New insight into how brain cells die in Alzheimer's and FTD

(Epi)genetic hallucinations induced by loss of LSD1 resemble Alzheimer's. Another surprise: LSD1 aggregates in Alzheimer's brain, looking like Tau Read more

2B4: potential immune target for sepsis survival

Emory immunologists have identified a potential target for treatments aimed at reducing mortality in sepsis, an often deadly reaction to Read more

EHR data superior for studying sepsis

Analysis of EHR data says sepsis rates and mortality have been holding steady, contrary to what is suggested by after-the-fact Read more

Research

An indicator of aberrant stem cell reprogramming

The 2012 Nobel Prize in Medicine was awarded to Shinya Yamanaka and John Gurdon for the discovery that differentiated cells in the body can be reprogrammed. This finding led to the development of “induced pluripotent stem cells.”

These cells were once skin or blood cells. Through a process of artificial reprogramming in the lab, scientists wipe these cells’ slates clean and return them to a state very similar to that of embryonic stem cells. But not exactly the same.

It has become clear that iPS cells can retain some memories of their previous state. This can make it easier to change an iPS cell that used to be a blood cell (for example) back into a blood cell, compared to turning it into another type of cell. The finding raised questions about iPS cells’ stability and whether http://www.troakley.com/ iPS cell generation – still a relatively new technique – would need some revamping for eventual clinical use.

Hotspots where iPS cells differ from ES cells

Chromosomal hotspots where iPS cells differ from ES cells

It turns out that iPS cells and embryonic stem cells have differing patterns of methylation, a modification of DNA that can alter how genes behave even if the underlying DNA sequence remains the same. Some of these differences are the same in all iPS cells and some are unique for each batch of reprogrammed cells.

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Alphabet of modified DNA keeps expanding

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 http://www.raybani.com/ 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.

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Detecting clandestine chlamydia

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.

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.

Most infections are asymptomatic but left untreated, Chlamydia infection can lead to pelvic inflammatory disease, infertility and ectopic pregnancy. It is also a Ray Ban online 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.”

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

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 Cheap Oakleys 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.

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A Sherer of Parkinson’s research

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 ray ban outlet 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.

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Stress of public speaking mobilizes progenitor cells from bone marrow

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 Magliette Calcio A Poco Prezzo 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.

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Old drug = new treatment for parasitic skin disease?

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 http://www.troakley.com/ 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.

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Emory scientists co-signers of H5N1 flu letter

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 cheap oakley 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.

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Highlights and links from PSA debate

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 Ray Ban outlet 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.”

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