From Washington University in St.Louis: “Takes a licking and keeps on storing”

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From Washington University in St.Louis

April 23, 2019
Talia Ogliore
talia.ogliore@wustl.edu

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By controlling the formation of rust in solution, researchers in Arts & Sciences grew a micrometer-thick porous mat of conducting fibers affixed to a soft, pliable layer of organic plastic. This new energy storage device can withstand a hammer striking it more than 40 times. (Image: D’Arcy laboratory / Washington University)

Researchers at Washington University in St. Louis made an energy storage device that can withstand a hammer striking it more than 40 times. The shatterproof supercapacitor is also nonflammable, unlike lithium-ion batteries. The new work is the cover story of the April 23 issue of the journal Sustainable Energy and Fuels.

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Julio D’Arcy,

“Accidentally dropping electronics, such as a laptop or cellphone, is a common scenario that may lead to the failure of the device,” said Julio D’Arcy, assistant professor of chemistry in Arts & Sciences. “In some cases, energy storage devices catch on fire due to impact-caused failure. The chance of impact damage will only increase as electronics become more flexible and worn on the human body.”

Hongmin Wang, a PhD candidate in chemistry who works in D’Arcy’s lab, led the effort to create the new material.

By controlling the formation of rust in solution, researchers grew a micrometer-thick porous mat of conducting fibers affixed to a soft, pliable layer of organic plastic. The result is somewhat similar to an open-faced sandwich.

“This is the same mechanism that is responsible for the formation of rust on the surface of a wet piece of steel,” D’Arcy said. “Here, we have carefully designed the nanostructure orientation so that a polymer film assembles parallel to a rusted surface. It produces an interwoven mat of polymer nanofibers with a textile-like structure that is flexible and ideal for storing energy in a supercapacitor.”

The researchers bent their new material to different angles over and over again. They hammered it repeatedly, and they also tested it against an impact equivalent to a car collision at 30 mph. The same amount of impact would fracture other materials such as metal and carbon.

The device held up well against these extreme tests: after the first hammer strike, it retained 80 percent of its ability to store energy at peak efficiencies; after 40 repeated strikes, it was still at 74 percent.

See the full article here .

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Wash U campus

Washington University’s mission is to discover and disseminate knowledge, and protect the freedom of inquiry through research, teaching, and learning.

Washington University creates an environment to encourage and support an ethos of wide-ranging exploration. Washington University’s faculty and staff strive to enhance the lives and livelihoods of students, the people of the greater St. Louis community, the country, and the world.

#applied-research-technology, #accidentally-dropping-electronics-such-as-a-laptop-or-cellphone-is-a-common-scenario-that-may-lead-to-the-failure-of-the-device-said-julio-darcy, #chemistry, #in-some-cases-energy-storage-devices-catch-on-fire-due-to-impact-caused-failure, #it-produces-an-interwoven-mat-of-polymer-nanofibers-with-a-textile-like-structure-that-is-flexible-and-ideal-for-storing-energy-in-a-supercapacitor, #physics, #the-chance-of-impact-damage-will-only-increase-as-electronics-become-more-flexible-and-worn-on-the-human-body, #wash-u-st-louis, #we-have-carefully-designed-the-nanostructure-orientation-so-that-a-polymer-film-assembles-parallel-to-a-rusted-surface

From Washington University in St.Louis: “Reaching for neutron stars”

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Washington University in St.Louis

November 29, 2017.
Chuck Finder
chuck.finder@wustl.edu

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Crab Nebula in the constellation Taurus contains a pulsar at its core that is a younger neutron star, the very type brought into clearer focus by a Physics Review Letters study by researchers at Washington University in St. Louis. Elements of this image are furnished by NASA. (Photo: Shutterstock)

For more than a decade, a cross-disciplinary team of chemists and physicists in Arts & Sciences at Washington University in St. Louis has been chasing the atomic nucleus. With progressive studies, they moved up the element chain to Calcium-48, an extremely rare solid commodity that has more neutrons than protons and, as such, carries a hefty price tag of $100,000 per gram.

It is a quirky material, with this particular study taking Washington University chemists Robert J. Charity and Lee G. Sobotka from Duke’s Triangle Universities Nuclear Laboratory to the Department of Energy’s Los Alamos (N.M.) National Laboratory.

“If you leave it on a table, it turns to powder,” said co-author Charity, a research professor of chemistry in Arts & Sciences. “Calcium oxidizes very quickly in air. It was a worry.”

Ultimately, three grams of Ca-48 helped to produce a double-edged finding for Charity and co-author Willem H. Dickhoff, professor of physics. Their team discovered both a framework to predict where neutrons will inhabit a nucleus and a way to predict the skin thickness of a nucleus.

In their research published Nov. 29 in Physics Review Letters, they predicted how the neutrons would create a thick skin, and that this skin of Ca-48 — 3.5 femtometers (fm) in radius — measured 0.249 + 0.023 fm.

To convert that into centimeters, it would measure 2.49×10^-14 cm. The researchers say the key finding is that the skin is thicker and more neutron-rich than previously believed.

“That links us to astrophysics and, in particular, neutron-star physics,” Dickhoff said of the research results. “The Los Alamos experiment was critical for the analysis we pursued. In the end — because it has this additional set of neutrons — it gets us to information that helps us to further clarify the physics of neutron stars, where there are many more neutrons relative to protons.

“And it gives us the opportunity to predict where the neutrons are in Ca-48,” Dickhoff said. “That is the critical information, which leads to the prediction of the neutron skin.”

For Charity, Dickhoff and co-authors Hossein Mahzoon, PhD ’15, a lecturer in physics at Truman State University in Kirksville, Mo., and Mack Atkinson, a PhD candidate in physics at Washington University, the chase continues.

They watch with interest as Ca-48 is scheduled to undergo the cleanest skin-thickness test available via the electron accelerator at the Thomas Jefferson National Accelerator Facility in Newport News, Va.

Moreover, they proceed to move up the element chain of neutron-rich nuclei to what Charity called the “famous nucleus” of Lead-208. Michael Keim, a senior in physics, is spearheading a study of Lead-208.

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This graph basically shows where the protons are (more solid lines exp and ch ) and where the neutrons are (dotted lines n and w) in the nucleus. The neutrons are located in the thick skin, where the dotted lines separate from the solids. To be precise, the experimental (maroon staggered line) and fitted (black) charge distribution are the solids and the neutron matter distribution (blue) and the weak charge distribution (red hashes) are the dotted lines. (Graphic: the authors)

“It will give us an experimental handle on whether our analysis is really predictive,” Dickhoff said. “We think we have a good argument why we think it has a thick skin. There is a large group of people … who predict a smaller skin. This is directly relevant for the understanding of the size of neutron stars. It is not yet crystal clear how big a neutron star is — its radius.”

How they made their analysis and reached this predictive framework is part of their decade-long pursuit as well. Their chemistry-physics group subscribes to “dispersion relations,” which Sobotka, who is a professor of chemistry and of physics, explained simply: “It’s what tells you not to laugh before you are tickled. That means causality is properly taken into account.”

In short, they analyze all energies simultaneously rather than focusing on one single energy.

Since first publishing together in 2006, they have used the dispersive optical model (DOM) developed a quarter-century ago by Claude Mahauxa, a nuclear theorist from Belgium. They expanded upon it — across energy domains and isotopes — so they could attempt to predict where the nuclear particles are.

“When you put extra neutrons in, it doesn’t like that, right?” Charity said of the atomic nucleus. “It has to figure out how to accommodate these extra neutrons. It can put them evenly throughout the nucleus. Or it could put them on the surface. So the question is: Is this force stronger in the low density region of the nucleus or weaker?”

“We know where the protons are,” Dickhoff added. “That is well established experimentally. But you can’t do that easily with neutrons. I simply want to know what a nucleon, a proton or a neutron, is doing. How is it spending its time? Nucleons are more interactive — they do other things than sit quietly in their orbits. That’s what this method can sort of tell us.”

Their nonlocal DOM framework — a decade-plus in the making — uses computer modeling and computations as well as the lab experimentation. It allows them to “make a prediction that is well founded and taken seriously,” Dickhoff said. “Next, we will have a measurement for Lead-208.”

This study was funded by the U.S. Department of Energy, Division of Nuclear Physics grant DE-FG02-87ER-40316, and National Science Foundation grants PHY-1304242, PHY-1613362 and PHY-1520971.

See the full article here .

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Washington University’s mission is to discover and disseminate knowledge, and protect the freedom of inquiry through research, teaching, and learning.

Washington University creates an environment to encourage and support an ethos of wide-ranging exploration. Washington University’s faculty and staff strive to enhance the lives and livelihoods of students, the people of the greater St. Louis community, the country, and the world.

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From NIH via Wash U: “Snapshots of Life: Fighting Urinary Tract Infections”

Wash U Bloc

Washington University in St.Louis

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NIH

May 25, 2017
Dr. Francis Collins

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Source: Valerie O’Brien, Matthew Joens, Scott J. Hultgren, James A.J. Fitzpatrick, Washington University, St. Louis

For patients who’ve succeeded in knocking out a bad urinary tract infection (UTI) with antibiotic treatment, it’s frustrating to have that uncomfortable burning sensation flare back up. Researchers are hopeful that this striking work of science and art can help them better understand why severe UTIs leave people at greater risk of subsequent infection, as well as find ways to stop the vicious cycle.

Here you see the bladder (blue) of a laboratory mouse that was re-infected 24 hours earlier with the bacterium Escherichia coli (pink), a common cause of UTIs. White blood cells (yellow) reach out with what appear to be stringy extracellular traps to immobilize and kill the bacteria.

For patients who’ve succeeded in knocking out a bad urinary tract infection (UTI) with antibiotic treatment, it’s frustrating to have that uncomfortable burning sensation flare back up. Researchers are hopeful that this striking work of science and art can help them better understand why severe UTIs leave people at greater risk of subsequent infection, as well as find ways to stop the vicious cycle.

Here you see the bladder (blue) of a laboratory mouse that was re-infected 24 hours earlier with the bacterium Escherichia coli (pink), a common cause of UTIs. White blood cells (yellow) reach out with what appear to be stringy extracellular traps to immobilize and kill the bacteria.

Valerie O’Brien, a graduate student in Scott Hultgren’s lab at Washington University, St. Louis, snapped this battle of microbes and white blood cells using a scanning electron microscope and then colorized it to draw out the striking details. It was one of the winners in the Federation of American Societies for Experimental Biology’s 2016 BioArt competition.

As reported last year in Nature Microbiology, O’Brien and her colleagues have evidence that severe UTIs leave a lasting imprint on bladder tissue [1]. That includes structural changes to the bladder wall and modifications in the gene activity of the cells that line its surface. The researchers suspect that a recurrent infection “hotwires” the bladder to rev up production of the enzyme Cox2 and enter an inflammatory state that makes living conditions even more hospitable for bacteria to grow and flourish. This suggests that recurrent UTIs might be treated more effectively with drugs that control inflammation. In fact, the researchers already have preliminary evidence that Cox2 inhibitors used to treat arthritis pain and other conditions might do the job.

The Hultgren lab is also exploring new ways to treat or prevent recurrent UTIs using chemical compounds and peptides designed to prevent bacteria from sticking to the bladder wall and infecting cells. As more bacteria grow resistant to existing antibiotic drugs, this new line of investigation raises hope that it might one day be possible to knock out UTIs out for good, maybe even with no antibiotics required.

See the full article here .

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Wash U campus

Washington University’s mission is to discover and disseminate knowledge, and protect the freedom of inquiry through research, teaching, and learning.

Washington University creates an environment to encourage and support an ethos of wide-ranging exploration. Washington University’s faculty and staff strive to enhance the lives and livelihoods of students, the people of the greater St. Louis community, the country, and the world.

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From Wash U: “Researchers to model brain’s memory network”

Wash U Bloc

Washington University in St.Louis

May 11, 2017
Gerry Everding
gerry_everding@wustl.edu

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No image caption or credit.

Washington University in St. Louis brain scholars will join teams from four other universities in a five-year, $7.5 million research project that aims to build and test the most comprehensive model yet of how people understand and remember events.

“The ultimate goal is a system that can watch the same movies and read the same stories that we show to our human subjects and make detailed, moment-by-moment predictions about what is going on in their minds and brains,” said Jeff Zacks, lead investigator for the Washington University team and professor of psychological and brain sciences in Arts & Sciences.

“If we are successful, this research will enable computer systems that are better collaborators and better teachers, and it will reveal fundamental mechanisms of how people understand their complex everyday worlds.”

See the full article here .

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Wash U campus

Washington University’s mission is to discover and disseminate knowledge, and protect the freedom of inquiry through research, teaching, and learning.

Washington University creates an environment to encourage and support an ethos of wide-ranging exploration. Washington University’s faculty and staff strive to enhance the lives and livelihoods of students, the people of the greater St. Louis community, the country, and the world.

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From Wash U: “New imaging technique aims to ensure surgeons completely remove cancer”

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Washington University in St.Louis

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Caltech

May 17, 2017
Tamara Bhandari
tbhandari@wustl.edu

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A new imaging technique based on light and sound produces images doctors can use to distinguish cancerous breast tissue (below the dotted blue line) from normal tissue more quickly than is currently possible. Pathologists routinely inspect surgical specimens to make sure all cancerous tissue has been removed. The new technique (right) produces images as detailed and accurate as traditional methods (left), but in far less time. The researchers are working to make the technique fast enough to be used during a surgery, so patients don’t have to return for a second surgery. (Image: Terence T.W. Wong)

Of the quarter-million women diagnosed with breast cancer every year in the United States, about 180,000 undergo surgery to remove the cancerous tissue while preserving as much healthy breast tissue as possible.

However, there’s no accurate method to tell during surgery whether all of the cancerous tissue has been successfully removed. The gold-standard analysis takes a day or more, much too long for a surgeon to wait before wrapping up an operation. As a result, about a quarter of women who undergo lumpectomies receive word later that they will need a second surgery because a portion of the tumor was left behind.

Now, researchers at Washington University School of Medicine in St. Louis and California Institute of Technology report that they have developed a technology to scan a tumor sample and produce images detailed and accurate enough to be used to check whether a tumor has been completely removed.

Called photoacoustic imaging, the new technology takes less time than standard analysis techniques. But more work is needed before it is fast enough to be used during an operation.

The research is published May 17 in Science Advances.

“This is a proof of concept that we can use photoacoustic imaging on breast tissue and get images that look similar to traditional staining methods without any sort of tissue processing,” said Deborah Novack, MD, PhD, an associate professor of medicine, and of pathology and immunology, and a co-senior author on the study.

The researchers are working on improvements that they expect will bring the time needed to scan a specimen down to 10 minutes, fast enough to be used during an operation. The current gold-standard method of analysis, which is based on preserving the tissue and then staining it to make the cells easier to see, hasn’t gotten any faster since it was first developed in the mid-20th century.

For solid tumors in most parts of the body, doctors use a technique known as a frozen section to do a quick check of the excised lump during the surgery. They look for a thin rim of normal cells around the tumor. Malignant cells at the margins suggest the surgeon missed some of the tumor, increasing the chances that the disease will recur.

But frozen sections don’t work well on fatty specimens like those from the breast, so the surgeon must finish a breast lumpectomy without knowing for sure how successful it was.

“Right now, we don’t have a good method to assess margins during breast cancer surgeries,” said Rebecca Aft, MD, PhD, a professor of surgery and a co-senior author on the study. Aft, a breast cancer surgeon, treats patients at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine.

Currently, after surgery a specimen is sent to a pathologist, who slices it, stains it and inspects the margins for malignant cells under a microscope. Results are sent back to the surgeon within a few days.

To speed up the process, the researchers took advantage of a phenomenon known as the photoacoustic effect. When a beam of light of the right wavelength hits a molecule, some of the energy is absorbed and then released as sound in the ultrasound range. These sound waves can be detected and used to create an image.

“All molecules absorb light at some wavelength,” said co-senior author Lihong Wang, who conducted the work when he was a professor of biomedical engineering at Washington University’s School of Engineering & Applied Science. He is now at Caltech. “This is what makes photoacoustic imaging so powerful. Essentially, you can see any molecule, provided you have the ability to produce light of any wavelength. None of the other imaging technologies can do that. Ultrasound will not do that. X-rays will not do that. Light is the only tool that allows us to provide biochemical information.”

The researchers tested their technique by scanning slices of tumors removed from three breast cancer patients. For comparison, they also stained each specimen according to standard procedures.

The photoacoustic image matched the stained samples in all key features. The architecture of the tissue and subcellular detail such as the size of nuclei were clearly visible.

“It’s the pattern of cells – their growth pattern, their size, their relationship to one another – that tells us if this is normal tissue or something malignant,” Novack said. “Overall, the photoacoustic images had a lot of the same features that we see with standard staining, which means we can use the same criteria to interpret the photoacoustic imaging. We don’t have to come up with new criteria.”

Having established that photoacoustic techniques can produce usable images, the researchers are working on reducing the scanning time.

“We expect to be able to speed up the process,” Wang said. “For this study, we had only a single channel for emitting light. If you have multiple channels, you can scan in parallel and that reduces the imaging time. Another way to speed it up is to fire the laser faster. Each laser pulse gives you one data point. Faster pulsing means faster data collection.”

Aft, Novack and Wang are applying for a grant to build a photoacoustic imaging machine with multiple channels and fast lasers.

“One day we think we’ll be able to take a specimen straight from the patient, plop it into the machine in the operating room and know in minutes whether we’ve gotten all the tumor out or not,” Aft said. “That’s the goal.”

This work was supported by the National Institutes of Health, grant number DP1 EB016986 and R01 CA186567, and by Washington University’s Siteman Cancer Center’s 2014 Research Development Award.

See the full article here .

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The California Institute of Technology (commonly referred to as Caltech) is a private research university located in Pasadena, California, United States. Caltech has six academic divisions with strong emphases on science and engineering. Its 124-acre (50 ha) primary campus is located approximately 11 mi (18 km) northeast of downtown Los Angeles. “The mission of the California Institute of Technology is to expand human knowledge and benefit society through research integrated with education. We investigate the most challenging, fundamental problems in science and technology in a singularly collegial, interdisciplinary atmosphere, while educating outstanding students to become creative members of society.”


Caltech campus

Wash U campus
Wash U campus

Washington University’s mission is to discover and disseminate knowledge, and protect the freedom of inquiry through research, teaching, and learning.

Washington University creates an environment to encourage and support an ethos of wide-ranging exploration. Washington University’s faculty and staff strive to enhance the lives and livelihoods of students, the people of the greater St. Louis community, the country, and the world.

#applied-research-technology, #caltech, #cancer, #medicine, #new-imaging-technique-aims-to-ensure-surgeons-completely-remove-cancer, #wash-u-st-louis

From Wash U: “Study unveils new way to starve tumors to death”

Wash U Bloc

Washington University in St.Louis

January 24, 2017
Julia Evangelou Strait

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Unlike a healthy cell, a sarcoma cell (above) relies on environmental sources of arginine, an important protein building block. Remove environmental arginine and the cell must begin a process called autophagy, or “self-eating,” to survive. A second hit to its survival pathways then kills the cell, according to a new study at Washington University School of Medicine in St. Louis. Areas of autophagy are shown in green and the cell nucleus in blue. (Image: Jeff Kremer)

For decades, scientists have tried to halt cancer by blocking nutrients from reaching tumor cells, in essence starving tumor cells of the fuel needed to grow and proliferate. Such attempts often have disappointed because cancer cells are nimble, relying on numerous backup routes to continue growing.

Now, scientists at Washington University School of Medicine in St. Louis have exploited a common weak point in cancer cell metabolism, forcing tumor cells to reveal the backup fuel supply routes they rely on when this weak point is compromised. Mapping these secondary routes, the researchers also identified drugs that block them. They now are planning a small clinical trial in cancer patients to evaluate this treatment strategy.

The research is published Jan. 24 in Cell Reports [link is below].

Studying human cancer cells and mice implanted with patients’ tumor samples, the researchers demonstrate that a double hit — knocking out the weak point and one of the tumor cells’ backup routes — shows promise against many hard-to-treat cancers. Though present in multiple cancer types, the weak point is particularly common in sarcomas — rare cancers of fat, muscle, bone, cartilage and connective tissues. Doctors treat sarcomas primarily with traditional surgery, radiation and chemotherapy, but such treatments often are not effective.

“We have determined that this metabolic defect is present in 90 percent of sarcomas,” said senior author Brian A. Van Tine, MD, PhD, an associate professor of medicine. “Healthy cells don’t have this weakness. We have been trying to create a therapy that takes advantage of the metabolic defect because, in theory, it should target only the tumor. Basically, the defect allows us to force the tumor cells to starve.”

To grow and proliferate, tumor cells must have basic building materials. The researchers’ strategy relies on the fact that the vast majority of sarcomas have lost the ability to manufacture their own arginine, a protein building block that cells need to make more of themselves. Lacking this ability, the cells must harvest arginine from the surrounding environment. The supply of arginine in the blood is abundant, and cancer cells have no trouble scavenging it. But remove this environmental supply of arginine and the cells have a problem.

“When we use a drug to deplete arginine in the blood, the cancer cells panic because they’ve lost their fuel supply,” Van Tine said. “So they rewire themselves to try to survive. In this study, we used that rewiring to identify drugs that block the secondary routes.”

Unlike most cancer therapies, depleting arginine in the blood does not affect healthy cells. Normal cells don’t rely on external sources of arginine because they don’t have the cancer’s metabolic defect. They continue to make their own arginine, so there is no induced starvation in normal cells even when there is no arginine in the blood. Van Tine said this strategy is based on the properties of a tumor — it shuts down tumor metabolism specifically and nothing else.

Unable to make or obtain external arginine, the tumor cells’ fuel supply routes are forced inward. The cells must begin to metabolize their internal supply of arginine in a process called autophagy, or “self-eating.” In the case of sarcomas, this state slows or pauses cancer growth but does not kill the cell. During this period, tumor cells appear to be buying time to find yet another internal work-around.

“Cancer doesn’t die when you halt its primary fuel supply,” Van Tine said. “Instead, it turns on all these salvage pathways. In this paper, we identified the salvage pathways. Then we showed that when you drug them, too, you kill cells. Our study showed that tumors actually shrink under these conditions. This is the first time tumors have been shown to shrink using just metabolism drugs and no other anti-cancer strategies.”

The arginine-depleting drug is currently in clinical trials investigating its safety and effectiveness against liver, lung, pancreatic, breast and other cancers. But so far, it has been ineffective likely because it has activated the salvage pathways allowing cancer growth to continue. The researchers said the drug may yet become a vital metabolic therapy for cancer as long as it is used in combination with other drugs targeting the backup pathways.

Van Tine and the study’s first author, Jeff C. Kremer, a PhD student in Van Tine’s lab, explained that when cancer cells with this metabolic defect are deprived of environmental arginine, they are forced to shift from a system that burns glucose to a system that burns a different fuel called glutamine. They showed that adding a glutamine inhibitor to the arginine-depleting drug is lethal to the cells. Eliminating arginine from the blood also rewires serine biology, another backup fuel, so adding serine inhibitors also causes cell death.

This strategy could be applied beyond rare sarcoma tumors because the metabolic defect is often present in other cancers, including certain types of breast, colon, lung, brain and bone tumors, the researchers said. The new study includes data showing similar anti-tumor responses in cell lines from these cancer types. Van Tine also pointed out that all of the drugs used in the study are either already approved by the U.S. Food and Drug Administration for other conditions or in ongoing clinical trials investigating cancer drugs.

Based on this study and related research, Van Tine and his colleagues at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine are planning a clinical trial of the arginine-depleting drug in patients with sarcomas.

“We will start with a baseline trial testing the arginine-depleting drug against sarcomas with this defect, and then we can begin layering additional drugs on top of that therapy,” Van Tine said. “Unlike breast cancer, for example, sarcomas currently have no targeted therapies. If this strategy is effective, it could transform the treatment of 90 percent of sarcoma tumors.”
This work was supported by grants from CJ’s Journey; The Sarcoma Foundation of America; a Sarcoma Alliance for Research and Collaboration Career Development Award; and Polaris Pharmaceuticals. Polaris Pharmaceuticals provided funding and the arginine-depleting drug, ADI-PEG20 (pegylated arginine deiminase).

Kremer JC, Prudner BC, Lange SES, Bean GR, Schultze MB, Brashears CB, Radyk MD, Redlich N, Tzeng S, Kami K, Shelton L, Li A, Morgan Z, Bomalaski JS, Tsukamoto T, McConathy J, Michel LS, Held JM, Van Tine BA. Arginine deprivation inhibits the Warburg effect and upregulates glutamine anaplerosis and serine biosynthesis in ASS1-deficient cancers. Cell Reports. Jan. 24, 2017.

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Washington University’s mission is to discover and disseminate knowledge, and protect the freedom of inquiry through research, teaching, and learning.

Washington University creates an environment to encourage and support an ethos of wide-ranging exploration. Washington University’s faculty and staff strive to enhance the lives and livelihoods of students, the people of the greater St. Louis community, the country, and the world.

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From Wash U: “Persistent infection keeps immune memory sharp, leading to long-term protection”

Wash U Bloc

Washington University in St.Louis

January 16, 2017
Tamara Bhandari

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For many infectious diseases, a single bout of the illness protects a person against contracting it again. In some cases, the infecting microbe persists in the body long after symptoms resolve, and can cause disease later in life. Now, researchers studying the tropical parasite Leishmania have found a clue to explain the link between long-term immunity and long-term infection: The parasite (shown in green) is constantly multiplying and being killed by immune cells (pink and blue), keeping the immune system alert and prepared for any new encounters with the parasite. (Image: M.A. Mandell and S.M. Beverley)

Many infectious diseases are one and done; people get sick once and then they are protected from another bout of the same illness. For some of these infections – chickenpox, for example – a small number of microbes persist in the body long after the symptoms have gone away. Often, such microbes can reactivate when the person’s immunity has waned with age or illness, and cause disease again.

Now, researchers at Washington University School of Medicine in St. Louis studying leishmaniasis, a tropical disease that kills tens of thousands of people every year, believe they have found an explanation for the seemingly paradoxical connection between long-term infection and long-term immunity. By constantly reminding the immune system what the parasite that causes leishmaniasis looks like, a persistent infection keeps the immune system on alert against new encounters, even while it carries the risk of causing disease later in life, the researchers found.

Understanding how persistent infection leads to long-term immunity could help researchers design vaccines and treatments for persistent pathogens.

The research is published the week of Jan. 16 in Proceedings of the National Academy of Sciences.

“People had been thinking of the role of the immune system in persistent infection in terms of mowing down any pathogens that reactivate in order to protect the body from disease,” said Stephen Beverley, the Marvin A. Brennecke Professor of Molecular Microbiology and the study’s senior author. “What was often overlooked was that in the process of doing this, the immune system is constantly being stimulated, which potentially promotes protection against future illness.”

In a persistent infection, a small population of microbes remains in the body long after the patient’s symptoms are gone. In addition to the parasite that causes leishmaniasis, many kinds of microbes can cause persistent infections, including bacteria responsible for tuberculosis and viruses that lead to herpes and chickenpox.

“A lot of pathogens cause persistent infections, but the process was something of a black box,” said Michael Mandell, the first author on the study. Mandell, who conducted the research for the study as a graduate student, is now an assistant professor at the University of New Mexico. “Nobody really knew what was going on during persistent infection and why it was associated with immunity.”

To find out, Mandell and Beverley studied Leishmania, a group of parasites that cause ulcers on the skin and can infect internal organs. An estimated 250 million people worldwide are infected with the parasite – found in tropical areas – and 12 million have active disease. The disease can be disfiguring or even fatal, but once a person is infected, he or she is protected from getting sick a second time. In other words, infection confers long-term immunity.

People are thought to continue to harbor the parasite at low numbers for years after they recover from the disease, including some people treated with anti-leishmania drugs. This persistence may be to the benefit of their human hosts; studies in mice have shown that completely clearing the parasite often makes the animals susceptible to another bout of disease if they encounter the parasite again.

Studying mice, the researchers used fluorescent markers to distinguish different types of mouse cells, and found that most of the parasites live in immune cells capable of killing the parasites. Yet, despite their dangerous homes, the parasites appeared normal in shape and size.

Further, most of the parasites continued to multiply, yet the total number of parasites stayed the same over time.

“Mike Mandell called it the ‘Jimmy Hoffa effect’ because we couldn’t locate the body,” Beverley said. “We were unable to show directly that the parasites were being killed. But some of them must have been dying because the numbers weren’t going up.”

The immune cells that housed the parasites are responsible for killing pathogens and activating a more robust immune response. It is this process – the ongoing multiplication and killing of parasites – that the researchers believe underlies the long-term immunity associated with persistent infection, and thus explains why people typically can’t get sick with the same pathogen twice.

“It seems that our immunologic memory needs reminding sometimes,” Mandell said. “As the persistent parasites replicate and get killed, they are continually stimulating the immune system, keeping it primed and ready for any new encounters with the parasite.”

These findings suggest that there are benefits as well as dangers to persistent infection, and, for some organisms at least, developing a vaccine that elicits life-long immunity might require a live vaccine that has the ability to persist without sickening people.

“Usually scientists design vaccines to get sterilizing immunity. They’re trying to just kill all the bugs,” Beverley said. “But what you really need is protection against the pathologic consequences of the disease, not necessarily sterilizing immunity. For some of these organisms, solid, long-term protection may come at the price of persistent infection.”

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