Year: 2015

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Nature’s Medicine Cabinet

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More than 70 percent of new drugs approved within the past 30 years originated from trees, sea creatures and other organisms that produce substances they need to survive. Since ancient times, people have been searching the Earth for natural products to use—from poison dart frog venom for hunting to herbs for healing wounds. Today, scientists are modifying them in the laboratory for our medicinal use. Here’s a peek at some of the products in nature’s medicine cabinet.

Vampire bat

A protein called draculin found in the saliva of vampire bats is in the last phases of clinical testing as a clot-buster for stroke patients. Vampire bats are able to drink blood from their victims because draculin keeps blood from clotting. The first phases of clinical trials have shown that the protein’s anti-coagulative properties could give doctors more time to treat stroke patients and lower the risk of bleeding in the brain.

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Data-Mining Study Explores Health Outcomes from Common Heartburn Drugs

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Results of a data-mining study suggest a link between a common heartburn drug and heart attacks. Credit: Stock image.

Scouring through anonymized health records of millions of Americans, data-mining scientists found an association between a common heartburn drug and an elevated risk for heart attacks. Their preliminary results suggest that there may be a link between the two factors.

For 60 million Americans, heartburn is a painful and common occurrence caused by stomach acid rising through the esophagus. It’s treated by drugs such as proton-pump inhibitors (PPIs) that lower acid production in the stomach. Taken by about one in every 14 Americans, PPIs, which include Nexium and Prilosec, are the most popular class of heartburn drugs.

PPIs have long been thought to be completely safe for most users. But a preliminary laboratory study published in 2013 suggested that this may not be the case. The study, led by a team of researchers at Stanford University, showed that PPIs could affect biochemical reactions outside of their regular acid suppression action that would have harmful effects on the heart. Continue reading “Data-Mining Study Explores Health Outcomes from Common Heartburn Drugs”

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Meet Sarkis Mazmanian and the Bacteria That Keep Us Healthy

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Sarkis K. Mazmanian
Credit: New York Academy of Sciences
Sarkis K. Mazmanian, Ph.D.
Born in: The country of Lebanon, moved to Los Angeles when he was 1
Fields: Microbiology, immunology, neuroscience
Works at: California Institute of Technology
Awards won: Many, including the MacArthur Foundation “Genius” grant
Most proud of: The success of his trainees! “There’s nothing that comes close to the gratification and joy I feel when a student or research fellow goes on to be an independent scientist.”
When not in the lab or mentoring students, he’s: Spending time with his family, including his 1-year-old-son or going for an occasional run

As a child, Sarkis Mazmanian frequently took things apart to figure out how they worked. At the age of 12, he dismantled his family’s entire television set—to the dismay of his parents and the unsuccessful TV repairman.

“I wasn’t aware of this at the time, but maybe that was some sort of a foreshadowing that I would enjoy science,” Mazmanian says. “Scientists take biological systems apart to understand how they work.”

Mazmanian never thought he’d become a microbiologist, let alone a leading expert in the field. He began studying microbiology at the University of California, Los Angeles (UCLA), because it was the major that allowed him to do the most hands-on research. But as soon as he entered the field, he fell in love with the complexities of microbial organisms and the efficiency of their functions. Continue reading “Meet Sarkis Mazmanian and the Bacteria That Keep Us Healthy”

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Food for Thought: Nutrient-Detecting Brain Sensor in Flies

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If you participated in a cupcake taste test, do you think you’d be able to distinguish a treat made with natural sugar from one made with artificial sweetener? Scientists have known for decades that animals can tell the difference, but what’s been less clear is how.

Fruit fly neurons in the brain (red) with nerve fibers (white) that extend to the gut.
For fruit flies, nutritive sugars activate a set of neurons in the brain (red) with nerve fibers (white) that extend to the gut. Credit: Jason Lai and Greg Suh, New York University School of Medicine.

Now, researchers at the New York University School of Medicine have identified a collection of specialized nerve cells in fruit flies that acts as a nutrient-detecting sensor, helping them select natural sugar over artificial sweetener to get the energy they need to survive.

“How specific sensory stimuli trigger specific behaviors is a big research question,” says NIGMS’ Mike Sesma. “Food preferences involve more than taste and hunger, and this study, which was done in an organism with many of the same cellular components as humans, gives us a glimpse of the complex interplay among the many factors.”

The study, described in the July 15 issue of Neuron, builds on the researchers’ earlier studies of feeding behavior that showed hungry fruit flies, even ones lacking the ability to taste, selected calorie-packed sugars over zero-calorie alternatives. The scientists, led by Greg Suh and Monica Dus Exit icon, suspected that the flies had a molecular system for choosing energy-replenishing foods, especially during periods of starvation. Continue reading “Food for Thought: Nutrient-Detecting Brain Sensor in Flies”

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From Basic Research to Bioelectronic Medicine

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Kevin Tracey
Kevin J. Tracey of the Feinstein Institute for Medical Research, the research branch of the North Shore-LIJ Health System, helped launch a new discipline called bioelectronic medicine. Credit: North Shore-LIJ Studios.

By showing that our immune and nervous systems are connected, Kevin J. Tracey of the North Shore-LIJ Health System’s Feinstein Institute for Medical Research helped launch a new discipline called bioelectronic medicine. In this field, scientists explore how to use electricity to stimulate the body to produce its own disease-fighting molecules.

I spoke with Tracey about his research, the scientific process and where bioelectronic medicine is headed next.

How did you uncover the connection between our immune and nervous systems?

My lab was testing whether a chemical we developed called CNI-1493 could stop immune cells from producing inflammation-inducing molecules called TNFs in the brain of rats during a stroke. It does. But we were surprised to find that this chemical also affects neurons, or brain cells. The neurons sense the chemical and respond by sending an electrical signal along the vagus nerve, which runs from the brain to the internal organs. The vagus nerve then releases molecules that tell immune cells throughout the body to make less TNF. I’ve named this neural circuit the inflammatory reflex. Today, scientists in bioelectronic medicine are exploring ways to use tiny electrical devices to stimulate this reflex to treat diseases ranging from rheumatoid arthritis to cancer. Continue reading “From Basic Research to Bioelectronic Medicine”

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Elements That Keep Us Alive Also Give Color to Fireworks

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Looking up at the night sky this Fourth of July, you might wonder what gives fireworks their vivid colors. The bright hues result from chemical elements that are also essential for life. Chemists and other researchers have been uncovering their roles in a range of important biological processes.

By mass, about 96 percent of our bodies are made of four key elements: oxygen (65 percent), carbon (18.5 percent), hydrogen (9.5 percent) and nitrogen (3.3 percent). These elements do not give color to fireworks, but they are found in our body’s most abundant and important molecules, including water, proteins and DNA.

A dozen or so other elements—mostly metals—make up the remaining 4 percent. Present in minuscule amounts, these elements are involved in everything from transporting oxygen and releasing hormones to regulating blood pressure and maintaining bone strength. They also add a burst of color when put in to a fireworks recipe. Here are several examples.

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Designing Drugs That Kill Invasive Fungi Without Harming Humans

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Top to bottom: Cryptococcus, Candida, Aspergillus, Pneumocystis
Invasive fungal infections kill more than 1 million people worldwide every year. Almost all of these deaths are due to fungi in one of these four groups. Credit: Centers for Disease Control and Prevention.

Invasive fungal infections—the kind that infect the bloodstream, lung and brain—are inordinately deadly. A big part of the problem is the lack of drugs that are both effective against the fungi and nontoxic to humans.

The situation might change in the future though, thanks to the work of a multidisciplinary research team led by chemist Martin Burke at the University of Illinois. For years, the team has focused on an antifungal agent called amphotericin B (AmB for short). Although impressively lethal to fungi, AmB is also notoriously toxic to human cells.

Most recently, the research team chemically modified the drug to create compounds that kill fungi, but don’t disrupt human cells. The scientists explain it all in the latest issue of Nature Chemical Biology.

Invasive fungal infections are so intractable because most antifungal drugs aren’t completely effective. Plus, fungi have a tendency to develop resistance to them. AmB is a notable exception. Isolated 50 years ago from Venezuelan dirt, AmB has evaded resistance and remains highly effective. Unfortunately, it causes side effects so debilitating that some doctors call it “ampho-terrible.” At high doses, it is fatal.

For decades, scientists believed that AmB molecules kill fungal cells by forming membrane-piercing pores, or ion channels, through which the cells’ innards leak out. Last year, Burke’s group overturned this well-established concept using evidence from nuclear magnetic resonance, chemistry and cell-based experiments. The researchers showed that AmB molecules assemble outside cells into lattice-like structures. These structures act as powerful sponges, sucking vital lipid molecules, called ergosterol, right out of the fungal cell membrane, destroying the cell. Continue reading “Designing Drugs That Kill Invasive Fungi Without Harming Humans”

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Unusual DNA Form May Help Virus Withstand Extreme Conditions

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A, B and Z DNA.
DNA comes in three forms: A, B and Z. Credit: A-DNA, B-DNA and Z-DNA by Zephyris (Richard Wheeler) under CC BY-SA 3.0.

DNA researcher Rosalind Franklin Exit icon first described an unusual form of DNA called the A-form in the early 1950s (Franklin, who died in 1958, would have turned 95 next month). New research on a heat- and acid-loving virus has revealed surprising information about this DNA form, which is one of three known forms of DNA: A, B and Z.

“Many people have felt that this A-form of DNA is only found in the laboratory under very non-biological conditions, when DNA is dehydrated or dry,” says Edward Egelman Exit icon in a University of Virginia news release Exit icon about the recent study. But considered with earlier studies on bacteria by other researchers, the new findings suggest that the A-form “appears to be a general mechanism in biology for protecting DNA.” Continue reading “Unusual DNA Form May Help Virus Withstand Extreme Conditions”

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Preventing Sepsis in Half the Time

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Human digestive system
A new study suggests that an antibiotic regimen half as long as the standard course could be just as effective in treating intra-abdominal infections and preventing sepsis. Credit: Stock image.

When treating infections, the most critical actions are to quash the infection at its site of origin and prevent it from spreading. If allowed to spread to the bloodstream, an infection could result in body-wide inflammation known as sepsis that can cause organ failure and death.

Intra-abdominal infections, most often caused by gut bacteria, can lead to painful inflammation and present a high risk for sepsis. These infections, which include appendicitis, are some of the most common illnesses around the world.

A standard treatment regimen includes surgically removing the original infection and then prescribing antibiotics to keep the infection from coming back and to prevent sepsis. Currently, doctors administer antibiotics until 2 days after the symptoms disappear, for a total of up to 2 weeks.

Like many other researchers, University of Virginia’s Robert Sawyer Exit icon wondered if treating intra-abdominal infections with shorter antibiotic courses could be just as effective as the standard treatment. To find out, he and a team of researchers from around the country designed the Study to Optimize Peritoneal Infection Therapy (STOP-IT). Continue reading “Preventing Sepsis in Half the Time”

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How a Cell Knows Friend From Foe

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We asked the heads of our scientific divisions to tell us about some of the big questions in fundamental biomedical science that researchers are investigating with NIGMS support. This article is the first in an occasional series that will explore these questions and explain how pursuing the answers could advance understanding of important biological processes.

Video screen shot showing different strains of amoeba cells in red and green.
This video shows different strains of amoeba cells in red and green. As cells move toward one another, they use two sets of proteins to recognize others from the same strain. When close relatives meet, their proteins match and the cells join together to form a multicellular structure. When cells from different strains meet, their proteins don’t match, so they can’t aggregate. Credit: Shigenori Hirose, Baylor College of Medicine.

Cells are faced with many decisions: When’s the best time to produce a new protein? To grow and split into two? To treat another cell as an invader? Scientists are working to understand how cells make these and many other decisions, and how these decisions contribute to health and disease.

An active area of research on cell decisions focuses on allorecognition, the ability of an organism to distinguish its own cells from those of another. Immune cells use a system called the major histocompatibility complex (MHC) to identify which cells belong to the body and which are foreign. The particular set of MHC proteins on the outer surface of a cell helps immune cells decide whether it does not belong and should be attacked.

But the system isn’t perfect. Invading pathogens can go undetected, and the body can mistake its own cells for intruders. Continue reading “How a Cell Knows Friend From Foe”