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ScienceSeeker honors Anna’s story

May 15, 2013

The story of Anna Sumner’s extraordinary experience — disabling chronic sleepiness, leading to scientific discovery and treatment at Emory — has been told in several places, among them the Wall Street Journal and the Today Show.

One of the most extensive and elegant approaches, in our opinion, was science journalist Virginia Hughes‘ post “Re-Awakenings,” originally written for the group blog Last Word on Nothing. (Hughes is now part of National Geographic’s Phenomena quartet of bloggers.) Yesterday “Re-Awakenings” won some recognition, receiving the “Post of the Year” award from ScienceSeeker, a community square for science blogging.

Note: We here at Emory Health Now are still learning about the thriving world of science blogging, but Scientific American’s blog impresario Bora Zivkovic calls ScienceSeeker “the main portal for collecting, connecting and filtering science writing online.” The judges for the awards were Fraser Cain, Maggie Koerth-Baker, and Maryn McKenna.

In addition, the most recent issue of Emory Medicine has a feature on Anna’s story, and neurologist David Rye, who leads the Emory team who treated Anna, has his own take in the June issue of Discover magazine.

 

Quinn Eastman 15 May 2013 News , , , , , , , , No Comments

Alphabet of modified DNA keeps expanding

April 19, 2013

Move over, A, G, C and T. The alphabet of epigenetic DNA modifications keeps getting longer.

A year ago, we described research on previously unseen information in the genetic code using this metaphor:

Imagine reading an entire book, but then realizing that your glasses did not allow you to distinguish “g” from “q.” What details did you miss?

Geneticists faced a similar problem with the recent discovery of a “sixth nucleotide” in the DNA alphabet. Two modifications of cytosine, one of the four bases that make up DNA, look almost the same but mean different things. But scientists lacked a way of reading DNA, letter by letter, and detecting precisely where these modifications are found in particular tissues or cell types.

Now, a team… has developed and tested a technique to accomplish this task.

Well, Emory geneticist Peng Jin and his collaborator Chuan He at the University of Chicago are at it again.

It turns out that 5-hydroxymethylcytosine or 5-hmC, the DNA modification Jin’s and He’s laboratories figured out how to read precisely, was just the beginning. Jin and He have a new paper in Cell describing a method for mapping a related modification: 5-formylcytosine. The co-first authors are U of C graduate student Chun-Xiao Song and Emory research specialist Keith Szulwach.

FormylUsing the “g” vs “q” analogy, it’s as if DNA has lots of g’s, some q’s, and a few letters that look similar to g but have an extra squiggle. What do those extra squiggles mean?

However, it gets complicated because DNA – the book of life – is subtly different in every cell, and is often being edited or repaired. The g’s and q’s aren’t simply static. Maybe those extra squiggles are editing marks that are going to get cleaned up soon? Or do they highlight words or sentences that should be pronounced differently? That’s what Jin and He are trying to figure out.

Let’s back up a bit. The DNA modification generally known as methylation (5-mC) has been studied for decades. It is generally found on genes that are turned off, and it plays an important role in keeping them off. In contrast, 5-hmC – which is basically an oxidized form of 5-mC — appears to be enriched on active genes, especially in brain cells.

[Graduate student Tao Wang, in Steve Warren’s lab, has a recent paper on how the distribution of 5-hmC changes during human brain development.]

The focus of the new Cell paper, 5-formyl C, is an even more oxidized form of 5mC. Based on its distribution in the genomes of mouse embryonic stem cells, it looks like 5-formyl C is a sign that a cell is turning on a gene after it was turned off. 5-formyl C is significantly rarer, present at levels of 60 parts per million, compared to levels of a few percent for 5-hmC in some active genes.

Jin says: “5fC would represent active DNA demethylation. It is enriched at poised enhancers, but it is also present in other genomic features such as promoters or active enhancers.”

A similar paper in Cell from Yi Zhang and colleagues at Harvard looks at the same issue. This is a particularly active area of research, since 5-hmC appears to have important functions in stem cells and the brain.

Quinn Eastman 19 April 2013 News, Research , , , , , , , , No Comments

Detecting clandestine chlamydia

April 16, 2013

In recent years public health authorities have raised concern that many strains of Chlamydia trachomatis, a bacterium that is the most common cause of sexually transmitted infections around the world, can be missed by conventional genetic tests. A mutation in part of its genomc can make Chlamydia undetectable by the most commonly used tests.

Most infections are asymptomatic but left untreated, Chlamydia infection can lead to pelvic inflammatory disease, infertility and ectopic pregnancy. It is also a leading cause of blindness in developing countries.

Microbial geneticist Tim Read at Emory has been collaborating with Deborah Dean at Children’s Hospital Oakland and the Massachusetts firm NetBio to develop a fast, accurate and sensitive genetic test for Chlamydia.

“We used tools that were developed initially to answer basic scientific questions,” Read says. “We compared multiple genomes of C. trachomatis to find targets that would work across a broad selection of bacterial strains.”

Microfluidic

The Chlamydia tests are performed in a microfluidic cassette platform and data is returned about an hour after sample collection. In comparison, standard tests take a day or longer.

The results of a head-to-head comparison of the new test against a standard commercially available test for Chlamydia were published in PLOS One in December. Samples came from 263 women in the San Francisco Bay area. The sensitivity and specificity of the assay were 91 percent and 100 percent, compared to 62 percent and 96 percent for the the commercial test.

The new test combines 9 separate genetic probes at different spots in the genome, reducing the chances of false negatives.

The Emory/Oakland/NetBio team has also been funded by the National Institute of Allergy and Infectious Diseases to develop a similar test for Neisseria gonorrhoeae, a bacterium that causes another major sexually transmitted infection. Separately, NetBio is being funded by the Federal Bureau of Investigation, Department of Defense and Department of Homeland Security to develop a rapid DNA processing system for forensic investigators.

 

Quinn Eastman 16 April 2013 News, Research , , , No Comments

Where does learning to touch more sensitively “live” in the brain?

March 20, 2013

When someone’s sense of touch becomes more acute through training, the brain itself changes. Using functional magnetic resonance imaging (fMRI), researchers have devised ways to see which areas of the brain become more active.

Surprisingly, the changes in activity appear in parts of the brain thought to be responsible for decision-making, rather than the “somatosensory” regions involved in processing touch signals from the fingers.

The results were reported Tuesday in the Journal of Neuroscience.

Participants were asked to discriminate between three-dot patterns, while the horizontal offset became less and less.

Participants were asked to discriminate between three-dot patterns, while the horizontal offset became less and less.

Sighted college undergraduates were trained to discriminate between patterns of raised dots with their fingers. After several sessions, the threshold of differences study participants could detect became much smaller. They could detect differences of less than 0.2 millimeters, when they had started out only being able to detect 1 millimeter changes.

“It is a task that resembles reading braille, and it tests for the same kind of fine level discrimination needed to read braille,” says Krish Sathian, MD, PhD, professor of neurology, rehabilitation medicine, and psychology at Emory University.

Sathian is also medical director of the Center for Systems Imaging at Emory University School of Medicine and director of the Rehabilitation R&D Center of Excellence at the Atlanta Veterans Affairs Medical Center.

Sathian says what the students were engaged in is an example of perceptual learning, a category of learning also including learning to read letters of the alphabet, discriminate tumors on an X-ray and recognize musical tones or instruments.

The study’s findings could have implications for helping people with conditions such as stroke and Parkinson’s disease – in which areas in the brain involved in perceptual learning can be damaged — but also more fundamentally, in understanding where perceptual learning “lives” in the brain.

“It’s a shift away from thinking that each part of the brain has one modular function,” Sathian says. “It suggests that changes seen in perceptual learning are found more in the network, in the connections and interactions between regions of the brain.”

Study participants had their brains scanned with fMRI while performing the dot-reading task. After a week of practice, their ability to discriminate increased. A control group had no training (and didn’t experience either perceptual improvement or brain changes). Another control consisted of all study participants also performing a slightly different task: estimating how long the dots were present before being taken away. Participants were not trained on this control task, and the fMRI scans identified brain regions showing changes specific for the trained (spatial) task.

For neuroscience aficionados — the areas of the brain where activity increased specifically when someone was trained in the spatial-touch-discrimination task were: the anterior insula, the pre-SMA (supplementary motor area), the putamen, anterior thalamus and cerebellum.

Brain areas specifically activated by the tactile "reading" task in people who had trained on it

Brain areas specifically activated during the tactile perception task in people who had trained on it

Quinn Eastman 20 March 2013 News, Research No Comments

A Sherer of Parkinson’s research

March 13, 2013

The name of the guest speaker at Emory’s Office of Technology Transfer’s annual celebration on March 7 provoked some double takes around campus last week.

Todd B. Sherer, PhD

Todd B. Sherer, PhD

Todd B. Sherer, PhD, CEO of the Michael J. Fox Foundation for Parkinson’s Research (MJFF), described how the Fox Foundation is trying to build bridges between the worlds of basic and clinical research to speed development of new drugs for the treatment of Parkinson’s disease, and offered a perspective on how independent research funders can help move drug candidates from the lab to the clinic and closer to market.

Sherer, a former postdoctoral fellow at Emory, also has the same first and last name (but not middle initial!) as OTT’s director. Sherer – the one who works for the Fox Foundation – joined that non-profit charity’s staff in 2004. While at Emory, he worked on models for Parkinson’s based on exposure to the pesticide rotenone, alongside Ranjita Betarbet, Gary Miller and J. Timothy Greenamyre, who himself moved on to the University of Pittsburgh in 2005.

In his talk Thursday, Sherer cited three areas of recent progress that all have links to Emory:

1. MJFF has been shepherding a potential drug target, the glutamate receptor mGluR5. Researchers from Lund University in Sweden, supported by MJFF, were first to show that mGluR5 blockers can prevent dyskinesia in pre-clinical models, and these compounds have now entered clinical trials, also supported by MJFF, sponsored by Swiss biotech Addex Pharmaceuticals.

At the same time, compounds that block mGluR5 are under investigation for their ability to correct the problems with synaptic function seen in patients with fragile X syndrome, and Emory genetics chair Steve Warren was recognized for progress in this area Thursday.

2. Jeff Conn of Vanderbilt, formerly a faculty member in Emory’s Department of Pharmacology from 1988 to 2000, has worked with MJFF dating back to 2004 on the development of blockers for another glutamate receptor, mGluR4. In 2013, Conn announced a major partnership between Vanderbilt and Bristol-Myers Squibb to further develop these compounds.

3. MJFF has provided funding for a Parkinson’s gene therapy clinical trial being conducted by the firm Ceregene.  Emory is one of the sites participating in the clinical trial.

Emory researchers who have received grants from MJFF include:

Malu Tansey, Nick Seyfried, Zixu Mao, Stephen Traynelis, Jim Greene, Thomas Wichmann and Jeremy Boss.

Quinn Eastman 13 March 2013 News, Research , , No Comments

Stress of public speaking mobilizes progenitor cells from bone marrow

March 12, 2013

The stress of public speaking is enough to drive damage-repairing progenitor cells out of the bone marrow into the blood, a study of patients with heart disease has found.

Public speaking raises the blood pressure -- it also drives progenitor cells out of the bone marrow

Public speaking raises the blood pressure — it also drives progenitor cells out of the bone marrow

Endothelial progenitor cells (EPCs) are found in the bone marrow, and thought to repair damaged blood vessels once mobilized into the blood by injury or stress. Previous research has shown that strenuous exercise can lead to a dramatic increase in blood EPC levels, but the effects of psychological stress on EPCs had not been examined before.

This report emerges from a large NHLBI-funded study of mental stress ischemia previously described in Emory Public Health magazine.

The new findings were presented Saturday, March 9 at the American College of Cardiology conference in San Francisco. The presenter was cardiovascular research fellow Ronnie Ramadan, MD. Senior authors are Arshed Quyyumi, MD, professor of medicine and director of the Emory Cardiovascular Research Institute, and Viola Vaccarino, MD, PhD, professor and chair of the Department of Epidemiology, Rollins School of Public Health.

In some patients with coronary artery disease, mental stress may precipitate ischemia– a deficiency in blood flow to the heart – a risk factor for adverse events and death independent of other cardiovascular risk factors such as smoking, cholesterol and diabetes.

The Emory researchers are examining mental stress-induced ischemia (MSI) more closely, to understand whether it predicts future cardiac events independent of established risk factors. They looked at 141 patients with documented coronary artery disease, and asked them to perform a standardized public speaking task. 16 percent of this group developed MSI, judged by cardiac imaging with SPECT (single photon emission computed tomography).

The researchers discovered that patients who develop MSI have significantly higher levels of a specialized population of progenitor cells in their blood that have the ability to home to areas of ischemia, but they don’t increase in response to the public speaking task.

In contrast, patients without MSI have their levels of endothelial progenitor cells increase by an average of 21 percent in response to the speaking test.

“It could be that patients with MSI are already at a ceiling, that they’re fully mobilized already,” Quyyumi says. “Or it could be that there is an impairment in the mobilization.”

Both groups had their systolic blood pressure increase by about 40 mm Hg in response to speaking test — so they’re both feeling physiological effects from the mental stress. The MSI group did have more hypertension (baseline blood pressure was 10 mm Hg higher) and a higher prevalence of diabetes.

Ramadan was specifically monitoring rare progenitor cells [1 in 100,000] that have a receptor on their surfaces that allow them to home to areas of injury. The significance of the number and mobilization of these cells and whether they function properly in this setting needs further investigation, he says.

In a separate presentation, Ramadan also described how patients with MSI have higher CAIx (central augmentation index), a measure of arterial stiffness.

 

Quinn Eastman 12 March 2013 News, Research , , , , , , , , No Comments

Old drug = new treatment for parasitic skin disease?

January 31, 2013

A coal-tar dye first produced in the 19th century, gentian violet is available over the counter as an antifungal agent.

Dermatologist Jack Arbiser has been a champion of the inexpensive drug gentian violet for skin diseases. He recently teamed up with collaborators in Brazil to find that gentian violet is active against leishmaniasis, a disfiguring skin disease found in many tropical and subtropical countries.

Caused by protozoan parasites and transmitted by sand flies, leishmaniasis’ most common form produces skin sores but can also affect the nose and mouth and even vital organs. The World Health Organization has identified Kabul, Afghanistan as a world hot spot for leishmaniasis.

In the journal PLOS One, Ana Paula Fernandes and colleagues at the Federal University of Minas Gerais showed that gentian violet and related compounds are active against Leishmania species in animal models.

Conventionallly, therapy for leishmaniasis has involved antimony compounds, but resistance is growing. More recently, clinicians have used the drugs miltefosine and amphotericin against leishmaniasis, but severe side effects have been reported.

“Because it has a proven safety record, gentian violet might be a useful treatment that can be used in developing countries as well as by US troops serving in Afghanistan,” Arbiser says.

Arbiser also recently published a case report on the use of gentian violet, in combination with the immune modulator imiquimod, to treat melanoma.

Quinn Eastman 31 January 2013 News, Research, Winship , , , , , , No Comments

Emory scientists co-signers of H5N1 flu letter

January 23, 2013

Emory influenza researchers Richard Compans, Anice Lowen and John Steel are co-signers of a statement announcing the end of a self-imposed moratorium on H5N1 avian flu research.

Last year, an international group of researchers called for the moratorium after public concern over studies of H5N1 transmissibility in ferrets, a model for spread of infection between humans. The group of researchers has now recommended ending the moratorium, citing safeguards and safety review procedures put in place by the National Institutes of Health and authorities in other countries. From the letter published today in Science and Nature:

In January 2012, influenza virus researchers from around the world announced a voluntary pause of 60 days on any research involving highly pathogenic avian influenza H5N1 viruses leading to the generation of viruses that are more transmissible in mammals. We declared a pause to this important research to provide time to explain the public-health benefits of this work, to describe the measures in place to minimize possible risks, and to enable organizations and governments around the world to review their policies (for example on biosafety, biosecurity, oversight, and communication) regarding these experiments.

…Thus, acknowledging that the aims of the voluntary moratorium have been met in some countries and are close to being met in others, we declare an end to the voluntary moratorium on avian flu transmission studies.

Dan Vergano has a more extensive story in USA Today.

Compans is professor of microbiology and immunology at Emory University School of Medicine and scientific director of Emory’s Influenza Pathogenesis and Immunology Research Center. Lowen and Steel are assistant professors of microbiology and immunology at Emory and IPIRC investigators.

Quinn Eastman 23 January 2013 News, Research , , , , , , , , No Comments

Highlights and links from PSA debate

January 17, 2013

On January 8, Emory University School of Medicine’s Department of Medicine Grand Rounds had an unusual format: a debate between Otis Brawley, MD and John Petros, MD on the topic of PSA testing.

Otis Brawley, MD

Prostate cancer is the second leading cause of cancer death for American men. PSA (prostate specific antigen) is a protein produced by the prostate gland and its levels can be measured by a simple blood test.  A higher number could indicate prostate cancer, but the test doesn’t differentiate between an aggressive, fast-growing cancer, and one that is so slow-growing it wouldn’t threaten a man’s life.

Brawley, professor of hematology and medical oncology and chief medical officer for the American Cancer Society, led off the debate arguing that studies show PSA testing to be unreliable and possibly leading to too many diagnoses and unnecessary treatment for prostate cancer. Petros, a professor of urology who treats prostate cancer patients, looked at other studies (more details below), which show the PSA test to be a tool that has helped save lives by detecting prostate cancer at earlier stages.

In May 2012, the U.S. Preventive Services Task Force issued a “grade D” rating for PSA screening, saying the practice offers more harms — in terms of complications from PSA-test-driven treatment such as incontinence and blood clots — than benefits. Brawley agreed with this assessment and says he’s not convinced the PSA test saves lives, but he doesn’t rule out its use. He framed this issue this way:

Pretend you are offered the choice of taking a pill that will double the risk of prostate cancer diagnosis from 10 to 20 percent, but could decrease risk of prostate cancer death by one fifth: from 3 to 2.4 percent.  “Do you feel lucky?” Brawley quipped.

John Petros, MD

As a counterpoint, Petros cited National Cancer Institute epidemiology data indicating that the rate of metastatic prostate cancer has substantially decreased over the last few decades, since prostate cancers are now being diagnosed at an earlier stage. He also went over studies conducted in Sweden (Goteborg) and in Austria (Tyrol), which show significant reductions in prostate cancer-related mortality coming from PSA testing.

Five things Brawley and Petros agreed on:

  1. PSA testing should be performed in the context of a physician-patient relationship, with men making an informed decision about the value of the information they will receive and the associated risks.
  2. Vans in supermarket parking lots – more broadly, community- or employer-based screening  — are not the ideal setting for PSA testing.
  3. The PLCO study, a NCI-sponsored randomized clinical trial to examine the effects of screening on cancer-related mortality, was flawed. In particular, the “control” arm had a substantial rate of PSA testing.
  4. Brawley said: “Some cancers that are detected early do not pose a threat and do not need to be treated.” Similarly, Petros said: “Prostate cancer can be low risk if safely observed, but high risk forms are lethal. We need to focus on cancers that matter.”
  5. Biomarkers that are better than PSA alone are needed. Brawley said: “We need a 2013 definition of prostate cancer, informed by genomics, rather than going by what Virchow decided prostate cancer looks like under the microscope 160 years ago.”

Petros agreed with this last point and noted that more sophisticated tests than PSA already have been identified such as the prostate health index, which measures levels for three forms of PSA and may be more cancer-specific. Research being conducted at Emory by Carlos Moreno and colleagues also moves toward this goal. In 2011, his team published results in the American Journal of Pathology on a panel of biomarkers that can predict prostate cancer outcomes after prostatectomy. The Atlanta Business Chronicle recently had a story on a patent related to Moreno’s research.

Petros said a key question, and one he and Moreno are planning on testing, is whether the same biomarkers could be useful on prostate biopsy samples. This could help make treatment decisions regarding surgery vs radiation. Biopsy-based tests could be combined with data based on urine biomarkers, to get around the problem of tumor heterogeneity and imperfect sampling, Petros said.

For now, Petros said he believes in initiating a conversation about PSA screening with patients 50 and older, or younger if they have risk factors for the disease.   He said the decision to have routine PSA testing, follow-up tests and prostate cancer treatments, is a very individualized process.

“It comes down to, what do you tell the man standing in front of you?” he said. “You have to consider where they are in life and what their goals are, and that varies with every man.”

Quinn Eastman 17 January 2013 News, Research, Winship , , , , , , , , , , No Comments
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