery (open access)

Graphical abstract

Rats use ultrasound to boost their fine sense of smell for dynamic social interactions

Amazing stuff!

"... For decades scientists have recorded rodents vocalizing at ultrasonic frequencies, which is believed to be a form of communication and might help them find mates. It might even be a kind of laugh, since they also do it when researchers tickle them, according to one of the most endearing studies of recent years.

In a new study, scientists ... have identified another potential, unexpected benefit of rodents’ ultrasound pulses. The animals could use these sounds to stir up particles in the air around them, which they can quickly inhale to boost their already strong sense of smell. ...

The researchers were first inspired to investigate the idea by previous studies into how rodents navigate their environment. It was found that the animals would usually sniff the air immediately after making each ultrasound vocalization (USV). ..."

"... Vibroacoustics, or artificially produced ultrasonic vibrations, cause airborne particles to cluster, leading Mercado to suggest that rodents are using USVs to create odor clusters enhancing the reception of pheromones (chemical signals), thus making it easier for the vocalizer to detect and identify friends, strangers, and competitors. ..."

From the highlights and abstract:

"Highlights

• Rodent vocalizations could contribute to a unique mode of active olfactory sensing.

• Ultrasonic vocalizations may affect how rodents smell by clustering inhaled odorants.

• Coordinating sniffing with sound production might enhance reception of pheromones.

Abstract

Chemosensation via olfaction is a critical process underlying social interactions in many different species. Past studies of olfaction in mammals often have focused on its mechanisms in isolation from other systems, limiting the generalizability of findings from olfactory research to perceptual processes in other modalities. Studies of chemical communication, in particular, have progressed independently of research on vocal behavior and acoustic communication. Those bioacousticians who have considered how sound production and reception might interact with olfaction often portray odors as cues to the kinds of vocalizations that might be functionally useful. In the olfaction literature, vocalizations are rarely mentioned. Here, we propose that ultrasonic vocalizations may affect what rodents smell by altering the deposition of inhaled particles and that rodents coordinate active sniffing with sound production specifically to enhance reception of pheromones. In this scenario, rodent vocalizations may contribute to a unique mode of active olfactory sensing, in addition to whatever roles they serve as social signals. Consideration of this hypothesis highlights the perceptual advantages that parallel coordination of multiple sensorimotor processes may provide to individuals exploring novel situations and environments, especially those involving dynamic social interactions."

Rats use ultrasound to boost their sense of smell, suggests new study

‘Use the force,’ Mickey: Study suggests that ‘Jedi’ rodents remotely move matter using sound to enhance their sense of smell (original news release) "It’s so far off the scale of what we know … it almost seems like magic,’ says University at Buffalo researcher Eduardo Mercado III"

Do rodents smell with sound? (no public access)

AI is giving computers a sense of smell

Recommendable! When will AI beat the nose of canines? Soon!

"... Research on machine olfaction faces a formidable challenge due to the complexity of the human sense of smell. Whereas human vision mainly relies on receptor cells in the retina – rods and three types of cones – smell is experienced through about 400 types of receptor cells in the nose. ...

However, things started to change in 2015 when researchers launched the DREAM Olfaction Prediction Challenge. The competition released data collected by Andreas Keller and Leslie Vosshall, biologists who study olfaction, and invited teams from around the world to submit their machine learning models. The models had to predict odor labels like “sweet,” “flower” or “fruit” for odor-causing compounds based on their molecular structure. ...

The top performing models were published in a paper in the journal Science in 2017. A classic machine learning technique called random forest, which combines the output of multiple decision tree flow charts, turned out to be the winner. ...

By 2019, the largest datasets had grown from less than 500 molecules in the DREAM challenge to about 5,000 molecules.
[October 2019] A Google Research team led by Alexander Wiltschko was finally able to bring the deep learning revolution to machine olfaction. Their model, based on a type of deep learning called graph neural networks, established state-of-the-art results in machine olfaction. Wiltschko is now the founder and CEO of Osmo, whose mission is “giving computers a sense of smell.”

Recently

[August 2023] , Wiltschko and his team used a graph neural network to create a “principal odor map,” where perceptually similar odors are placed closer to each other than dissimilar ones. This was not easy: Small changes in molecular structure can lead to large changes in olfactory perception. Conversely, two molecules with very different molecular structures can nonetheless smell almost the same. ..."

AI is cracking a hard problem – giving computers a sense of smell

Body odor samples from infants and post-pubertal children differ in their volatile profiles

Amazing and smelly stuff! Life never smelled so good! 😊

"... babies gave notes of flowers and soap ..." while teenager smell like goat, musk, and sandalwood.

From the abstract:

"Body odors change during development, and this change influences the interpersonal communication between parents and their children. The molecular basis for this chemical communication has not been elucidated yet. Here, we show by combining instrumental and sensory analyses that the qualitative odorant composition of body odor samples is similar in infants (0-3 years) and post-pubertal children (14-18 years). The post-pubertal samples are characterized by higher odor dilution factors for carboxylic acids and by the presence of 5α-androst-16-en-3-one and 5α-androst-16-en-3α-ol. In addition to the olfaction-guided approach, the compounds 6-methylhept-5-en-2-one (6MHO), geranyl acetone (GA) and squalene (SQ) were quantified. Both age groups have similar concentrations of 6MHO and GA, whereas post-pubertal children tend to have higher concentration of SQ. In conclusion, sexual maturation coincides with changes to body odor chemical composition. Whether those changes explain differences in parental olfactory perception needs to be determined in future studies with model odors."

Body odor samples from infants and post-pubertal children differ in their volatile profiles | Communications Chemistry (open access)

Credits: Global Health NOW: A ‘Tidal Wave’ of Cancer Diagnoses; Decisive Action Needed to Stop Cervical Cancer Deaths; and Why Do Teens Smell Like Goats?

Fig. 2: Study overview regarding preparation of sampling material, participants, and analysis. (this study comes only with two figures, go figure)

AI rivals the human nose when it comes to naming smells

You have to smell it to believe it! 😊 This is only the beginning. 

What will we find out about pecunia non olet (money does not stink)? Just kidding. Or do you smell a rat?

This Google research dates back to 2019. 

"... Today [9/6/2022 (yes exactly one year ago)] we introduce the “Principal Odor Map” (POM), which identifies the vector representation of each odorous molecule in the model’s embedding space as a single point in a high-dimensional space. The POM has the properties of a sensory map: first, pairs of perceptually similar odors correspond to two nearby points in the POM (by analogy, red is nearer to orange than to green on the color wheel). Second, the POM enables us to predict and discover new odors and the molecules that produce them. In a series of papers, we demonstrate that the map can be used to prospectively predict the odor properties of molecules, understand these properties in terms of fundamental biology, and tackle pressing global health problems. ..."

"... The results, reported today in Science, show that the program, a so-called graph neural network, is excellent at imitating human sniffers, at least when it comes to simple odors. It reliably predicted what the volunteers smelled, a feat sensory biologists have been working toward for decades. It also predicted the smells of 500,000 other molecules, with no need to make or sniff them. ...

The findings may also help establish olfactory research as a field on par with sight or vision. Smell, which in humans involves a smaller proportion of the brain and fewer types of receptor cells than in other mammals, was long considered “a primitive sense that wasn’t worth studying by neurobiologists,” ... It has also defied systematic study. Whereas what we see and hear reflects quantifiable properties such as wavelength and frequency, smell doesn’t neatly correspond with the shape of a molecule. Similarly structured molecules can smell different, whereas dissimilar molecules can produce the same odor. ..."

From the editor's summary and abstract:

"Editor's summary

For vision and hearing, there are well-developed maps that relate physical properties such as frequency and wavelength to perceptual properties such as pitch and color. The sense of olfaction does not yet have such a map. Using a graph neural network, Lee et al. developed a principal odor map (POM) that faithfully represents known perceptual hierarchies and distances. This map outperforms previously published models to the point that replacing a trained human’s responses with the model output would improve overall panel description. The POM coordinates were able to predict odor intensity and perceptual similarity, even though these perceptual features were not explicitly part of the model training. These results were used to build a variety of olfactory predictions that outperformed previous feature sets even without fine-tuning. Abstract

Mapping molecular structure to odor perception is a key challenge in olfaction. We used graph neural networks to generate a principal odor map (POM) that preserves perceptual relationships and enables odor quality prediction for previously uncharacterized odorants. The model was as reliable as a human in describing odor quality: On a prospective validation set of 400 out-of-sample odorants, the model-generated odor profile more closely matched the trained panel mean than did the median panelist. By applying simple, interpretable, theoretically rooted transformations, the POM outperformed chemoinformatic models on several other odor prediction tasks, indicating that the POM successfully encoded a generalized map of structure-odor relationships. This approach broadly enables odor prediction and paves the way toward digitizing odors."

AI rivals the human nose when it comes to naming smells | Science | AAAS

Digitizing Smell: Using Molecular Maps to Understand Odor

A principal odor map unifies diverse tasks in olfactory perception (no public access)

Left: An example of a color map (CIE 1931) in which coordinates can be directly translated into values for hue and saturation. Similar colors lie near each other, and specific wavelengths of light (and combinations thereof) can be identified with positions on the map. Right: Odors in the Principal Odor Map operate similarly. Individual molecules correspond to points (grey), and the locations of these points reflect predictions of their odor character.

Disease Scent Signatures Disclose What the Nose Knows

Recommendable!

I would also argue that the sense of smell has been underutilized in medical diagnosis for the past 130 years or so (e.g. 1895 discover of X rays). Other diagnostic techniques took over.

Despite the fact we have had very powerful chemical analysis techniques at our disposal to analyze air and so on for many decades, but they were not really applied to smell coming from breath or body odor etc.

I bet machine learning & AI will make a huge difference in the near future!

"... Scent is a powerful time portal, reviving long-forgotten memories in stark detail. The human brain begins to build a library of smells in infancy, which grows into adulthood. For people with hereditary hyperosmia—a rare, heightened ability to detect and discern scents—this smell repository can be vast and remarkably fine-tuned. Joy Milne, a retired nurse, patient advocate, researcher, and grandmother, discovered this superpower as a child.1 Milne’s grandmother—also a super sniffer—trained her to identify scent signatures, as her own mother had taught her. As a nurse, Milne acquired an extensive clinical scent library, recognizing patterns between disease symptoms and diagnoses. After her late husband’s Parkinson’s disease (PD) diagnosis, she realized that the musky smell he wore at the nape of his neck for over a decade was an early warning sign and that she could detect it in other PD patients. "

Disease Scent Signatures Disclose What the Nose Knows | The Scientist Magazine® Researchers redefine the lost art of smelling illness using one woman’s exquisitely sensitive nose.

Domestic cat noses function just like high-tech chemical analyzers

Are cat noses now competing with dog noses?

"... A computer simulation suggests that the nasal structures involved in their sense of smell work like parallel coiled gas chromatographs -- highly sensitive lab gear used for the analysis of the chemical makeup of substances.

Until now, the intricate mechanism by which mammalian noses detect odors has remained elusive. While previous studies hinted at the similarity between the nose and a gas chromatography device in terms of odor detection through inhaled air, the specific parallels were not clear.

According to the research team, the evolutionary change in cats' nasal structure, driven by their small heads, has resulted in a labyrinthine airway system that not only fits but also enables cats to adapt to diverse environments. ...
kthrough was achieved through micro-CT scans of a cat's skull, allowing for the identification of tissue types in the feline nasal cavities. ...
“The cat nose probably has a similar complexity level as the dog’s, and it’s more complex than a rodent’s ...

team observed two distinct zones of airflow. The first zone comprised respiratory air that underwent filtration and gradually dispersed over the palate before reaching the lungs. The second zone, however, traveled through a central passage and reached the olfactory region at the rear of the nasal cavity.

The simulation revealed another intriguing finding: the air directed towards the olfactory region is subsequently recirculated through parallel channels upon arrival."

From the abstract:

"The peripheral structures of mammalian sensory organs often serve to support their functionality, such as alignment of hair cells to the mechanical properties of the inner ear. Here, we examined the structure-function relationship for mammalian olfaction by creating an anatomically accurate computational nasal model for the domestic cat (Felis catus) based on high resolution microCT and sequential histological sections. Our results showed a distinct separation of respiratory and olfactory flow regimes, featuring a high-speed dorsal medial stream that increases odor delivery speed and efficiency to the ethmoid olfactory region without compromising the filtration and conditioning purpose of the nose. These results corroborated previous findings in other mammalian species, which implicates a common theme to deal with the physical size limitation of the head that confines the nasal airway from increasing in length infinitely as a straight tube. We thus hypothesized that these ethmoid olfactory channels function as parallel coiled chromatograph channels, and further showed that the theoretical plate number, a widely-used indicator of gas chromatograph efficiency, is more than 100 times higher in the cat nose than an “amphibian-like” straight channel fitting the similar skull space, at restful breathing state. The parallel feature also reduces airflow speed within each coil, which is critical to achieve the high plate number, while feeding collectively from the high-speed dorsal medial stream so that total odor sampling speed is not sacrificed. The occurrence of ethmoid turbinates is an important step in the evolution of mammalian species that correlates to their expansive olfactory function and brain development. Our findings reveal novel mechanisms on how such structure may facilitate better olfactory performance, furthering our understanding of the successful adaptation of mammalian species, including F. catus, a popular pet, to diverse environments."

Cat noses function just like high-tech chemical analyzers Researchers create 3D computer model of cats nose

Domestic cat nose functions as a highly efficient coiled parallel gas chromatograph (open access)

Fig 1.

CT scans showing nasal cavity cross sections of a) human, b) rat, and c) domestic cat. The dark spaces on the scans are the nasal airways. As odorous air is drawn into the nose, it flows through these labyrinthine structures.

Dogs can literally smell when you're stressed

As if dog owners did not know that already for many, many years!

Dogs can literally smell when you're stressed Dogs can not only read stress on your face [questionable!], but also smell it dripping through your pores.

Dogs can discriminate between human baseline and psychological stress condition odours (open access)

Fig 1. Timeline of the data collection process for the in-person protocol.

Scents and Sense-Abilities: Using locust Brainpower to Smell oral Cancer

Amazing stuff! I smell a rat (just kidding)! 😊 Cancer is history (soon)!

To use olfaction biosensors and exhaled volatile organic compounds (VOCs) to detect human diseases appears to be very promising!

This research is a bit dated! Mea culpa!

From bomb sniffing to cancer sniffing! From an ancient much feared plague to cutting edge medicine!

It is very fast too and might be able to distinguish oral cancer stages.

"... This dramatic body and lifestyle [of locust] makeover depends on their exquisite ability to detect and differentiate subtle odors. ...
Recently, [a] team tapped into the odor-sensing circuitry of the locust brain to detect the scent signatures of human oral cancers. ... previously used locusts for sniffing out bombs ...
“Cancer changes [cellular] metabolism and those changes are reflected in exhaled breath,” ... Known as volatile organic compounds (VOCs), these unique chemical signatures are promising biomarkers of disease—if scientists can detect them. ...
They performed brain surgery on a locust and inserted electrodes into the brain regions that process smell. ... team then collected gas samples from the cell cultures of three different types of human oral cancer cells and healthy human oral cells. They wafted the gas samples—each of which contained a distinct mixture of VOCs from the corresponding cells—over the locust’s antennae and recorded the brain’s electrical activity. ..."

From the abstract:

"There is overwhelming evidence that presence of cancer alters cellular metabolic processes, and these changes are manifested in emitted volatile organic compound (VOC) compositions of cancer cells. Here, we take a novel forward engineering approach by developing an insect olfactory neural circuit-based VOC sensor for cancer detection. We obtained oral cancer cell culture VOC-evoked extracellular neural responses from in vivo insect (locust) antennal lobe neurons. We employed biological neural computations of the antennal lobe circuitry for generating spatiotemporal neuronal response templates corresponding to each cell culture VOC mixture, and employed these neuronal templates to distinguish oral cancer cell lines (SAS, Ca9-22, and HSC-3) vs. a non-cancer cell line (HaCaT). Our results demonstrate that three different human oral cancers can be robustly distinguished from each other and from a non-cancer oral cell line. By using high-dimensional population neuronal response analysis and leave-one-trial-out methodology, our approach yielded high classification success for each cell line tested. Our analyses achieved 76–100% success in identifying cell lines by using the population neural response (n = 194) collected for the entire duration of the cell culture study. We also demonstrate this cancer detection technique can distinguish between different types of oral cancers and non-cancer at different time-matched points of growth. This brain-based cancer detection approach is fast as it can differentiate between VOC mixtures within 250 ms of stimulus onset. Our brain-based cancer detection system comprises a novel VOC sensing methodology that incorporates entire biological chemosensory arrays, biological signal transduction, and neuronal computations in a form of a forward-engineered technology for cancer VOC detection."

Scents and Sense-Abilities: Using Bug Brainpower to Smell Cancer | The Scientist Magazine® Scientists use locust brains as living biosensors to perform cancer cell breath tests.

Sniffing out cancer with locust brains (a primary news source, but from August 2022)

Harnessing insect olfactory neural circuits for detecting and discriminating human cancers (no public access) Michigan State research shows insects can differentiate between cancer cells and healthy cells, which could help detect the disease earlier

Harnessing insect olfactory neural circuits for noninvasive detection of human cancer (open access; this seems to be the preprint version of the journal article)

Fig. 1: Individual projection neurons respond differentially to the oral cancer vs. control VOCs.

Whiff of the future: Face mask lets users smell in virtual reality

Old fashion olfaction arrived in the 21st century! 😊

Now we need better treatments for those humans who lost their sense of smell! (just kidding) 😊

Whiff of the future: Face mask lets users smell in virtual reality Virtual reality just got more immersive with this face mask that lets you smell things in real time.

Study Uncovers Biological Mechanism Behind Loss of Smell in Parkinson’s Patients

Good news! Making progress one step at a time!

"About 75-90 percent of Parkinson’s patients report diminishing sense of smell, even prior to the onset of motor symptoms, and is now recognized a non-motor symptom of Parkinson’s disease.

Researchers ... determined the biological mechanisms behind this olfactory impairment by using an alpha-synuclein A30P mouse model used to mimic symptoms of Parkinson’s in mice.

Using buried food tests, the researchers found that the mice with later stage symptoms of Parkinson’s disease exhibited olfactory impairment. They found that those mice with olfactory deficits exhibited severe pathology in projection neurons of the olfactory pathway. They also found these mice showed reduced neurogenesis in the olfactory bulb. In contrast, studies have shown that healthy aging brains continue to form new neurons in the olfactory bulb throughout life. ..."

From the abstract:

"Parkinson's disease (PD) is characterized by multiple symptoms including olfactory dysfunction, whose underlying mechanisms remain unclear. Here, we explored pathologic changes in the olfactory pathway of transgenic (Tg) mice of both sexes expressing the human A30P mutant α-synuclein (α-syn; α-syn-Tg mice) at 6–7 and 12–14 months of age, representing early and late-stages of motor progression, respectively. α-Syn-Tg mice at late stages exhibited olfactory behavioral deficits, which correlated with severe α-syn pathology in projection neurons (PNs) of the olfactory pathway. In parallel, olfactory bulb (OB) neurogenesis in α-syn-Tg mice was reduced in the OB granule cells at six to seven months and OB periglomerular cells at 12–14 months, respectively, both of which could contribute to olfactory dysfunction. Proteomic analyses showed a disruption in endocytic and exocytic pathways in the OB during the early stages which appeared exacerbated at the synaptic terminals when the mice developed olfactory deficits at 12–14 months. Our data suggest that
(1) the α-syn-Tg mice recapitulate the olfactory functional deficits seen in PD;
(2) olfactory structures exhibit spatiotemporal disparities for vulnerability to α-syn pathology;
(3) α-syn pathology is restricted to projection neurons in the olfactory pathway;
(4) neurogenesis in adult α-syn-Tg mice is reduced in the OB; and
(5) synaptic endocytosis and exocytosis defects in the OB may further explain olfactory deficits.

SIGNIFICANCE STATEMENT Olfactory dysfunction is a characteristic symptom of Parkinson's disease (PD). Using the human A30P mutant α-synuclein (α-syn)-expressing mouse model, we demonstrated the appearance of olfactory deficits at late stages of the disease, which was accompanied by the accumulation of α-syn pathology in projection neurons (PNs) of the olfactory system. This dysfunction included a reduction in olfactory bulb (OB) neurogenesis as well as changes in synaptic vesicular transport affecting synaptic function, both of which are likely contributing to olfactory behavioral deficits."

Study Uncovers Biological Mechanism Behind Loss of Smell in Parkinson’s Patients < Neurosurgery

α-Synuclein Pathology and Reduced Neurogenesis in the Olfactory System Affect Olfaction in a Mouse Model of Parkinson's Disease (no public access)

Lessons Learned From a COVID-19 Dog Screening Pilot in California K-12 Schools. Really!

Why do we still need dogs for sniffing? It should be a high priority to replace dog noses at the end of the first quarter of the 21st century!!!

"... A team led by researchers from the California Department of Public Health, which also sponsors a statewide school-based COVID-19 antigen testing program, used two trained dogs in 50 visits to 27 schools from April 1 to May 25, 2022, a period dominated by the SARS-CoV-2 Omicron variant. The medical-alert dogs had undergone 2 months of COVID-19 scent training in a lab, where they achieved greater than 95% sensitivity and specificity. ..."

"... Scent-trained dogs are a strategy for rapid, noninvasive, low-cost, and environmentally responsible COVID-19 screening. We conducted a dog screening program to complement a school antigen testing program. ..."

Scent-trained dogs highly accurate in detecting COVID-19 in schools Scent-trained dogs detected COVID-19 infection with 83% sensitivity and 90% specificity in nearly 3,900 screenings at California K-12 schools in spring 2022

Lessons Learned From a COVID-19 Dog Screening Pilot in California K-12 Schools | Infectious Diseases | JAMA Pediatrics | JAMA Network

Credits: Johns Hopkins Bloomberg School of Public Health: Global Health NOW

Flies smell the motion of odors and use it to navigate

Amazing stuff! Chasing turbulent odors!

"... They found that the fly antennae worked in tandem to recognize the direction that odor packets were moving, allowing flies to adjust course based on signals from odor packets alone.  ...
This knowledge will not only aid agriculture (how bees find flowers) and public health (how mosquitoes find people), but also the development of robots that can sense dangers in the environment (where landmines are buried) ..."

From the abstract:

"Odour plumes in the wild are spatially complex and rapidly fluctuating structures carried by turbulent airflows. To successfully navigate plumes in search of food and mates, insects must extract and integrate multiple features of the odour signal, including odour identity, intensity and timing. Effective navigation requires balancing these multiple streams of olfactory information and integrating them with other sensory inputs, including mechanosensory and visual cues. Studies dating back a century have indicated that, of these many sensory inputs, the wind provides the main directional cue in turbulent plumes, leading to the longstanding model of insect odour navigation as odour-elicited upwind motion. Here we show that Drosophila melanogaster shape their navigational decisions using an additional directional cue—the direction of motion of odours—which they detect using temporal correlations in the odour signal between their two antennae. Using a high-resolution virtual-reality paradigm to deliver spatiotemporally complex fictive odours to freely walking flies, we demonstrate that such odour-direction sensing involves algorithms analogous to those in visual-direction sensing. Combining simulations, theory and experiments, we show that odour motion contains valuable directional information that is absent from the airflow alone, and that both Drosophila and virtual agents are aided by that information in navigating naturalistic plumes. The generality of our findings suggests that odour-direction sensing may exist throughout the animal kingdom and could improve olfactory robot navigation in uncertain environments."

Flies smell the motion of odors and use it to navigate, Yale study finds | YaleNews A team of Yale scientists, using genetically modified fly antennae to detect light, show flies can detect the motion of odor packets, independent of the wind.

Odor motion sensing enables complex plume navigation (preprint)

Odour motion sensing enhances navigation of complex plumes  (open access)

AI Model Links Smell Molecules With Metabolic Processes

Are we finally going to learn more about our sense of smell thanks to machine learning? Quite possible! I did not have time read it, but it piqued my interest!

AI Model Links Smell Molecules With Metabolic Processes | Quanta Magazine Efforts to build a better digital “nose” suggest that our perception of scents reflects both the structure of aromatic molecules and the metabolic processes that make them.

Metabolic activity organizes olfactory representations (open access)

Credits: Synced Global AI Weekly

With This Bionic Nose, COVID Survivors May Smell the Roses Again

And when will I get a dog nose?

"... the e-nose sensor transmits its signal to a small array of electrodes taken from a cochlear implant. ...
Anosmia, or the inability to smell, can be caused not only by head injuries but also by exposure to certain toxins and by a variety of medical problems—including tumors, Alzheimer’s, and viral diseases, such as COVID. The sense of smell also commonly atrophies with age; in a 2012 study in which more than 1,200 adults were given olfactory exams, 39 percent of participants age 80 and above had olfactory dysfunction. ..."

With This Bionic Nose, COVID Survivors May Smell the Roses Again - IEEE Spectrum A decades-long quest pairs an e-nose with a brain implant

A newfound nose-brain link helps explain why dogs are good sniffers

I want a dog nose too! 👃😄 Or how blind dogs can still see!

"... Their noses hold between 200 million and 1 billion odor molecule sensors, compared with the 5 million receptors estimated to dwell in a human nose. And dogs’ olfactory bulbs can be up to 30 times larger than people’s.  ...

But one tract was totally new. ... connected the olfactory bulb to the occipital lobe, the part of the dog brain that handles vision. “There have been lots of people who theorized that this connection existed, based on the behavior of trained dogs and detection dogs,” ... But this newfound connection between smell and sight suggests that the two are intricately linked. Perhaps this anatomical link could be why smell can often compensate when a dog’s sight goes  ... “Blind dogs can still play fetch.” ..."

From the abstract:

"The domestic dog’s olfactory sense is widely recognized as being highly sensitive with a diverse function, however, little is known about the structure of their olfactory system. This study examined a cohort of mixed sex mesaticephalic canines and used Diffusion MRI (DTI), to map connections from the olfactory bulb to other cortical regions of the brain. The results were validated using the Klingler dissection method. An extensive pathway composed of five white matter tracts connecting to the occipital lobe, cortical spinal tract, limbic system, piriform lobe and entorhinal pathway was identified. This is the first documentation of a direct connection between the olfactory bulb and occipital lobe in any species and is a step towards further understanding how the dog integrates olfactory stimuli in their cognitive function. ..."

A newfound nose-brain link helps explain why dogs are good sniffers | Science News Information highways connect smell and vision in a way that hadn’t been described before

Extensive Connections of the Canine Olfactory Pathway Revealed by Tractography and Dissection (no public access)