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.”

15 Positively Reinforcing Facts About B.F. Skinner

Silly rabbit via Wikimedia Commons // CC BY 3.0
Silly rabbit via Wikimedia Commons // CC BY 3.0

Burrhus Frederic Skinner was one of the preeminent American psychologists of the 20th century. B.F. Skinner founded “radical behaviorism”—a twist on traditional behaviorism, a field of psychology that focused exclusively on observable human behavior. Thoughts, feelings, and perceptions were cast aside as unobservable.

B.F. Skinner dubbed his own method of observing behavior “operant conditioning,” which posited that behavior is determined solely by its consequences—either reinforcements or punishments. He also coined the term "positive reinforcement." 

To Skinner’s critics, the idea that these “principles of reinforcement,” as he called them, lead to easy “behavior modification” suggested that we do not have free will and are little more than automatons acting in response to stimuli. But his fans considered him visionary. Controversial to the end, B.F. Skinner was well known for his unconventional methods, unusual inventions, and utopian—some say dystopian—ideas about human society.

1. B.F. Skinner invented the "operant conditioning" or "Skinner" box.

Skinner believed that the best way to understand behavior is to look at the causes of an action and its consequences. He called this approach “operant conditioning.” Skinner began by studying rats interacting with an environment inside a box, where they were rewarded with a pellet of food for responding to a stimulus like light or sound with desired behavior. This simple experiment design would over the years take on dark metaphorical meaning: Any environment that had mechanisms in place to manipulate or control behavior could be called a "Skinner box." Recently, some have argued that social media is a sort of digital Skinner box: Likes, clicks, and shares are the pellet-like rewards we get for responding to our environment with certain behavior. Yes, we are the rats.

2. B.F. Skinner believed that all behavior was affected by one of three "operants."

Skinner proposed there were only three “operants” that had affected human behavior. Neutral operants were responses from the environment that had a benign effect on a behavior. Reinforcers were responses that increased the likelihood of a behavior’s repetition. And punishers decreased the likelihood of a behavior’s repetition. While he was correct that behavior can be modified via this system, it’s only one of many methods for doing so, and it failed to take into account how emotions, thoughts, and—as we learned eventually—the brain itself account for changes in behavior.

3. He's responsible for the term "positive reinforcement."

B.F. Skinner eventually moved on to studying pigeons in his Skinner box. The pigeons would peck at a disc to gain access to food at various intervals, and for completing certain tasks. From this Skinner concluded that some form of reinforcement was crucial in learning new behaviors. To his mind, positive reinforcement strengthens a behavior by providing a consequence an individual finds rewarding. He concluded that reinforced behavior tends to be repeated and strengthened.

4. Some critics felt "positive reinforcement" amounted to bribery.

Critics were dubious that Skinner's focus on behavior modification through positive reinforcement of desired behavior could actually change behavior for the long term, and that it was little more than temporary reward, like bribery, for a short-term behavioral change.

5. B.F. Skinner's idea of "negative reinforcement" isn't what you think.

Skinner believed negative reinforcement also helped to strengthen behavior; this doesn't mean exposing an animal or person to a negative stimulus, but rather removing an “unpleasant reinforcer.” The idea was that removing the negative stimulus would feel like a “reward” to the animal or person.

6. B.F. Skinner taught pigeons to play ping-pong.

As part of his research into positive reinforcement, he taught pigeons to play ping-pong as a first step in seeing how trainable they were. He ultimately wanted to teach them to guide bombs and missiles and even convinced the military to fund his research to that effect. He liked working with pigeons because they responded well to reinforcements and punishments, thus validating his theories. We know now that pigeons can be trained in a whole host of tasks, including distinguishing written words from nonsense and spotting cancer.

7. B.F. Skinner's first book, The Behavior of Organisms, broke new ground.

Published in 1938, Skinner’s debut book made the case that simple observation of cause and effect, reward and punishment, were as significant to understanding behavior as other “conceptual or neural processes.”

Skinner believed behavior was everything. Thoughts and feelings were just unreliable byproducts of behaviors, he argued—and therefore dismissed them. Many of his fellow psychologists disagreed. Regardless, Skinner’s theories contributed to a greater understanding of the relationship between stimuli and resulting behavior and may have even laid the groundwork for understanding the brain’s reward circuitry, which centers around the amygdala.

8. B.F. Skinner created the "baby tender."

Skinner was fond of inventions, and having children gave him a new outlet for his tendencies. He designed a special crib for his infant daughter called “the baby tender.” The clear box, with air holes, was heated so that the baby didn't need blankets. Unlike typical cribs, there were no slats in the sides, which he said prevented possible injury. Unsurprisingly, it did not catch on with the public.

9. B.F. Skinner also developed his own "teaching machine."


Silly rabbit via Wikimedia Commons // CC BY 3.0

You may have Skinner to thank for modern school workbooks and test-taking procedures. In 1954 Skinner visited his daughter’s classroom and found himself frustrated with the “inefficiencies” of the teaching procedures. His first "teaching machine"—a very basic program to improve teaching methods for spelling, math, and other school subjects—was little more than a fill-in-the-blank method on workbook or computer. It’s now considered a precursor to computer-assisted learning programs.

10. Skinner imaged an ideal society based on his theories of human behavior.

Skinner admired Henry David Thoreau’s famous book Walden, in which Thoreau writes about his retreat to the woods to get in greater contact with his inner nature. Skinner's "Ten Commandments" for a utopian world include: “(1) No way of life is inevitable. Examine your own closely. (2) If you do not like it, change it. (3) But do not try to change it through political action. Even if you succeed in gaining power, you will not likely be able to use it any more wisely than your predecessors. (4) Ask only to be left alone to solve your problems in your own way. (5) Simplify your needs. Learn how to be happy with fewer possessions.”

11. B.F. Skinner wrote a utopian novel, Walden Two.

Though inspired by Walden, Skinner also felt the book was too self-indulgent, so he wrote his own fictional follow-up with the 1948 novel Walden Two. The book proposed a type of utopian—some say dystopian—society that employed a system of behavior modification based on operant conditioning. This system of rewards and punishments would, Skinner proposed, make people into good citizens:

“We can achieve a sort of control under which the controlled, though they are following a code much more scrupulously than was ever the case under the old system, nevertheless feel free. They are doing what they want to do, not what they are forced to do. That's the source of the tremendous power of positive reinforcement—there's no restraint and no revolt. By careful cultural design, we control not the final behavior, but the inclination to behave—the motives, desires, the wishes.”

12. Some felt Skinner's ideas were reductionist ...

Critics, of which there were many, felt he reduced human behavior to a series of actions and reactions: that an individual human “mind” only existed in a social context, and that humans could be easily manipulated by external cues. He did not put much store in his critics. Even at age 83, just three years before he died, he told Daniel Goleman in a 1987 New York Times article, “I think cognitive psychology is a great hoax and a fraud, and that goes for brain science, too. They are nowhere near answering the important questions about behavior.”

13. ... and others were horrified by Walden Two.

Astronomer and colleague JK Jessup wrote, “Skinner's utopian vision could change the nature of Western civilization more disastrously than the nuclear physicists and biochemists combined.”

14. B.F. Skinner implied that humans had no free will or individual consciousness.

In the late 1960s and early '70s, Skinner wrote several works applying his behavioral theories to society, including Beyond Freedom and Dignity (1971). He drew fire for implying that humans had no free will or individual consciousness but could simply be controlled by reward and punishment. His critics shouldn't have been surprised: this was the very essence of his behaviorism. He, however, was unconcerned with criticism. His daughter Julie S. Vargas has written that “Skinner felt that by answering critics (a) you showed that their criticism affected you; and (b) you gave them attention, thus raising their reputation. So he left replies to others.”

15. He died convinced that the fate of humanity lay in applying his methods of behavioral science to society.

In 1990, he died of leukemia at age 86 after receiving a Lifetime Achievement Award from the American Psychological Association. Proud of his work, he was nonetheless concerned about the fate of humanity and worried “about daily life in Western culture, international conflict and peace, and why people were not acting to save the world.”

A New DNA Test Will Break Down Your Cat's Breed

Basepaws
Basepaws

Modern DNA testing kits can reveal a lot of information about you just by sending your spit off to a lab for analysis. As a result, it's easier than ever to learn about your personal ancestry and health risks. And now, the same goes for your cat, too.

Basepaws is now offering what it calls the "world's first DNA test for cats," which can tell you which breeds your beloved fur baby likely descended from, in addition to other information about their characteristics. The CatKit will reveal whether your little Simba is more similar to an American Shorthair, Abyssinian, or one of the other 30 breeds on record, as well as determining which of the "big cats" (think lions) your kitty has the most in common with.

Here's how it works: After receiving your kit in the mail, you will be asked to collect a DNA sample from your feline friend. The current kit includes adhesives for collecting cat hair, but Basepaws will soon roll out new kits that call for saliva samples instead. (This will provide a more consistent DNA sample, while also allowing staff to process more samples at once, according to a company spokesperson. It also will make it easier to collect samples from hairless cats like Sphinxes.)

A cat DNA test result
Basepaws

Once you collect the sample, just mail it in and wait eight to 12 weeks for your report. Basepaws uses sequencing machines to "read" your kitty's genetic code, comparing it to the sequences of other cats in its network. "More than 99 percent of your cat's genetic sequence will be similar to every other cat; it's the small differences that make your cat unique," Basepaws writes on its website.

In the future, Basepaws will also be able to determine your cat's predisposition for certain diseases, as well as their personality and physical traits. The company holds on to your cat's genetic data, allowing it to provide updates about your cat as the Basepaws database continues to grow.

Order a kit on the Basepaws website for $95. Enter the code "MEOWRCH-I5W3RH" at the checkout for a 10 percent discount.

And don't feel left out if you're a dog lover rather than a cat person—Wisdom Panel offers a similar service for canine companions. Its kit is available for $73 on Amazon.

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