Research

Dog owners often make inferences about what their four-legged companions are thinking or feeling. But how correct are such assumptions? A recent study by Emory University researchers aimed to answer this question and others about the minds of man’s best friend.

During the study, researchers spent eight months training two canines to sit motionless inside a functional magnetic resonance imaging (fMRI) machine. They then analyzed the animals’ brain activity while using hand signals indicating the dogs would either receive or not receive a hot dog. Results showed the appropriate brain regions lit up in anticipation of a treat.

In the above Emory video, researchers discuss their findings and their motivation for embarking on the study.

Via Healthland

Chemotherapy saves lives, but it also kills healthy tissue like bone marrow. According to a new study involving three patients with glioblastoma, a deadly cancer of the brain, stem cells from cancer patients’ own blood may protect their bone marrow from the toxic effects of treatment.

Glioblastomas often carry an active form of a gene called MGMT, which is a DNA repair enzyme that protects the cancer cells against chemotherapy. To overcome that protective effect, doctors use benzylguanine, a drug that blocks MGMT – but that drug also makes bone marrow and blood cells vulnerable. For this study, scientists at Fred Hutchinson Cancer Research Center in Washington took a different approach by transplanting gene-modified stem cells into study participants.

From a release:

By giving bone marrow stem cells P140K, which is a modified version of MGMT, those cells are protected from the toxic effects of benzylguanine and chemotherapy, while the tumor cells are still sensitive to chemotherapy. “P140K can repair the damage caused by chemotherapy and is impervious to the effects of benzylguanine,” [lead author Hans-Peter Kiem, MD] said.

“This therapy is analogous to firing at both tumor cells and bone marrow cells, but giving the bone marrow cells protective shields while the tumor cells are unshielded,” said Jennifer Adair, Ph.D., who shares first authorship of the study with Brian Beard, Ph.D., both members of Kiem’s lab.

The three patients in this study survived an average of 22 months after receiving transplants of their own circulating blood stem cells. One, an Alaskan man, remains alive 34 months after treatment. Median survival for patients with this type of high-risk glioblastoma without a transplant is just over a year.

A paper on the work appears today in Science Translational Medicine.  The clinical trial is ongoing and more research is needed to see whether the potential treatment will work for others.

Previously: Clinical trials: my next good chance, In-womb exposure to chemotherapy appears safe for babies and New discovery suggests tumor suppression can be had without killing healthy cells
Photo by the National Cancer Institute

It could be the name (which has a somewhat Avengers-esque feel) but I find myself intrigued with Mcubed, a new research funding initiative from the University of Michigan. Described on its website as “a modern alternative to the traditional year-long government grant review process,” the program will award funds to “three researchers from different disciplines… [who] come up with an idea and agree to work together.”

Nature’s newsblog further describes:

A total of $15 million will be doled out to projects continuously posted on the MCubed website, beginning with its launch in October. On the site, faculty can start their own projects by publicly describing what they want to do, why, and vow to report back on their project’s status at a MCubed symposium. Or they can sign up to be the second or third member of a project already posted. If they happen to be third, boom: within 24 hours the threesome wins $60 thousand. The competition for funds depends only on speed, and isn’t fierce. [Thomas Zurbuchen, PhD, associate dean for entrepreneurial programs at the College of Engineering] estimates that some 1500 faculty will be competing for 750 so-called tokens worth $20,000 each (but only cashed out in threes).

Zurbechen and the two other professors who conceived of the initiative thought it would be a great way to stimulate interdisciplinary collaborations and encourage newborn ideas in a timely fashion. “I’ve sat on review boards for different agencies, and it’s really damn hard to judge who the best person is to execute a project,” says Zurbechen. “Instead we are allowing people to just execute their project themselves, and after the fact we’ll see how they do. So really, it will be the purist form of a review.”

In March, sculptor Alyson Shotz visited Stanford as the annual Sterling Visiting Professor in the Department of Chemical and Systems Biology. While here, she collaborated with students for a week of creativity building. Among the activities, Shotz and students visited a studio to stress glass in various ways, including enclosing foods in it, and then returned to campus to examine and photograph the samples microscopically.

The above video captures snippets from the experiments and features Shotz discussing the relationship between empirical research and experimentation in art.

Previously: Image of the Week: Kiwi under glass and Stanford’s explosive exercise in creativity

When you fall ill or have an allergic reaction, special immune cells churn out antibodies to identify invaders such as bacteria (or allergens like pollen). Now, scientists at The Scripps Research Institute have figured out how some of those cells know what to do.

As described in a release today, the first time young B cells find pieces of an invader, perhaps bits of a virus or bacteria, they learn how to make antibodies. Some B cells turn into plasma B cells and manufacture antibodies immediately, slowly ratcheting up production over time. Others become memory B cells, which can remain dormant for years until a second infection triggers them to respond.

Those memory B cells fall into different classes. Immune cells called helper T cells secrete chemical signals that tell the B cells which class to choose. One of them, the IgG class, is populated by B cells that respond to most viruses and bacteria. IgA-class B cells are found in mucosal surfaces like the intestines. Cells in the IgE class respond to parasites like intestinal worms.

Exactly how the cells choose which class to join has been unclear. The Scripps researchers nailed down two specific molecules needed to change young, ‘naive’ B cells into IgG2a-class memory B cells. The proteins are called T-bet and RORα, according to a paper recently published in the advance online edition of Nature Immunology.

“This is a real breakthrough, in the sense that we now have a much better understanding of how B cell class is regulated, and how we might target that regulatory process in vaccine and drug design,” said lead author Michael McHeyzer-Williams, PhD, in the release.

The discovery could help researchers design more-effective vaccines. With the addition of a specific protein, the vaccine itself could encourage cells to fall in certain classes and induce long-term immunity. For example, the vaccine might include addition of T-bet and RORα, to help push more B-cells into the IgG2a class, which is effective against viruses. The same concept, reversed, could discourage memory B cells and reduce over-the-top immune reactions common in autoimmune, allergic and lymphoma conditions.

“Being able to target just that class of B cell would be an obvious advantage over existing therapies, such as steroids, that knock down large parts of the immune system,” said McHeyzer-Williams.

Photo by Wellcome Images

Cancer tumors shed cells that circulate through the blood steam. And, according to a Stanford study published today in PLoS ONE, those mobile cells have a high level of genetic diversity even within a single patient.

For the study, researchers here looked at circulating tumor cells (CTCs) first in mouse cell-lines and then in blood drawn from breast cancer patients. To find the very small number of CTCs in blood, the team used a device they developed in 2008 called the MagSweeper, which zeros in on specific protein on the surface of tumor cells. Next, they measured the levels of 95 different genes using another Stanford technology: real-time PCR microfluidic chips, developed by Stephen Quake, PhD, professor of bioengineering. They found as many as five different groups of cancer cells – all with different patterns of genes turned on or off. 

Study senior author Stefanie Jeffrey, MD, explained the significance of the findings in our release:

The diversity, Jeffrey said, means that tumors may contain multiple types of cancer cells that may get into the bloodstream, and a single biopsy from a patient’s tumor doesn’t necessarily reflect all the molecular changes that are driving a cancer forward and helping it spread. Moreover, different cells may require different therapies. One breast cancer patient studied, for example, had some CTCs positive for the marker HER2 and others lacked the marker. When the patient was treated with a drug designed to target HER2-positive cancers, the CTCs lacking the molecule remained in her bloodstream.

…

These results don’t have immediate impacts for cancer patients in the clinic because more work is needed to discover whether different types of CTCs respond to different therapies and whether that will be clinically useful for guiding treatment decisions. But the finding is a step forward in understanding the basic science behind the bits of tumors that circulate in the blood

Previously: Researchers take a step toward understanding the genetics behind breast cancer

I’m never really sure what to say when people ask me why I run. I stammer about enjoying the accomplishment of crossing the finish line, I mumble about the stress relief or I joke that it’s a preemptive strike against my fondness for Chipotle burritos.

Truth be told, I think that’s only part of it. The other part is how I feel after a good run: the rush of lightness, the release of tension lingering in my muscles and the thought that I’m stronger than I was before.

According to David Raichlen, PhD, a researcher at the University of Arizona and a runner, the so-called runner’s high is a legitimately addictive feeling and may be part of the reason I’m hitting the trails and doing laps around my neighborhood on a regular basis. In recent research published in the Journal of Experimental Biology, Raichlen explored similarities between this feeling and the addictive nature of drugs. And today, NPR Shots discusses Raichlen’s findings and how the runner’s high may have had evolutionary advantages for early humans:

When people exercise aerobically, their bodies can actually make drugs — cannabinoids, the same kind of chemicals in marijuana. Raichlen wondered if other distance-running animals also produced those drugs. If so, maybe runner’s high is not some peculiar thing with humans. Maybe it’s an evolutionary payoff for doing something hard and painful, that also helps them survive better, be healthier, hunt better or have more offspring.

So he put dogs — also distance runners — on a treadmill. Also ferrets, but ferrets are not long-distance runners. The dogs produced the drug, but the ferrets did not. Says Raichlen: “It suggests some level of aerobic exercise was encouraged by natural selection, and it may be fairly deep in our evolutionary roots.”

Raichlen himself admits that his research is not conclusive, saying that he would like to continue to experiment with more animals. But whether or not my ancestors ran to be more adept at chasing after food, I’m just happy to be addicted.

Photo by Infomatique

A year ago, researchers raised the red flag on popular smoking-cessation drug Chantix, citing findings that taking the medication was associated with an increased risk of serious heart problems. Today, a San Francisco Chronicle article takes a look at a new UC San Francisco study that challenges the earlier research and found no significant difference in rates of heart attacks and other serious  problems between smokers who took Chantix and those who didn’t.

In the story, Sean David, MD, PhD, a clinical associate professor of medicine at Stanford, comments on what the findings may mean for physicians. He says:

[The previous work] hasn’t really changed whether or not I prescribe the medication that works the best for my patients. But I know that there are a lot of physicians that were alarmed and probably have stopped prescribing it… Hopefully this new study will help physicians reconsider.

It’s worth noting that both studies involved a large number of participants: 14 clinical trials and 8,200 patients in the 2011 study compared with the 22 trials and 9,200 patients in the UCSF study.

The article brought to mind an entry posted on Scope earlier this week about an Institute of Medicine report recommending ways to improve the U.S. Food and Drug Administration’s drug-approval and tracking systems. The report’s goal is to determine how best to identify unanticipated side effects prior to a drug reaching the market — an important issue in cases such as Chantix, a drug that has been shown to have high success rates in helping patients kick the nicotine habit.

Previously: New ideas to help FDA discover drug risks, Hey doc, got a light? Research highlights Big Tobacco’s long history with the medical community and Kicking the smoking habit for good
Photo by snailo86

News coverage of the first-of-its-kind World Health Organization (WHO) report on preterm birth has been headlined by the staggering number of preterm births (15 million a year, worldwide) and by dismal U.S. statistics that show a far higher preterm birth rate here than in any other developed country.

But some of the coverage mentions another shocking fact about babies born a week or more early: In about half of these early deliveries, we can’t pinpoint a clear reason that the baby arrived too soon. And the reasons we’ve already identified for preterm delivery probably don’t tell the whole story. For instance, the New York Times reports that

Dr. Gordon C. S. Smith, an expert in [preterm birth] at the University of Cambridge, noted that his native Scotland had many of the same risk factors as the United States — teenage pregnancies, poverty, obesity and older mothers — and yet had much lower rates.

“If somebody had a simple explanation of why the U.K. and Europe do much better, I wouldn’t believe them,” Dr. Smith said. “The reality is, for most preterm births, we just don’t understand the cause.”

But researchers at Stanford are working to change that. Last year, a generous funding commitment from the March of Dimes facilitated the opening of the March of Dimes Prematurity Research Center at Stanford University School of Medicine, which is taking a new approach to studying the causes of preterm birth. The “transdisciplinary” research center pulls scientists from across many disciplines together for collaboration at every stage of research, from developing hypotheses to analyzing the results.

Today I asked Gary Shaw, DrPH, co-investigator of the center and a professor of pediatrics at Stanford, for his take on the WHO report.

“The report highlights that this is a bigger problem than we had previously thought,” Shaw said. “We don’t know the causes of preterm birth, but we know we need a new approach toward finding answers.”

Factors as diverse as an expectant mother’s age, blood pressure, socioeconomic status, perceived stress level and the presence of infections are already known to influence preterm birth. So it makes sense to bring together experts a diversity of fields, many of whom may not have ever thought about preterm birth, to find out how such factors could interact to ultimately determine whether or not a baby arrives early, he said.

“This is a different way to approach team science… a different way to tackle a complex problem,” Shaw told me. “And Stanford and the March of Dimes are the first to take on this new approach.”

Previously: Hormone could prevent 10,000 preterm births per year, New research center aims to understand premature birth, Device designed to better detect preterm labor and Moms who were born prematurely more likely to have premature babies themselves
Photo by The Hudson Family

In a story online today, I describe how a team led by Stanford’s Carlos Bustamante, PhD, and Sean Myles, PhD, discovered that the gene for blond hair arose independently in the South Pacific nation of the Solomon Islands. The researchers identified the islanders’ “blond” gene and discovered it’s not the same gene that causes blond hair in Europeans.

Reporting the story was so much fun. I learned from Myles, who spent a month there gathering the data, how important it is to get the village chief on board when doing genetic research in the Solomon Islands, that Solomon Islanders’ saliva (which he collected for the study) is often bright red from chewing betel nut, and that on one of the islands (with an active volcano) you can cook by simply burying the food in the hot ground for a while. “The beaches are pristine, water super blue. You can hear the fish jumping in the water. It’s what a lot of people would think of as paradise,” he told me. Wow, what a trip.

The genetic finding, published in the May 4 issue of  Science, has a certain “wow” appeal too, and the researchers say there’s a serious message that comes along with it. As Bustamante told me, the finding underscores the importance of genetic studies on isolated populations like the Solomon Islanders:

If we’re going to be designing the next generation of medical treatments using genetic information and we don’t have a really broad spectrum of populations included, you could disproportionately benefit some populations and harm others.

Myles, now an assistant professor at Nova Scotia Agricultural College, expands on this on his lab’s website:

Our result is therefore a call for action. We must take steps now to ensure that the benefits of current genomics research extend beyond privileged populations and provide an increase in well-being for people everywhere. Humanity’s natural genetic diversity is vast and fascinating – we should be measuring and assessing it all! The same applies for genomics research in agriculture. A continued focus on a small number of elite individuals in plant and animal breeding is myopic and dangerous. An immense amount of existing genetic diversity that is essential to our future well-being is being ignored. Whether it’s us or our food that we research, our aim is to cultivate an appreciation for natural genetic diversity. Our future depends on it.

Photo of a child from the Solomon Islands by Sean Myles

In case you missed it, the U.K. government has announced its plans to make publicly funded research freely available online. A portal called Gateway To Research, which will provide links to published studies and related data, is currently being developed.

paidContent’s Robert Andrews reports today:

The news will prove unpopular with academic publishers, which license and peer-review researchers’ work and charge libraries to make it available.

“As taxpayers put their money towards intellectual enquiry, they cannot be barred from then accessing it,” science minister David Willetts said in a speech to the Publishers Association on Wednesday (transcript).

“They should not be kept outside with their noses pressed to the window – whilst, inside, the academic community produces research in an exclusive space.”

The Guardian also ran an interesting piece earlier this week on Wikipedia co-founder Jimmy Wales’ role in the government’s endeavor.

A New Scientist story published today highlights work by Swedish researchers to identify the basic molecular structure of the skin layer that forms our body’s watertight barrier. The findings may help further efforts to develop new technology to deliver drugs directly through the skin.

In the (small) study, researchers shaved a layer of skin from volunteers’ arms, cooled the tissue to below -140 Celsius in a high-pressure freezer and then sliced the skin samples into layers 25-50 nanometers thick. The tissue was then examined using an electron microscope. Helen Thomson writes:

What the researchers saw surprised them. Lipids have a hydrophilic (water-attracting) head and two hydrophobic (water-repelling) tails. Normally, the two tails point in the same direction, giving the molecule a hairpin-like appearance.

A group of lipid molecules typically arrange themselves into a two-layered sheet – or bilayer – with all of the tails pointing inwards. However, the lipid molecules in between the cells of the stratum corneum are splayed outwards so that the two tails of each molecule point in opposite directions.

…

This uniquely structured fatty layer prevents any water from getting past in either direction – except where the skin layer is modified to form pores. “There’s no water present within this extracellular space,” says [study author Lars Norlen, MD, PhD.] “It cannot perturb the barrier so it’s completely robust to hydration, which is necessary for the changing environment that we live in.”

The research team now plans to use the findings to create a computer model to use in developing a method for screen drugs that could potentially be administered through the skin.

Photo by Monik Markus

Focusing on a highly engaging visual-spatial task, such as playing the tile-matching puzzle video game Tetris, may help in reducing patients’ frequency of flashbacks and enhance treatment of post-traumatic stress disorder (PTSD), according to findings presented at the British Psychology Society Annual Conference in London.

A recent Scientific American story describes the Oxford University research:

To test their idea, researchers asked subjects to view a disturbing film — an admittedly poor but sufficient simulation of real trauma. Within six hours of viewing this film, the period during which memories are thought to be consolidated for long-term storage, test subjects were randomly assigned to one of three tasks: answering trivia; playing Tetris, a 1980s video game that involves optimizing visual-spatial cues; or engaging in nothing in particular.

Over the following week, subjects who had played Tetris reported experiencing significantly fewer flashbacks of the film than the others did. (For reasons that are unclear, those who answered trivia actually had the most flashbacks.) The finding supported previous research on Tetris therapy.

When played immediately following exposure to trauma, “the Tetris game had a protective effect,” lead researcher Emily Holmes, a professor at Oxford, said. She and colleagues hypothesize that the visual-spatial demands of Tetris disrupt the formation of the mental imagery involved in flashbacks.

Researchers noted that these results do not suggest that playing video games is a substitute for conventional treatment of PTSD, but rather that this could offer an alternative method for addressing patients’ symptoms.

Previously: Stanford and other medical schools to increase training and research for PTSD, combat injuries, As soldiers return home, demand for psychologists with military experience grows and Can training soldiers to meditate combat PTSD?
Photo by jon jordan

Genomics and electronic medical records hold a wealth of information for health researchers. But privacy concerns and ethical issues of data ownership prevent scientists from using that data. Now an open-data project aims to create a huge pool of user-contributed information on health and genomics.

A Nature News article today gave details on the newly-launched Portable Legal Consent for Common Genomics Research. The system will remove identifying details from data and require data donors to sit through a lengthly consent process.

Stanford physician and researcher Atul Butte, MD, PhD, commented on the approach:

“For folks who already have well-established cohorts of patients and controls, sharing is not the first thing on their priority list,” says Atul Butte, a physician, researcher and entrepreneur at the Stanford University School of Medicine in California.

But, Butte says, Portable Legal Consent could benefit researchers without the means to assemble large data sets. “For the little guy, or the lab that has something unique to offer but has trouble accessing the patients or the data, this is going to be an enormous movement forward,” he says.

In a Stanford study appearing today in PLoS ONE, researchers show that anxiety-prone mice develop more severe cancer then their calm counterparts. The work, which is detailed in a release, is “the first to biologically connect the personality trait of high anxiety to greater cancer threats.”

Saying that studies in humans are now needed, stress expert and study author Firdaus Dhabhar, PhD, notes:

It’s bad enough that cancer diagnosis and treatment generates stress and anxiety, but this study shows that anxiety and stress can accelerate cancer progression, thus perpetuating a vicious cycle. The goal is to ameliorate or eliminate the effects of anxiety and chronic stress, at least at the time of cancer diagnosis and during treatment.