Monday, August 30, 2021

Promiscuous Pattern Recognition

Study reveals how smell receptors work
Aug 2021,

Big smell news - for the first time ever, using cryo-electron microscopy, we can see an olfactory receptor in action. And as expected, it doesn't work like any other receptor.

Odorant receptors are known for their 'promiscuous chemical sensitivity;' that's a scientific term, by the way. It means that any one receptor might be sensitive to hundreds of molecules, so it's been really hard  to figure out what makes any particular molecule match with a receptor.

They looked at the jumping bristletail (surprise - not the fruit fly) because it has only five types of receptors, and because one of those receptors (OR5) is really broad, responding to 60% of the smell molecules they presented to it (promiscuous).

So they look at this receptor in its default state, and then again as they expose it to smell molecules (either eugenol or DEET).

And? Its ion channel pore dilates. That's it. Both of the competing theories about how smells work were wrong. It turns out they work via nonspecific chemical interactions -- they are not recognizing a specific chemical characteristic, but something more general about the molecule itself.

And there you have it! Olfaction is still one of the strangest senses we have.

Don't forget to thank cryo-electron microscopy, and the hundreds of scientists who have been trying to figure this out over the past hundred years.

via Rockefeller University: del M√°rmol, J., Yedlin, M.A. & Ruta, V. The structural basis of odorant recognition in insect olfactory receptors. Nature (2021).

Tuesday, August 24, 2021

Amoore' Anosmias Get a Tune-Up

Back in the 1960's, a scientist named John Amoore tried to get a number on how much our sense of smell varies from person to person. In his study (limited mostly to Europeans), he found that half are anosmic to something. That was long before we sequenced the human genome. This study goes a bit further:

There's a gene for detecting that fishy smell, olfactory GWAS shows
Oct 2020,
9,000 people in Iceland showed that not only do they smell licorice and cinnamon differently, but there's a mutation that makes rotten fish smell a little less fishy. (The odors they used weren't limited to these three, there were also lemon, peppermint, and banana.)

One of the genes is called a "non-canonical olfactory receptor gene" or a trace amine receptor, TAAR 5 in this case. People with a particular variant of this gene were more likely to not smell anything when presented with the fish odor or to use descriptors for it that were neutral or positive and not seafood related, such as "potatoes," "caramel," and "rose."

"Carriers of the variant find the fish odor less intense, less unpleasant, and are less likely to name it accurately," Gisladottir said. 

"We discovered a common variant in a cluster of olfactory receptors which is associated with increased sensitivity to trans-anethole, found in black licorice products but also in spices and plants such as anise seed, star anise, and fennel," Gisladottir said. "Carriers of the variant find the licorice odor more intense, more pleasant, and can name it more accurately. Interestingly, the variant is much more common in East Asia than in Europe."

The cinnamon variant influenced the perception of trans-cinnamaldehyde, the major ingredient in both Chinese and Ceylon cinnamon. Carriers of the variant can name the cinnamon odor more accurately, they report. They also find it more intense.

via deCODE Genetics in Reykjavik, Iceland: Current Biology, Gisladottir et al.: "Sequence variants in TAAR5 and other loci affect human odor perception and naming. DOI: 10.1016/j.cub.2020.09.012

Post Script:
Here's another way to measure the difference in how we smell things -- we have a 30% variation from person to person:
378-dimensional individual olfactory receptor subtype genome:
Individual olfactory perception reveals meaningful nonolfactory genetic information.
Secundo L, Snitz K, Weissler K, Pinchover L, Shoenfeld Y, Loewenthal R, Agmon-Levin N, Frumin I, Bar-Zvi D, Shushan S, Sobel N. Proc Natl Acad Sci U S A. 2015 Jul 14; 112(28):8750-5.

Friday, August 20, 2021

On Handshakes and Animal Behavior

AKA Olfactory Sampling

Non-human primates Mark Zuckerberg and Pope Francis shaking hands and about to smell each other's chemosignals once they start covertly raising their hands near their face in about 20 seconds from now.

After you shake someone's hand, you smell your own hand. Sometimes the shaking hand, and sometimes the opposite, depending on the gender match. They call it "olfactory sampling," but we call it "smelling your fingers," and despite its being in poor taste while in public view, we do it almost neurotically, albeit covertly -- so covertly that even we don't notice ourselves doing it. 

I'm surprised this didn't resurface at the outset of the pandemic when we were all paying so much attention to how often we touch our face. In fact, the authors set us up thus:
Consistent with previous studies (Nicas and Best, 2008), we observed that humans often bring their hands to their noses. Of 153 subjects, 85 (55.55%) touched their nose with their hand at least once during baseline before the greet. Idle subjects had a hand (either right or left) at the vicinity of their nose for 22.14% of the time. (that's a lot of time!)
But this isn't just about how you can't keep your own hands off yourself:
Whereas facial self-touching has been considered a form of displacement stress response (Troisi, 2002), akin to rodent grooming, the novel framework we propose here for this behavior is that of olfactory sampling.
In this really carefully controlled study, they videotaped  hundreds of people after shaking hands with a greeter at the lab, and even outfitted the subjects tubes near their nose to monitor their sniffing behavior. The results were "unequivocal," and remind us that we are in fact animals, sniffing up a storm:
We found that humans often sniff their own hands*, and selectively increase this behavior after handshake. After handshakes within gender, subjects increased sniffing of their own right shaking hand by more than 100%. In contrast, after handshakes across gender, subjects increased sniffing of their own left non-shaking hand by more than 100%. Tainting participants with unnoticed odors significantly altered the effects, thus verifying their olfactory nature. Thus, handshaking may functionally serve active yet subliminal social chemosignaling, which likely plays a large role in ongoing human behavior.

*For example, by touching their nose when they were in the room on their own; ... Criterion for scoring was any application of a hand to the face, as long as touching was under the eyebrows and above the chin; n=271 down to 153.
And later on in the report, things get even more complicated:
The body odor of some of the experimenters was tainted by perfumes or gender-specific odors. Volunteers who shook hands with these tainted individuals behaved differently; when the experimenter was tainted with perfume the volunteers spent more time sniffing their own hands, but when the experimenter was tainted with a gender-specific odor they spent less time sniffing of their own hands. This shows that different smells influenced the hand sniffing behavior of the volunteers.
Now that you know, you might notice yourself doing it constantly. What would be really interesting now would be to somehow get some anosmics up in the mix, maybe congenitally, maybe some recent long covid anosmics, and see how these numbers change?

Frumin I, et al. [incl Noam Sobel] A social chemosignaling function for human handshaking. eLife. 2015 Mar 03;4.

Tuesday, August 17, 2021

Did Someone Say Cheese?

Those funky cheese smells allow microbes to 'talk' to and feed each other
Oct 2020,

The more you learn, the more complicated it gets. So we know that the funky cheese smell of isovaleric acid is produced by bacteria, and we know that (some) cheese has fungus growing on it. But now we're told that they're all talking to each other, using other odor molecules.

The "cheese microbiome." Cheese doesn't house only one bacteria species, and it doesn't make only one smell, although isovaleric acid is a pretty good representative. There's a whole cheese microbiome, made of bacteria, yeast and fungi. Each one of these organisms secretes goop that digests their food, in this case that's the cheese. Their goop is kind of like making the whole world your stomach, where your digestive juices aid your digesting al fresco. As their external digestion approach does its thing, the target nutrients get broken down, and a by-product of that breakdown are odorous volatile organic compounds. 

What these researchers have discovered is that fungi also release VOCs, but instead of being an important part of the smell of cheese, they communicate to bacteria. Some bacteria accelerate their growth in the presence of the right fungi-gas. Others get real shy and shut down. These fungus VOCs do real-time genetic modification on the bacteria, changing the way they metabolize nutrients. They also eat the VOCs themselves. They eat smells. We can't eat smells. 

Anyway, the cheese microbiome now contains a VOC-ome sub-component, and this study hints that one day we may be looking very carefully at these VOC-omes, especially in the bio-factories of the future. 

via Tufts University: Casey M. Cosetta et al, Fungal volatiles mediate cheese rind microbiome assembly, Environmental Microbiology (2020). DOI: 10.1111/1462-2920.15223

Thursday, August 12, 2021

Odeuropa's Olfactory Iconographies

€2.8M grant for research project on European olfactory heritage and sensory mining:

Odeuropa bundles expertise in sensory mining and olfactory heritage. We develop novel methods to collect information about smell from digital text and image collections. They will identify and trace olfactory information in text and image datasets using AI, and promote Europe’s tangible and intangible cultural heritage.

Here's one of their ongoing projects, seen in the picture above, an odor wheel based on art historical references to smells: The Odeuropa Art Historical Scent Wheel from the Mediamatic Aroma Lab.

The Odeuropa “Nose first art historical odour wheel” starting from scent families in the centre, connected to odorants in the second ring, and then to artworks and artefacts around that, ending with an outer ring with Iconclass codes. Iconclass is a multilingual online database that museums use to tag historical images and artworks. -link

This wheel is based on imagery like paintings that were then coded with words, allowing a machine-readable dataset of odors, which will become increasingly more popular as we apply this approach to larger and more recent datasets, such as the Wikimedia Commons, or the running corpus of Instagram's zero-liked images.
Speaking of datasets, there are many to choose, from dog breeds to aerial photographs to 3 million "Clickbait, spam, crowd-sourced headlines from 2010 to 2015," to "4,000 physical dimensions of abolone." Wikimedia commons has 7.5 million images.

Looking back at the odor wheel, there are some interesting associations here. But they do reflect the dataset. I'm having a hard time finding details on Iconoclass but it was developed by one person in the 1950's, and based I assume on Western Art. It's currently maintained by RKD Netherlands Institute for Art History.

Here's some examples -- "street scenes and horses;" not a common conjunction in today's world. "Unicorns and cinnamon," anyone? "Prostitutes and civet," less unexpected. The two "body odors" are armpit and vagina, fyi. 

The most interesting part of all this? The lead researcher Sofia Ehrich has "become familiar with detecting depictions of smell." She can smell words and pictures. 

And speaking of words and pictures: 
Ocularcentric - like a visual bias, like we as humans tend to have an ocularcentric view of the world, with our trichromatic vision and fancy visual cortices, etc. 

Mediamatic (in Amsterdam) is an art centre dedicated to new developments in the arts since 1983. We organize lectures, workshops and art projects, focusing on nature, biotechnology and art+science in a strong international network.

IconoClass dataset -  specialized library classification designed for art and iconography.

Lifting One's Hat

Layers of IconClass system

This is an example of the layers of the IconoClass system, pretty deep stuff. You can see how the image has words attached to it, making it a machine-readable cultural object. This is how we will teach robots of the future how to better understand us, and maybe we can even teach them how to smell.

Mario Klongmann x BigGAN - 2019

Mostly Unrelated Post Script:
An AI Artist’s Twitter Feed Is an Art Gallery
The images and videos Mario Klingemann posted under the hashtag #BigGAN can only be appreciated by treating his Twitter feed as a digital exhibition. (Images taken from the ImageNet dataset)
Feb 2019, Hyperallergenic

This AI Creates Art From Instagram Posts With Zero Likes
“Zero Likes” is trained to create glitchy visuals from forgotten social media images.
May 2017, Vice

Melbourne artist and coder Sam Hains created Zero Likes, an AI trained to respond only to those lost and lonely images that miss out on attention.

Tuesday, August 10, 2021

Headline Party

My first master's degree was in architecture, and I graduated the day the United States housing market collapsed. So my second master's was in public health, and I got my first job the day Planet Earth went into pandemic lockdown. Expertise in indoor air quality and occupant exposure during an airborne pandemic will make your life pretty busy. Hence, a list of smell-related headlines I've been collecting in the meantime:

Unparalleled inventory of the human gut ecosystem
Jul 2020,
The Unified Human Gastrointestinal Genome (UHGG) collection, comprising 204,938 nonredundant genomes from 4,644 gut prokaryotes. These genomes encode >170 million protein sequences, which we collated in the Unified Human Gastrointestinal Protein (UHGP) catalog. 

via the European Bioinformatics Institute: Alexandre Almeida et al. A unified catalog of 204,938 reference genomes from the human gut microbiome, Nature Biotechnology (2020). DOI: 10.1038/s41587-020-0603-3
Fresh sea spray turns 'sour' after being airborne
Jan 2021,
"The smallest particles become 100,000 times more acidic than the ocean within two minutes," said Angle, first author of the paper.

via University of California San Diego: Kyle J. Angle et al. Acidity across the interface from the ocean surface to sea spray aerosol, Proceedings of the National Academy of Sciences (2020). DOI: 10.1073/pnas.2018397118
Researchers create a highly sensitive biohybrid olfactory sensor
Jan 2021,
So we decided to combine existing biological sensors directly with artificial systems to create highly sensitive volatile organic compound (VOC) sensors. We call these biohybrid sensors."

Takeuchi and his team essentially grafted a set of olfactory receptors from an insect into a device that feeds certain odors to the receptors and also reads how the receptors respond to these odors. 

via the University of Tokyo: T. Yamada el al. Highly sensitive VOC detectors using insect olfactory receptors reconstituted into lipid bilayers. Science Advances (2021). DOI: 10.1126/sciadv.abd2013
Male butterflies mark their mates with repulsive smell during sex to 'turn off' other suitors
Jan 2021,

Butterfly genitals secrete an odor that covers female genitals, deterring other males from mating with them. Occimene - it's the anti-aphrodisiac (for moths).

via University of Cambridge: Darragh K, Orteu A, Black D, Byers KJRP, Szczerbowski D, Warren IA, et al. (2021) A novel terpene synthase controls differences in anti-aphrodisiac pheromone production between closely related Heliconius butterflies. PLoS Biol 19(1): e3001022. 

Cosmic mouthful - Tasters savor fine wine that orbited Earth
Mar 2021,
This comes via the Institute for Wine and Vine Research in Bordeaux, and of course the International Space Station.
Researchers develop new smell test for Parkinson's, Alzheimer's and COVID-19
May 2021,
A new smell test developed by Queen Mary University of London researchers has been found to be easy to use in patients with Parkinson's disease, and could also be helpful in diagnosing COVID-19 in the broader population.

via  Queen Mary, University of London: A. Said Ismail et al. A novel capsule-based smell test fabricated via coaxial dripping, Journal of The Royal Society Interface (2021). DOI: 10.1098/rsif.2021.0039
Scientists invent an artificial nose for continuous bacterial monitoring
Jun 2021,
via Americans for Ben-Gurion University: Nitzan Shauloff et al, Sniffing Bacteria with a Carbon-Dot Artificial Nose, Nano-Micro Letters (2021). DOI: 10.1007/s40820-021-00610-w

Thursday, August 5, 2021

Diabetes x Anosmia

Interesting theme here; anosmia, insulin and Covid:

It appears that long-Covid has more to do with the pancreas and insulin regulation than we thought, and this has implications for the health of our olfactory receptors.

Research from the Monell Center found that insulin may be able to treat smell loss:
1. Insulin plays a critical role in the maturation, after injury, of immature olfactory sensory neurons (OSNs). 

2. The research team induced diabetes type 1 in mice to reduce levels of circulating insulin reaching the OSNs. The reduced insulin interfered with the regeneration of OSNs, resulting in an impaired sense of smell. 

3. In addition, the team injured OSNs, which have a unique ability to regenerate in mammals. This approach allowed the investigators to ask whether OSNs required insulin to regenerate, which they found to be true. What’s more, they discovered that OSNs are highly susceptible to insulin deprivation-induced cell death eight to 13 days after an injury. This time window indicates that during a critical stage newly generated OSNs are dependent on insulin. They also found that insulin must be applied to regenerating OSNs at this critical time point in the neurons’ growth to be able to restore a mouse’s sense of smell.

4. Insulin promotes regeneration of regenerating OSNs in both type 1 diabetic and nondiabetic mice.

Monell Center Scientists Find that Insulin is Necessary for Repairing Olfactory Neurons: Findings Point to Possible Treatment for Smell Loss, May 2021
Post Script:
July 2021,
An increase in new-onset hyperglycemia and abnormal hormone levels lasting months after Covid infection in Italy; "This study is one of the first to show that COVID-19 has a direct effect on the pancreas," says Fiorina.

via Children's Hospital Boston: Laura Montefusco et al, Acute and long-term disruption of glycometabolic control after SARS-CoV-2 infection, Nature Metabolism (2021). DOI: 10.1038/s42255-021-00407-6

Sebastiano Bruno Solerte et al, Sitagliptin Treatment at the Time of Hospitalization Was Associated With Reduced Mortality in Patients With Type 2 Diabetes and COVID-19: A Multicenter, Case-Control, Retrospective, Observational Study, Diabetes Care (2020). DOI: 10.2337/dc20-1521

Tuesday, August 3, 2021

Nanon Nanoff

Please ignore the potential environmental disaster of embedding nanoparticles all over the planet, and instead focus on how we are reverse engineering the process of chemosensation.

Plants communicate with chemicals the way we use words. Many, almost all, of the chemicals that populate the aromatic repertoire of the fragrance industry are plant-derived. If they do not come from the plant itself, as an essential oil, then they are synthetically produced in chemical reactors, yet, the target product will have originated to imitate the molecule found in nature.

Now, we get one example of synthetic biology doing the work. Imagine the scaled-up version, the chemical factory is now a biological plant, like a factory, but modeled on an actual plant, like lemongrass, but then run through bacteria programmed to produce citronellol.

Granted the nanosized sensors described in this article below are not producing any molecules, only sensing them. But any synbio fragrance plant would need a good sensor network. 

Also, "nanobionic plants" 

Carbon nanotubes embedded in leaves detect chemical signals that are produced when a plant is damaged
Apr 2020,
These sensors can be embedded in plant leaves, where they report on hydrogen peroxide signaling waves.

Plants use hydrogen peroxide to communicate within their leaves, sending out a distress signal that stimulates leaf cells to produce compounds that will help them repair damage or fend off predators such as insects. The new sensors can use these hydrogen peroxide signals to distinguish between different types of stress, as well as between different species of plants.

"Plants have a very sophisticated form of internal communication, which we can now observe for the first time. That means that in real-time, we can see a living plant's response, communicating the specific type of stress that it's experiencing," says Michael Strano, the Carbon P. Dubbs Professor of Chemical Engineering at MIT.

via Massachusetts Institute of Technology: Tedrick Thomas Salim Lew et al. Real-time detection of wound-induced H2O2 signalling waves in plants with optical nanosensors, Nature Plants (2020). DOI: 10.1038/s41477-020-0632-4
Unrelated image credit: Krzysztof Marczak via Deviant Art

Post Script:
Center for Strategic and International Studies Headquarters, Washington DC
February 6, 2020