Elevated troponin after exercise refines cardiac risk prediction

Elevated troponin levels in response to exercise can predict future outcomes in patients with coronary artery disease -- better than stress tests with Read more

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Detecting heart failure via wearable devices

Cardiology researchers have been eagerly taking up consumer electronic devices that include pulse oximeters. Being able to conveniently measure the level of oxygen in someone’s blood is a useful tool, whether one is interested in sleep apnea or COVID-19.

The news that the new Apple Watch includes a pulse oximeter prompted Lab Land to check in with Amit Shah, an Emory cardiologist who has been experimenting with similar devices to discriminate patients with heart failure from those with other conditions.

Shah, together with Shamim Nemati, now at UCSD, and bioinformatics chair Gari Clifford recently published a pilot study on detecting heart failure using the Samsung Simband. The Simband was a prototype device that didn’t make it to the consumer market, but it carried sensors for optical detection of blood volume changes (photoplethysmography), like on the Apple Watch. 

Heart failure causes symptoms such as shortness of breath and leg swelling, but other conditions such as anemia or lung diseases can appear similarly. The idea was to help discriminate people who might need an examination by echocardiogram (cardiac ultrasound).

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Several ways to survey for SARS-CoV-2 exposure

How many people out there have been exposed to SARS-CoV-2? It’s a tricky question, once you think about all the people who have experienced COVID-19 symptoms over the last several months, but didn’t go to the hospital. And there’s a murkier penumbra of people who may have fended off the virus with a minor immune skirmish.

A recent Emerging Infectious Diseases paper from Emory investigators includes antibody tests on a group of more than 100 adults in the Atlanta area who experienced mild flu-like symptoms this spring, but couldn’t get tested for SARS-CoV-2 itself.

A sizable fraction (22 to 48 percent, depending on when they provided blood samples) had elevated levels of IgM against the coronavirus. IgM is the “rookie” antibody produced when the immune system is first encountering something, as opposed to the more seasoned IgG, which appears later in an immune response and tended to rise only in people who were hospitalized. The Emory authors came to a conclusion that others are also reaching:

“Examining IgM and IgG against multiple SARS-CoV-2–related antigens may thus better inform natural history and vaccine studies than any one antibody.”

To answer these kinds of questions more comprehensively, investigators will need to go broader. For example, this week the American Red Cross published data on what proportion of its blood donors have antibodies against SARS-CoV-2. About 3 percent of first-time donors did, using their criteria.

For big answers, we can look to studies such as Emory’s COVID-Vu, a nationwide population-based study using antibody and virus tests taken at home. Rollins School of Public Health researchers received a $6.6 million grant to launch the study this summer. This type of study is designed to cover everyone, whether they were sick or not.

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For genetically altered mice/rats, freeze and recharge

With a pandemic threatening the health and safety of Emory researchers in March 2020, university leadership made the difficult decision to ramp down some types of research. For investigators that use laboratory mice or rats in their research, this posed a significant challenge.

How could investigators maintain valuable, often unique, lines of genetically engineered animals for future research? The Mouse Transgenic and Gene Targeting Core (TMF) had a solution: cryopreservation. Animals’ sperm — and occasionally, embryos – can be carefully preserved in cold-resistant straws and stored in liquid nitrogen.

“Cryopreservation is a reliable and efficient method for archiving and distributing genetically engineered mouse lines,” says Karolina Piotrowska-Nitsche, PhD, director of the Core.

The TMF is located on the ground floor of the Emory Health Sciences Research Building and provides a suite of services related to transgenics and gene editing, working with tools such as CRISPR/Cas9 to make subtle or complex changes in the DNA of living animals.

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Georgia survey on COVID-19 testing/vaccination shows group differences

Public health experts stress that adequate representation of Black and Latinx people in COVID-19 vaccine studies is a priority. Given how COVID-19 is impacting vulnerable communities, acceptance of a future vaccine – whenever it may become available – is important. A recent article in the Atlanta Journal Constitution highlights how this issue is playing out in Georgia, given the legacy of lack of trust in biomedical research.

“The issue of minority participation in clinical trials is not just in vaccines, it really is in every clinical trial and the point is that the population that is most impacted and most affected needs to be represented in trials,” Emory’s Carlos del Rio said at a media briefing last week.

In a Sunday Op-Ed in the AJC, emergency physician Monique Smith called attention to the disparities in COVID-19 testing and follow-up. In the communities she serves, it is not just a challenge to get a test but to also understand what the results mean, or what to do while waiting for the results, she says.

Lab Land can add some data to that – a survey conducted by neurologist William Hu and colleagues in early August on attitudes toward COVID-19 testing and vaccination among Georgia residents. Non-Hispanic white respondents were more likely than Black/African-American respondents to recommend their loved ones to participate in a COVID-19 clinical trial or be vaccinated after FDA approval.

Green = Black/African-Americans, Clear = non-Hispanic white

From August survey data

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Tweaks to corticosteroids may reduce side effects

Steroid anti-inflammatory drugs such as dexamethasone and prednisone are widely used to treat conditions such as allergies, asthma, autoimmune diseases, cancer – and now, COVID-19. Yet they can have harmful side effects on the skin, bones and metabolism.

The side effects are thought to come from a molecular mechanism that is separate from the anti-inflammatory one, and scientists have envisioned that it may be possible to divide the two. A new paper in PNAS from Emory biochemist Eric Ortlund’s lab sketches out how one potential alternative may work.

Synthetic corticosteroids mimic the action of the stress hormone cortisol; both bind the glucocorticoid receptor (GR) protein. Ortlund’s group obtained structural information on how vamorolone, an experimental drug, sticks to the part of GR that binds hormones.

The American company ReveraGen and Swiss partner Santhera are developing vamorolone for Duchenne muscular dystrophy, but it is possible to envision several other conditions such as ulcerative colitis for which vamorolone or a similar drug could be helpful. Vamorolone is NOT approved by the FDA for Duchenne muscular dystrophy or any other indication.

As far as its interaction with GR, what sets vamorolone apart from conventional corticosteroids is quite subtle: a missing hydrogen bond. This means that GR doesn’t interact as well with various partner proteins, which are needed to turn on genes involved in processes such as metabolism and bone growth.  However, the anti-inflammatory effects result mainly from turning inflammatory and immune system genes off, and those interactions are maintained. More on that distinction here and here.

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Improve old antibiotics rather than discover new ones, BME researchers propose

The resistance of bacteria to antibiotics is a global challenge that has been exacerbated by the financial burdens of bringing new antibiotics to market and an increase in serious bacterial infections as a result of the COVID-19 pandemic.

Biomedical engineering researchers at Georgia Tech and Emory are tackling the problem of antibiotic resistance not by creating new drugs, but by enhancing the safety and potency of ones that already exist.

Aminoglycosides are antibiotics used to treat serious infections caused by pathogenic bacteria like E. coli or Klebsiella.  Bacteria haven’t developed widespread resistance to aminoglycosides, as compared to other types of antibiotics.  These antibiotics are used sparingly by doctors, in part because of the toxic side effects they can sometimes cause.

In research published in the journal PLOS One, Christopher Rosenberg, Xin Fang and senior author Kyle Allison demonstrated that lower doses of aminoglycosides could be used to treat bacteria when combined with specific metabolic sugars.  Low concentrations of antibiotics alone often cannot eliminate dormant, non-dividing bacterial cells, but the researchers hypothesized based on a past study that combining aminoglycosides with metabolites such as glucose, a simple sugar, or mannitol, a sugar alcohol often used as sweetener, could stimulate antibiotic uptake.

The authors tested these treatment combinations against Gram-negative pathogens E. coli, Salmonella and Klebsiella. The results showed that aminoglycoside-metabolite treatment significantly reduced the concentration of antibiotic needed to kill those pathogens. The authors also demonstrated that this treatment combination did not increase bacterial resistance to aminoglycosides and was effective in treating antibiotic-tolerant biofilms, which are bacterial communities that act as reservoirs of infection.

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Galanin: the ‘keep calm and carry on’ hormone?

A few celebrity neuropeptides have acquired a reputation – sometimes exaggerated — and a flavor, corresponding to their functions in the brain.

Oxytocin has the aura of a “cuddle hormone” because of its role in social bonding and reproduction. Endorphins are the body’s natural pain-killers, long thought to be responsible for “runner’s high.” Hypocretin/orexin, missing in narcolepsy, is a stabilizer of wakefulness as well as motivation.

Galanin, studied by Emory neuroscientist David Weinshenker’s lab, is not as flashy as other neuropeptides. While it is accumulating an intriguing track record, galanin appears to play subtly different roles depending on where it is expressed. It is tempting to call galanin the “keep calm and carry on” hormone, but the research on galanin is so complex it’s difficult to pin down.

Graduate student Rachel Tillage and colleagues have a paper this week in Journal of Neuroscience detailing how galanin’s production by one group of neurons in the brainstem confers stress resilience in mice.

This image shows the rough location for the locus coeruleus in the human brain. In mice, production of galanin in the locus coeruleus cushions against stress.

The new paper shows that exercise increases galanin in the locus coeruleus, a region in the brainstem that produces norepinephrine (important for attention, alertness, anxiety and muscle tone). Galanin can provide protection against the anxiety-inducing effects of artificial but very specific locus coeruleus activation by optogenetics.

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Delayed mechanical strain promotes angiogenesis in bone/wound healing

The natural processes of wound or bone healing rely on the growth of new blood vessels, or angiogenesis. If someone breaks a bone, it is standard practice to apply a cast and immobilize the broken bone, so that healing can proceed without mechanical distortion. 

After those initial stages of healing, applying surprising amounts of pressure can encourage angiogenesis, according to a new paper in Science Advances from biomedical engineer Nick Willett’s lab.

“These data have implications directly on bone healing and more broadly on wound healing,” Willett says. “In bone healing or grafting scenarios, physicians are often quite conservative in how quickly patients begin to load the repair site.”

Willett’s lab is part of both Emory’s Department of Orthopedics and the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory, and is based at the Atlanta Veterans Affairs Medical Center.

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Burning fat like a baby

Newborn humans and hibernating mammals have high levels of brown adipose tissue, which they use to generate heat. Adult humans generally don’t have abundant brown adipose tissue, even if they have lots of “white” fat. Increasing brown fat’s activity may be an approach to treat obesity and related metabolic disorders.

Recently researchers identified an enzyme called Them1 (thioesterase superfamily member 1) as a factor that limits heat generation in brown adipose tissue. Emory biochemist Eric Ortlund and his lab showed how part of the Them1 enzyme binds a certain type of lipid molecule, and also how that part of the enzyme anchors the enzyme close to lipid droplets in adipose cells. Former graduate student Matt Tillman, now a postdoc at Duke, was the first author of the new paper in Proceedings of the National Academy of Sciences.

“In this study, we show Them1 contains a lipid sensor module that detects specific lipids within the cell to regulate its activity,” says Tillman.

In brown adipose cells, the lipid-sensing domain of Them1 is needed for localization around lipid droplets

From Tillman et al PNAS (2020)

He and his colleagues showed that a lipid known for its role in cell signaling, lysophosphatidylcholine or LPC, inhibits Them1 activity, which in turn activates thermogenesis in brown adipose tissue. In contrast, other fatty acids that serve as fuel tend to activate Them1. This regulatory system within Them1 allows the cell to sense its metabolic state and decide when to burn or conserve fat.

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Triple play in science communication

Emory BCDB graduate student Emma D’Agostino

We are highlighting Emory BCDB graduate student Emma D’Agostino, who is a rare triple play in the realm of science communication.

Emma has her own blog, where she talks about what it’s like to have cystic fibrosis. Recent posts have discussed the science of the disease and how she makes complicated treatment decisions together with her doctors. She’s an advisor to the Cystic Fibrosis Foundation on patient safety, communicating research and including the CF community in the research process. She’s also working in biochemist Eric Ortlund’s lab on nuclear receptors in the liver:drug targets for the treatment of diabetes and intestinal diseases.

The triple play is this — on her blog, Emma has discussed how she has to deal with antibiotic resistance. Emory Antibiotic Resistance Center director David Weiss’ lab has published a lot on colistin: how it’s a last-resort drug because of side effects, and how difficult-to-detect resistance to it is spreading. Emma has some personal experience with colistin that for me, brought the issue closer. Read more

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