Connections between starvation and immunological memory

Focus on autophagy's functions in memory T cells

Effects of cocaine exposure in adolescent rodents

The effects on neurons are like losing entire branches from a tree, neuroscientists are finding

Frailty: we know it when we can measure it

Look beyond the cane. Emory researchers are seeking to define and measure frailty, to aid in surgery-related decision-making.

Ebola’s capriciousness in kids

Anita McElroy, a pediatric infectious disease specialist at Emory, and her colleagues at the CDC, led by Christina Spiropoulou, have been getting some attention for their biomarker research on Ebola virus infection. Sheri Fink from the New York Times highlighted their work in a Nov. 9 report on the infection’s capriciousness. Genetics may also play a role in surviving Ebola infection, as recent animal research has suggested.

McElroy’s team’s findings attracted notice because their results suggest that Ebola virus disease may affect children differently and thus, children may benefit from different treatment regimens than those for adults. The authors write that early intervention to prevent injury to the lining of blood vessels — using statins, possibly — might be a therapeutic strategy in pediatric patients. Read more

Posted on by Quinn Eastman in Immunology Leave a comment

Acidity of aging leads to new Alzheimer’s drug target

Pathologist Keqiang Ye and his colleagues have been studying the functions of an enzyme called AEP, or asparagine endopeptidase, in the brain. AEP is activated by acidic conditions, such as those induced by stroke or seizure.

AEP is a protease. That means it acts as a pair of scissors, snipping pieces off other proteins. In 2008, his laboratory published a paper in Molecular Cell describing how AEP’s acid-activated snipping can unleash other enzymes that break down brain cells’ DNA.

Following a hunch that AEP might be involved in neurodegenerative diseases, Ye’s team has discovered that AEP also acts on tau, which forms neurofibrillary tangles in Alzheimer’s disease.

“We were looking for additional substrates for AEP,” Ye says. “We knew it was activated by acidosis. And we had read in the literature that the aging brain tends to be more acidic, especially in Alzheimer’s.”

The findings, published in Nature Medicine in October, point to AEP as a potential target for drugs that could slow the advance of Alzheimer’s, and may also lead to improved diagnostic tools. Read more

Posted on by Quinn Eastman in Neuro Leave a comment

No junk: long RNA mimics DNA, restrains hormone responses

It arises from what scientists previously described as “junk DNA” or “the dark matter of the genome,” but this gene is definitely not junk. The gene Gas5 acts as a brake on steroid hormone receptors, making it a key player in diseases such as hormone-sensitive prostate and breast cancer.

Unlike many genes scientists are familiar with, Gas5 does not encode a protein. It gets transcribed into RNA, like many other genes, but with Gas5 the RNA is what’s important, not the protein. The RNA accumulates in cells subjected to stress and soaks up steroid hormone receptors, preventing them from binding DNA and turning genes on and off.

Emory researchers have obtained a detailed picture of how the Gas5 RNA interacts with steroid hormone receptors. Their findings show how the Gas5 RNA takes the place of DNA, and give hints as to how it evolved.

The results were published Friday in Nature Communications.

Scientists used to think that much of the genome was “fly-over country”: not encoding any protein and not even accessed much by the cell’s gene-reading machinery. Recent studies have revealed that a large part of the genome is copied into lincRNAs (long intergenic noncoding RNAs), of which Gas5 is an example. Read more

Posted on by Quinn Eastman in Cancer, Immunology Leave a comment

Shout out for SWAE

Loud applause for the members of SWAE. The student group Science Writers at Emory, previously dormant, has relaunched the publication “In Scripto”. We look forward to seeing more from SWAE.

The new Halloween-themed issue of In Scripto is published in “ISSUU”, but I’ve broken it down into a table of contents by author, graduate program and article: Read more

Posted on by Quinn Eastman in Uncategorized Leave a comment

FDA approves treatment for acquired hemophilia

On Oct. 24, the Food and Drug Administration approved Obizur, a treatment for acquired hemophilia A. Obizur was originally developed by a research team led by Emory hematologist Pete Lollar. The Obizur technology was licensed by Emory in 1998 to startup company Octagen (more about Octagen from Philadelphia Business Journal) and eventually brought to commercial availability by the pharmaceutical firm Baxter International.

Lollar is Hemophilia of Georgia Professor of Pediatrics in the Aflac Cancer and Blood Disorders Center at Emory University School of Medicine and Children’s Healthcare of Atlanta. The team that developed the drug included Ernest Parker, John Healey and Rachel Barrow, and followed a research collaboration between Lollar and Emory cardiologist Marschall Runge (now at UNC).

Hemophilia is a group of blood clotting disorders leading to excessive bleeding that can occur spontaneously or following injury or surgery. Hemophilia A is caused by a deficiency of clotting factor VIII, and can be either inherited or acquired.

In acquired hemophilia A, the immune system is somehow provoked into making antibodies against factor VIII that inactivate it. Acquired hemophilia is a challenge for doctors to deal with because patients frequently present with severe, life threatening bleeding and also because it’s a surprise: patients do not have a previous personal or family history of bleeding episodes. Antibodies to factor VIII also can be a problem for approximately 30 percent of patients with inherited hemophilia.

Lollar’s team developed a modified form of factor VIII, derived from the protein sequence of pigs, which is less of a red flag to the immune system. Read more

Posted on by Quinn Eastman in Immunology Leave a comment

Plaque erosion: heart attacks triggered by a whimper, not a bang

Cardiologist Bob Taylor and colleagues have a new paper in PLOS One this week, looking at the biomechanical forces behind plaque erosion.

Plaque erosion is a mechanism for blood clots formation in coronary arteries that is not as well-understood as its more explosive counterpart, plaque rupture. Plaque erosion disproportionally affects women more than men and is thought to account for most heart attacks in younger women (women younger than 50).

“We believe that this work has implications for our better understanding of the underlying biology of coronary artery disease in women,” Taylor says. The first author of the paper is biomedical engineering graduate student Ian Campbell, who now has his PhD. The team collaborated with cardiovascular pathologist Renu Virmani in Maryland.

Cardiologists have well-developed ideas for how plaque rupture works*; see the concept of “vulnerable plaque.” Cholesterol and inflammatory cells build up in the coronary arteries over several years. At one point in a particular artery, the plaque has a core of dying inflammatory cells, covered by a fibrous cap. If the cap is thin (the patterns of blood flows near the cap influence this), there is a risk that the cap will break and the contents of the core will spill out, triggering a blood clot nearby.

Plaque erosion is more mysterious and can occur more gradually, the researchers have found. Read more

Posted on by Quinn Eastman in Heart Leave a comment

Rules of thumb for drug discovery

People interested in drug discovery may have heard of “Lipinski’s rule of five,” a rough-and-ready set of rules for determining whether a chemical structure is going to be viable as a orally administered drug or not. They basically say that if a compound is too big, too greasy or too complicated, it’s not going to get into the body and make it to the cells you want to affect. These guidelines have been the topic of much debate among medicinal chemists and pharmacologists.

The namesake for this set of rules, Chris Lipinski, will be speaking at Winship Cancer Institute Wednesday afternoon (4:30 pm, Nov 5, C5012) on “The Rule of 5, Public Chemistry-Biology Databases and Their Impact on Chemical Biology and Drug Discovery.” Lipinski spent most of his career at Pfizer (while there, he published the “rule of 5 paper“) and now is a consultant at Melior Discovery.

Posted on by Quinn Eastman in Cancer, Uncategorized Leave a comment

Explainer: the locus coeruleus

The locus coeruleus is a part of the brain that has been getting a lot of attention recently from Emory neuroscience researchers.

The locus coeruleus is the biggest source of the neurotransmitter norepinephrine in the brain. Located deep in the brainstem, it has connections all over the brain, and is thought to be involved in arousal and attention, stress, memory, the sleep-wake cycle and balance.

Researchers interested in neurodegenerative disease want to look at the locus coeruleus because it may be one of the first structures to degenerate in diseases such as Alzheimer’s and Parkinson’s. In particular, the influential studies of German neuro-anatomist Heiko Braak highlight the locus coeruleus as a key “canary in the coal mine” indicator of neurodegeneration.

That’s why neurologist Dan Huddleston, working with biomedical imaging specialists Xiangchuan Chen and Xiaoping Hu and colleagues at Emory, has been developing a method for estimating the volume of the locus coeruleus by magnetic resonance imaging (MRI). Their procedure uses MRI tuned in such a way to detect the pigment neuromelanin (see panel), which accumulate in both the locus coeruleus and in the substantia nigra. Read more

Posted on by Quinn Eastman in Neuro Leave a comment

Scaling up to a speck of dust

DNA bricks keep getting larger. In 2012, a team of researchers at Harvard described their ability to make self-assembling structures –made completely out of DNA — that were about the size of viruses (80 nanometers across).

Yonggang Ke, PhD

Now they’re scaling up, making bricks that are 1000 times larger and getting close to a size that could be barely visible to the naked eye.

The advances were reported in Nature Chemistry.

Who: a team of researchers at the Wyss Institute at Harvard led by Peng Yin, and including Yonggang Ke, PhD, now an assistant professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.

At Emory, Ke and his team are continuing to design 3D DNA machines, with potential functions such as fluorescent nanoantennae, drug delivery vehicles and synthetic membrane channels.

How: The DNA brick method uses short, synthetic strands of DNA that work like interlocking Lego® bricks to build complex structures. Structures are first designed using a computer model of a molecular cube, which becomes a master canvas. Each brick is added or removed independently from the 3D master canvas to arrive at the desired shape. The DNA strands that would match up to achieve the desired structure are mixed together and self assemble — with the help of magnesium salts — to achieve the designed crystal structures.

“Therein lies the key distinguishing feature of our design strategy–its modularity,” Ke says. “The ability to simply add or remove pieces from the master canvas makes it easy to create virtually any design.”

What for: As part of this study the team demonstrated the ability to position gold nanoparticles less than two nanometers apart from each other along the crystal structure — a critical feature for future quantum computational devices and a significant technical advance for their scalable production.

More here.

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Clot dissolver tPA’s tardy twin could aid in stroke recovery

Emory researchers led by neurologist Manuel Yepes, MD have identified a protein released by neurons while the brain is recovering from a stroke. The results were published online today in Journal of Neuroscience.

The protein, called urokinase-type plasminogen activator or uPA, has been approved by the FDA to dissolve blood clots in the lungs. It has been tested in clinical trials in some countries as a treatment for acute stroke.

The Emory team’s findings suggest that in stroke, uPA’s benefits may extend beyond the time when doctors’ principal goal is dissolving the blood clot that is depriving the brain of blood.
Instead, uPA appears to help brain cells recover from the injuries induced by loss of blood flow. Treating mice with uPA after an experimental stroke can improve their recovery of motor function, the researchers found.

Read more

Posted on by Quinn Eastman in Neuro Leave a comment
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