Researchers Make Mice Smell Odors that Aren’t Really There

On June 19, 2020 By A.P.In UncategorizedLeave a comment

by Ruth Williams

By activating a particular pattern of nerve endings in the brain’s olfactory bulb, researchers can make mice smell a non-existent odor, according to a paper published June 18 in Science. Manipulating these activity patterns reveals which aspects are important for odor recognition.

“This study is a beautiful example of the use of synthetic stimuli . . . to probe the workings of the brain in a way that is just not possible currently with natural stimuli,” neuroscientist Venkatesh Murthy of Harvard University who was not involved with the study writes in an email to The Scientist.

A fundamental goal of neuroscience is to understand how a stimulus—a sight, sound, taste, touch, or smell—is interpreted, or perceived, by the brain. While a large number of studies have shown the various ways in which such stimuli activate brain cells, very little is understood about what these activations actually contribute to perception.

In the case of smell, for example, it is well-known that odorous molecules traveling up the nose bind to receptors on cells that then transmit signals along their axons to bundles of nerve endings—glomeruli—in a brain area called the olfactory bulb. A single molecule can cause a whole array of different glomeruli to fire in quick succession, explains neurobiologist Kevin Franks of Duke University who also did not participate in the research. And because these activity patterns “have many different spatial and temporal features,” he says, “it is difficult to know which of those features is actually most relevant [for perception].”

To find out, neuroscientist Dmitry Rinberg of New York University and colleagues bypassed the nose entirely. “The clever part of their approach is to gain direct control of these neurons with light, rather than by sending odors up the animal’s nose,” Caltech neurobiologist Markus Meister, who was not involved in the work, writes in an email to The Scientist.

The team used mice genetically engineered to produce light-sensitive ion channels in their olfactory bulb cells. They then used precisely focused lasers to activate a specific pattern of glomeruli in the region of the bulb closest to the top of the animal’s head, through a surgically implanted window in the skull. The mice were trained to associate this activation pattern with a reward—water, delivered via a lick-tube. The same mice did not associate random activation patterns with the reward, suggesting they had learned to distinguish the reward-associated pattern, or synthetic smell, from others.

Although the activation patterns were not based on any particular odors, they were designed to be as life-like as possible. For example, the glomeruli were activated one after the other within the space of 300 milliseconds from the time at which the mouse sniffed—detected by a sensor. “But, I’ll be honest with you, I have no idea if it stinks [or] it is pleasant” for the mouse, Rinberg says.

Once the mice were thoroughly trained, the team made methodical alterations to the activity pattern—changing the order in which the glomeruli were activated, switching out individual activation sites for alternatives, and changing the timing of the activation relative to the sniff. They tried “hundreds of different combinations,” Rinberg says. He likened it to altering the notes in a tune. “If you change the notes, or the timing of the notes, does the song remain the same?” he asks. That is, would the mice still be able to recognize the induced scent?

From these experiments, a general picture emerged: alterations to the earliest-activated regions caused the most significant impairment to the animal’s ability to recognize the scent. “What they showed is that, even though an odor will [induce] a very complex pattern of activity, really it is just the earliest inputs, the first few glomeruli that are activated that are really important for perception,” says Franks.

Rinberg says he thinks these early glomeruli most likely represent the receptors to which an odorant binds most strongly.

With these insights into the importance of glomeruli firing times for scent recognition, “the obvious next question,” says Franks, is to go deeper into the brain to where the olfactory bulb neurons project and ask, “ How does the cortex make sense of this?”

E. Chong et al., “Manipulating synthetic optogenetic odors reveals the coding logic of olfactory perception,” Science, 368:eaba2357, 2020.

https://www.the-scientist.com/news-opinion/researchers-make-mice-smell-odors-that-arent-really-there-67643?utm_campaign=TS_DAILY%20NEWSLETTER_2020&utm_medium=email&_hsmi=89854591&_hsenc=p2ANqtz–BMhsu532UL56qwtB0yErPYlgoFTIZWsNouvTV9pnT1ikTw6CvyIPyun3rPGdciV29we7ugRVWYc1uuBDh5CN_F-0FzA&utm_content=89854591&utm_source=hs_email

AI can pick out specific odours from a combination of smells

On March 17, 2020 By A.P.In UncategorizedLeave a comment

A new AI can detect odours in a two-step process that mimics the way our noses smell

An AI can sniff out certain scents, giving us a glimpse of how our nose might work in detecting them.

Thomas Cleland at Cornell University, New York, and Nabil Imam at tech firm Intel created an AI based on the mammalian olfactory bulb (MOB), the area of the brain that is responsible for processing odours. The algorithm mimics a part of the MOB that distinguishes between different smells that are usually present as a mixture of compounds in the air.

This area of the MOB contains two key types of neuron: mitral cells, which are activated when an odour is present but don’t identify it, and granule cells that learn to become specialised and pick out chemicals in the smell. The algorithm mimics these processes, says Imam.

Cleland and Imam trained the AI to detect 10 different odours, including those of ammonia and carbon monoxide. They used data from previous work that recorded the activity of chemical sensors in a wind tunnel in response to these smells.

When fed that data, the AI learns to detect that a smell is present based on the sensors’ responses to the chemicals, and then goes on to identify it on the basis of the patterns in that data. As it does so, the AI has a spike of activity analogous to the spikes of electrical activity in the human brain, says Imam.

The AI refined its learning over five cycles of exposure, eventually showing activity spikes specific to each odour. The researchers then tested the AI’s ability to sniff out smells among others that it hadn’t been trained to detect. They considered an odour successfully identified when the AI’s fifth spike pattern matched or was similar to the pattern produced by the sensors.

The AI got it almost 100 per cent correct for eight of the smells and about 90 per cent correct for the remaining two. To test how it might identify odorous contaminants in the environment, the researchers blocked 80 per cent of the smell signal to mimic more realistic scenarios. In these tests, the AI’s accuracy dipped to less than 30 per cent.

“I think the link [to the MOB] is quite strong – this algorithm might be an explanation to how it works in the human nose, to some abstraction,” says Thomas Nowotny at the University of Sussex, UK. But the AI’s ability to solve real life problems, such as detecting bombs by picking out hazardous smells associated with them, is still some way off, he says.

How conservation dogs help track endangered species

On November 2, 2019 By A.P.In UncategorizedLeave a comment

By Ashley Strickland

Dogs and their sensitive noses are known for finding people during search and rescue efforts, sniffing out drugs and even diseases like cancer. But the powerful canine nose can also act like radar for other things that are hidden from our sight.

Now, they’re acting like watchdogs for endangered species and assisting with conservation efforts.
Organizations like Working Dogs for Conservation train dogs to identify the scents of endangered animals and their droppings, which helps scientists track species that may be declining.

Tracking animal scat, or fecal matter, can reveal where endangered species live, how many of them are living in an area and what might be threatening them. And it’s a less stressful way of monitoring species than trapping and releasing them.

Previously, conversation dogs have successfully tracked the San Joaquin kit fox, gray wolves, cougars, bobcats, moose, river otters, American minks, black-footed ferrets and even the North Atlantic right whale, according to a new study published Wednesday in the Journal of Wildlife Management.

In the new study, scientists trained conservation dogs to focus on a new kind of animal: reptiles. They wanted to track the elusive and endangered blunt-nosed leopard lizard in the San Joaquin Valley. The experienced conservation dogs, including one female German shepherd and two male border collies, were trained to detect the scent of the lizard’s scat.

Then, the scientists could retrieve the samples and determine the gender, population genetics, diet, hormones, parasites, habitat use and health of the lizards. Humans have a difficult time identifying such small samples by sight because they are hard to distinguish from the environment. They can also be very similar to other scat.

The blunt-nosed leopard lizard is a fully protected species in California. It’s endangered because its habitat has been destroyed. Surveying the species and their habitat can help scientists to understand if existing conservation efforts are helping.

Over four years, scientists took the dogs out to the desert to detect and collect samples. The dogs would signal their discovery by laying down next to the scat. Then, they would be rewarded by a toy or play session.

Working between one and two hours a day, the dogs went out with survey teams from the end of April to mid May, when the lizards would emerge from brumation, otherwise known as reptile hibernation, according to the study. The dogs were trained not to approach the lizards if they saw them.

Over four years, they collected 327 samples and 82% of them were confirmed as belonging to blunt-nosed leopard lizards.

The researchers believe this method of tracking has potential and now they want to refine the method to see if it will work on a larger scale.

“So many reptilian species have been hit so hard,” said Mark Statham, lead study author and associate researcher with the Mammalian Ecology and Conservation Unit of the UC Davis School of Veterinary Medicine. “A large proportion of them are endangered or threatened. This is a really valuable way for people to be able to survey them.”

https://www.cnn.com/2019/10/30/world/conservation-dogs-endangered-lizard-scn/index.html?utm_source=The+Good+Stuff&utm_campaign=91b09c3d68-EMAIL_CAMPAIGN_2019_10_30_05_15&utm_medium=email&utm_term=0_4cbecb3309-91b09c3d68-103653961

Stem Cells Sprayed into the Nose Restore Mice’s Ability to Smell

On May 31, 2019 By A.P.In UncategorizedLeave a comment

by KERRY GRENS

In mice whose sense of smell has been disabled, a squirt of stem cells into the nose can restore olfaction, researchers report today (May 30) in Stem Cell Reports. The introduced “globose basal cells,” which are precursors to smell-sensing neurons, engrafted in the nose, matured into nerve cells, and sent axons to the mice’s olfactory bulbs in the brain.

“We were a bit surprised to find that cells could engraft fairly robustly with a simple nose drop delivery,” senior author Bradley Goldstein of the University of Miami Miller School of Medicine says in a press release. “To be potentially useful in humans, the main hurdle would be to identify a source of cells capable of engrafting, differentiating into olfactory neurons, and properly connecting to the olfactory bulbs of the brain. Further, one would need to define what clinical situations might be appropriate, rather than the animal model of acute olfactory injury.”

Goldstein and others have independently tried stem cell therapies to restore olfaction in animals previously, but he and his coauthors note in their study that it’s been difficult to determine whether the regained function came from the transplant or from endogenous repair stimulated by the experimental injury to induce a loss of olfaction. So his team developed a mouse whose resident globose basal cells only made nonfunctional neurons, and any restoration of smell would be attributed to the introduced cells.
The team developed the stem cell transplant by engineering mice that produce easily traceable green fluorescent cells. The researchers then harvested glowing green globose basal cells (as identified by the presence of a receptor called c-kit) and delivered them into the noses of the genetically engineered, smell-impaired mice. Four weeks later, the team observed the green cells in the nasal epithelium, with axons working their way into the olfactory bulb.

Behaviorally, the mice appeared to have a functioning sense of smell after the stem cell treatment. Unlike untreated animals, they avoided an area of an enclosure that had a bad smell to normal mice.

To move this technology into humans suffering from a loss of olfaction, more experiments in animals are necessary, says James Schwob, an olfactory researcher at Tufts University who has collaborated with Goldstein but was not involved in the latest study, in an interview with Gizmodo. “The challenge is going to be trying to [engraft analogous cells] in humans in a way . . . that [would] not make things worse.”

https://www.the-scientist.com/news-opinion/stem-cells-delivered-to-the-nose-restore-mices-ability-to-smell-65953

Can a smell test be used to diagnose early autism?

On July 7, 2015 By A.P.In autismLeave a comment

An image depicting the measurement of nasal airflow while a child is presented with pleasant and unpleasant odors. Throughout the 10-minute study the children were seated comfortably in front of a computer monitor while viewing a cartoon. The nasal airflow measurement and the presentation of odorants were done using a modified pediatric nasal cannula and a custom built olfactometer.

Imagine the way you might smell a rose. You’d take a nice big sniff to breathe in the sweet but subtle floral scent. Upon walking into a public restroom, you’d likely do just the opposite–abruptly limiting the flow of air through your nose. Now, researchers reporting in the Cell Press journal Current Biology on July 2 have found that people with autism spectrum disorder (ASD) don’t make this natural adjustment like other people do. Autistic children go right on sniffing in the same way, no matter how pleasant or awful the scent.

The findings suggest that non-verbal tests related to smell might serve as useful early indicators of ASD, the researchers say.

“The difference in sniffing pattern between the typically developing children and children with autism was simply overwhelming,” says Noam Sobel of the Weizmann Institute of Science in Israel.

Earlier evidence had indicated that people with autism have impairments in “internal action models,” the brain templates we rely on to seamlessly coordinate our senses and actions. It wasn’t clear if this impairment would show up in a test of the sniff response, however.

To find out, Sobel, along with Liron Rozenkrantz and their colleagues, presented 18 children with ASD and 18 normally developing children (17 boys and 1 girl in each group) with pleasant and unpleasant odors and measured their sniff responses. The average age of children in the study was 7. While typical children adjusted their sniffing within 305 milliseconds of smelling an odor, the researchers report, children on the autism spectrum showed no such response.

That difference in sniff response between the two groups of kids was enough to correctly classify them as children with or without a diagnosis of ASD 81% of the time. Moreover, the researchers report that increasingly aberrant sniffing was associated with increasingly severe autism symptoms, based on social but not motor impairments.

The findings suggest that a sniff test could be quite useful in the clinic, although the researchers emphasize that their test is in no way ready for that yet.

“We can identify autism and its severity with meaningful accuracy within less than 10 minutes using a test that is completely non-verbal and entails no task to follow,” Sobel says. “This raises the hope that these findings could form the base for development of a diagnostic tool that can be applied very early on, such as in toddlers only a few months old. Such early diagnosis would allow for more effective intervention.”

The researchers now plan to test whether the sniff-response pattern they’ve observed is specific to autism or whether it might show up also in people with other neurodevelopmental conditions. They also want to find out how early in life such a test might be used. But the most immediate question for Sobel is “whether an olfactory impairment is at the heart of the social impairment in autism.”

Current Biology, Rozenkrantz et al.: “A Mechanistic Link between Olfaction and Autism Spectrum Disorder” http://dx.doi.org/10.1016/j.cub.2015.05.048

6 Tools to Help Predict Your Life Expectancy

On April 5, 2015April 5, 2015 By A.P.In ageing, aging, death1 Comment

There’s always the Magic 8 Ball, but when it comes to determining life expectancy, some people want a little more scientific help. Thankfully, there are some useful tests and calculators to help us figure out how many more years we have left — at least until the Fountain of Youth is available in pill form. With that in mind, here are six ways to help predict whether you should keep on working and paying the mortgage or just blow it all on a big beach vacation.

Treadmill test
Want to know if you’ll survive the decade? Hop on a treadmill. Johns Hopkins researchers analyzed more than 58,000 stress tests and concluded that the results of a treadmill test can predict survival over the next 10 years. They came up with a formula, called the FIT Treadmill Score, which helps use fitness to predict mortality.

“The notion that being in good physical shape portends lower death risk is by no means new, but we wanted to quantify that risk precisely by age, gender and fitness level, and do so with an elegantly simple equation that requires no additional fancy testing beyond the standard stress test,” says lead investigator Haitham Ahmed, M.D. M.P.H., a cardiology fellow at the Johns Hopkins University School of Medicine.

In addition to age and gender, the formula factors in your ability to tolerate physical exertion — measured in “metabolic equivalents” or METs. Slow walking equals two METs, while running equals eight.

Researchers used the most common treadmill test, called the Bruce Protocol. The test utilizes three-minute segments, starting at 1.7 mph and a 10 percent grade, which slowly increase in speed and grade.

Researchers analyzed information on the thousands of people ages 18 to 96 who took the treadmill test. They tracked down how many of them died for whatever reason over the next decade. They found that fitness level, as measured by METs and peak heart rate reached during exercise, were the best predictors of death and survival, even after accounting for important variables such as diabetes and family history of premature death.

Sitting test
You don’t need special equipment for this adult version of crisscross applesauce that uses flexibility, balance and strength to measure life expectancy. Brazilian physician Claudio Gil Araujo created the test when he noticed many of his older patients had trouble picking things up off the floor or getting out of a chair.

To try, start by standing upright in the middle of a room. Without using your arms or hands for balance, carefully squat into a cross-legged sitting position. Once you’re settled, stand up from the sitting position — again, without using your arms for help.

You can earn up to 10 points for this maneuver. You get five points for sitting, five for standing, and you subtract a point each time you use an arm or knee for leverage or 1/2 point any time you lose your balance or the movement gets clumsy.

The test seems fairly simple, but Araujo found that it was an accurate predictor of life expectancy. He tested it on more than 2,000 of his patients age 51 to 80, and found that those who scored fewer than eight points were twice as likely to die within the next six years. Those who scored three points or even lower were five times more likely to die within the same time frame.

Araujo didn’t have anyone under 50 try the test, so the results won’t mean the same if you’re younger. As MNN’s Bryan Nelson writes, “If you’re younger than 50 and have trouble with the test, it ought to be a wake-up call. The good news is that the younger you are, the more time you have to get into better shape.”

Test your telomeres

A simple test may help determine your “biological age” by measuring the length of your telomeres. Telomeres are protective sections of DNA located at the end of your chromosomes. They’re sometimes compared to the plastic tips of shoelaces that keep the laces from fraying.

Each time a cell replicates, the telomeres become shorter. Some researchers believe that lifespan can be roughly predicted based upon how long your telomeres are. Shorter telomeres hint at a shorter lifespan for cells. Longer telomeres may mean you have more cell replications left.

Originally offered a few years ago only as an expensive — and relatively controversial — blood test in Britain, telomere testing in now available all over the world, and some companies even test using saliva. The results tell you where your telomere lengths fall in relation to other participants your age.

The link between genetics and longevity has been so embraced that testing companies have since been founded by respected scientists and researchers including Nobel laureate Elizabeth Blackburn of UC San Francisco and George Church, director of Harvard University’s Molecular Technology Group.

The increase in the number of at-home tests is getting the attention of concerned federal regulators and other researchers who question whether the science should stay in the lab.

“It is worth doing. It does tell us something. It is the best measure we have” of cellular aging, aging-researcher and Genescient CEO Bryant Villeponteau told the San Jose Mercury News. But testing still belongs in a research setting, he said, not used as a personal diagnostic tool.

As more people take them, he said, “I think the tests will get better, with more potential to learn something.”

Grip strength

Do you have an iron handshake or a limp fish grasp? Your grip strength can be an indicator of your longevity.

Recent research has shown a link between grip strength and your biological age. Hand-grip strength typically decreases as you age, although many studies have shown links between stronger grip strength and increased mortality.

You can keep your grip strong by doing regular hand exercises such as slowly squeezing and holding a tennis or foam ball, then repeating several more times.

Take a sniff

Does every little smell bug you? People who wear too much perfume? Grilled fish in the kitchen? A sensitive sense of smell is good news for your lifespan.

In a study last fall, University of Chicago researchers asked more than 3,000 people to identify five different scents. The found that 39 percent of the study subjects who failed the smelling test died within five years, compared to 19 percent of those with moderate smell loss and just 10 percent of those with a healthy sense of smell.

“We think loss of the sense of smell is like the canary in the coal mine,” said the study’s lead author Jayant M. Pinto, M.D., an associate professor of surgery at the University of Chicago who specializes in the genetics and treatment of olfactory and sinus disease. “It doesn’t directly cause death, but it’s a harbinger, an early warning that something has gone badly wrong, that damage has been done. Our findings could provide a useful clinical test, a quick and inexpensive way to identify patients most at risk.”

Life expectancy calculator

There are many online calculators that can serve up you estimated last birthday — thanks to some fancy algorithms. Some only take into account a few simple factors such as your age, height and weight. The better ones consider a range of variables including family health history, diet and exercise practices, marital and education status, smoking, drinking and sex habits, and even where you live.

Enter as much data as you can into an online form, like this one from researchers at the University of Pennsylvania, and click to get your results: http://gosset.wharton.upenn.edu/mortality/perl/CalcForm.html

Man experiencing headaches, seizures, memory flashbacks and strange smells discovered to have had tapeworm living in his brain for 4 years

On January 2, 2015 By A.P.In MedicineLeave a comment

Parasitic worm normally found in amphibians and crustaceans in China may have scavenged nutrients from patient’s brain

A man who went to see his doctor after suffering headaches and experiencing strange smells was found to have been living for more than four years with a rare parasitic worm in his brain.

In the first case of its kind in Britain, the ribbon-shaped tapeworm was found to have burrowed from one side of the 50-year-old man’s brain to the other.

Doctors were left baffled after spotting strange ring-like patterns moving 5cm through his brain tissue in a series of scans taken over four years.

Surgeons only discovered the 1cm worm while carrying out a biopsy at Addenbrooke’s hospital in Cambridge and took it to parasite experts to be identified.

Geneticists at the Wellcome Trust Sanger Institute in Cambridge found the creature was a rare species of tapeworm known as Spirometra erinaceieuropaei.

Only 300 cases of infection by this parasite in humans have been reported since 1953, with only two previous cases identified in Europe.

The worm is normally found in amphibians and crustaceans in China and as it goes through its life cycle it later infects the guts of cats and dogs, where it can grow into 1.5-metre adult worms. Even in China, where the parasite is normally found, there have only been 1,000 cases reported in humans since 1882.

The unfortunate patient, who was of Chinese descent but lived in East Anglia, is thought to have picked up the parasite while on a visit to China, where he visited regularly. However, exactly how he came to be infected is not known, but he could have picked it up from infected meat or water and the worm then burrowed through his body to his brain.

Now scientists believe they have been able to learn new information about this rare parasite after studying its DNA.

Rather than living on the brain tissue of its unknowing victim, the parasite is thought to have simply absorbed nutrients from the man’s brain through its body as the worm has no mouth.

Dr Hayley Bennett said they hoped to use the result of the study to help diagnose infections in humans more quickly in the future and even find ways of treating it.

She said: “This worm is quite mysterious and we don’t know everything about what species it can infect or how. Humans are a rare and accidental host. for this particular worm. It remains as a larva throughout the infection. We know from the genome that the worm has fatty acid binding proteins that might help it scavenge fatty acids and energy from its environment, which may be one the mechanisms for how it gets its food.

“This genome will act as a reference, so that when new treatments are developed for the more common tapeworms, scientists can cross-check whether they are also likely to be effective against this very rare infection.” The research is published in the journal Genome Biology.

The patient first noticed something was wrong in 2008 when he began suffering headaches, seizures, memory flashbacks and strange smells.

After visiting his doctor, an MRI scan revealed a cluster of rings in the right medial temporal lobe.

He was given tests for a wide range of other diseases including syphilis, HIV and tuberculosis but tested negative for them all. Later scans showed the rings moving through his brain.

After undergoing two biopsies, surgeons found the worm moving around in his brain and removed it in 2012. The man was then given drugs to help treat the infection but he continues to suffer from problems associated with having had the worm living in his brain.

It is not known how he first became infected, but one source of infection is the use of frog poultice, a traditional Chinese remedy where raw frog meat is used to calm sore eyes.

“We did not expect to see an infection of this kind in the UK, but global travel means that unfamiliar parasites do sometimes appear,” said Dr Effrossyni Gkrania-Klotsas, one of the clinicians involved in the man’s treatment at Addenbrooke’s NHS Trust.

“We can now diagnose sparganosis using MRI scans, but this does not give us the information we need to identify the exact tapeworm species and its vulnerabilities.

“Our work shows that, even with only tiny amounts of DNA from clinical samples, we can find out all we need to identify and characterise the parasite.”

http://www.theguardian.com/science/2014/nov/21/tapeworm-parasite-mans-brain-four-years-china

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Tag: smell