Scientists Shine Light on What Triggers REM Sleep

Illustration of a brain.
While studying how the brain controls REM sleep, researchers focused on areas abbreviated LDT and PPT in the mouse brainstem. This illustration shows where these two areas are located in the human brain. Credit: Wikimedia Commons. View larger image

Has the “spring forward” time change left you feeling drowsy? While researchers can’t give you back your lost ZZZs, they are unraveling a long-standing mystery about sleep. Their work will advance the scientific understanding of the process and could improve ways to foster natural sleep patterns in people with sleep disorders.

Working at Massachusetts General Hospital and MIT, Christa Van Dort Exit icon, Matthew Wilson Exit icon and Emery Brown Exit icon focused on the stage of sleep known as REM. Our most vivid dreams occur during this period, as do rapid eye movements, for which the state is named. Many scientists also believe REM is crucial for learning and memory.

REM occurs several times throughout the night, interspersed with other sleep states collectively called non-REM sleep. Although REM is clearly necessary—it occurs in all land mammals and birds—researchers don’t really know why. They also don’t understand how the brain turns REM on and off. Continue reading

Meet Maureen L. Mulvihill

Maureen L. Mulvihill, Ph.D.
Credit: Actuated Medical, Inc.
Maureen L. Mulvihill, Ph.D.
Fields: Materials science, logistics
Works at: Actuated Medical, Inc., a small company that develops medical devices
Second job (volunteer): Bellefonte YMCA Swim Team Parent Boost Club Treasurer
Best skill: Listening to people
Last thing she does every night: Reads to her 7- and 10-year-old children until “one of us falls asleep”

If you’re a fan of the reality TV show Shark Tank, you tune in to watch aspiring entrepreneurs present their ideas and try to get one of the investors to help develop and market the products. Afterward, you might start to think about what you could invent.

Maureen L. Mulvihill has never watched the show, but she lives it every day. She is co-founder, president and CEO of Actuated Medical, Inc. (AMI), a Pennsylvania-based company that develops specialized medical devices. The devices include a system for unclogging feeding tubes, motors that assist MRI-related procedures and needles that gently draw blood.

AMI’s products rely on the same motion-control technologies that allow a quartz watch to keep time, a microphone to project sound and even a telescope to focus on a distant object in a sky. In general, the devices are portable, affordable and unobtrusive, making them appealing to doctors and patients.

Mulvihill, who’s trained in an area of engineering called materials science, says, “I’m really focused on how to translate technologies into ways that help people.” Continue reading

A Bright New Method for Rapidly Screening Cancer Drugs

Illustration of red, green and blue fluorescent proteins.
Chemists have devised a new approach to screening cancer drugs that uses gold nanoparticles with red, green and blue outputs provided by fluorescent proteins. Credit: University of Massachusetts Amherst.

Scientists may screen billions of chemical compounds before uncovering the few that effectively treat a disease. But identifying compounds that work is just the first step toward developing a new therapy. Scientists then have to determine exactly how those compounds function.

Different cancer therapies attack cancer cells in distinct ways. For example, some drugs kill cancer cells by causing their outer membranes to rapidly rupture in a process known as necrosis. Others cause more subtle changes to cell membranes, which result in a type of programmed cell death known as apoptosis.

If researchers could distinguish the membrane alterations of chemically treated cancer cells, they could quickly determine how that chemical compound brings about the cells’ death. A new sensor developed by a research team led by Vincent Rotello Exit icon of the University of Massachusetts Amherst can make these distinctions in minutes. Continue reading

New Streamlined Technique for Processing Biological Samples

Illustration of Slug flow microextraction.
Researchers have discovered a faster, easier and more affordable technique for processing biological samples. Credit: Weldon School of Biomedical Engineering, Purdue University.

It’s not unusual for the standard dose of a drug to work well for one person but be less effective for another. One reason for such differences is that individuals can break down drugs at different rates, leading to different concentrations of drugs and of their breakdown products (metabolites) in the bloodstream. A promising new process Exit icon called slug-flow microextraction could make it faster, easier and more affordable to regularly monitor drug metabolites so that medication dosages could be tailored to each patient’s needs, an approach known as personalized medicine. This technique could also allow researchers to better monitor people’s responses to new drug treatments during clinical trials. Continue reading

Outwitting Antibiotic Resistance

Marine scene with fish and corals
The ocean is a rich source of microbes that could yield infection-fighting natural molecules. Credit: National Oceanic and Atmospheric Administration Exit icon.

Antibiotics save countless lives and are among the most commonly prescribed drugs. But the bacteria and other microbes they’re designed to eradicate can evolve ways to evade the drugs. This antibiotic resistance, which is on the rise due to an array of factors, can make certain infections difficult—and sometimes impossible—to treat.

Read the Inside Life Science article to learn how scientists are working to combat antibiotic resistance, from efforts to discover potential new antibiotics to studies seeking more effective ways of using existing ones.

 
 

New Research Sheds Light on Drug-Induced Salivary Issues

Open human mouth
Scientists have discovered a possible mechanism behind the bad taste and dry mouth caused by some drugs. Credit: Stock image.

The effects some medicines have on our salivary glands can at times extend beyond the fleeting flavor we experience upon ingesting them. Sometimes drugs cause a prolonged bad taste or dryness in the mouth, both of which can discourage people from taking medicines they need. Now, a research team led by Joanne Wang of the University of Washington has discovered a possible mechanism behind this phenomenon. Working primarily with mice and using a commonly prescribed antidiabetic drug known to impair taste, the scientists identified a protein in salivary gland cells that takes up the drug from the bloodstream and secretes it in saliva. Wang and her colleagues were also able to pinpoint a specific gene that, when removed, hindered this process. They hope their new insights will aid efforts to develop medicines that do not cause salivary issues.

This work also was funded by NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Learn more:
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Anesthesia and Brain Cells: A Temporary Disruption?

Hippocampal neuron in culture.
Hippocampal neuron in culture. Dendrites are green, dendritic spines are red, and DNA in cell’s nucleus is blue. Credit: Shelley Halpain, University of California, San Diego.

Anesthetic drugs are vital to modern medicine, allowing patients to undergo even the longest and most invasive surgeries without consciousness or pain. Unfortunately, studies have raised the concern that exposing patients, particularly children and the elderly, to some anesthetics may increase risk of long-term cognitive and behavioral issues.

A scientific team led by Hugh Hemmings Exit icon of Weill Cornell Medical College and Shelley Halpain Exit icon of the University of California, San Diego, examined the effects of anesthesia on neurons isolated from juvenile rats. Given at doses and durations frequently used during surgery, the commonly administered general anesthetic isoflurane did in fact reduce the number and size of important structures within neurons called dendritic spines. Dendritic spines help pass information from neuron to neuron, and disruption of these structures can be associated with dysfunction in thinking and behavior.

Promisingly, the shrinkage observed by the researchers appeared to be temporary: After the researchers washed the anesthetic out of the cell cultures, the dendritic spines grew back. But because neurons in culture do not reproduce all aspects of intact neuronal networks, the scientists explain that the findings should be verified in more complex models. Other molecular mechanisms may also potentially contribute to late effects of anesthesia exposure.

This work also was funded by NIH’s National Institute of Mental Health.

Learn more:
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Understanding Anesthesia from Inside Life Science

The “Virtuous Cycle” of Technology and Science

A scientist looking through a  microscope. Credit: Stock image.
Whether it’s a microscope, computer program or lab technique, technology is at the heart of biomedical research. Credit: Stock image.

Whether it’s a microscope, computer program or lab technique, technology is at the heart of biomedical research. Its central role is particularly clear from this month’s posts.

Some show how different tools led to basic discoveries with important health applications. For instance, a supercomputer unlocked the secrets of a drug-making enzyme, a software tool identified disease-causing variations among family members and high-powered microscopy revealed a mechanism allowing microtubules—and a cancer drug that targets them—to work.

Another theme featured in several posts is novel uses for established technologies. The scientists behind the cool image put a new spin on a long-standing imaging technology to gain surprising insights into how some brain cells dispose of old parts. Similarly, the finding related to sepsis demonstrates yet another application of a standard lab technique called polymerase chain reaction: assessing the immune state of people with this serious medical condition.

“We need tools to answer questions,” says NIGMS’ Doug Sheeley, who oversees biomedical technology research resource grants. “When we find the answers, we ask new questions that then require new or improved tools. It’s a virtuous cycle that keeps science moving forward.”

A Drug-Making Enzyme in Motion

Mutated enzyme, LovD9. Credit: Silvia Osuna and Gonzalo Jiménez-Osés, University of California, Los Angeles.
The movement of this mutated enzyme, LovD9, facilitates rapid production of the cholesterol reducing-drug simvastatin. Credit: Silvia Osuna and Gonzalo Jiménez-Osés, University of California, Los Angeles.

LovD9, a mutated version of an enzyme extracted from mold growing in soil, produces the cholesterol-reducing drug simvastatin 1,000 times faster than its natural predecessor. But scientists didn’t understand why because the enzyme’s mutations are far from the active site, where the drug is actually made. Now they do.

Yi Tang of the University of California, Los Angeles (UCLA), in partnership with the pharmaceutical company Codexis, generated LovD9 by repeatedly inducing random mutations, each time selecting the mutated versions of the enzyme with the most promise for industrial simvastatin production.

Then, the team collaborated with UCLA colleagues Kendall Houk and Todd Yeates to unlock the secret of the enzyme’s speed. Using ANTON, a special-purpose supercomputer at the Pittsburgh Supercomputing Center, they simulated how different parts of the enzyme rotate and twist when synthesizing the drug. The scientists discovered that as LovD9 moves, it forms shapes that facilitate simvastatin production more often than the natural enzyme does.

With their better understanding of how mutations far from an active site may affect an enzyme’s motion, the researchers hope to one day directly engineer enzymes with precise mutations that enhance drug production.

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Houk Exit icon, Tang Exit icon and Yeates Exit icon Labs

Carbohydrates as Bacterial Camouflage: How Our Immune System Responds

bacteria
Although invisible to our immune system’s antibodies, strains of a pneumonia-causing bacteria, Pseudomonas aeruginosa (orange), are easily detected by galectins. Credit: Centers for Disease Control and Prevention.

When harmful strains of bacteria invade our bodies, our immune system produces antibodies that identify the intruders by the specific carbohydrate structures coating them. Some strains, however, have coatings that mimic the carbohydrate structures found on our own cells, and this disguise allows them to evade detection by antibodies.

A team of scientists led by Richard Cummings of Emory University found that galectins, a class of proteins naturally produced by our bodies, can identify and kill these concealed bacteria without damaging our own mimicked cells. To make this discovery, the team used glass slides covered with more than 300 different carbohydrates extracted from the surface of bacterial cells. After testing the ability of galectins and antibodies to bind to specific carbohydrates on these slides, the researchers observed that the galectins easily detected the mammalian-like carbohydrates that the antibodies failed to recognize.

These findings provide a clearer understanding of the complementary roles played by galectins and antibodies in protecting us from a broad range of infections.

This work also was funded by NIH’s National Institute of Allergy and Infectious Diseases and National Heart, Lung, and Blood Institute.

Learn more:
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