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From the first bite, our sense of taste helps pace our eating

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From the first bite, our sense of taste helps pace our eating


When you eagerly dig into a long-awaited dinner, signals from your stomach to your brain keep you from eating so much you’ll regret it — or so it’s been thought. That theory had never really been directly tested until a team of scientists at UC San Francisco recently took up the question.

The picture, it turns out, is a little different.

The team, led by Zachary Knight, PhD, a UCSF professor of physiology in the Kavli Institute for Fundamental Neuroscience, discovered that it’s our sense of taste that pulls us back from the brink of food inhalation on a hungry day. Stimulated by the perception of flavor, a set of neurons — a type of brain cell — leaps to attention almost immediately to curtail our food intake.

“We’ve uncovered a logic the brainstem uses to control how fast and how much we eat, using two different kinds of signals, one coming from the mouth, and one coming much later from the gut,” said Knight, who is also an investigator with the Howard Hughes Medical Institute and a member of the UCSF Weill Institute for Neurosciences. “This discovery gives us a new framework to understand how we control our eating.”

The study, which appears Nov. 22, 2023 in Nature, could help reveal exactly how weight-loss drugs like Ozempic work, and how to make them more effective.

New views into the brainstem

Pavlov proposed over a century ago that the sight, smell and taste of food are important for regulating digestion. More recent studies in the 1970s and 1980s have also suggested that the taste of food may restrain how fast we eat, but it’s been impossible to study the relevant brain activity during eating because the brain cells that control this process are located deep in the brainstem, making them hard to access or record in an animal that’s awake.

Over the years, the idea had been forgotten, Knight said.

New techniques developed by lead author Truong Ly, PhD, a graduate student in Knight’s lab, allowed for the first-ever imaging and recording of a brainstem structure critical for feeling full, called the nucleus of the solitary tract, or NTS, in an awake, active mouse. He used those techniques to look at two types of neurons that have been known for decades to have a role in food intake.

The team found that when they put food directly into the mouse’s stomach, brain cells called PRLH (for prolactin-releasing hormone) were activated by nutrient signals sent from the GI tract, in line with traditional thinking and the results of prior studies.

However, when they allowed the mice to eat the food as they normally would, those signals from the gut didn’t show up. Instead, the PRLH brain cells switched to a new activity pattern that was entirely controlled by signals from the mouth.

“It was a total surprise that these cells were activated by the perception of taste,” said Ly. “It shows that there are other components of the appetite-control system that we should be thinking about.”

While it may seem counterintuitive for our brains to slow eating when we’re hungry, the brain is actually using the taste of food in two different ways at the same time. One part is saying, “This tastes good, eat more,” and another part is watching how fast you’re eating and saying, “Slow down or you’re going to be sick.”

“The balance between those is how fast you eat,” said Knight.

The activity of the PRLH neurons seems to affect how palatable the mice found the food, Ly said. That meshes with our human experience that food is less appetizing once you’ve had your fill of it.

Brain cells that inspire weight-loss drugs

The PRLH-neuron-induced slowdown also makes sense in terms of timing. The taste of food triggers these neurons to switch their activity in seconds, from keeping tabs on the gut to responding to signals from the mouth.

Meanwhile, it takes many minutes for a different group of brain cells, called CGC neurons, to begin responding to signals from the stomach and intestines. These cells act over much slower time scales — tens of minutes — and can hold back hunger for a much longer period of time.

“Together, these two sets of neurons create a feed-forward, feed-back loop,” said Knight. “One is using taste to slow things down and anticipate what’s coming. The other is using a gut signal to say, ‘This is how much I really ate. Ok, I’m full now!'”

The CGC brain cells’ response to stretch signals from the gut is to release GLP-1, the hormone mimicked by Ozempic, Wegovy and other new weight-loss drugs.

These drugs act on the same region of the brainstem that Ly’s technology has finally allowed researchers to study. “Now we have a way of teasing apart what’s happening in the brain that makes these drugs work,” he said.

A deeper understanding of how signals from different parts of the body control appetite would open doors to designing weight-loss regimens designed for the individual ways people eat by optimizing how the signals from the two sets of brain cells interact, the researchers said.

The team plans to investigate those interactions, seeking to better understand how taste signals from food interact with feedback from the gut to suppress our appetite during a meal.



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Bird flu: Diverse range of vaccines platforms ‘crucial’ for enhancing human pandemic preparedness

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Bird flu: Diverse range of vaccines platforms ‘crucial’ for enhancing human pandemic preparedness


Vaccination remains the most effective strategy for avian influenza prevention and control in humans, despite varying vaccine efficacy across strains.

That’s according to the authors of a new review which delves into existing research into bird flu vaccines for humans.

Published in the peer-reviewed journal Human Vaccines & Immunotherapeutics, the results of the paper are particularly timely following news last week (Wednesday 22nd May) that the bird flu strain H5N1 had once again, for a second time, jumped from cattle in America to a human — prompting fears of subsequent human-to-human infection, with possible critical consequences.

Instances of the avian influenza were first recognized in US cattle in March. Since then, this strain has mainly spread from cow-to-cow and scientists have discovered very high levels of virus in raw milk (pasteurized milk is safe, having shown viral RNA but not infectious virus). To-date two people, however, are known to have contracted the bird flu virus. Both patients — US farmers — only reported eye symptoms and with treatment they made a full recovery.

Following tests on the first human instance, it was seen that the strain had mutated to be better adapted to mammalian cells, but as long as that human didn’t pass it onto another person it likely stopped the spread at that point. With the second case, the CDC has released a statement to say it has been monitoring influenza surveillance systems intently, especially in impacted states. “There has been no sign of unusual influenza activity in people, including in syndromic surveillance,” they report.

The concern now, though, is that if H5N1 continues to be given the environment in which to mutate (such as in close quarter cattle farms) — and this continues long enough — it has the potential to find a combination that will easily spread to humans.

The results of this new research, carried out by a team at the University of Georgia, USA, suggests vaccines still remain our “primary defense” against potential spread of avian influenzas such as the H5N1 and others assessed.

“The H5N1, H7N9, and H9N2 subtypes of avian influenza virus pose a dual threat, not only causing significant economic losses to the global poultry industry but also presenting a pressing public health concern due to documented spillover events and human cases,” explains lead author Flavio Cargnin Faccin, who alongside his mentor Dr. Daniel Perez of the University of Georgia, USA, analyzed the current landscape of research into human vaccines for these bird flus.

“This deep delve into the landscape of avian influenza vaccines for humans shows vaccination remains the primary defense against the spread of these viruses.”

The team examined studies of vaccines tested in mice, ferrets, non-human primates, and clinical trials of bird flu vaccines in humans, and assessed both established platforms and promising new directions.

The review carried out suggests inactivated vaccines are a safe and affordable option that primarily activate humoral immunity — the part of our immune system that produces antibodies.

Live attenuated influenza vaccines (LAIVs) are known to induce a wider immune response than inactivated vaccines, activating not only antibody production but also mucosal and cellular defenses. In this review, the authors suggest this broader response may offer greater protection, though, the authors suggest further research is needed to fully understand and harness its potential benefits for both human and agricultural applications.

The review also examined alternatives, such as virus-like particle (VLP) vaccines and messenger RNA (mRNA) vaccines, that have emerged more recently. Although VLP vaccines for bird flu have limited clinical trial data in humans, results from studies in mice and ferrets showed promise, the authors found. mRNA vaccines against H5N1 and H7N9 bird flu subtypes also generated a rapid and strong immune response in mice and ferrets, and, while data in humans is scarce, results from a phase 1 study of an H7N9 mRNA vaccine in healthy humans were “encouraging.”

Overall, the team suggests “exploring and employing a diverse range of vaccine platforms,” will be “crucial for enhancing pandemic preparedness and mitigating the threat of avian influenza viruses.”



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When should you neuter or spay your dog?

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When should you neuter or spay your dog?


Researchers at the University of California, Davis, have updated their guidelines on when to neuter 40 popular dog varieties by breed and sex. Their recent paper in Frontiers in Veterinary Science adds five breeds to a line of research that began in 2013 with a study that suggested that early neutering of golden retrievers puts them at increased risk of joint diseases and certain cancers.

That initial study set off a flurry of debate about the best age to neuter other popular breeds. Professors Lynette and Benjamin Hart of the School of Veterinary Medicine, the study’s lead authors, set out to add more breed studies by examining more than a decade of data from thousands of dogs treated at the UC Davis veterinary hospital. Their goal was to provide owners with more information to make the best decision for their animals.

They specifically looked at the correlation between neutering or spaying a dog before 1 year of age and a dog’s risk of developing certain cancers. These include cancers of the lymph nodes, bones, blood vessels or mast cell tumors for some breeds; and joint disorders such as hip or elbow dysplasia, or cranial cruciate ligament tears. Joint disorders and cancers are of particular interest because neutering removes male and female sex hormones that play key roles in important body processes such as closure of bone growth plates.

For the most recent study, they focused on German short/wirehaired pointer, mastiff, Newfoundland, Rhodesian ridgeback and Siberian husky. Data was collected from the UC Davis veterinary hospital’s records that included more than 200 cases for each of these five breeds weighing more than 20 kg (or 44 pounds), spanning January 2000 through December 2020.

The Harts said their updated guidelines emphasize the importance of personalized decisions regarding the neutering of dogs, considering the dog’s breed, sex and context. A table representing guidelines reflecting the research findings for all 40 breeds that have been studied, including the five new breeds, can be found here.

Health risks different among breeds

“It’s always complicated to consider an alternate paradigm,” said Professor Lynette Hart. “This is a shift from a long-standing model of early spay/neuter practices in the U.S. and much of Europe to neuter by 6 months of age, but important to consider as we see the connections between gonadal hormone withdrawal from early spay/neuter and potential health concerns.”

The study found major differences among these breeds for developing joint disorders and cancers when neutered early. Male and female pointer breeds had elevated joint disorders and increased cancers; male mastiff breeds had increased cranial cruciate ligament tears and lymphoma; female Newfoundland breeds had heightened risks for joint disorders; female Ridgeback breeds had heightened risks for mast cell tumors with very early neutering; and Siberian huskies showed no significant effects on joint disorders or cancers.

“We’re invested in making contributions to people’s relationship with their animals,” said Benjamin Hart, distinguished professor emeritus. “This guidance provides information and options for veterinarians to give pet owners, who should have the final decision-making role for the health and well-being of their animal.”

Their combined research studies will soon be available with others in the open access journal, Frontiers of Veterinary Science, as a free e-book, Effective Options Regarding Spay or Neuter of Dogs.

Other researchers on this UC Davis study include: Abigail Thigpen, Maya Lee, Miya Babchuk, Jenna Lee, Megan Ho, Sara Clarkson and Juliann Chou with the School of Veterinary Medicine; and Neil Willits with the Department of Statistics.

The research received a small amount of funding from the Center for Companion Animal Health, but was primarily conducted by the above authors as volunteers.



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Why do Dyeing poison frogs tap dance?

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Why do Dyeing poison frogs tap dance?


The toe tapping behavior of various amphibians has long attracted attention from researchers and pet owners. Despite being widely documented, the underlying functional role is poorly understood. In a new paper, researchers demonstrate that Dyeing poison frogs modulate their taps based on specific stimuli.

Dyeing poison frogs, Dendrobates tinctorius, have been shown to tap their posterior toes in response to a range of prey sizes, from small fruit flies to large crickets. In the present study, the researchers hypothesized that if the tapping has a role in feeding, the frogs would adjust their behavior in response to different environmental cues.

To test their hypothesis, the researchers recorded the frogs under varying conditions. “I used the slow-motion camera on my iPhone to take minute-long videos of the frogs tapping. Afterwards, I went back to each video and counted the number of taps on each foot and how long they were visible since they were often hidden behind a leaf or the frog itself. I used those two numbers to get a “taps per minute” on each foot and added them up,” said Thomas Parrish, a former undergraduate student in the Fischer lab (GNDP), and the first author on the paper.

The researchers first tested whether the frogs tapped their toes more when they were feeding. To do so, the researchers fed the terrariums with half a teaspoon of fruit flies and recorded their hunting.

“We already knew the answer to this, but it was great to see that the tapping increased in the presence of the prey,” said Eva Fischer, an assistant professor of integrative biology. “We wanted to ask ‘Why?’ and we wondered whether it had a function in prey capture or it was just a excitatory response like how dogs wag their tails because they are excited.”

The researchers then used different surfaces to see whether the tapping behavior changed when the frogs could see the prey but not feed on it. They placed the fruit flies in small, clear Petri dishes in the frogs’ home and measured the rate of toe tapping. They found that the frogs had an average of 50 taps/minute when they couldn’t access the flies compared to 166 taps/minute when they fed on free-moving flies.

“The idea was that if they’re excited, we might see something different based on whether they can catch the flies,” Fisher said. “These results suggested that since they kept trying to eat in both cases, the tapping was not just out of excitement.”

The researchers wondered, then, whether the toe taps were a form of vibrational signaling where the frogs used it as a way to startle or distract the prey before they fed. They used four different surfaces to test this question: soil, leaf surfaces, gel, and glass.

“Soil and leaves are natural substances, but soil is not very responsive while leaves are. On the other hand, gels are responsive and glass is not, but they are both unnatural surfaces to frogs,” Fischer said.

They found that while the tap rate differed depending on the surface, with leaves being the highest at 255 taps/minute and glass the lowest at 64 taps/minute, there was no difference in the total number of feeding attempts or success.

“Although we saw that the frogs ate in every context, it was exciting to see that they changed their behavior based on what they’re standing on,” Fischer said. “We were surprised, however, that we didn’t see a difference in how successful they were at eating. It’s possible that the experiment is like sending them to a buffet instead of what happens in the forest where the tapping may help in stirring the prey.”

The researchers are now hoping to understand what other stimuli might trigger this behavior. “Although we’ve conclusively shown that it is important in feeding, it could also be important in other contexts. For example, we have seen that the frogs tap more when there are other frogs nearby, so there may be a social aspect to it,” Fischer said.

They are also interested in studying the underlying biomechanical aspects of the muscles. “It would be cool to look at the anatomy and see how the muscles work,” Fischer said. “Ultimately, we could ask whether all frogs can tap their toes if they have the right muscles or whether there’s something special about the anatomy of poison frogs.”



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