INDIANAPOLIS – If you really want a drink right now, the source of your craving may be a pea-sized structure deep inside the right side of your brain, according to scientists at the Indiana University School of Medicine.

Using two different kinds of advanced brain imaging techniques (PET and fMRI), the researchers compared the results of giving beer drinkers a taste of their favorite beer versus a sports drink. After tasting the beer the participants reported increased desire to drink beer, whereas the sports drink did not provoke as much desire for beer. The brain scans also showed that the beer flavor induced more activity in both frontal lobes and in the right ventral striatum of the subjects’ brains than did the sports drink.

More specifically, both methods of brain imaging showed increased activity in the right ventral striatum, a deep structure inside the brain that is linked to motivated behavior and reward. The researchers previously showed that beer flavor triggered dopamine release; the addition of fMRI showed that craving for alcohol correlated with frontal as well as right ventral striatum activation. The study was published recently in the journal Alcoholism: Clinical and Experimental Research.

In an earlier study of 49 men , the research team, led by David A. Kareken, Ph.D., professor of neurology at the IU School of Medicine and the deputy director of the Indiana Alcohol Research Center, found that just the taste of beer, without any intoxicating effects of alcohol, was enough to cause the release of dopamine, a brain neurotransmitter. Much research has linked dopamine to consumption of drugs of abuse.

The new study was conducted with 28 beer drinkers who had participated in the first study, who then underwent functional magnetic resonance imaging – fMRI scans – during the separate beer and Gatorade tastings.

"We believe this is the first study to use multiple brain imaging modalities to reveal both increased blood oxygen levels and dopamine activity in response to the taste of an alcoholic beverage," said Brandon G. Oberlin, Ph.D., assistant research professor of neurology and first author of the paper. "The combination of these two techniques in the same subjects strengthens the evidence that these effects may be strongest in the right ventral striatum.

"Our results indicate that the right ventral striatum may be an especially important area for addiction research," Dr. Oberlin said.

In addition to Drs. Oberlin and Kareken, investigators contributing to the research were Mario Dzemidzic, Jaroslaw Harezlak, Maria A. Kudela, Stella M. Tran, Christina M. Soeurt and Karmen K. Yoder of the IU School of Medicine.

The research was supported by grants from the National Institutes of Health, R01AA017661-01A1S1, T32AA007462 and K99AA023296, as well as the Indiana Alcohol Research Center (P60AA07611), the Indiana Clinical and Translational Sciences Institute Clinical Research Center, UL1TR001108, NIH, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award.

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The center of the Milky Way galaxy is currently a quiet place where a supermassive black hole slumbers, only occasionally slurping small sips of hydrogen gas. But it wasn’t always this way. A new study shows that 6 million years ago, when the first human ancestors known as hominins walked the Earth, our galaxy’s core blazed forth furiously. The evidence for this active phase came from a search for the galaxy’s missing mass.

Measurements show that the Milky Way galaxy weighs about 1 trillion-2 trillion times as much as our sun. About five-sixths of that is in the form of invisible and mysterious dark matter. The remaining sixth of our galaxy’s heft, or 150 billion-300 billion solar masses, is normal matter. However, if you count up all the stars, gas, and dust we can see, you only find about 65 billion solar masses. The rest of the normal matter — stuff made of neutrons, protons, and electrons — seems to be missing.

“We played a cosmic game of hide-and-seek. And we asked ourselves, where could the missing mass be hiding?” says lead author Fabrizio Nicastro, a research associate at the Harvard-Smithsonian Center for Astrophysics (CfA) and astrophysicist at the Italian National Institute of Astrophysics (INAF).

“We analyzed archival X-ray observations from the XMM-Newton spacecraft and found that the missing mass is in the form of a million-degree gaseous fog permeating our galaxy. That fog absorbs X-rays from more distant background sources,” Nicastro continues.

The astronomers used the amount of absorption to calculate how much normal matter was there, and how it was distributed. They applied computer models but learned that they couldn’t match the observations with a smooth, uniform distribution of gas. Instead, they found that there is a “bubble” in the center of our galaxy that extends two-thirds of the way to Earth.

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Clearing out that bubble required a tremendous amount of energy. That energy, the authors surmise, came from the feeding black hole. While some infalling gas was swallowed by the black hole, other gas was pumped out at speeds of 2 million miles per hour (1,000 km/sec).

Six million years later, the shock wave created by that phase of activity has crossed 20,000 light-years of space. Meanwhile, the black hole has run out of nearby food and gone into hibernation.

This timeline is corroborated by the presence of 6-million-year-old stars near the galactic center. Those stars formed from some of the same material that once flowed toward the black hole.

“The different lines of evidence all tie together very well,” says co-author Martin Elvis of the CfA. “This active phase lasted for 4 [million] to 8 million years, which is reasonable for a quasar.”

The observations and associated computer models also show that the hot, million-degree gas can account for up to 130 billion solar masses of material. Thus, it just might explain where all of the galaxy’s missing matter was hiding: It was too hot to be seen.

More answers may come from the proposed next-generation space mission known as X-ray Surveyor. It would be able to map out the bubble by observing fainter sources, and see finer detail to tease out more information about the elusive missing mass. The European Space Agency’s Athena X-ray observatory, planned for launch in 2028, offers similar promise.

These results have been accepted for publication in The Astrophysical Journal and are available online.

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As new freshmen spread through Harvard and the surrounding neighborhoods, food options do too, whether in dining halls, restaurants, late-night convenience stores, or departmental receptions. A Harvard dietitian has advice for students fully in charge of their diets for the first time: learn. Don’t worry too much, and remember that food is supposed to be enjoyable.

Michelle Gallant, a nutritionist at Harvard University Health Services (HUHS), said students come to campus from such a wide range of countries, cultures, and culinary backgrounds that the common freshman dietary trend as the fall waxes and wanes may simply be that it’s time to be uncommon, that it’s a time of change.

Food may be more abundant, less familiar, and more diverse than it was at home. Mealtimes may be different. Athletes have to make sure they’re eating right — and enough — to fuel their physical expenditures. There will also be new opportunities for social eating, and, with College students’ famously late bedtimes, there may be moments to squeeze in an extra meal, whether it’s needed or not.

“It’s a tremendous transition time,” Gallant said.

As a result, Gallant said that freshmen sometimes come to HUHS for advice on how to navigate the dining halls, how to fit unfamiliar foods into their diets, what to do about digestive concerns, or stressed over changing habits. In addition to formal office visits, she recommends that students stop by during “dinners with a dietitian” or other informational programs run in the dining halls, and that those with food allergies make sure to talk to their dining managers.

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For those without specific health concerns, Gallant said it can be counterproductive to overanalyze diets, to count calories, to eat by focusing on a specific food group — whether to include or exclude it — or to embrace what she called “rule-based” eating. For example, she said, one popular diet restricts carbohydrates, but they are an important energy source for the brain.

“It’s a balance,” Gallant said. “Enjoy food. Avoid skipping meals. Tune in to your body’s own signals of hunger and fullness. We’re trying to avoid rigid thinking about food.”

With a population of high-achieving students, used to striving for academic perfection, too tight a focus on food rules can rob the joy from meals and potentially foster anxiety at the table.

“Eating is one of life’s pleasures,” Gallant said. “Enjoying food means you’re well.”

Harvard abounds with food-related resources, from Harvard University Dining Services’ (HUDS) “Recipes From Home” web form for those who want to share a favorite dish, to The Nutrition Source website at the Harvard T.H. Chan School of Public Health highlighting the latest dietary science, to a certified sports nutritionist available to counsel athletes, to the University’s Science and Cooking lecture series (kicking off Sept. 5), to the “Eaters Digest” newsletter from the Food Literacy Project, to a steady research drumbeat of scientific findings about diet and health.

With all these available resources, Food Literacy Project manager Carolyn Chelius encouraged incoming freshmen to satisfy their curiosity about food and learn, in particular, about nutrition and availability — where and how food is grown — and its social and community aspects. The project itself consists of three areas: a paid student fellowship, a weekly farmer’s market on the Science Center plaza (Tuesdays from noon to 6 p.m.), and events and programs open to the public. The project also partners with the student-run community garden on Mount Auburn Street outside of Lowell House, whose produce is donated to local charities.

Students interested in becoming more involved in such efforts can apply to be food literacy fellows, whose job Chelius said is to “learn more and engage their peer community on topics around the food system.” That mandate translates into organizing educational events and cooking demonstrations in the residence halls, attendance at other food-related events, such as tours of local farms and suppliers, and highlighting food-related issues on campus.

“It’s important to learn as much as possible,” Chelius said.

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PHILADELPHIA —Penn Medicine has completed its 1000th lung transplant at the Hospital of the University of Pennsylvania (HUP), an accomplishment shared with only four other lung transplant programs in the Unites States.

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“We’re excited to have reached such a momentous milestone for the Penn Lung Transplant Program,” said James C. Lee, MD, medical director of the Penn Lung Transplantation Program and an assistant professor of Clinical Medicine. “This milestone celebrates the positive impact we’ve had on the lives of our patients, and the difference we have made for those who have received lung transplants at Penn Medicine.”

The Penn Lung Transplant Program, part of the Penn Transplant Institute, the largest multi-organ transplant center in the Philadelphia region, was established in 1991 and has been at the forefront of care and clinical advances in the area of lung transplantation for a quarter century. Since its inception, the program has performed more adult lung transplants than any other program in the Philadelphia area, with an average of 50 lung transplants per year over the last 15 years. In 2016, the program is on track to complete over 80 lung transplants. This is made possible, in part, by our patient-centered approach to care which ensures patients are moved through the evaluation swiftly and safely.

“Together, working closely with our patients and their families, our partners at Gift of Life Donor Program, and many groups within the health system, we have made tremendous progress in the field, and have been able to help so many patients who are struggling just to breathe,” said Edward Cantu, III, MD, an assistant professor of Cardiovascular Surgery, and the surgeon who performed the 1,000th lung transplant. “Our multidisciplinary approach to patient care allows us to treat some of the sickest patients in the timeliest way possible.”
Penn Medicine’s physicians, nurses, counselors and surgeons, among others, work with patients and their families to determine eligibility for transplantation, and follow them through post-operative care to ensure the transplanted organ is functioning properly and patients are recovering well. The success of the program is a direct result of the combined efforts of multiple clinical departments across Penn Medicine and a unique, multidisciplinary approach to the treatment of end-stage organ disease.

“With so many awaiting organs on United Organ Sharing Network’s (UNOS) waiting list, the goal of the Penn Transplant Institute is to provide a superior level of care to our patients while they are listed, during their transplant, and in the days, weeks and years to follow,” said Abraham Shaked, MD, PhD, director of the Penn Transplant Institute and the Eldridge L. Eliason Professor of Surgery. “Our team, whether involved in a lung transplant, or a liver, kidney or heart transplant, are dedicated to helping the sickest of patients, and to finding ways to change even more lives through organ transplantation.”

The Penn Lung Transplant Program, and Penn Transplant Institute, delivers compassionate care with a goal to dramatically improve patient’s survival and quality of life. This achievement was also made possible by donor families and their loved ones who gave the gift of life through organ donation.

“With the expertise our team has gained over the years, we are committed to offering all available treatment options, and alternatives, that allow patients to receive a lung transplant swiftly," said Christian A. Bermudez, MD, the surgical director of Lung Transplantation and ECMO, director of Thoracic Transplantation, and an associate professor of Cardiovascular Surgery. "Following this tremendous milestone, it is my hope, and the goal of the program that our multidisciplinary team continues to further our expertise, advance the field of transplantation and give our patients the opportunity to really get their lives back."

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PHILADELPHIA – A new biomaterial can be used to study how and when stem cells sense the mechanics of their surrounding environment, found a team led by Robert Mauck, PhD, the Mary Black Ralston Professor for Education and Research in Orthopaedic Surgery, in thePerelman School of Medicine at the University of Pennsylvania. With further development, this biomaterial could be used to control when immature stem cells differentiate into more specialized cells for regenerative and tissue-engineering-based therapies. Their study appears as an advance online publication in Nature Materialsthis month.

During early development in an embryo, the progenitor cells of many types of musculoskeletal tissue start out in close contact to each other and over time transition into an organized network of individual cells surrounded by an extracellular matrix. Throughout the course of embryo development, the it gets stiffer due to increased amounts of matrix material and crosslinking

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During early development in an embryo, the progenitor cells of many types of musculoskeletal tissue start out in close contact to each other and over time transition into an organized network of individual cells surrounded by an extracellular matrix (ECM). This matrix is made up of polysaccharides and fibrous proteins secreted by cells, providing structural and biochemical support to the cells within.

Throughout the course of embryo development, the ECM gets stiffer due to increased amounts of matrix material and crosslinking, eventually guiding stem cells to develop into more specialized cells across various tissue types. It also acts as a medium through which mechanical information is transmitted to cells (such as forces generated with such normal activities as walking or running).

Mauck and his colleagues developed a new biomaterial that allows scientists to systematically study how the cell-to-cell interactions present in early development combined with cell-ECM interactions to regulate stem-cell differentiation.

Cells can sense the inherent stiffness of their surrounding environment, which plays an important role in guiding stem-cell differentiation and generating the mechanical properties of tissues. During musculoskeletal development, a cell’s surrounding environment gradually transitions from one that is rich in cell-to-cell interactions to one that is dominated by cell–extracellular matrix interactions. However, how these stem cells balance their interpretation of seeing one another and seeing this increasingly stiff matrix are not well understood.

To examine the response of stem cells to different mechanical and material inputs, Mauck and colleagues looked at protein complexes that move to the nucleus in response to these signals, called YAP/TAZ proteins. Once in the nucleus, these proteins help guide the differentiation of stem cells to become the specialized cells that reside in various tissue types.

The team showed that this new biomaterial platform can enable scientists to study how the proteins involved in cell-cell contact (N-cadherins) are able to mask stem cell inputs from the accumulating ECM (fibronectins) across a range of tissue stiffness.

The cell-to-cell cues presented by the biomaterial reduced the ability of stem cells to pull on the ECM molecules, which in turn reduced the amount of YAP/TAZ molecules present in the nuclei of developing cells. This resulted in an altered interpretation of ECM stiffness by the cells and ultimately how these cells differentiated.

“Our long-term goal is to be able to intercept how a cell determines the stiffness of its surrounding environment,” said first author Brian D. Cosgrove, a doctoral student in the Mauck lab. “For example, we ideally want to put stem cells into stiff materials for cartilage repair that would withstand the forces present in everyday life, but then the stem cells preferentially turn into bone and other fibrous tissue types. We need to find new ways to trick them into thinking they’re in the correct environment so they will remain specialized cartilage cells.”

This fine control of what a precursor cell ultimately senses and the resulting tissue it produces may be important for treating disorders, such as out-of-place bone growth called heterotopic ossification.

Co-authors are Keeley L. Mui, Tristan P. Driscoll, Steven R. Caliari, Kush D. Mehta, Richard K. Assoian, and Jason A. Burdick

This work was funded by the National Institutes of Health (R01 EB008722, R01 HL115553) and the Penn Center for Musculoskeletal Disorders (P30 AR050950).

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