Warren symposium follows legacy of geneticist giant

If we want to understand how the brain creates memories, and how genetic disorders distort the brain’s machinery, then the fragile X gene is an ideal place to start. That’s why the Stephen T. Warren Memorial Symposium, taking place November 28-29 at Emory, will be a significant event for those interested in neuroscience and genetics. Stephen T. Warren, 1953-2021 Warren, the founding chair of Emory’s Department of Human Genetics, led an international team that discovered Read more

Mutations in V-ATPase proton pump implicated in epilepsy syndrome

Why and how disrupting V-ATPase function leads to epilepsy, researchers are just starting to figure Read more

Tracing the start of COVID-19 in GA

At a time when COVID-19 appears to be receding in much of Georgia, it’s worth revisiting the start of the pandemic in early 2020. Emory virologist Anne Piantadosi and colleagues have a paper in Viral Evolution on the earliest SARS-CoV-2 genetic sequences detected in Georgia. Analyzing relationships between those virus sequences and samples from other states and countries can give us an idea about where the first COVID-19 infections in Georgia came from. We can draw Read more

Islet transplants from fish?

The shortage of human organ donors has led scientists to investigate animals as a potential source for transplantable organs or tissues. Pigs are often mentioned because of their size: similar to ours.

Recently, prospects for xenotransplantation brightened when Harvard geneticist George Church demonstrated the removal of dozens of endogenous retroviruses from the pig genome, in a tour de force of the CRISPR/Cas9 gene editing technique.

Emory researchers Susan Safley and Collin Weber have been exploring the possibility of using different animals for xenotransplantation: fish, specifically tilapia.

Why fish? This review details several advantages tilapia may offer in the field of islet transplant, but first – a reminder about islets.

Islets are the clusters of cells in the pancreas that produce insulin. Several clinical trials, including this one led by Emory’s Nicole Turgeon, have shown that islets isolated from deceased human donors can restore normal blood sugar regulation in patients with type 1 diabetes. Still, obstacles remain such as the shortage of human islets, and the loss of insulin independence over time, even with the use of drugs that hold off immune rejection.

For islet transplant, here are some of the proposed advantages presented by tilapia:

*tilapia have large, distinct islet organs called Brockmann bodies that are easy to isolate

*tilapia grow quickly and cost less to raise than pigs

*tilapia islets are resistant to hypoxia, thought to contribute to graft loss

*tilapia do not express alpha (1,3) gal, a carbohydrate structure present on mammalian cells that causes hyperacute rejection Read more

Posted on by Quinn Eastman in Immunology Leave a comment

Nudging physician behavior on antibiotic orders

Part of the problem of antibiotic resistance involves physicians’ habits. Doctors are used to prescribing antibiotics in certain situations, even when they may be inappropriate or when alternatives may be best. However, they may be susceptible to “nudges”, even if health care organization policies don’t formally restrict their choices. Former White House regulatory policy guru Cass Sunstein has written several books on this concept.

In March 2015, MD/PhD student Kira Newman and colleagues published a study in Journal of General Internal Medicine that has some bearing on this idea, although it doesn’t address antibiotic resistance directly:

Yelp for Prescribers: a Quasi-Experimental Study of Providing Antibiotic Cost Data and Prescription of High-Cost Antibiotics in an Academic and Tertiary Care Hospital.

The authors describe a shift involving the Emory University hospital electronic health record and order entry system. When a patient has systemic or urinary tract bacterial infection, the system shows a table of antibiotic sensitivity data alongside blood or urine culture results.

Beginning in May 2010, cost category data for antibiotics were added. Explicit numbers were not included – too complicated. Instead, the information was coded in terms of $ to $$$$. For the year after the change, the authors report a 31 percent reduction in average cost per unit of antibiotics prescribed. Read more

Posted on by Quinn Eastman in Uncategorized 1 Comment

Low-level cadmium toxicity and fatty liver disease

A recent study concluded that it’s more difficult for adults today to maintain the same weight as those a few decades ago, even with the same levels of food intake and exercise. On one level, this news is comforting to anyone in middle age, who may have been athletic as a teenager in the 1980s but isn’t anymore. It’s just harder nowadays!

However, the study authors also suggested, in an interview with The Atlantic’s Olga Khazan, an array of factors that might be contributing to the rise in obesity: exposure to chemicals such as pesticides and flame retardants, prescription drugs such as antidepressants, and altered microbiomes linked with antibiotic use in livestock.

The heavy metal cadmium may belong on that list of chemicals, not primarily as a booster of obesity, but instead in connection with the increase in prevalence in NAFLD (non-alcoholic fatty liver disease) over the last few decades.

Researchers led by Young-Mi Go and Dean Jones exposed mice to low levels of cadmium, so that the amounts of cadmium in their livers were comparable to those present in average middle age Americans, without tobacco or occupational exposure. They observed that cadmium-treated mice had more fat accumulation in the liver and elevated liver enzymes in their blood, compared with control mice with 10 times less cadmium.

Cadmium accumulates in the body over time. Tobacco smoke and the industrial workplace can be routes for cadmium exposure, but food is the major source for most non-smokers. Until the 1990s, most batteries were made with cadmium, and much cadmium production still goes into batteries. It is also found in paint and in corrosion-resistant steel. Read more

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Gabbing about GABA — implications for hypersomnia treatments

Anesthesiologist Paul Garcia and his colleagues are presenting two posters at the Society of Neuroscience meeting this week, whose findings may raise concerns about two non-stimulant drugs Emory sleep specialists have studied for the treatment of hypersomnia: flumazenil and clarithromycin.

For both, the data is in vitro only, so caution is in order and more investigation may be needed.

With flumazenil, Garcia and colleagues found that when neurons are exposed to a low dose for 24 hours, the cells increase expression of some GABA receptor forms.

This could be part of a mechanism for tolerance. I heard some anecdotes describing how flumazenil’s wake-promoting effects wear off over time at the Hypersomnia Foundation conference in July, but it’s not clear how common the phenomenon is.

Flumazenil’s utility in hypersomnia became known after the pioneering experience of Anna Sumner, who has reported being able to use the medicine for years. See this 2013 story in Emory Medicine. Read more

Posted on by Quinn Eastman in Neuro Leave a comment

Epigenetic inheritance via sperm RNA

In 2013, Brian Dias (at Yerkes) and Kerry Ressler (now at Harvard) described a surprising example of epigenetic inheritance.

They found that a mouse, exposed to a smell in combination with stress, could transmit the resulting sensitivity to that smell to its offspring. At the time, there wasn’t a lot of information about mechanism.

Now other scientists have substantiated a proposal that micro RNA in playing a role in sperm. See this story (“Sperm RNAs transmit stress”) from Kate Yandell in The Scientist or this one from Rachel Zamzow at Spectrum, the Simons Foundation’s autism news site, for more. An added wrinkle is that this research shows that descendants of stress-exposed mice show a muted response to stress.

Note for Emory readers: Dias is scheduled to give a Frontiers in Neuroscience talk on Friday.

Posted on by Quinn Eastman in Neuro Leave a comment

Orange lichens are source for potential anticancer drug

An orange pigment found in lichens and rhubarb called parietin may have potential as an anti-cancer drug, scientists at Winship Cancer Institute of Emory University have discovered.

The results were published in Nature Cell Biology on October 19.

Caloplaca_Fenwick

Parietin, shown to have anticancer activity in the laboratory, is a dominant pigment in Caloplaca lichens. Note: this study did not assess the effects of eating lichens or rhubarb. Photo courtesy of www.aphotofungi.com

Parietin, also known as physcion, could slow the growth of and kill human leukemia cells obtained directly from patients, without obvious toxicity to human blood cells, the authors report. The pigment could also inhibit the growth of human cancer cell lines, derived from lung and head and neck tumors, when grafted into mice.

A team of researchers led by Jing Chen, PhD, discovered the properties of parietin because they were looking for inhibitors for the metabolic enzyme 6PGD (6-phosphogluconate dehydrogenase). 6PGD is part of the pentose phosphate pathway, which supplies cellular building blocks for rapid growth. Researchers have already found 6PGD enzyme activity increased in several types of cancer cells.

“This is part of the Warburg effect, the distortion of cancer cells’ metabolism,” says Chen, professor of hematology and medical oncology at Emory University School of Medicine and Winship Cancer Institute. “We found that 6PGD is an important metabolic branch point in several types of cancer cells.” Read more

Posted on by Quinn Eastman in Cancer Leave a comment

Transformative awards for Mocarski’s malleable cells, lung fibrosis

The National Institutes of Health has announced a five-year, $1.9 million Transformative Research Award to Emory virologist Edward Mocarski, PhD for his work on how the mechanisms of programmed cell death can be subverted.

Mocarski is Robert W. Woodruff professor of microbiology and immunology at Emory University School of Medicine and Emory Vaccine Center. His research, which originated in probing how cells commit suicide when taken over by viruses, could lead to advances in regenerative medicine and organ transplant.

Barker Mocarski

Thomas Barker, PhD (left) and Edward Mocarski, PhD (right)

The grant, funded through the National Institute of Allergy and Infectious Diseases, is one of nine “high-risk-, high-reward” Transformative Research Awards (13 recipients) announced by the NIH on October 6.

In the same group this year, Thomas Barker in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University received a Transformative Research Award for his research on mechanosensors + pulmonary fibrosis.

The Transformative Research Award program supports “exceptionally innovative, unconventional, paradigm-shifting research projects that are inherently risky and untested.” Emory has achieved only one other TRA since the program was established in 2009: Shuming Nie’s project on imaging to guide cancer surgery. Read more

Posted on by Quinn Eastman in Immunology Leave a comment

Cancer metastasis: isolating invasive cells with a color change

The capacity of cancer cells to spread throughout the body and metastasize (invade new tissues) makes them deadly. What makes metastatic cells different?

Scientists at Winship Cancer Institute of Emory University have developed a technique for isolating individual cells that display invasive behavior out of a large group in culture by changing their color.

Read more

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Tools for illuminating brain function make their own light

Optogenetics has taken neuroscience by storm in recent years because the technique allows scientists to study the brain conveniently in animals, activating or inhibiting selected groups of neurons at the flip of a switch.  Most often, scientists use a fiber optic cable to deliver light into the brain.

Researchers at Emory and Georgia Tech have developed tools that could allow neuroscientists to put aside the fiber optic cable, and use a glowing protein from coral as the light source instead.

Biomedical engineering student Jack Tung and neurosurgeon/neuroscientist Robert Gross, MD, PhD have dubbed these tools “inhibitory luminopsins” because they inhibit neuronal activity both in response to light and to a chemical supplied from outside.

A demonstration of the luminopsins’ capabilities was published September 24 in the journal Scientific Reports.  The authors show that these tools enabled them to modulate neuronal firing, both in culture and in vivo, and modify the behavior of live animals.

Tung and Gross are now using inhibitory luminopsins to study ways to halt or prevent seizure activity in animals.

“We think that this approach may be particularly useful for modeling treatments for generalized seizures and seizures that involve multiple areas of the brain,” Tung says. “We’re also working on making luminopsins responsive to seizure activity: turning on the light only when it is needed, in a closed-loop feedback controlled fashion.” More here. Read more

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Trio with Emory roots probing PTSD-hypertension links

This grant announcement from the American Heart Association caught Lab Land’s eye. All three of the scientists involved in this project, examining the connections between hypertension, inflammation and the sympathetic nervous system in PTSD, have Emory connections:

*Kerry Ressler, previously Emory Psychiatry/HHMI-supported/Yerkes-based lab/Grady Trauma Project, who moved this summer to Harvard’s McLean Hospital

Related finding that emerged from the Grady Trauma Project: Blood pressure drugs linked with lower PTSD symptoms

*Paul Marvar, who worked with both David Harrison and Kerry Ressler at Emory, and is now at George Washington University

Related item on Marvar’s work: Immune cells required for stress-induced rise in blood pressure in animals

*Jeanie Park, kidney specialist who is here now! The grant is exploring the relationship between the sympathetic nervous system, regulation of blood pressure and PTSD.

2015 TV interview with Park on her chronic kidney disease research

Posted on by Quinn Eastman in Heart, Neuro Leave a comment