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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An effective alternative to fecal transplant for C. difficile?

Bacterial spores in capsules taken by mouth can prevent recurrent C. difficile infection, results from a preliminary study suggest.

Clostridium difficile is the most common hospital-acquired infection in the United States and can cause persistent, sometimes life-threatening diarrhea. Fecal microbiota transplant has shown promise in many clinical studies as a treatment for C. difficile, but uncertainty has surrounded how such transplants should be regulated and standardized. Also, the still-investigational procedure is often performed by colonoscopy, which may be difficult for some patients to tolerate.

The capsule study, published Monday in Journal of Infectious Diseases, represents an important step in moving away from fecal microbiota transplant as a treatment for C. difficile, says Colleen Kraft, MD, assistant professor of pathology and laboratory medicine and medicine (infectious diseases) at Emory University School of Medicine.

Kraft and Tanvi Dhere, MD, assistant professor of medicine (digestive diseases) have led development of the fecal microbiota transplant program at Emory. They are authors on the capsule study, along with investigators from Mayo Clinic, Massachusetts General Hospital, Miriam Hospital (Rhode Island), and Seres Therapeutics, the study sponsor.

While this study involving 30 patients did not include a control group, the reported effectiveness of 96.7 percent compares favorably to published results on antibiotic treatment of C. difficile infection or fecal microbial transplant. Read more

Posted on February 12, 2016 by Quinn Eastman in Uncategorized Leave a comment

Wound-healing intestinal bacteria: like shrubs after a forest fire

In injured mouse intestines, specific types of bacteria step forward to promote healing, Emory scientists have found. One oxygen-shy type of bacteria that grows in the wound-healing environment, Akkermansia muciniphila, has already attracted attention for its relative scarcity in both animal and human obesity.

NMicro

An intestinal wound brings bacteria (red) into contact with epithelial cells (green). The bacteria can provide signals that promote healing, if they are the right kind.

The findings emphasize how the intestinal microbiome changes locally in response to injury and even helps repair breaches. The researchers suggest that some of these microbes could be exploited as treatments for conditions such as inflammatory bowel disease.

The results were published on January 27 in Nature Microbiology. Researchers took samples of DNA from the colon tissue of mice after they underwent colon biopsies. They used DNA sequencing to determine what types of bacteria were present.

“This is a situation resembling recovery after a forest fire,” says Andrew Neish, MD, professor of pathology and laboratory medicine at Emory University School of Medicine. “Once the trees are gone, there is an orderly succession of grasses and shrubs, before the reconstitution of the mature forest. Similarly, in the damaged gut, we see that certain kinds of bacteria bloom, contribute to wound healing, and then later dissipate as the wound repairs.” Read more

Posted on February 9, 2016 by Quinn Eastman in Immunology, Uncategorized Leave a comment

Rescuing existing antibiotics with adjuvants

One of the speakers at Thursday’s Antibiotic Resistance Center symposium, Gerald Wright from McMaster University, made the case for fighting antibiotic resistance by combining known antibiotics with non-antibiotic drugs that are used to treat other conditions, which he called adjuvants.

As an example, he cited this paper, in which his lab showed that loperamide, known commercially as the anti-diarrheal Immodium, can make bacteria sensitive to tetracycline-type antibiotics.

Wright said that other commercial drugs and compounds in pharmaceutical companies’ libraries could have similar synergistic effects when combined with existing antibiotics. Most drug-like compounds aimed at human physiology follow “Lipinski’s rule of five“, but the same rules don’t apply to bacteria, he said. What might be a more rewarding place to look for more anti-bacterial compounds? Natural products from fungi and plants, Wright proposed.

“I made a little fist-pump when he said that,” says Emory ethnobotanist Cassandra Quave, whose laboratory specializing in looking for anti-bacterial activities in medicinal plants.

Medical thnobotanist Cassandra Quave collecting plant specimens in Italy.

Medical ethnobotanist Cassandra Quave collecting plant specimens in Italy

Indeed, many of the points he made on strategies to overcome antibiotic resistance could apply to Quave’s approach. She and her colleagues have been investigating compounds that can disrupt biofilms, thus enhancing antibiotic activity. More at eScienceCommons and at her lab’s site.

Posted on January 15, 2016 by Quinn Eastman in Uncategorized Leave a comment

Looking back – Lab Land Top 10 posts in 2015

Happy New Year, and thank you for reading Emory Lab Land. Here are the top ten posts during 2015, according to Google Analytics. I pledge to bring you more quirky and insightful research, striking images and explanations of hard-to-grasp concepts in 2016.

  1. Hypersomnia update: beyond subject one [post is from summer of 2014, reflects long tail/lasting interest from hypersomnia community]
  2. Anticancer drug strategy: making cells choke on copper
  3. Microbiome enthusiasm at Emory
  4. The unsweetened option [Not about iced tea, but about low-sugar diet and fatty liver disease]
  5. Fragile X regulation is a finely tuned machine
  6. Stem cell/cardiology researcher Hee Cheol Cho joins Emory
  7. There will be micro particles (in stored blood)
  8. Hypersomnia update: clarithromycin study
  9. Gabbing about GABA — implications for hypersomnia treatments
  10. Nudging physician behavior on antibiotic orders
Posted on December 30, 2015 by Quinn Eastman in Uncategorized Leave a comment

Metagenomics explainer

A term we heard a bunch at the Emory Microbiome Symposium in November was “metagenomics”. Time for an explainer, with some help from Emory geneticist Tim Read.

Nature Reviews Microbiology defines metagenomics as “genomic analysis of microbial DNA that is extracted directly from communities in environmental samples.”

This technology — genomics on a huge scale — enables a survey of the different microorganisms present in a specific environment, such as water or soil, to be carried out. Metagenomics is also emerging as a tool for clinical diagnosis of infectious diseases.

Read notes that the term specifically refers to “shotgun” sequencing of environmental DNA.

“The shotgun approach is to randomly sample small pieces of the DNA in the tube, no matter which organism they came from,” he says. “The output is a mélange of different genes from bacteria, viruses, fungi, plants and humans.  The data is fascinating but the analysis is daunting.” Read more

Posted on December 15, 2015 by Quinn Eastman in Uncategorized 1 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 November 3, 2015 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

Posted on October 26, 2015 by Quinn Eastman in Uncategorized Leave a comment

The unsweetened option

Pediatric hepatologist Miriam Vos is starting a new study testing the effects of a low-sugar diet in children with NAFLD (non-alcoholic fatty liver disease). The study is supported by the Nutrition Science Initiative and conducted in a partnership with UCSD/Rady Children’s Hospital, San Diego. See below for more on NUSI.

While there are no medications approved for NAFLD – a healthy diet and exercise are the standard of care – plenty of drugs are under development, as a recent article from Mitch Leslie in Science illustrates. As a reality check and benchmark, the NUSI study will address whether the low-tech intervention of altering diet can be effective.

Lab Land has delved into NAFLD and its increasing prevalence in previous posts. Plenty of correlational data shows that sugar intake is linked to NAFLD (a recent paper from the Framingham Heart Study), but Vos points out that there are no studies showing that reducing sugar is sufficient to drive improvement in the disease.

Diet is a challenge to examine in humans rigorously. In observational studies, investigators are always bumping up against the limits of memory and accurate reporting. In an interventional study with adults, it’s possible to provide them a completely defined menu for a short time in a closed environment, but that’s less practical for longer periods or with children.

The press release announcing the NUSI study says: half of the families will eat and drink what they normally do while the rest will be put on sugar-free meals and snacks, all of which will be provided for the participants and their families for eight weeks.

Miriam Vos, MD

I was curious about how this would work, especially for boys aged 11 to 16 (the participants in her study), so I asked Vos more about it for Lab Land.

“We try to provide them a diet that is otherwise similar to what the family is used to,” she says. “For example, if they’re accustomed to home-cooked meals, our team of nutritionists will work with them to find different recipes.” Read more

Posted on September 2, 2015 by Quinn Eastman in Uncategorized Leave a comment

Adaptive mutation mechanism may drive some forms of antibiotic resistance

Evolutionary theory says mutations are blind and occur randomly. But in the controversial phenomenon of adaptive mutation, cells can peek under the blindfold, increasing their mutation rate in response to stress.

Scientists at Winship Cancer Institute, Emory University have observed that an apparent “back channel” for genetic information called retromutagenesis can encourage adaptive mutation to take place in bacteria.

The results were published Tuesday, August 25 in PLOS Genetics.

“This mechanism may explain how bacteria develop resistance to some types of antibiotics under selective pressure, as well as how mutations in cancer cells enable their growth or resistance to chemotherapy drugs,” says senior author Paul Doetsch, PhD.

Doetsch is professor of biochemistry, radiation oncology and hematology and medical oncology at Emory University School of Medicine and associate director of basic research at Winship Cancer Institute. The first author of the paper is Genetics and Molecular Biology graduate student Jordan Morreall, PhD, who defended his thesis in April.

Retromutagenesis resolves the puzzle: if cells aren’t growing because they’re under stress, which means their DNA isn’t being copied, how do the new mutants appear?

The answer: a mutation appears in the RNA first. Read more

Posted on August 27, 2015 by Quinn Eastman in Cancer, Uncategorized Leave a comment

Anti-aging tricks from dietary supplement seen in mice

Our recent news item on a Cell Reports paper from ShiQin Xiong and Wayne Alexander describes a connection between two important biological molecules: the exercise-induced transcription coactivator PGC1-alpha and the enzyme telomerase, sometimes described as a “fountain of youth” because telomeres protect the ends of chromosomes.

While the Emory researchers did not directly assess the effects of exercise in their experiments, their findings provide molecular clues to how exercise might slow the effects of aging or chronic disease in some cell types.

Xiong and Alexander found that the dietary supplement alpha lipoic acid (ALA) can stimulate telomerase, with positive effects in a mouse model of atherosclerosis. ALA is a sulfur-containing fatty acid used to treat diabetic neuropathy in Germany, and has previously been shown to combat atherosclerosis in animal models. The Emory authors’ main focus was on vascular smooth muscle cells and note that more study of ALA’s effects on other cell types is needed.

Below are four key references that may help you put the Cell Reports paper in context: Read more

Posted on August 24, 2015 by Quinn Eastman in Uncategorized Leave a comment
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