Scientists Make Progress Toward a New Potential Treatment for Asthma

Some 24.6 million American adults and children have asthma, which can range from mild to life threatening. A chronic pulmonary disorder, asthma is characterized by inflammation of the lungs, narrowing of the airways, and excessive mucus production—essentially, causing difficulty breathing.

Researchers looking for new drugs to treat this condition at Cincinnati Children’s Hospital Medical Center (CCHMC) have made a recent breakthrough by identifying long-sought transcription factors, proteins responsible for turning genes on or off in the nucleus of cells. These transcription factors are buried deep inside the nucleus of cells where it’s challenging to access or study them.

But the CCHMC researchers managed to identify a small molecule which blocks a key inflammatory transcription factor, FOXM1. FOXM1 stimulates excessive mucus production and inflammation, leading to respiratory distress, and is often found in severe asthma and other pulmonary diseases. Their results were published in the journal Science Signaling.

Asthma is usually triggered by an outside stimulus, ranging from mold to animal fur to pollen. “In response to [a] particular insult from outside, our lungs start to be inflamed, so the cells from the blood come into the lung and start populating our alveoli, which we need to keep clear to breathe,” lead author Vladimir Kalinichenko tells Mental Floss. Kalinichenko is the director for the Center for Lung Regenerative Medicine and a member of the Division of Pulmonary Biology at CCHMC. He explains that in response to an allergen, epithelial (lung) cells start differentiation, or metaplasia, and produce a lot of the goblet cells that secrete the mucus that narrows airways and makes breathing difficult.

Kalinichenko found that inside the lungs, FOXM1 is an important transcription factor responsible for cells becoming mucus-producing goblet cells—a key step in what makes it hard to breathe. His research team’s aim was to find a compound that would specifically target FOXM1, and by blocking its activation, keep the whole process of pro-inflammatory molecules stimulating goblet cells into over-producing mucus from launching.

To do this, the CCHMC researchers screened a database of 50,000 small molecule compounds that have been created in previous scientific research to see if they could find one that inhibited FOXM1. After narrowing it down to 20, they settled on a molecule called RCM-1, which exhibited the inhibiting function they sought.

They first tested RCM-1 on dish-cultured human epithelial cells, with good results; it prevented the transcription factor, FOXM1, from going to the nucleus, says Kalinichenko.

Next they exposed mice that were genetically modified to express high amounts of the FOXM1 transcription factor to dust mites, a common allergen in humans, over the course of two weeks. With repeated exposure to the allergen, the mice began to exhibit asthma symptoms. When they gave the mice just two injections of RCM-1, Kalinichenko says, “The mice would not develop mucus overproduction in the airways and their breathing would be much clearer.”

Then Kalinichenko’s team evoked asthma symptoms in another group of mice, by injecting an inflammatory molecule called interleukin-13—which is normally produced by T-cell lymphocytes as a response to an allergen. Just giving the interleukin-13 to mice (even without the presence of an allergen) causes asthma-like symptoms of lung inflammation, narrowing airways, and difficulty breathing. When the mice were given RCM-1, these symptoms abated, essentially demonstrating a kind of “downstream inflammatory effect” of the immune system.

The team was pleased not to observe any symptoms of toxicity in the mice, which bodes well for human applications, though Kalinichenko cautions that human clinical trials are still far off. First, they’ll have to test the molecule in other animal models, such as non-human primates, assess toxicity levels in different concentrations of the compound, and work on perfecting the compound itself.

“We are just in discovery mode. We have proven in two mouse models of asthma that [RCM-1] works," he notes. "That is a long way to human use.”

Still, Kalinichenko thinks RCM-1 is promising. It could be especially helpful in treating the progressive nature of asthma, which damages the lungs over time from repeat acute attacks. “With every new asthmatic attack, the lungs become much worse. This drug, with others, could be used to prevent these attacks and treat patients in earlier stages, before the lungs get bad,” he says.

However, Kalinichenko says its real value could be in treating serious diseases such as chronic obstructive pulmonary disease, cystic fibrosis, and even lung cancer. “Those diseases are associated with excess mucus production and clogging airways. For those diseases where FOXM1 is expressed in high levels, this drug could be highly beneficial—and even life-saving.”

Lítla Dímun: The Smallest of the Faroe Islands Has Its Very Own Cloud

While some islands are known for their unusual geography or unique history, Lítla Dímun is notable for its weather. The island, which is the smallest of Denmark's Faroe Islands chain, is often capped by a lens-shaped cloud, making it resemble a scene from a fairytale.

According to Mental Floss's own Kerry Wolfe writing for Atlas Obscura, the cloud floating above Lítla Dímun is a lenticular cloud. This type of cloud forms when moist air flows over a protruding geological feature, like a mountain top. When the wind moving up the landmass hits the air current directly above it, a sort of wave is created on the downwind side of the mountain. The moist air falling down this wave evaporates and then condenses into a large, flying-saucer-shaped cloud atop the mountain peak as a result.

Another factor that makes Lítla Dímun distinct is that it's the only one of the 18 main Faroe Islands without human inhabitants. Visitors to the mystical location will instead find a thriving population of sheep. Originally, Lítla Dímun was home to a group of feral sheep likely dating back to the Neolithic era. But they were hunted to extinction in the 19th century. Domesticated sheep were introduced there around the same time, and today, farmers visit the island once a year to round up their flocks.

One of the few signs of human life are the ropes farmers use to scale the cliff faces bordering the island. Even if you have rock-climbing skills, Lítla Dímun may be dangerous to visit. A boat ride to the rocky shore is only possible when the surrounding sea is calm.

[h/t Atlas Obscura]

Why Are Sloths So Slow?

Sloths have little problem holding still for nature photographers.
Sloths have little problem holding still for nature photographers.
Geoview/iStock via Getty Images

When it comes to physical activity, few animals have as maligned a reputation as the sloth. The six sloth species, which call Brazil and Panama home, move with no urgency, having seemingly adapted to an existence that allows for a life lived in slow motion. But what makes sloths so sedate? And what horrible, poop-related price must they pay in order to maintain life in the slow lane?

According to HowStuffWorks, the sloth’s limited movements are primarily the result of their diet. Residing mainly in the canopy vines of Central and South American forests, sloths dine out on leaves, fruits, and buds. With virtually no fat or protein, sloths conserve energy by taking a leisurely approach to life. On average, a sloth will climb or travel roughly 125 feet per day. On land, it takes them roughly one minute to move just one foot.

A sloth’s digestive system matches their locomotion. After munching leaves using their lips—they have no incisors—it can take up to a month for their meals to be fully digested. And a sloth's metabolic rate is 40 to 45 percent slower than most mammals' to help compensate for their low caloric intake. With so little fuel to burn, a sloth makes the most of it.

Deliberate movement shouldn’t be confused for weakness, however. Sloths can hang from branches for hours, showing off some impressive stamina. And because they spend most of their time high up in trees, they have no need for rapid movement to evade predators.

There is, however, one major downside to the sloth's leisurely lifestyle. Owing to their meager diet, they typically only have to poop once per week. Like going in a public bathroom, this can be a stressful event, as it means going to the ground and risking detection by predators—which puts their lives on the line. Worse, that slow bowel motility means they’re trying to push out nearly one-third of their body weight in feces at a time. It's something to consider the next time you feel envious of their chill lifestyle.

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