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
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Cardiologists change their minds — not all at once

What happens when cardiologists learn that a widely performed procedure might not be as helpful as they once thought? Investigators at Emory have taken one of the first detailed looks at how geographical patterns in practice changed after publication of results from a large clinical trial.

The federal government has invested billions of dollars in comparative effectiveness research — comparing different healthcare interventions to determine which works best — with the aim of reducing variations in care. This paper shows that these types of investment can have the desired effect.

Recently Medscape Cardiology talked with lead author Arun Mohan, who is medical director for care coordination at Emory University Hospital, about his work. [You may have missed this news item over the holidays.] Read more

Posted on January 10, 2014 by Quinn Eastman in Heart Leave a comment

Hypoxia is bad, except when it’s good

Randy Trumbower and his colleagues in Emory’s Department of Rehabilitation Medicine recently published a study showing that “daily intermittent hypoxia,” combined with walking exercise, can help patients with incomplete spinal cord injury walk for longer times. What is it about being deprived of oxygen for short periods that has a positive effect?

This research was puzzling at first (at least to your correspondent) because “daily intermittent hypoxia” is a good description of the gasping and snorting interruptions of sleep apnea.

Sleep apnea is a very common condition that increases the risk of high blood pressure, diabetes, heart attack and stroke. On the other side of the coin, many endurance athletes have been harnessing the body’s ability to adapt to low oxygen levels — so-called altitude training — to increase their performance for years.

So we have an apparent clash: hypoxia is bad, except when it’s good. Looking closely, there are some critical differences between sleep apnea and therapeutic hypoxia. The dose makes the poison, right? Read more

Posted on January 8, 2014 by Quinn Eastman in Neuro Leave a comment

HIV discordant couples

On Thursday, NPR had a nicely done story on discordant couples (one partner is HIV positive, the other is HIV negative) in Kenya.

It provided a reminder of Susan Allen’s work in Rwanda and Zambia with discordant couples. It also very simply laid out the policy issues connected with treating discordant couples:

Medical workers are http://www.raybani.com/ extremely interested in discordant couples for two reasons. One is that almost half of new infections in Kenya happen in these relationships. It’s one place where HIV is spreading. The second reason is that when couples are open with each other about their HIV status, managing HIV is more successful…

The World Health Organization now recommends that any HIV-positive individual in a discordant relationship be supplied HIV treatment. But discordant couples are still being treated on an ad hoc basis in Kenya, primarily because the funding for the medication just isn’t there.

Allen’s research provided critical data about HIV Ray Ban outlet transmission and prevention methods, and led to the adoption of the WHO guidelines mentioned in the story. She has said that the WHO guidelines were designed to help partners in a stable relationship work together to prevent the uninfected person from getting the virus and that low-tech, inexpensive prevention methods like condoms are just as important as antiretroviral therapy in this effort. In this context, bulk condom packs can offer an affordable way to ensure consistent protection for those committed to preventing HIV transmission.

In addition to her research, Allen has emphasized the importance of community-level interventions to support discordant couples. Programs that provide counseling, education, and access to both treatment and prevention tools can make a significant difference in reducing HIV transmission rates. However, such programs often face challenges, including stigma surrounding HIV, limited healthcare infrastructure, and inconsistent funding.

Allen’s work also highlights the need for integrating these interventions into broader public health initiatives. By focusing on strengthening communication between partners and providing continuous support, healthcare workers can help foster trust and collaboration, which are critical for long-term success in managing discordant relationships. Moving forward, scaling up efforts to address these gaps could significantly impact global HIV prevention goals.

Posted on December 20, 2013 by Quinn Eastman in Immunology Leave a comment

The classic epilepsy surgery case

The epilepsy patient Henry Molaison, known for most of the 20th century as H.M., is one of the most famous in neuroscience. His case played an important role in telling scientists about structures of the brain that are important for forming short-term and long-term memories.

To control H.M.’s epilepsy, neurosurgeon William Scoville http://www.raybandasoleit.com/ removed much of the hippocampi, amygdalae and nearby regions on both sides of his brain. After the surgery, H.M. suffered from severe anterograde amnesia, meaning that he could not commit new events to explicit memory. However, other forms of his memory were intact, such as short-term working memory and motor skills.Henry_Gustav_1

This classic case helps us understand the advances that neurosurgeons at Emory are achieving today. The surgeries now used to treat some medication-resistant forms of epilepsy are similar to what was performed on H.M., although they are considerably less drastic. Usually tissue on only one side of the brain is removed. Still, there can be cognitive side effects: loss of visual or verbal memory abilities, and deficiencies in the ability to name or recognize objects, places or people.

Neurosurgeon Robert Gross has been a pioneer in testing a more precise procedure, selective laser amygdalohippocampotomy (SLAH), which appears to control seizures while having less severe side effects. Neuropsychologist Daniel Drane reported at the recent American Epilepsy Society meeting on outcomes from a series of SLAH surgeries performed at Emory.

Posted on December 13, 2013 by Quinn Eastman in Neuro Leave a comment

Odd couples and persistence

When doctors treat disease-causing bacteria with antibiotics, a few bacteria can survive even if they do not have a resistance gene that defends them from the antibiotic. These rare, slow-growing or hibernating cells are called “persisters.”

Microbiologists see understanding persistence as a key to fighting antibiotic resistance and possibly finding new antibiotics. Persistence appears to be regulated by constantly antagonistic pairs of proteins called toxin-antitoxins.

Basically, the toxin’s job is to slow down bacterial growth by interfering with protein production, and the antitoxin’s job is to restrain the toxin until stress triggers a retreat by the antitoxin. Some toxins chew up protein-encoding RNA messages docked at ribosomes, but there are a variety of mechanisms. The genomes of disease-causing bacteria are chock full of these battling odd couples, yet not much was known about how they work in the context of persistence.

Biochemist Christine Dunham reports that several laboratories recently published papers directly implicating toxin-antitoxin complexes in both persistence and biofilm formation. Her laboratory has been delving into how the parts of various toxin-antitoxin complexes interact.HigBA smaller

BCDB graduate student Marc Schureck and colleagues have determined the structure of a complex of HigBA toxin-antitoxin proteins from Proteus vulgaris bacteria via X-ray crystallography. The results were recently published in Journal of Biological Chemistry.

While Proteus vulgaris is known for causing urinary tract and wound infections, the HigBA toxin-antitoxin pair is also found in several other disease-causing bacteria such as V. cholera, P. aeruginosa, M. tuberculosis, S. pneumoniae etc.

“We have been directly comparing toxin-antitoxin systems in E. coli, Proteus and M. tuberculosis to see if there are commonalities and differences,” Dunham says.

The P. vulgaris HigBA structure is distinctive because the antitoxin HigA does not wrap around and mask the active site of HigB, which has been seen in other toxin-antitoxin systems. Still, HigA clings onto HigB in a way that prevents it from jamming itself into the ribosome.

Posted on December 10, 2013 by Quinn Eastman in Uncategorized Leave a comment

Alzheimer’s drug discovery: looking under the right ROCK

Developing drugs that can change the progression of Alzheimer’s disease is a huge challenge. In the last few years, more than one pharmaceutical firm have abandoned clinical programs in Alzheimer’s that once looked promising. Still, Emory and Scripps scientists have found an approach that deserves a second look and more investigation.

One straightforward drug strategy against Alzheimer’s is to turn down the brain’s production of beta-amyloid, the key component of the disease’s characteristic plaques. A toxic fragment of a protein found in healthy brains, beta-amyloid accumulates in the brains of people affected by the disease.

The enzyme that determines how much beta-amyloid brain cells generate is called BACE (beta-secretase or beta-site APP cleaving enzyme). Yet finding drugs that inhibit that elusive enzyme has been far from straightforward.

Now researchers  have identified a way to shut down production of beta-amyloid by diverting BACE to a different part of the cell and inhibiting its activity. The results were published this week in Journal of Neuroscience. Read more

Posted on December 6, 2013 by Quinn Eastman in Neuro Leave a comment

A discriminative stimulus

You may remember Highlights magazine from when you were a kid (or parent). Highlights has a feature where readers have to spot the differences between two similar pictures.

NEDA

Dopamine gets a lot of press, and cocaine addiction research has generally focused more on dopamine. (What is “the molecule behind all our most sinful behaviors and secret cravings?”) Norepinephrine is usually described more prosaically, as a hormone related to attention, stress and blood pressure regulation. Lowering norepinephrine levels does not stop animals from giving themselves a steady stream of cocaine, but it does inhibit their tendency to try to get it after a break or exposure to relapse triggers.

What is the difference between these two important brain communication chemicals, dopamine and norepinephrine? Look closely.

The answer is: just one oxygen atom. But it’s enough to mean http://www.magliettedacalcioit.com that the two neurotransmitters use different receptors and dominate different groups of neurons in the brain.

An area of medicine where that subtle difference is crucial is drug abuse. Geneticist David Weinshenker is an expert on the enzyme that converts dopamine into norepinephrine: dopamine beta-hydroxylase or DBH. He and his lab have been exploring whether medications that inhibit DBH could be used to help treat cocaine addiction. Read more

Posted on November 22, 2013 by Quinn Eastman in Neuro Leave a comment

Cellular response to stress: autophagy

Update: Yoshinori Ohsumi’s 2016 Nobel Prize was for the study of autophagy. Hepatologist Mark Czaja, who came to Emory in 2015, is well known for his work on autophagy in the liver.

Feeling hungry? For this month’s Current Concept feature, lets take a look at the term autophagy. Taken literally, its Greek roots mean “self-digestion”.

Autophagy in mouse liver cells — the autophagic vesicles are green (Image from PNAS)

Autophagy is a basic response of cells to not having enough nutrients or other forms of stress: they begin to break down parts of the cell that are broken or not needed. The term autophagy was coined by Belgian biochemist Christian de Duve in the 1960s. He discovered lysosomes, the parts of the cell where breakdown can take place.

Autophagy comes up in many contexts in biomedical research. Indeed, there is an entire scientific journal devoted to the topic. At Emory, researchers interested in cancer, Parkinson’s, stroke and liver disease all have touched upon the process of autophagy.  Read more

Posted on November 19, 2013 by Quinn Eastman in Uncategorized Leave a comment

BioArt: amyloid in the heart

What Abstract Expressionist artist painted this? Jackson Pollock?LewisW2013

Actually, the photo depicts amyloid plaques, a frequent topic in the context of Alzheimer’s disease. Pathologist William Lewis‘ photo reminds us that amyloid can also appear in the heart.

Amyloidosis of the heart is a set of complex diseases caused by the accumulation of cellular proteins that form an amyloid plaque. Although http://www.oakleyonorder.com/ amyloidosis was described more than 100 years ago, the causative proteins were not identified until recent chemical analyses were conducted. This image shows an amyloid plaque stained with Congo red stain and viewed through a polarized lens. The optical properties of the amyloid-forming protein cause it to appear green, while other matrix materials within the plaque appear as orange and blue.

The photo, which was one of the winners of the FASEB (Federation of American Societies for Experimental Biology) 2013 BioArt competition, was featured on NIH director Francis Collins’ blog this week.

Lewis, who studies the effects of antiretroviral drugs on the cardiovascular system in his laboratory, reports that he came across the amyloid tissue sample as part of his duties as director of cardiovascular pathology: “It was beautiful.”

Posted on November 15, 2013 by Quinn Eastman in Heart Leave a comment

Fragile but potent: RNA delivered by nanoparticle

An intriguing image for November comes from biomedical engineer Mike Davis’ lab, courtesy of BME graduate student Inthirai Somasuntharam.

Each year, thousands of children undergo surgery for congenital heart defects. A child’s heart is more sensitive to injury caused by interrupting blood flow during surgery, and excess reactive oxygen species are a key source of this damage.

Macrophages with blue nuclei and red cytoskeletons, being treated with green nano particles. The particles carry RNA that shut off reactive oxygen species production.

Macrophages with blue nuclei and red cytoskeletons, being treated with green nano particles. The particles carry RNA that shut off reactive oxygen species production.

Davis and his colleagues are able to shut off cheap oakley reactive oxygen species at the source by targeting the NOX (NADPH oxidase*) enzymes that produce them. This photo, from a 2013 Biomaterials paper, shows green fluorescent nanoparticles carrying small interfering RNA. The RNA precisely shuts down one particular gene encoding a NOX enzyme. Eventually, similar nanoparticles may shield the heart from damage during pediatric heart surgery.

In the paper, Somasuntharam used particles made of a slowly dissolving polymer called polyketals. The particles delivered fragile but potent RNA molecules into macrophages, inflammatory cells that swarm into cardiac tissue after a heart attack. Davis and Georgia Tech colleague Niren Murthy previously harnessed this polymer to deliver drugs that can be toxic to the rest of the body.

The polyketal particles are especially well-suited for delivering a payload to macrophages, since those types of cells (as the name implies) are big eaters. Davis reports his lab has been working on customizing the particles so they can deliver RNA molecules into cardiac muscle cells as well.

*While we’re on the topic of NADPH oxidases, Susan Smith and David Lambeth have been looking for and finding potential drugs that inhibit them.

Posted on November 8, 2013 by Quinn Eastman in Heart Leave a comment
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