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

Evolution doesn’t run backwards: Insights from protein structure

“The past is difficult to recover because it was built on the foundation of its own history, one irrevocably different from that of the present and its many possible futures.”

Whoa. This quote comes from a recent Nature paper. How did studying the protein that helps cells respond to the stress hormone cortisol inspire such philosophical language?

Biochemist Eric Ortlund at Emory and collaborator Joe Thornton at the University of Oregon specialize in “resurrecting”and characterizing ancient proteins. They do this by deducing how similar proteins from different organisms evolved from a common root, mutation by mutation. Sort of like a word ladder puzzle.

Ortlund and Thornton have been studying the glucocorticoid receptor, a protein that binds the hormone cortisol and turns on genes in response to stress. The glucocorticoid receptor is related to the mineralocorticoid receptor, which binds hormones such as aldosterone, a regulator of blood pressure and kidney function.

If these receptors have a common ancestor, you can model each step in the transformation that led from the ancestor to each descendant. But Ortlund says that protein evolution isn’t like a word ladder puzzle, which can be turned upside-down: “You can’t rewind the tape of life and have it take the same path.”

The reason: Mutations arise amidst a background of selective pressure, and mutations in one part of a protein set the stage for whether other ones will be viable. The researchers describe this as an “epistatic rachet”.

Mutations that occurred during the transformation between the ancestral protein (green) and its descendant (orange) would clash if put back to their original position.

Mutations that occurred during the transformation between the ancestral protein (green) and its descendant (orange) would clash if put back to their original position.

This work highlights the increasing number of structural biologists like Ortlund, Christine Dunham, Graeme Conn and Xiaodong Cheng at Emory. Structural biologists use techniques such as X-ray crystallography to figure out how the parts of biology’s machines fit together. Recently Emory has been investing in the specialized equipment necessary to conduct X-ray crystallography.

As part of his future plans, Ortlund says he wants to go even further back in evolution, to examine the paths surrounding the estrogen receptor, which is also related to the glucocorticoid receptor.

Besides giving insight into the mechanisms of evolution, Ortlund says his research could also help identify drugs that activate members of this family of receptors more selectively. This could address side effects of drugs now used to treat cancer such as tamoxifen, for example, as well as others that treat high blood pressure and inflammation.

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Obesity ups risk for endometrial cancer

Increasing numbers of obesity in both men and women nationwide are resulting in a growing rate of multiple health consequences. Recent research suggests that overweight women are at an increased risk of developing endometrial cancer, especially if menopause occurs in women younger than age 45.

One study has found that women with a body mass index (BMI) of greater than 35, who experienced their last menstrual period at an age younger than 45, had more than 20 times the risk of developing endometrial cancer than normal-weight women.

BMI is a measure of body fat based on height and weight that applies to both adult men and women. A BMI of 18.5 to 24.9 is considered normal weight, 25 to 29.9 is considered overweight and a number over 30 is considered obese.

Mary Dolan, MD, MPH, assistant professor of gynecology and obstetrics, Emory School of Medicine, notes that experts already know that obesity is linked to cardiovascular disease, high blood pressure, diabetes, joint complications and other diseases. Now the connection between obesity and endometrial cancer is on experts’ radar.

Mary Dolan, MD, MPH

Mary Dolan, MD, MPH

Endometrial cancer forms in the tissue lining the uterus or endometrium – the lining that is “shed” monthly during menstruation. Endometrial cancer is more common in older women and fortunately is usually diagnosed early since it causes abnormal bleeding, says Dolan.

In a report published recently, Dolan and colleagues from the Centers for Disease Control and Prevention (CDC) discuss findings from a review of data from the Cancer and Steroid Hormone study from the 1980s. This study examined the relationship between oral contraceptive use and breast, ovarian and endometrial cancers in women ages 20-54 years.

Since many of the study patients with endometrial cancer were overweight, the study gave researchers an opportunity to look at the risk for endometrial cancer among younger, overweight women using BMI.

The study found that women who were younger than 45 when they had their last period and had a BMI over 35 had a 21.7 times greater risk of developing endometrial cancer than a woman of normal weight.

In comparison, older women with a BMI of 35 or higher, who had their last period at age 45 or older, had a 3.7 times greater risk of developing endometrial cancer than a woman of normal weight.

Elevated risks were also seen for women who had been overweight or obese at age 18 and who had their last period before age 45.

Dolan says obesity can lead to higher levels of estrogen because of chronic “anovulation,” where a woman fails to ovulate. Because the condition brings on irregular or no menstruation, estrogen levels remain high while opposing progesterone levels remain low. Experts believe this combination leads to an increased risk of endometrial cancer.

Dolan says physicians need to counsel patients even more to maintain a healthy weight. By both losing weight and then maintaining it, a woman’s risk for endometrial cancer likely decreases.

This study is one of only a few which have focused on younger women and the relationship between obesity and endometrial cancer. The results were published in the July 2009 issue of Obstetrics & Gynecology

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Raising awareness for sickle cell disease

September is National Sickle Cell Awareness Month, and when it comes to assessing and treating sickle cell disease, there is no other place in the world like the Georgia Comprehensive Sickle Cell Center at Grady Memorial Hospital.

James R. Eckman, MD

James R. Eckman, MD, with a patient

Led by James R. Eckman, MD, pioneering medical director and professor of medicine at Emory School of Medicine, the Center is the world’s first 24-hour comprehensive primary care clinic for patients with sickle cell syndromes. It is comprised of a multidisciplinary team with the a mission to educate and provide preventative and comprehensive primary care, while responding to sickle cell emergencies quickly and efficiently.

Millions of people worldwide suffer from the affects of sickle cell anemia – especially those of African, Mediterranean and Indian descent. According to CDC, more than 70,000 people in the United States have sickle cell disease, mostly African Americans. Each year more than 1,000 babies are born with sickle cell disease.

The inherited disorder affects the blood’s hemoglobin, which produces stiff, misshapen red blood cells that deliver less oxygen and can disrupt blood flow, resulting in joint and organ damage and potential clots and strokes. The sickling of red blood cells is aggravated by infections, extreme hot or cold temperatures, poor oxygen intake, not drinking enough fluids and stress.

Read more

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Attending to neglected tropical diseases

As Georgia’s immigrant and refugee communities grow, so do Georgia’s cases of infectious tropical diseases. Also known as neglected tropical diseases, these illnesses are endemic in some low-resource countries and cause considerable disability and dysfunction.

Carlos Franco-Paredes, MD, MPH

Carlos Franco-Paredes, MD, MPH

Carlos Franco-Paredes, MD, MPH, a researcher and clinician at the Emory TravelWell Clinic at Emory’s midtown campus, provides pre- and post-travel health care to international travelers, including faculty, staff, students, business travelers and missionaries. Franco-Paredes, an expert in infectious diseases, also treats immigrants and refugees affected by neglected tropical diseases. He and colleagues recently received funding to study the epidemiology and treatment outcomes of tropical infectious diseases in immigrant and refugee communities in Georgia.

With a grant from the Healthcare Georgia Foundation, Franco-Paredes and his colleagues are assessing the prevalence and the outcomes of hepatitis B, Chagas disease and leprosy.

In fact, the clinic is the main referral center for leprosy in the region, and physicians there currently care for about 25 patients with leprosy, a chronic disease. Most of the cases are found in foreign-born individuals, particularly patients from Central and South America and Asia.

Franco-Paredes’ collaborators include Uriel Kitron, PhD, Emory professor and chair, Environmental Studies, and Sam Marie Engle, senior associate director, Emory’s Office of University Community Partnerships.

To hear Franco-Paredes’ own words about his research into neglected tropical diseases, listen to Emory’s Sound Science podcast.

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Reality check for HIV vaccine design

HIV doesn’t have a brain and it doesn’t strategize.

But the way that the virus mutates and evades the immune system in the early part of an infection, you might think it did.

Emory Vaccine Center researcher Cynthia Derdeyn and her colleagues have a new paper in PLOS Pathogens that is a reality check for researchers designing possible HIV vaccines. The results come from a collaboration with the Rwanda Zambia HIV Research Group. (Although the patients in this paper are from Zambia only.)

Red and green depict the parts of the HIV envelope protein that mutated in two patients (185F and 205F) in response to pressure from their immune systems. The rest of the envelope protein is blue.

Red and green depict the parts of the HIV envelope protein that mutated in two patients (185F and 205F) in response to pressure from their immune systems.

Recently there has been some excitement over the discovery of robust neutralizing antibodies in patients.

The bottom line, according to Derdeyn’s team: even if a vaccine succeeds in stimulating antibodies that can neutralize HIV, the virus is still going to mutate furiously and may escape those antibodies. To resist HIV, someone’s immune system may need to have several types of antibodies ready to go, their results suggest.

A companion paper in the same issue of PLOS Pathogens from South African scientists has similarly bracing results.

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World Alzheimer’s Day – brain health tips from Emory

Today is World Alzheimer’s Day 2009 and Emory’s Alzheimer’s Disease Research Center is part of an effort nationwide to address this disease through research and state-of-the-art care for patients.

Allan Levey, MD, PhD, chair of Emory’s Department of Neurology and an Alzheimer’s researcher and clinician, says millions of baby boomers are entering late adulthood and experts expect the number of patients with Alzheimer’s disease to increase drastically over the next several decades. Prevention and early detection are extremely important, he says.

Emory’s Center is a National Institute on Aging funded center focused on clinical trials and research for Alzheimer’s disease. It is the only comprehensive program in Georgia and one of only 32 nationwide.

Levey, who directs the Center, offers the tips for good brain health:

Stay socially active
Remaining socially engaged in activities that stimulate the mind and body can reduce stress levels and help maintain healthy connections among brain cells.

Stay active, say experts

Stay active, say experts

Be physically active
Exercising your body regularly is vital for maintaining good blood flow to the brain and encouraging the growth of new brain cells.

Stay mentally active
Your brain needs mental stimulation to allow it to function at its peak. Research shows that keeping the brain active helps increase its vigor and may strengthen brain cells and the connections between them, and may even generate new ones.

Protect your head
Injury to the head can increase your risk of dementia as you get older. Make sure you wear a helmet when you ride a bike, skate, ski or engage in any activity where you may injure yourself.

Eat brain healthy foods
The brain, like the heart, needs the proper balance of nutrients, including protein and sugar, to optimally function. According to current research, certain foods appear to protect brain cells so increase your intake of these protective foods.

Levey says scientists are finding more clues that high blood pressure, high cholesterol and diabetes may increase a person’s risk of getting Alzheimer’s disease. He says to keep your weight in a healthy range, lower your cholesterol if it is high and maintain control of your blood glucose and blood pressure.

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National Cholesterol Month: Check your numbers

Emory’s Cheryl Williams, RD, LD, clinical nutritionist for the Emory Heart & Vascular Center and Emory HeartWise Cardiac Risk Reduction Program, says you should make it a priority to know your cholesterol levels and learn how what you eat can impact cholesterol and your heart’s health.Williams heart

Since diets high in saturated fat and trans fat have been linked to chronic disease, specifically, heart disease, this knowledge could save your life.

During National Cholesterol Month Williams notes in her blog for the Atlanta Journal-Constitution’s “Doctor Is In” that eating too many fatty foods especially those high in saturated fat and trans fat is the primary cause of high cholesterol. Thin, active people may not be aware of how much bad fat they consume, she says.

According to Williams, “Saturated fats are derived primarily from animal products and are known to raise cholesterol levels. They are found in common foods like butter, cheese, whole milk, pork and red meat. Lower-fat versions of these foods usually contain saturated fats, but typically in smaller quantities than the regular versions. Certain plant oils, like palm and coconut oils, are another source of saturated fats. You may not use these oils when you cook, but they are often added to commercially baked foods, such as cookies, cakes, doughnuts and pies. However, when it comes to celebrating milestones like work anniversaries, consider opting for homemade work anniversary cookies instead, made with healthier alternatives to ensure a thoughtful and nutritious treat.

Even more detrimental to cholesterol levels are trans fats, artificially created during food processing when liquid oils are converted into solid fats — a process called hydrogenation. Many fried restaurant foods and commercially baked goods contain trans fats, as well as vegetable shortening and stick margarine. Read labels and avoid foods that contain partially or fully hydrogenated oils.”

For more tips from Williams about managing for healthy cholesterol levels, visit ajc.com. To learn more about heart disease from Laurence Sperling MD, director of the Emory HeartWise Cardiac Risk Reduction Program, watch videos on health.com.

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Delivering nutrition to critical care patients

Emory clinical nutrition expert Thomas Ziegler, MD, has a case report article in the Sept. 10 issue of the New England Journal of Medicine.

The case report describes a woman with diabetes who needed surgery because of loss of blood flow to abdominal organs. While she is in intensive care after surgery, it becomes clear that a feeding tube leading from her nose to her stomach is not working. That makes her a good candidate for parenteral nutrition, or bypassing the digestive system and delivering nutrients directly into her blood.

Malnutrition is common in patients who are critically ill and often worsens with prolonged hospitalization. Some patients can’t eat normal food or benefit from a feeding tube into the stomach.

Thomas Ziegler, MD, Director, Center for Clinical and Molecular Nutrition, Department of Medicine

Thomas Ziegler, MD, Director, Center for Clinical and Molecular Nutrition, Department of Medicine

Yet few well-designed clinical trials studying parenteral nutrition have been conducted, Ziegler writes. He also notes that there is considerable debate over when parenteral nutrition is appropriate during critical care and how to administer it.

Ziegler’s own research has shown the beneficial effects of the amino acid glutamine, which must be added fresh to feeding formulas, for some critical care patients.

Several of the questions Ziegler outlines in his article will be issues investigators at Emory’s new Center for Critical Care will tackle. Recently, Timothy Buchman, MD, PhD, joined Emory to lead the critical care team.

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Pancreatic cancer: Front and center

With the sad news today of the death of actor Patrick Swayze, the public is again focused on pancreatic cancer and searching for more information on this aggressive cancer.

Recently, David Kooby, MD, Emory Winship Cancer Institute, and an assistant professor, Department of Surgical Oncology, authored a blog for the Atlanta Journal-Constitution’s “Doctor Is In” on this topic.

Emory Winship Cancer Institute

Emory Winship Cancer Institute

The following is an excerpt from the blog:

Pancreatic cancer is an aggressive malignancy that begins in the cells of the duct (or tube) running along the length of the pancreas. Each year about 42,000 new cases of pancreatic cancer are diagnosed and more than 35,000 people die from this cancer. A diagnosis of pancreatic cancer is usually made after discovery of a mass or a dilated duct in the pancreas.

Pancreatic cancer can be difficult to diagnose. Patients often come in for a doctor’s visit with non-specific symptoms such as abdominal or back pain or weight loss. Some patients will develop jaundice (yellowing of the skin) as a result of the tumor blocking the duct draining bile from the liver

No one knows the exact causes of pancreatic cancer, although some risk factors are known through research that has been done.

According to the National Cancer Institute, the following are risk factors for development of pancreatic cancer:

  • Age — The likelihood of developing pancreatic cancer increases with age. Most pancreatic cancers occur in people over the age of 60.
  • Smoking — Cigarette smokers are two or three times more likely than nonsmokers to develop pancreatic cancer.
  • Diabetes mellitus — Pancreatic cancer occurs more often in people who have diabetes than in people who do not.
  • Being male — More men than women are diagnosed with pancreatic cancer.
  • Being African-American — African-Americans are more likely than Asians, Hispanics or whites to get pancreatic cancer.
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Voles and the neurochemistry of social behavior

A new study has shown that prairie voles may be a useful model in understanding the neurochemistry of social behavior. By influencing early social experience in prairie voles, researchers hope to gain greater insight into what aspects of early social experience drive diversity in adult social behavior.

VolesPrairie voles are small, highly social rodents that often form stable, life-long bonds between mates. In the wild, there is striking diversity in how offspring are reared. Some pups are reared by single-mothers, some by both parents (with the father providing much of the same care as the mother) and some in communal family groups.

Researchers Todd Ahern, a graduate student in the Emory Neuroscience Program, and Larry Young, PhD, professor of psychiatry and behavioral sciences at the Yerkes National Primate Research Center and Emory School of Medicine, compared pups raised by single mothers (SM) to pups raised by both parents (BP) to determine the effects of these types of early social environments on adult social behavior.

The study showed SM- and BP-reared animals experienced different levels of care during the neonatal period and that these differences significantly influenced bonding social behaviors in adulthood. Pups raised by single mothers were slower to make life-long partnerships, and they showed less interest in nurturing pups in their communal families.

Researchers also found differences in the oxytocin system. Oxytocin is best known for its roles in maternal labor and suckling, but, more recently, it has been tied to prosocial behavior, such as bonding, trust and social awareness. Very simply, altering their early social experience influenced adult bonding.

Further studies will look at the altered oxytocin levels in the brain to determine how these hormonal changes affect relationships.

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