Patients, families, employees and friends will Beat Feet for ALS at 8 a.m. Saturday, Sept. 26, at Augusta’s Riverwalk in an effort to raise money for the GRHealth ALS Clinic.
This annual fundraising walk posted a record year in 2014, pulling in almost $145,000 in donations, perhaps driven in part by the popularity and timing of the ice bucket challenge – a unique dare that several Georgia Regents University leaders participated in to raise financial support for ALS.
But much more funding is needed, says ALS Clinic Director Dr. Michael H. Rivner, in order to explore better treatments and improve the quality of life for patients with this debilitating disease that kills most patients within two to five years.
“With ALS, the muscles start to deteriorate rapidly until you are essentially trapped inside your own body, and there is no cure,” said Rivner, Charbonnier Professor of Neurology at GRU’s Medical College of Georgia. “There’s no way to sugarcoat it; ALS is a death sentence.”
But effects of the disease vary, and many people can live with quality in their last years with the help of nationally accredited clinics like the one at Georgia Regents Medical Center.
The clinic, which opened in 2004 through a partnership between the Georgia Regents Neuroscience Center and the ALS Association of Georgia, takes a multidisciplinary and coordinated approach to patient care. Instead of scheduling multiple appointments and trips, patients are able to see neurologists; nurses; physical, occupational and speech therapists; social workers; dietitians; respiratory therapists; and equipment specialists all on the same day. This is especially helpful for ALS patients because of diminishing mobility.
The Georgia Regents ALS team sees patients on the second Friday of each month in Augusta and the fourth Friday of each month at a satellite clinic in Macon. They assess disease progression, functional status, family concerns, and equipment, transportation and referral needs. In addition, family and caregiver training and support are incorporated into the time spent with each patient.
It could cost as much as $250,000 a year to treat just one patient with ALS, so fundraising dollars are financing medical equipment and therapies – often not covered by health insurance – such as wheelchair ramps, home modifications and speech and breathing assistance devices. Funds are also used to purchase gas cards and other items for patients and families who are under financial strains due to ALS.
In addition, donations are supporting several vital research efforts, including a clinical trial of a new ALS drug that follows disease progression and a study on ALS antibodies.
“We were able to fund a pilot project which allowed us to study LRP4 and Agrin antibodies in ALS. Our research thus far has identified these antibodies in around 10 percent of patients with ALS, generating a lot of excitement in the ALS research community,” Rivner said. “If this allows us to pinpoint the cause of ALS in that 10 percent of patients, then perhaps we can identify these patients more quickly and develop better treatments for them.”
Funds raised from the Beat Feet for ALS Walk also support programs administered by the ALS Associations of Georgia and South Carolina and the Muscular Dystrophy Association for patients and families affected by ALS.
To register for the walk or make a donation, visit walk.ALSGRU.com or contact Brandy Quarles at email@example.com or 706-721-2681. You can also make a donation directly to the Georgia Regents ALS Clinic on the website or make a check payable to ALS Clinic (Fund 1078) and mail it to 1120 15th St., BP-4390, Augusta, GA 30912.
ALS, or amyotrophic lateral sclerosis, is more commonly known as Lou Gehrig’s disease, named for the late first baseman and power hitter for the New York Yankees. Gehrig was stricken with the neurodegenerative disease that causes muscular atrophy and forced into retirement at age 36. It claimed his life two years later.
About 6,000 people are diagnosed with ALS each year. The GRHealth ALS Clinic cares for about 150 patients between the Augusta and Macon locations.
Two proteins that share the ability to help cells deal with their trash appear to need each other to do their jobs and when they don’t connect, it appears to contribute to development of Parkinson’s disease, scientists report.
Much like a community’s network for garbage handling, cells also have garbage sites called lysosomes, where proteins, which are functioning badly because of age or other reasons, go for degradation and potential recycling, said Dr. Wen-Cheng Xiong, developmental neurobiologist and Weiss Research Professor at the Medical College of Georgia at Georgia Regents University.
Inside lysosomes, other proteins, called proteases, help cut up proteins that can no longer do their job and enable salvaging of things like precious amino acids. It’s a normal cell degradation process called autophagy that actually helps cells survive and is particularly important in cells such as neurons, which regenerate extremely slowly, said Xiong, corresponding author of the study in The Journal of Neuroscience.
Key to the process – and as scientists have shown, to each other – are two more proteins, VPS35 and Lamp2a. VPS35 is essential for retrieving membrane proteins vital to cell function. Levels naturally decrease with age, and mutations in the VPS35 gene have been found in patients with a rare form of Parkinson’s. VPS35 also is a critical part of a protein complex called a retromer, which has a major role in recycling inside cells. Lamp2a enables unfit proteins to be chewed up and degraded inside lysosomes.
If the two sound like a natural couple, scientists now have more evidence that they are. They have shown that without VPS35 to retrieve Lamp2a from the trash site for reuse, Lamp2a, or lysosomal-associated membrane protein 2, will be degraded and its vital function lost.
When the scientists generated VPS35-deficient mice, the mice exhibited Parkinson’s-like deficits, including impaired motor control. When they looked further, they found the lysosomes inside dopamine neurons, which are targets in Parkinson’s, didn’t function properly in the mice. In fact, without VPS35, the degradation of Lamp2a itself is accelerated. Consequently, yet another protein, alpha-synuclein, which is normally destroyed by Lamp2a, is increased. Alpha-synuclein is a major component of abnormal protein clumps, called Lewy bodies, found in the brains of patients with Parkinson’s.
“If alpha-synuclein is not degraded, it just accumulates. If VPS35 function is normal, we won’t see its accumulation,” Xiong said.
Conversely, when MCG scientists increased expression of Lamp2a in the dopamine neurons of the VPS35-deficient mice, alpha-synuclein levels were reduced, a finding that further supports the linkage of the three proteins in the essential ability of the neurons to deal with undesirables in their lysosomes.
Without lamp2a, dopamine neurons essentially start producing more garbage rather than eliminating it. Recycling of valuables such as amino acids basically stops, and alpha-synuclein is free to roam to other places in the cell or other brain regions where it can damage still viable proteins.
The bottom line is dopamine neurons are lost instead of preserved. Brain scans document the empty spaces where neurons used to be in patients with neurodegenerative diseases such as Parkinson’s and Alzheimer’s. One of the many problems with treatment of these diseases is that by the time the empty spaces and sometimes the associated symptoms are apparent, much damage has occurred, Xiong said.
Putting these pieces together provides several new, early targets for disease intervention. “Everything is linked,” Xiong said.
Dopamine is a brain chemical with many roles, including motor control, and patients with Parkinson’s have a loss of the neurons that secrete this neurotransmitter. At least in mice, VPS35 is naturally expressed in dopamine neurons in areas of the brain affected by Parkinson’s.
Xiong and her colleagues reported in 2011 that reduced expression of VPS35 enables activity of the dormant-in-healthy-adults protein BACE1 to increase along with accumulation of the brain plaque that is a hallmark of Alzheimer’s. Xiong said then that impaired VPS35 function likely also was a factor in Parkinson’s.
In a definite vicious circle, trash starts overwhelming the brain cell’s natural garbage disposal system. Proteins start getting misfolded and dysfunctional, potentially destructive proteins such as BACE1 and Lamp2a end up in the wrong place and get activated/inactivated, while good proteins get chopped up and/or bad proteins accumulate.
Parkinson’s disease is characterized by uncontrolled shaking, an unstable gait and cognitive loss. The research was funded by the National Institutes of Health and the Department of Veterans Affairs. Postdoctoral Fellow Dr. Fulei Tang is the study’s first author.
The cancer research building at Georgia Regents University is getting a larger footprint and a new name.
The 170,000-square-foot facility on the corner of Laney Walker and R.A. Dent boulevards will expand upward and outward, gaining 72,000 square feet of new space and 6,000 square feet of renovations to become the GRU Cancer Center M. Bert Storey Research Building, in recognition of the Augusta philanthropist and longtime university supporter.
“This $62.5 million project will be a significant expansion for the GRU Cancer Center that will physically connect our clinical and research missions as we continue the momentum toward National Cancer Institute designation,” said GRU President Brooks Keel. “We couldn’t make this happen without the generosity of supporters like M. Bert Storey, who understand the impact that our discoveries make in the fight against cancer.”
The state of Georgia is providing $50 million in bond funding and the university is securing the remaining funds that will finance two main components: a five-story expansion to the existing research building and an elevated connector that stretches across Laney-Walker Boulevard linking the research building to GRU Cancer Center Outpatient Services. The naming was approved by the University System of Georgia Board of Regents on Aug. 12.
“Philanthropy is a fundamental trait of a healthy university, and we are very pleased to be a part of it,” said Regent James M. “Jim” Hull. “You couldn’t ask for a more philanthropic man to be the namesake for the cancer research building than M. Bert Storey,” said Hull, a longtime friend and business partner.
The Greater Augusta Chapter of the Association of Fundraising Professionals recognized Storey and his son Barry in 2010 with the Outstanding Philanthropist Award. Storey was instrumental in fundraising for the Kroc Center in Augusta and serves as a GRU fundraising campaign cabinet member.
“It is my honor to lend my name to such a worthy endeavor. Cancer research truly touches all our lives, and I encourage others to join me in supporting this vital effort,” said Storey, the president and owner of Bert Storey Associates, LLC, a commercial real estate development company, and Chair of the Storey Foundation.
“The entire GRU Cancer Center family is profoundly grateful for the generosity and goodwill the Storey family has shown us. This gift – the partnership – greatly contributes to the wellbeing of our patients and the continued growth and evolution of the Cancer Center, our research, clinical trials and patient care,” said Dr. Samir N. Khleif, Cancer Center Director. “It is an incredibly important and exciting moment for our Cancer Center family, and one we are overjoyed to be able to share with this community.”
Building renovations are expected to improve the Cancer Center’s ability to host community events focusing on prevention, awareness and education. Construction is expected to be completed in early 2018.
An estimated 1.6 million new cancer cases will be diagnosed and about 590,000 cancer deaths will occur this year, according to the American Cancer Society.
The GRU Cancer Center is a multidisciplinary academic cancer center whose mission is to reduce the burden of cancer in Georgia and across the globe through superior care, innovation and education. Its patient-centered approach includes first-in-the-nation treatment protocols, an experimental therapeutics program and specialized clinics for Phase I trials and immunotherapy.
Even without losing fat, more muscle appears to go a long way in fighting off the bad cardiovascular effects of obesity.
That emerging evidence has scientists looking hard for new targets to uncouple the unhealthy relationship between fat and cardiovascular disease.
“If you look at the exercise literature, we understand very well that if you exercise, things get better. What we don’t really understand is what about exercise is good; what does it tell us about physiology and how disease starts, and how can you customize it to different populations?” said Dr. David Stepp, vascular biologist in the Vascular Biology Center at the Medical College of Georgia at Georgia Regents University.
Stepp and his colleagues have evidence that an increase in muscle mass – a huge consumer of glucose, a natural energy source that is often elevated in obesity – could mean a healthier ticket for some.
While fat has the unhealthy habit of storing fuel, “muscle is a much more metabolically active tissue, even when it’s just sitting there,” Stepp said. “It burns more oxygen at rest; it burns more energy at rest; so it burns more calories at rest.” Some of things scientists don’t know is if muscles secrete something that improves glucose metabolism or if just having more glucose-consuming muscle is the apparent magic.
A new $2.2 million grant from the National Heart, Lung, and Blood Institute is helping fill in those important blanks as it illuminates new points for intervening in one of the worst consequences of obesity.
“We are trying to establish links between the health of skeletal muscles and the circulatory system,” said Dr. David Fulton, Director of the MCG Vascular Biology Center and Co-Principal Investigator with Stepp on the grant. “When you eat, most of the glucose ends up in your skeletal muscle. When you are young, most of your body mass is skeletal muscle, so that glucose is efficiently distributed in the places where it should go to get used for energy and work.”
Stepp and Fulton were authors on a 2014 study in the Journal of the American Heart Association that showed the benefits of adding muscle when fat is monopolizing the body. They looked at normal mice and mice genetically altered to be obese – mice with voracious appetites that soon doubled their normal weight – as examples of a healthy and unhealthy human. When they deleted myostatin, a natural, negative regulator of muscle growth, from both, both groups developed bigger muscles. The normal mice also had less fat tissue.
But it was the obese-with-muscles mice that truly benefited in the cardiovascular sense: glucose tolerance and blood vessel dilation went up and insulin resistance and superoxide production went down. More muscle didn’t result in these additional changes in the leaner mice.
“If the insulin burner gets bigger and the storage (fat) gets smaller, that’s good,” Stepp said. “What we have demonstrated is that if the burner gets bigger, no matter what the storage does, it’s still good.”
When they looked further at the obese mice, minus the muscles, they also found the superoxide- producing gene Nox1 is a major culprit in obesity-related vascular disease. In fact, the gene is overexpressed in the blood vessels of the fat mice, apparently driven by high glucose levels in the blood.
Obese mice with no muscle added but Nox1 removed also experience cardiovascular improvement, an observation that Postdoctoral Fellow Dr. Jennifer Thompson is pursuing further with a new American Heart Association grant.
Meanwhile, Stepp and Fulton are exploring how elevated blood glucose elevates Nox1, acknowledging that while it makes intuitive sense, the science needs to be clear. Because while the search is on for Nox1 inhibitors, there aren’t any at this moment. Fulton and Stepp hope their studies will further inspire the search and identify additional points of intervention as well.
“We know that high glucose goes to Nox1 goes to superoxide, and superoxide goes to cardiovascular disease. What we don’t know is what is in between glucose and Nox1,” Stepp said. A possibility is galectin-3, a receptor for proteins that get coated with glucose when circulating levels of the sugar get too high. At least in culture, when glucose is added to cells, they produce more Nox1. But when the scientists block galectin-3 and add glucose, Nox1 doesn’t increase.
While it’s known that sugar-coating messes up protein function, the scientists aren’t certain what galectin-3 is doing. Is it clearing the dysfunctional proteins, telling them to die, and/or driving up Nox1? So they are looking at the signaling between all of the above. They are also developing additional mice models, where Nox1 and galectin-3 are removed from already genetically fat mice, to further explore their role in vascular dysfunction. They will also explore the cardiovascular impact, such as blood pressure and how well blood vessels dilate in response to stress, in their fat mice models with added muscle as well as the two new knockouts.
The bottom line: they want to know if they can break “the metabolic connection” between fat and cardiovascular disease. “Where is the key event that causes all these bad things to happen?” Stepp said, and, of course, where and how best to intervene.
Myostatin is part of the yin and yang of muscle growth that enables us, with some effort, to have good, but not excessive, muscle mass. High myostatin levels can produce muscular dystrophy; low ones can mean incredible bulk. Myostatin levels tend to decrease with exercise and increase with aging.
Injectable or infusible myostatin inhibitors are under study for muscular dystrophy and frailty syndrome, where older individuals lose so much muscle mass that they fall frequently. But the drugs are not generally available, even to scientists. While experience with the inhibitors is limited, life with less myostatin appears to be a good thing: Stepp said mice short one copy of the myostatin gene live longer, and humans with documented myostatin deficiency tend to be Olympic athletes.
A receptor that is already a target for treating neurodegenerative disease also appears to play a key role in supporting the retina, scientists report.
Without sigma 1 receptor, the Müller cells that support the retina can’t seem to control their own levels of destructive oxidative stress, and consequently can’t properly support the millions of specialized neurons that enable us to transform light into images, scientists report in the journal Free Radical Biology and Medicine.
Without support, well-organized layers of retinal cells begin to disintegrate and vision is lost to diseases such as retinitis pigmentosa, diabetic retinopathy and glaucoma, said Dr. Sylvia Smith, retinal cell biologist and Chairwoman of the Department of Cellular Biology and Anatomy at the Medical College of Georgia at Georgia Regents University
The surprising finding makes the sigma 1 receptor a logical treatment target for these typically progressive and blinding retinal diseases, said Smith, the study’s corresponding author. It has implications as well for other major diseases, such as cardiovascular disease and cancer as well as neurodegenerative disease, where oxidative stress plays a role.
What most surprised the scientists was that simply removing sigma 1 receptor from Müller cells significantly increased levels of reactive oxygen species, or ROS, indicating the receptor’s direct role in the oxidative stress response, Smith said. They expected it would take them giving an oxidative stressor to increase ROS levels.
So they looked further at the sigma 1 receptor knockouts compared with normal mice, and found significantly decreased expression in the knockouts of several, well-known antioxidant genes and their proteins. Further examination showed a change in the usual stress response.
These genes that make natural antioxidants contain antioxidant response element, or ARE which, in the face of oxidative stress, gets activated by NRF2, a transcription factor that usually stays in the fluid part of the cell, or cytoplasm. NRF2 is considered one of the most important regulators of the expression of antioxidant molecules. Normally the protein KEAP1 keeps it essentially inactive in the cytoplasm until needed, then it moves to the cell nucleus where it can help mount a defense. “When you have oxidative stress, you want this,” Smith said of the stress response, which works the same throughout the body.
Deleting the sigma receptor in the Müller cells altered the desired response: NRF2 expression decreased while KEAP1 expression increased. The unhealthy bottom line was that ROS levels increased as well.
The study is believed to provide the first evidence of the direct impact of the sigma 1 receptor on the levels of NRF2 and KEAP1, the researchers write.
“We think we are beginning to understand the mechanism by which sigma 1 receptor may work and it may work because of its action on releasing antioxidant genes,” Smith said.
While the ubiquitous receptor was known to help protect neurons in the brain and eye, its impact on Müller cell function was previously unknown. The significant impact the MCG scientists have now found helps explain the dramatic change they documented after using pentazocine, a narcotic already used for pain relief, in animal models of both retinitis pigmentosa and diabetic retinopathy. Pentazocine, which binds to and activates the sigma 1 receptor, seems to preserve functional vision in these disease models by enabling many of the well-stratified layers of photoreceptor cells to survive.
Next steps include clarifying whether it’s actually preservation or regeneration of the essential cell layers and how long the effect lasts. “We do see some retention of function, that is clear and that I am very excited about,” Smith said.
Müller cells are major support cells for the retina, helping stabilize its complex, multi-layer structure, both horizontally and vertically; eliminating debris; and supporting the function and metabolism of its neurons and blood vessels. Typically bustling Müller cells can become even more activated when there is an insult to the eye, such as increased oxidative stress, and start forming scar tissue, which hinders rather than supports vision. Problems such as diabetes, can increase ROS levels.
ROS are molecules produced through normal body function such as breathing and cells using energy. The body needs a limited amount of ROS to carry out additional functions, such as cell signaling. Problems, from eye disease to cancer, result when the body’s natural system for eliminating excess ROS can’t keep up and ROS start to do harm, such as cell destruction.
Normally humans have about 125 million night-vision enabling rods intermingled with about 6 million cones that enable us to respond to light and see color.
The research was supported by the National Eye Institute and the James and Jean Culver Vision Discovery Institute at GRU. MCG Assistant Research Scientist Dr. Jing Wang is the study’s first author.
We are finalizing our research mission-based strategic plan that will guide the institution in advancing the core research purposes of the institution while supporting the GRU strategic priorities and organizational goals as expressed in the university’s strategic plan, Transition Forward.
The Research Mission Strategic plan development began in December 2014. Existing research-focused committees have reviewed initial drafts of the research mission focus areas and discussed future vision and goals. Academic leadership and staff have also provided input through meetings and focus group sessions.
Now we want your feedback. Please click here and join in the conversation and provide your thoughts on the plan. The discussion forum will be open through August 31, 2015.
AUGUSTA, Ga. – American voters will watch the top 10 Republican presidential candidates face off in the first GOP debate at 9 p.m. Thursday on Fox News, with the remaining candidates debating four hours earlier also on Fox News.
“This is the largest number of candidates for a Republican Primary in about 100 years,” Albert said. “It’s been growing since 2008 this lack of identity for the Republican Party and so many different voices. They don’t know who they are; they are so fractured right now. So everybody is trying to be the new voice, the new face, trying to show to the American voters who the Republican Party actually is.”
As a leading scholar in American politics and foreign affairs, Albert’s research interests include Islamic extremism and the rise of ISIS, the Russo-Chechen conflict and the life and work of French political thinker Alexis de Tocqueville. Albert is also a political contributor to The Augusta Chronicle and a blogger for ROAR: Renaissance for American Responsibility. He’s done interviews with many different media outlets, including a live interview with Megyn Kelly for Fox News Channel about the Boston Marathon bombers. He has also testified to the U.S. Congress on Islamic Extremism.
For most Americans, Cuba probably seems an unlikely vacation spot.
The largest of the Caribbean islands, the scenic little nation sits less than a hundred miles from the coast of Florida, little more than a 45-minute flight from Miami. Unfortunately, for the last 60 years, an ironclad embargo and rocky relations between the U.S. and Cuba’s former Soviet handlers have kept most beachgoers at bay.
As a result, today few Americans have ever set foot into Cuba. Of those who have, even fewer have done so legally. But Don Howard, professor of management in the Hull College of Business, has been multiple times. And in the company of Georgia Regents University students, no less.
His trips, facilitated by the GRU Study Abroad office, are the first of many possible American visits to Cuba in the coming years.
Having recently restored formal diplomatic relations with the United States, the country is moving into unprecedented territory in terms of tourism interests, a shift in economic upswing that, Howard says, Cuba was far from prepared for.
“The average state wage in Cuba is very low by our standards,” said Howard. “Whether you’re a taxi driver or a heart surgeon, you’ll make about the same per month, somewhere in the range of around twenty dollars. Tourism is changing all of that.”
A typical street salesman hawking wares to tourists might make that much in an hour, Howard said. The reason? Price differentials and tourist ignorance.
“A tourist might unthinkingly pay five dollars for a book or a banner on the street,” said Howard. “What’s five dollars to a tourist, you know? But in Cuba, those items may have been worth pennies. It adds up.”
Hearing that a street salesman makes as much as a heart surgeon may sound disconcerting at first, but the truth of Cuba’s health care system makes the realization all the more shocking. Cuba has some of the best health care in the world.
In its World Health Report, published in 2000, the World Health Organization ranked Cuba 39th among national health care systems. By comparison, the United States was ranked 37th. Cuban doctors are renowned throughout the world thanks to the Cuban Medical Internationalism program, a system designed to send Cuban doctors and medical relief to more than 100 countries around the world. The program seems to work, too. In 2007, according to an article published in Latin American Perspectives, Cuba provided more medical personnel to the developing world than all of the G7 nations combined.
Not to mention, at home, that same health care is free.
But the Cuban system definitely has its downsides.
The Cuban people make such low wages in part because the Cuban government rations certain food items. The Libreta de Abastecimiento, translated to “supplies booklet,” refers to the Cuban system of using vouchers and coupons to obtain certain types of foods. Some of the items rationed include dietary staples, but others are minor necessities that capitalist countries often take for granted.
“What surprised me,” Howard said, “was that Cubans eat more beans and rice per capita than any other country.”
Part of the reason for that, however, is that beans and rice tend to have long shelf lives, thus making them ideal for long-term storage. Other rationed items include things like sugar, matches and oil.
“Or you could get your one cigarette for the day, if you wanted,” said Howard.
While the practice of food rationing is a tried-and-true communist tactic, Cuba’s economic model is truly unique, especially when compared to the previous communist model under Fidel Castro. That was the primary focus of the study abroad trip, Howard said.
“There are government-owned stores, privately owned stores and co-ops in Cuba,” said Howard. “Co-ops, of course, being jointly owned by both the government and private entrepreneurs. We wanted to talk to students about the differences between the free market and communist systems, and there was no better place to do that.”
According to Howard, the atmosphere, availability of goods and public perception vary wildly between state-run stores and privately owned businesses. As a result, there tends to be a great deal of disparity in Cuban shops.
“Private shops and restaurants are usually run out of people’s homes,” said Howard. “They tend to be very affluent compared to state-run facilities, especially the privately owned markets. They’re usually very proud to have guests in their homes. The students can see the difference.”
Outside of its politics and economic system, Howard said, Cuba is a gorgeous country with an odd, but familiar, identity. Misconceptions abound around the little island, though.
One common misconception is that religion has been stamped out entirely in Cuba. Not true, said Howard, though the nation’s religious ambivalence is much greater than our own.
“The top two religions in Cuba are actually African religions,” he said. “Most people think they’d either be Roman Catholic or atheist, but no. Catholicism is a distant third, but there are several practitioners in Havana.”
Havana, Cuba’s once-gleaming capitol, was a favorite among his students. They enjoyed the sights and the culture, especially the music, which has long been one of Cuba’s greatest selling points. Howard himself said the city was breathtaking, though admittedly, it too has its flaws.
“Most of the best hotels in Cuba wouldn’t get a three-star rating in the United States,” he said. “The hotel we stayed in, the Ambos Mundos, was clean, though, and you could see most of the city from the roof.”
If the Ambos Mundos hotel sounds familiar, you might be a fan of fine literature. In the 1930s, the famous writer Ernest Hemingway spent seven years living in the Ambos Mundos hotel. There, amid the roaring culture and moral wilderness of Cuba’s golden age, he began one of his most famous works, “For Whom the Bell Tolls.” Today, the hotel still keeps his room on the fifth floor set aside as a museum and memorial, a living testament to a man many Cubans consider a tragic hero.
Howard said the rest of Havana, especially Old Havana (Hemingway’s favorite), was beautiful but “clearly in decay.”
“You won’t find a toilet seat anywhere in Cuba, most likely,” he said. “Those were the first things to go, and the people decided they didn’t need them. Their cars, the beautiful 50s Chevy replicas? They’re all Toyotas on the inside. It’s a very quaint style.”
In addition to their tour of Havana, students were taken out into the country to see an often unseen aspect of Cuban life: farm culture.
“I think that was a great experience for students,” said Howard. “Seeing how people live in the country in Cuba and how different it is from the city. I’m glad we got to see a tobacco farm.”
Mid-week, students left Havana to travel to Viñales, a mountain farm community in the Pinar del Río province of Cuba. On their trip, the students ate the way Cubans did.
“We stopped once to get ice cream,” said Howard. “There was a horse cart pulling ice cream, so we stopped with the locals and got some on the way.”
In the country, students got to meet and interact with guides, young men and women who worked in the fields. Howard said students took quickly to the Cuban youths, but that he cautioned them about what they said and asked.
“These guides, these young people, they’re state employees,” he said. “They were friendly, but you have to remember they have their own agendas, too.”
In addition, students met with faculty and staff of the University of Havana. All four of the individuals were Communists, Howard said, but readily admitted that their system had its flaws. All said, though, they remained committed to their country and the future of Cuba under Raul Castro.
Howard said there was some apprehension about traveling to Cuba at first, but that it wouldn’t stop him from returning. He plans to go again in the spring of 2016 with a new group of students. He encourages others to give Cuba a try as well.
“I think students were a little apprehensive at first, and rightly so,” he said. “Cuba is a beautiful nation, and something everyone should experience, but it is also a very different atmosphere. It’ll change you. For the better, but it’ll change you to see how differently people live. That much I guarantee.”
For more information about Study Abroad or upcoming trips, contact the Study Abroad Office at 706-729-2306 or email Maria Darley at firstname.lastname@example.org.
DNA damage increases the risk of cancer, and researchers have found that a protein, known to rally when cells get stressed, plays a critical, early step in its repair.
In the rapid, complex scenario that enables a cell to repair DNA damage or die, ATF3, or activating transcription factor 3, appears to be a true first responder, increasing its levels then finding and binding to another protein, Tip60, which will ultimately help attract a swarm of other proteins to the damage site.
“This protein is a so-called stress responder, so when a cell senses stress, such as DNA damage, this protein can be induced,” said Dr. Chunhong Yan, molecular biologist at the Georgia Regent University Cancer Center and the Department of Biochemistry and Molecular Biology at the Medical College of Georgia at GRU.
“One of the things we found is that ATF3 can bind to the Tip60 protein and promote the DNA damage repair function,” said Yan, corresponding author of the study published in the journal Nature Communications.
Like its partner Tip60, ATF3 is expressed at low levels until cells get stressed, and DNA mutation is one of the most common cell stressors. ATF3 then finds and binds to Tip60, increasing the usually unstable protein’s stability and level of expression. “If you look at the DNA under the microscope, you will see the damage site somehow labeled by this protein,” Yan said. Tip60, in turn, modifies the protein ATM, helping it form a sort of scaffold where other worker bee proteins soon assemble.
While it may take years for a cell to recognize DNA damage, once it does, the response occurs within minutes. One of the early arrivals to the ATM scaffold is p53, a known and powerful tumor suppressor. Once on the scene, p53 helps assess whether or not the damage is repairable. If not, it triggers cell suicide. If the damage is fixable, it will arrest cell proliferation and help start the repair.
There is clearly a protein connection. When researchers knock ATF3 down, Tip60 activation and ATM signaling both go down. Cells start accumulating DNA damage and become more vulnerable to additional stress, setting the stage for cancer and other problems. Previously there was no known relationship between ATF3 and Tip60.
Many factors, including sunlight, even chemotherapy, can cause DNA mutations. Mutations can even occur in the normal process of a cell multiplying, as cells do commonly in areas such as the skin and gastrointestinal tract, and tend to increase with aging. Cancer itself can cause additional mutations as it morphs to try to escape whatever treatment is being used against it. In fact, DNA repair likely is a constant in the body that works well most of the time. “That is why understanding DNA damage response is so important,” said Yan.
In human cancer cells, the researchers have shown that ATF3’s role precedes previously known steps. Future studies include finding a drug that could help cells make even more of this stress responder as a possible adjunct cancer therapy.
“We want to find a drug that can increase expression of this ATF3 in the body, and this increased ATF3 can promote Tip60 activity and overall promote cell response to DNA damage,” Yan said. The body naturally increases ATF3 levels in response to stress, including chemotherapy. In fact, many of the older cancer drugs intentionally damage DNA in an effort to promote cancer cell death. Now that ATF3’s connection to DNA repair has been made, that synergy likely explains another way chemotherapy works. However, additional study is needed to find a more targeted ATF3 activator without the numerous, known side effects of chemotherapy or other known stressors, Yan said.
While the protein ATF3 was known to be a stress responder, just how it responded has mostly remained a mystery. “We really don’t know much about this protein,” said Yan said. A decade ago, his research team found that ATF3 directly regulates the tumor suppressor p53.
“A next logical step is how can we make more ATF3?” While it’s not yet done clinically, in his lab, Yan has measured ATF3 levels in the tissue of cancer patients and found the levels are low and/or that the ATF3 gene itself is mutated. One day, measuring ATF3 levels might also help predict who is at highest risk for cancer, he said.
The research was funded by the National Institutes of Health. Postdoctoral Fellow, Dr. Hongmei Cui, is the study’s first author.
Patients with type 1 diabetes have significantly lower blood levels of four proteins that help protect their tissue from attack by their immune system, scientists report.
Conversely, their first-degree relatives, who share some of the high-risk genes but do not have the disease, have high levels of these proteins circulating in their blood, said Dr. Jin-Xiong She, director of the Center for Biotechnology and Genomic Medicine at the Medical College of Georgia at Georgia Regents University.
Healthy individuals without the risky genes also have higher levels of the four proteins, IL8, IL-1Ra, MCP-1 and MIP-1β, according to the study in the Journal of Clinical Endocrinology & Metabolism.
The findings point toward a sort of protein cocktail that could help at-risk children avoid disease development as well as new biomarkers in the blood that could aid disease diagnosis, prognosis and management, said She, Georgia Research Alliance Eminent Scholar in Genomic Medicine and the study’s corresponding author.
The scientists looked at a total of 13 cytokines and chemokines, which are cell signaling molecules involved in regulating the immune response. They first looked at blood samples from 697 children with type 1 diabetes and from 681 individuals without antibodies to insulin-producing cells, a hallmark of this autoimmune disease. They then analyzed the blood of a second and larger set of individuals, which included 1,553 children with type 1 diabetes and 1,493 individuals without any sign of antibodies.
In this largest study of its kind, they consistently found a higher percentage of type 1 diabetes patients had significantly lower levels of the same four proteins.
“Their pancreatic cells are not secreting enough of these proteins,” said Dr. Sharad Purohit, MCG biochemist and the study’s first author. “Normally you are secreting enough of these cytokines so you prevent attack by the immune system.”
Individuals who have three of the known high-risk genes for type 1 diabetes but high serum levels of these four proteins are less likely to have disease, suggesting that these proteins may provide dominant levels of protection against type 1 diabetes even in a genetically high-risk group, Purohit said.
“If the individuals with high-risk genes weren’t making more of the proteins, they likely would have diabetes, said Dr. Ashok Sharma, an MCG bioinformatics expert and study co-first author.
One of the proteins found at low levels in patients, MIP-1β, has been shown in animal models to protect against type 1 diabetes development. A recombinant version of IL-1Ra, already used to combat rheumatoid arthritis, is also under study for both type 1 and 2 diabetes. And, human studies have shown that newly diagnosed patients with type 1 diabetes who go into remission have higher levels of IL-1Ra than those who don’t.
Cytokines and chemokines can promote or inhibit inflammation – cytokines such as MIP-1β can do both – and the proper mix helps keep inflammation in check. As an example, IL-1Ra, a cytokine secreted by several cell types, including immune cells, is a natural antagonist of the inflammation promoting cytokine IL-1β.
“We are providing evidence that clinical trials with any of these four molecules may work, and if we use them in combination, they may work even better,” She said. “One of the major research foci in our group is to identify biomarkers for various diseases, diabetes, cancer and others. We also want to identify new therapeutic strategies or targets through the discovery of biomarkers.”
Type 1 diabetes is an autoimmune disease, which primarily surfaces in childhood, where the immune system attacks the insulin-producing cells of the pancreas, leaving children facing a lifetime of daily insulin therapy to try to keep blood sugar levels under control.
Some of the 13 cytokines and chemokines originally screened for the study were known factors in type 1 diabetes, and the scientists were curious about the role of others.
Research funding was provided by the National Institutes of Health and the Juvenile Diabetes Research Foundation. Endocrine clinics based in Atlanta, including Atlanta Diabetes Associates, Pediatric Endocrine Associates and Southeastern Endocrine and Diabetes, contributed to the study.