In a model of human fetal brain development, Emory researchers can see perturbations of epigenetic markers in cells derived from people with familial early-onset Alzheimer’s disease, which takes decades to appear. This suggests that in people who inherit mutations linked to early-onset Alzheimer’s, it would be possible to detect molecular changes in their brains before birth.
The results were published in the journal Cell Reports.
“The beauty of using organoids is that they allow us to Read more
Why do people with cystic fibrosis (CF) have such trouble with lung infections? The conventional view is that people with CF are at greater risk for lung infections because thick, sticky mucus builds up in their lungs, allowing bacteria to thrive. CF is caused by a mutation that affects the composition of the mucus.
Rabindra Tirouvanziam, an immunologist at Emory, says a better question is: what type of cell is supposed to be fighting the Read more
Cardiac muscle cells derived from stem cells could eventually be used to treat heart diseases in children or adults, reshaping hearts with congenital defects or repairing damaged tissue.
Cardiomyocytes produced with the help of simulated microgravity. Red represents the cardiac muscle marker troponin, and green is cadherin, which helps cells stick to each other. Blue = cell nuclei. From Jha et al SciRep (2016).
Using the right growth factors and conditions, it is possible to direct pluripotent stem cells into becoming cardiac muscle cells, which form spheres that beat spontaneously. Researchers led by Chunhui Xu, PhD, director of the Cardiomyocyte Stem Cell Laboratory in Emory’s Department of Pediatrics, are figuring out how to grow lots of these muscle cells and keep them healthy and adaptable.
As part of this effort, Xu and her team discovered that growing stem cells under “simulated microgravity” for a few days stimulates the production of cardiac muscle cells, several times more effectively than regular conditions. The results were published on Friday, Aug. 5 in Scientific Reports. The first author of the paper is postdoctoral fellow Rajneesh Jha, PhD. Read more
Zika virus can infect and replicate in immune cells from the placenta, without killing them, scientists have discovered. The finding may explain how the virus can pass through the placenta of a pregnant woman, on its way to infect developing brain cells in her fetus.
Infected placental macrophages. Zika antigens visible in red. From Quicke et al (2016).
“Our results substantiate the limited evidence from pathology case reports,” says senior author Mehul Suthar, PhD, assistant professor of pediatrics at Emory University School of Medicine. “It was known that the virus was getting into the placenta. But little was known about where the virus was replicating and in what cell type.”
Scientists led by Suthar and Emory pediatric infectious disease specialist Rana Chakraborty, MD, found that Zika virus could infect placental macrophages, called Hofbauer cells, in cell culture. The virus could also infect another type of placental cell, called cytotrophoblasts, but only after a couple days delay and not as readily. Other researchers recently reported that syncytiotrophoblasts, a more differentiated type of placental cell than cytotrophoblasts, are resistant to Zika infection.
The cells for the experiments were derived from full-term placentae, obtained from healthy volunteers who delivered by Cesarean section. The level of viral replication varied markedly from donor to donor, which hints that some women’s placentae may be more susceptible to viral infection than others. Read more
Emory researchers have identified molecular mechanisms that regulate motivation and persistence in mice. Their findings could have implications for intervention in conditions characterized by behavioral inflexibility, such as drug abuse and depression.
Scientists showedÂ that by manipulating a particular growth factor in one region of the brain, they couldÂ tune up or down a mouseâ€™s tendency to persist in seeking a reward. In humans, this region of the brain is located just behind the eyes and is called the medial orbitofrontal cortex or mOFC.
â€œWhen we make decisions, we often need to gauge the value of a reward before we can see it — for example, will lunch at a certain restaurant be better than lunch at another, or worth the cost,â€ says Shannon Gourley, PhD, assistant professor of pediatrics and psychiatry at Emory University School of Medicine. â€œWe think the mOFC is important for calculating value, particularly when we have to imagine the reward, as opposed to having it right in front of us.â€
Being able to appropriately determine the value of a perceived reward is critical in goal-directed decision making, a component of drug-seeking and addiction-related behaviors. While scientists already suspected that the medial orbitofrontal cortex was important for this type of learning and decision-making, the specific genes and growth factors were not as well-understood.
The researchers focused on brain-derived neurotrophic factor (BDNF), a protein that supports the survival and growth of neurons in the brain. BDNF is known to play key roles in long-term potentiation and neuronal remodeling, both important in learning and memory tasks. Variations in the human gene that encodes BDNF have been linked with several psychiatric disorders.
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).Â The study is supported by the Nutrition Science Initiative and conducted in a partnership with UCSD/Rady Childrenâ€™s Hospital, San Diego. See below for more on NUSI.
While there are no medications approved for NAFLD â€“ a healthy diet and exercise are the standard of care –Â 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, itâ€™s possible to provide them a completely defined menu forÂ a short timeÂ in a closed environment, but thatâ€™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 (theÂ participants in her study), so I asked Vos more about it for Lab Land.
â€œWe try to provide them a diet that is otherwise similar to what the family is used to,â€ she says. â€œFor example, if theyâ€™re accustomed to home-cooked meals, our team of nutritionists will work with them to find different recipes.â€ Read more
Tetherin is a host cell factor that mechanically links HIV-1 to the plasma membrane. This is the first time anyone has imaged tethered HIV-1 by cryo-electron tomography. In doing so, we were able to learn about the length and arrangement of the tethers.
Cryo-electron tomography is an imaging technique which enables scientists to look at biological specimens in a â€œnative-likeâ€ (frozen hydrated) state, without the chemical fixatives or heavy metal stains typically used for conventional electron microscopy.
The 3D reconstruction was manually segmented to highlight the different viral and cellular components: HIV-1 virions (lavender), mature conical-cores (aqua blue), immature Gag lattice (pink), plasma membrane (peach), rod-like tethers (sea green).
Pediatric infectious disease specialist Tracey Lamb earned recognition this week for her NIH New Innovator award. The goal of Lambâ€™s project is to develop a probiotic yeast as a platform for inexpensive oral vaccines.
â€œWe have a long way to go to develop this vaccine Magliette Calcio A Poco Prezzo delivery system to the point where it is ready for testing in the clinic,â€ she says. â€œNow my lab can undertake more intensive research on this project to demonstrate that our design is effective in protecting against infection.”
1. The probiotic yeast Lamb is planning to develop as a vaccine platform is Saccharomyces boulardii, which has been tested in clinical trials as a treatment for gastrointestinal disorders such as Clostridium dificile infection and several forms of diarrhea. It was originally isolated in the 1920s from fruit in Southeast Asia.
2. Saccharomyces boulardii is very close to standard bakerâ€™s yeast, Saccharomyces cerevisiae, and is actually considered a subspecies of S. cerevisiae. Genomic differences that http://www.magliettedacalcioit.com contribute to its probiotic properties are under investigation.
3. The New Innovator program, running since 2007, is one of the ways the National Institutes of Health seeks to reward especially creative or potentially transformative research proposals. The New Innovator awards, up to $1.5 million over five years, are meant for newly independent researchers building their careers. Lamb managed to snag Emoryâ€™s first.
In Americaâ€™s battle against obesity, there is some good news. According to a study conducted by Emory researchers, Americans consumed nearly a quarter less added sugars in 2008 than they did 10 years earlier.
The study, published in the American Journal of Clinical Nutrition in July 2011, found that the consumption of added sugars, such as those found in sodas, sports drinks, juices and sweetened dairy products, decreased among all age groups over a decade. The largest decrease came in the consumption of sodas, traditionally the largest contributor to added sugar consumption, according to Jean Welsh, MPH, PhD, RN, study author and post-doctoral fellow in pediatric nutrition at Emory University School of Medicine.
â€œWhile we were hopeful this would be the case, we were surprised when our research showed such a substantial reduction in the amount of added sugar Americans are consuming,â€ said Welsh. â€œWeâ€™re hopeful this trend will continue.â€
So, why the change? One of Welshâ€™s partners in the study, Miriam Vos, MD, MSPH, an assistant professor of pediatrics in the Emory University School of Medicine, and a physician on staff at Childrenâ€™s Healthcare of Atlanta, attributes much of the shift to public education.
â€œOver the past decade, there has been a lot of public health awareness about obesity and nutrition, and I think people are starting to get the message about sugar,â€ says Vos. â€œWeâ€™re not trying to send a message that sugar is inherently bad. Itâ€™s more that the large amounts of sugar we consume are having negative effects on our health, including increasing our risk of obesity, diabetes and cardiovascular disease.â€
The study interpreted data of 40,000 peopleâ€™s diets collected by the Centers for Disease Control and Prevention (CDC) over 10 years.Â From the surveys, researchers were able to calculate how much added sugar â€“ that is sugar that is not originally part of a food â€“ that Americans are consuming. In 1999-2000, the typical personâ€™s daily diet included approximately 100 grams of added sugar, a number that had dropped to 77 grams by 2007 and 2008.
While the study shows that the amount of added sugar Americans are consuming is lower, it doesnâ€™t mean the amount is low enough.
â€œThe American Heart Association recommends that we get about five percent of our calories from added sugars,â€ says Vos. â€œIn 1999 to 2000, people were consuming about 18 percent of their calories from added sugars. Over 10 years, that amount decreased to 14.5 percent of our daily calories, which is much better. But, clearly, 14.5 percent is still three times more than what is considered a healthy amount. Weâ€™re on the right track, but we still have room for improvement.â€
HematologistÂ Pete Lollar has devoted his career to developing treatments for hemophilia A, which is caused by a lack of blood clotting factor VIII. Lollar is a professor of pediatrics in Emory School of Medicine and director of hemostasis research at Children’s Healthcare of Atlanta. Last week, Lollar was honored by Emoryâ€™s Office of Technology Transfer for setting in motion research that has progressed to a phase III clinical trial of a new product, OBI-1, a special form of factor VIII.
John "Pete" Lollar, MD
Along with this milestone came a dramatic story, described by OTTâ€™s assistant director Cale Lennon. The first patient to enroll in the clinical trial did so in November 2010 because of what appeared to be acquired hemophilia, which led to severe uncontrolled hemorrhaging. As a result of treatment with OBI-1, developed by Lollar and his research team at Emory, the patientâ€™s bleeding was brought under control and it saved his life. He was treated at Indiana Hemophilia and Thrombosis Center in Indianapolis.
Acquired hemophilia is a challenge for doctors to deal with because it is such a surprise. Unlike people with inherited hemophilia, those with acquired hemophilia do not have a personal or family history of bleeding episodes. Their immune systems are somehow provoked into making antibodies against their own clotting factor VIII.Â These antibodies also appear over time in about 30 percent of patients with inherited hemophilia who take standard clotting factors.
OBI-1, a special form of clotting factor VIII, is less of a red flag to the immune system. This allows treatment of patients who cannot benefit from standard clotting factor VIII, because of the presence of auto-antibodies.
Emory originally licensed OBI-1 to Octagen Corporation, a â€œhomegrownâ€ startup company founded in 1997. Octagen sublicensed the OBI-1 technology to a French biotechnology firm,Â Ipsen Biopharm in 1998. Over the next decade, Octagen and Ipsen pursued preclinical and initial clinical studies and completed a phase II clinical trial in 2006. IpsenÂ purchased the OBI-1 program outright in May 2008.
In January 2010, Ipsen developed a partnership agreement withÂ Inspiration Biopharmaceuticals, which was founded by two businessmen whose children have hemophilia. Under the agreement’s terms, Inspiration licensed OBI-1 from Ipsen and is responsible for its clinical development, regulatory approval and commercialization.