Fall 2011 Issue by Carolina Scientific

Carolina

sc覺ent覺fic Fall 2011 | Volume 4 | Issue 1

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scıentific Mission Statement: Founded in Spring 2008, Carolina Scientific serves to educate undergraduates by focusing on the exciting innovations in science and current research that are taking place at UNC-Chapel Hill. Carolina Scientific strives to provide a way for students to discover and express their knowledge of new scientific advances, to encourage students to explore and report on the latest scientific research at UNCChapel Hill, and to educate and inform readers while promoting interest in science and research. From the Editor: As Carolina Scientific grows, we hope that our publication continues to foster strong relationships among the creative scientific thinkers at UNCChapel Hill. While researchers work to understand the stories of science, we strive to bring their discoveries to life. This issue, we are excited to provide our readers with an interesting and informative collection of the innovative research occurring in our community. Enjoy! - Garrick Talmage

on the cover

Editors Editor-in-Chief Garrick Talmage Physical Sciences Dasha Gakh Life Sciences Kelly Speare Applied Sciences Keith Funkhouser Production Kati Moore Production Hema Chagarlamudi Design Abbey Gonzales Copy Sophie Liu Contributors Writers Hannah Aichelman Bianca Desai Makani Dollinger Kelsey Ellis Keith Funkhouser Hannah Gavin Alexander Hess Sarayu Kumar Jana Lembke Hetali Lodaya Apurva Oza Kristen Rosano Joshua Thompson Olivia Wayne Braden Zahora Designers Hema Chagarlamudi Kristine Chambers Abbey Gonzales Oliver Isenrich Kati Moore Kristen Rosano Madelyn Roycroft Kristina Stanson

Contact: carolina_scientific@unc.edu Online: http://carolina.scientific.web.unc.edu Facebook: http://facebook.com/CarolinaScientific Twitter: @uncsci

An artist’s impression of the magnetar in the very rich and young star cluster Westerlund 1. See page 24 for full story. Image courtesy of ESO/L. Calçada.

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contents 4

An Attitude of Gratitude as a Relationship Rx Jana Lembke

The Big Fat Truth About Anxiety Bianca Desai

A Former Tar Heel at the Irish Nano-Frontier: Professor John J. Boland Alexander Hess

Ewing Sarcoma: Innovative Approaches to Studying a Malignant Tumor Joshua Thompson

22 24

The Telltale Heart: Uncovering the Genetics of Cardiac Development Kristen Rosano

Of Mice and Men: Insights into Glaucoma from Mouse Genetics Keith Funkhouser

28 30 32 34

Forever Young? Germ Cell Immortality and Telomere Replication Olivia Wayne

Get My Drift? What Rivers Have to Say About Climate Change Hannah Aichelman

Cyanobacteria Like It Hot Kelsey Ellis

Investigating the Role of Symbiotic Bacteria in Mediating GI Toxicity Makani Dollinger

Fundamental yet Elusive Dimensions of Dementia Sarayu Kumar

A Very Bright Future Indeed Braden Zahora

A Magnetizing Find

Apurva Oza

Investigating Two Key Pathways that Link Fat Consumption and Health Risk Hannah Gavin Fruits, Vegetables, and Food Deserts: The Case for Going Beyond Availability Hetali Lodaya SURF Scholar Interviews Hema Chagarlamudi

An Attitude of Gratitude as a Relationship Rx Jana Lembke, Staff Writer

eed a boost in your romantic relationship? A dose of gratitude may do the trick, according to Dr. Sara Algoe of UNC-Chapel Hill Department of Psychology’s Emotions and Social Interactions Laboratory. In a recent study, Dr. Algoe proposed that gratitude for everyday gestures helps build high-quality interpersonal connections [1]. “As a positive emotion, gratitude may act as a powerful force to sustain the most important relationships of our lives,” she says [2]. Gratitude is an emotion experienced in acknowledgment of an intentionally provided benefit, especially if the benefit is perceived as personally valuable and responsive to one’s own needs and preferences [2]. Gratitude facilitates

shown that compared to happiness, gratitude made people recall more positive qualities of a benefactor, feel closer to the benefactor and desire to spend more time with the benefactor in the future [1]. On the flip side Dr. Sara Algoe of gratitude lurks indebtedness, the feeling of obligation to repay someone for a benefit he or she has provided. Depending on how an individual interprets the situation, he or she could experience either gratitude or indebtedness after having received a benefit; however, while gratitude is associated with positive emotions, indebtedness is linked to negative emotions such as guilt [1]. Indebtedness drives people to resolve a debt in order to feel better but, unlike gratitude, does not facilitate communal relationships. Dr. Algoe and her collaborators hypothesized that because moments of gratitude remind an individual of his or her feelings toward a partner and inspire mutual responsiveness, they will strengthen interpersonal bonding. In this way, gratitude should serve as a “booster shot” for the ongoing relationship [1]. Alternatively, the researchers did not expect indebtedness to increase a recipient’s positive feelings about the relationship [1]. In the study, romantic partners independently completed nightly diaries to record their own and their partner’s thoughtful actions, emotional responses to interactions with their partner, and relationship well-being that day. As expected, thoughtful behaviors predicted feelings of gratitude, which in turn increased feelings of relationship satisfaction and connection.

Everyday experiences of gratitude toward a romantic partner are associated with increases in relationship connection and satisfaction. pro-social behavior, which is characterized by empathy and concern for others. Thus, gratitude might enhance social relationships by broadening our attention to people in our lives in a way that feelings related to self-interest or self-gratification do not. In fact, earlier research on gratitude has

Carolina Scientific Moreover, it did not matter whether people actually reported doing something kind for their partner. As long

Dr. Algoe explains. “This is illuminating because people sometimes mistakenly think these two emotional states are

relationships [3]. This study also opens the door for exploring the effects of gratitude in nonromantic contexts, such as how

and do the same thing. This error has historically short-changed us on our understanding of gratitude because gratitude research has been based in theory about indebtedness” [2]. Dr. Algoe argues that continued research on gratitude

it influences decision-making and motivation. Gratitude seems to have uniquely predictive power in relationship promotion, serving to remind us of a partner’s good qualities and to help people reconnect [2]. Even in

In the study, romantic partners independently completed nightly diaries to record their actions and emotions.

as the partner perceived caring behaviors and responded with gratitude on a given day, the benefactor got a boost from the appreciation and both partners appraised the relationship more positively overall [3]. “A key question for relationships research is to understand how happy couples stay happy,” Dr. Algoe said. “Because we were able to show increases in relationship evaluations from one day to the next, experiencing gratitude toward a partner on a given day may be one of the answers” [2]. Feelings of indebtedness, on the other hand, did not predict participants’ relationship wellbeing. “The ‘booster shot’ effects were only found for gratitude,”

“A key question for relationships research is to understand how happy couples stay happy.” is valuable because, like other positive emotions, it is hypothesized to be adaptive from an evolutionary standpoint, helping us to “find, remind and bind ourselves to people who seem to care about our welfare” [3]. The study’s findings forecast opportunities for helping people improve their own close

already-solid relationships, a little appreciation may go a long way toward maintaining those relationships [3]. Frequently recognizing your partner’s thoughtful deeds with a heartfelt “thank you” is perhaps the easiest pill you’ll have to swallow to keep your relationship healthy and thriving. References

1. S. B. Algoe, et al. Pers. Relationship. 2010, 17, 217-233. 2. Email with Sara Algoe, Ph.D. 9/27/11. 3. Wiley-Blackwell Article-level Press Release Author Briefing Form, Sara Algoe, Ph.D.

Figure 1. One proposed theoretical model of the association between gratitude and relationship maintenance. Image courtesy of Dr. Sara Algoe.

A Former Tar Heel at the Irish Nano-Frontier:

Professor John J. Boland Alexander Hess, Staff Writer

n inquisitive person may ask an esteemed metallurgist whether he could make pure copper ten times stronger than its most finely honed, refined, machined and sweated-over formulation without using an alloy. That expert would be hard pressed to find a solution — in fact, the expert might say that it is impossible. If only he could arrange the atoms with infinitely small tweezers and align them for strength and structural integrity, like a stonemason who can create a vaulted ceiling that Dr. John Boland could last for thousands of years with nothing more than shaped stone arranged for strength and a touch of mortar. Nanoscience has now made use of surprisingly similar techniques and ingenuity not only to tune and build incredibly strong and functional solids but also to examine their structure in incredible detail. This is the essence of the work that takes place in the Boland Laboratory. Professor John Boland, a former Tar Heel and past J.J. Hermans professor of chemistry at UNC-Chapel Hill, is now a Science Foundation Ireland principal investigator and director of the prestigious nanotechnology laboratory the Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN) based at my home university, Trinity College Dublin, in Ireland. At the nanoscale,

Figure 1. Fivefold twinned structure of silver nanowire crystallite (left). Transmission electron microscope (TEM) image of section of nanowire (right). Images courtesy of Dr. John Boland.

the picture of everyday materials to which we are accustomed changes to a great degree. Certain characteristics and properties of a material at the macroscale that one can hold in the palm of a hand can be radically different at the nanoscale, far beyond what the eye can see. In fact, approaches akin to traditional methods seen in the metal manufacturing world, like incorporating impurities, fail to work at the nanoscale due to repulsion of the impurities by the nanostructure [1]. For example, carbon is mixed with iron in the manufacturing of steel; however, this strategy is not feasible for nanomaterials. From these hurdles, it was realized that the control of the microstructure was key to strengthening the metal at very small scales. The Boland group adopted the approach of using the structurally well-defined silver fivefold twinned structure [1] to grow nanowires (Figure 1). This strategy imparts two important structural characteristics into the material: grain orientation and grain boundary organization. Grain orientation is analogous to the direction of the grain seen in an everyday piece of wood. Like the linear planes in wood, the periodic planes of the crystalline

repeating structure of the silver bulk material are oriented along a certain direction. The second element, the grain boundary, is the interface between two crystallites, which are the individual “floor tiles” of crystalline material that fit together along the boundaries (the shaded planes in Figure 1) to make a “tiled floor.” An example of this type of polycrystalline material is the nanowire shown in Figure 1. The Boland Laboratory seizes the potential of these commonly encountered concepts in materials science by using the slip directions of the crystallites — how the directional crystalline lattices (the grain orientations) within the “floor tiles” slide against each other. These slip directions intersect almost exactly with the uniform twinning boundaries (the grain boundaries or gaps between the “floor tiles” in question) of other fivefold or pentagonal crystallites along the entire length of the wire. This leads to a uniformly strengthened and hardened wire without defects. Taking advantage of this cooperation between grain orientation and grain boundary organization is almost exactly like how a bridge builder aligns bricks and a load-bearing capstone to bear its weight and the weights of the objects crossing the bridge with

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Figure 3. (a) AFM images of 23.6 nm nanowire before and (b) after brittle failure. (c) Force-displacement curve showing yield point before and (d) after brittle failure. Images courtesy of Professor John Boland.

Figure 2. Atomic force microscope setup.

little or no mortar at all. It is in principle and practice a self-supporting structure that will only fail when the components crumble. This contrasts to failures where the structure is at fault, like the agonizing collapse of a precarious Jenga blocks tower after a long and bitter game. One of the instruments used to look at these structures is the atomic force microscope (AFM, shown in Figure 2), a versatile tool used to provide a tactile analysis of the surface of nanoscale objects and the surfaces of other larger scale objects. Like an oldfashioned record player, this device drags a needle across all of the bumps and grooves it encounters on any given surface. It has a laser trained on the back of the needle that picks up the subtle up-and-down displacements that the needle makes when scanning a textured surface — creating a topographical “touch map” of the surface. Using this technology, the Boland group could monitor stress tests on the wires and see directly how they move and bend. They could also determine the wires’ strength by using compiled force-displacement curves [1] (Figure 3). The results demonstrate how strong these nanostructured materials really are. Whereas bulk silver is actually a relatively ductile and weak metal that can withstand only 83 GPa of longitudinal pressure, the nanostructured metal wire can withstand far upwards of 90 GPa of pressure before being unable to spring back elastically [1]. Data gathered in these strength tests showed that some nanowires could withstand as much as 140 GPa of pressure before yielding [1]. This data illustrates the nanowire’s potential, as it can be stronger than sturdy plate glass and even harder than titanium alloy [2]. With further refinements of the syntheses, these nanowires could possess those amazing properties consistently and reproducibly. Along with the work of many other colleagues all over the world, including many researchers here at

UNC-Chapel Hill, Dr. Boland’s research has contributed to making everyday materials stronger and more versatile by controlling the very atomic structure of what we see and use every day. The ability to see the result is even more enchanting and enlightening, inspiring thousands of scientists to work in the field of materials engineering and nanoscience.

References

1. B. Wu, et al. Nano. Lett. 2006, 6, 468-472. 2. Engineering Toolbox: Elastic Properties and Young Modulus for some Materials. 2011, <http://www.engineeringtoolbox.com/young-modulus-d_417.html>.

Ewing Sarcoma: Innovative Approaches to Studying a Malignant Tumor Joshua Thompson, Staff Writer

wing sarcoma is a highly aggressive and poorly differentiated tumor of bone and soft tissue. This disease is generally localized in the long bones, pelvis, chest walls and the spine [1]. Dr. Paul Jedlicka and his laboratory at the University of Colorado Denver have been studying this disease and looking at the functional role of microRNAs in the progression of Ewing sarcoma tumors. Because of the unique function of microRNAs within cells and their relative accessibility for manipulation, they are very enticing clinical targets for potential therapeutics. Ewing sarcoma is the second-most common form of bone tumor in adolescents and young adults and has strong clinical correlation to the cancer stem cell model. This model, and most notably cancer stem cells themselves, are defined as chemotherapy-resistant populations of cells that are capable of self-renewal and of regenerating the bulk tumor. Because of these regenerative properties, relapse is frequent in patients with Ewing sarcoma and is often fatal [2]. The overall long-term survival remains at about 50 percent. Furthermore, 25 percent of patients present with overt metastatic disease, and of these patients, 75 percent do not survive five years [3]. The Ewing sarcoma family of tumors (ESFT) are characterized by the expression of fusion oncogenes resulting from chromosomal translocations involving Figure 1. Histology image of a the EWS/ETS genes Ewing sarcoma tumor. Image (Figure 1). A fusion courtesy of Dr. Paul Jedlicka. protein is a novel protein produced because of a random recombination event between two separate chromosomes. The resultant proteins can cause downstream cascades of signaling events leading to uncontrolled cell proliferation (cancer) and are often termed oncoproteins. The most common oncogenic fusions occur between the EWS-FLI1 and EWS-ERG genes, with FLI1 and ERG both being ETS transcription factors [4]. The Jedlicka Laboratory has identified microRNAs downstream of EWS/FLI1 that may be involved in the biology of the

Ewing sarcoma tumor. MicroRNAs are non-coding RNAs (generally 19-24 nucleotides in length) that regulate gene expression [5]. MicroRNAs can modulate the expression of multiple target genes at the posttranscriptional level by binding messenger RNA (mRNA), generally Dr. Paul Jedlicka prohibiting translation of these mRNA transcripts into protein. MicroRNAs perform this function as part of the RNA-induced silencing complex (RISC). If the

Figure 2. The oncogenic fusion protein results from a chromosomal translocation event to join the EWS and ETS protein regions and causes Ewing sarcoma. Image courtesy of Sankar et al.

microRNA and its target are perfectly complementary, this complex will induce degradation of the transcript. If, however, the microRNA and the target mRNA do not achieve perfect complementarity, translational repression will be achieved, and the protein will not be expressed (Figure 3) [7]. As can be seen from the statements above, microRNAs are very effective regulatory molecules that can inhibit protein translation mainly through interactions with the mRNA transcript. Because of this fundamental regulatory role, microRNAs are active in almost every cell of the human body. Although their activities are still largely unknown, researchers are quickly uncovering just how essential these biomolecules are. One way to study and manipulate the function of microRNAs in cancer cell lines is through the use of microRNA “sponges.” The microRNA “sponge” method was introduced several years ago by Philip Sharp’s laboratory at the Massachusetts Institute of

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Figure 3. Schematic showing the functional role of microRNAs within the cell as they lead to either translational repression or mRNA transcript degradation. Image courtesy of Joshua Thompson.

Technology as a means to create continuous microRNA loss of function in cell lines and transgenic organisms by binding microRNAs found in the cell and preventing these microRNAs from interacting with their intended targets (Figure 4). This technique is particularly useful for simultaneous targeting of multiple microRNAs at once. Layne Dylla, a Medical Scientist Training Program student in the Jedlicka Laboratory with whom I worked has been using this technique to manipulate microRNAs regulated by the EWS/FLI1 oncoprotein in Ewing sarcoma. MicroRNAs have been shown to be potent regulators of the

biology of stem cells, both in normal development and in cancer. Stem cells in general are cells capable of dividing to produce a second stem cell as well as another cell that can then differentiate to a more specialized form. Cancer â&#x20AC;&#x153;stem cellsâ&#x20AC;? have recently been identified in Ewing sarcoma, but very little is known about their biology [8]. These cancer stem cells are of prime importance in looking at tumor cells that resist chemotherapy. If a tumor were to be treated but the chemotherapy-resistant, multi-potent cells remained, then the tumor has the possibility of regenerating. This results in a bleak prognosis when trying

to treat these patients. Various genes have been indicated in the reprogramming of cells to a pluripotent state including KLF4, Oct4, Nanog, and SOX2. These genes may be of prime importance once the relationship between cancer stem cells, microRNAs and tumor progression can be elucidated. By determining the pathways through which microRNAs function in Ewing sarcoma, novel targeted therapeutic options may be unlocked. Because of their composition and the ways in which they directly regulate translation, microRNAs provide a very promising targeted therapy. Ewing sarcoma has proven to be an approachable model to study their effects because of how closely tied microRNAs are to the pathogenesis of this disease.

References

Figure 4. (a) MicroRNAs (red) bound to mRNA transcripts (gray), which leads to translational repression. (b) MicroRNA sponges (green) are present, and the endogenous microRNAs now bind to the sponges, allowing the majority of the mRNAs to be translated into protein. Image courtesy of Ebert, et al.

1. P. Jedlicka. Int. J. Clin. Exp. Pathol. 2010, 3, 338-347. 2. O. Awad, et al. PLoS ONE 2010, 5, e13943. 3. P. Jedlicka. Int. J. Clin. Exp. Pathol. 2010, 3, 338-347. 4. X. Jiang, et al. BMC Cancer. 2010, 10:116. 5. Y. Lee, et al. EMBO J. 2004, 23, 40514060. 6. T. Haraguchi, et al. Nucleic Acids Res. 2009, 37, e43. 7. S. Zhang, et al. Clin Pharmacol Ther. 2010, 754-758. 8. C. von Levetzow, et al. PLos ONE 2011, 6, e19305.

GET MY DRIFT? WHAT RIVERS HAVE TO SAY ABOUT CLIMATE CHANGE Hannah Aichelman, Staff Writer

interesting subjects for the study of water quality because they are similar in almost all respects. The Tar-Pamlico and Neuse rivers flow adjacent to each other through similar geologic settings from where they begin at the edge of the Dr. Brent McKee Piedmont region to where they discharge into the Pamlico Sound. One significant difference is that over 1.5 million people live within the Neuse River’s watershed, which is the collective area that the river drains, while only 500,000 people live in the Tar-Pamlico River’s watershed [2]. Humans supply large amounts of organic matter into rivers from practices such as farming; therefore, Dr. McKee considers surrounding population density to affect the water quality of these two rivers. On a typical sampling trip, a team of researchers and volunteers travel to the Tar-Pamlico and Neuse rivers to collect data and return to campus with river water, and lots of it (Figure 2). Once a month and for every collection station (Figure 3), researchers collect approximately 30 liters of water to bring back to the lab along with measurements such as temperature, dissolved oxygen content, conductivity and pH. Back in the laboratory, the water is run through a device called a continuous flow centrifuge, which extracts particles such as carbon, nitrogen and other nutrients from the water. The group is most interested in the organic matter found in the water and how it affects the water quality of the Tar-Pamlico and Neuse rivers; however, several different labs in the marine Figure 1. A map of the Tar-Pamlico and Neuse rivers and their drainage basins. A nosciences department are also table feature is the proximity of the two rivers to Chapel Hill and Raleigh. Image courtesy of the UNC-Chapel Hill Smith Foundation Project. working with different aspects fter Hurricane Irene ravaged the North Carolina coast at the end of August, the last thing on most people’s minds was to take a boat ride down a river overflowing from the torrential rains. However, Dr. Brent McKee and his associates in the UNC-Chapel Hill Department of Marine Sciences found themselves in this exact situation on the Tar-Pamlico River (Figure 1) the day after Irene moved north and away from North Carolina’s coast. Of course, the researchers did not travel to the Tar-Pamlico River just to take a boat ride on water that was 15 feet above its normal level; they were collecting samples for an ongoing project in the department of marine sciences that studies the water quality of two North Carolina rivers [1]. Along with 34 other contributors, Dr. McKee studies water quality and the factors that control it for the Tar-Pamlico and Neuse rivers. Specifically, the group is interested in the effects that organic compounds have on water quality and what this data can tell us about how rivers such as the Tar-Pamlico and Neuse will respond to climate change [2]. The Tar-Pamlico and Neuse rivers prove to be

Carolina Scientific of this same set Pamlico and Neuse rivers in the future [2]. of data. Some are Since the project is just entering its second year, looking at how the researchers have not initiated any data synthesis; the microbial however, Professor McKee says that patterns are populations in the beginning to emerge. “We can already tell a big river break down difference between the Tar and Neuse in terms of the organic matter, [organic molecules] in that the human impacts in the while Professor Tar are, as we expected, much less than the Neuse.” McKee’s laboratory One finding that has surprised the researchers is tracks the the level of microbial activity that is breaking down suspended organic organic compounds, even in wintertime, when most particles through scientists believed that this sort of activity slowed Figure 2. Dr. Brent McKee and the river system down. Professor McKee says this discovery has given students examine a core sample using natural the project another objective, which is to look for the collected in coastal North Carolina. radioisotopes [1]. “hot spots” and the “hot moments” of river microbial Image courtesy of Dr. Brent McKee. P r o f e s s o r activity in the Tar and Neuse [1]. McKee believes that there could be another Although few were thinking about river sampling benefit to understanding the organic particles in the day after Hurricane Irene, Professor McKee would rivers. Ultimately, the researchers hypothesize that not have missed the important opportunity to measure characterizing an important the organic “hot moment” in matter found in the Tar River for the Tar-Pamlico anything. While and Neuse rivers the researchers could be useful are able to grasp in determining an idea of trends the effects that of the rivers climate change from monthly will have on other s a m p l i n g , rivers. Information Professor McKee about the types of stresses the materials present importance of and their source understanding allows predictions the rivers’ to be made responses to about what effect natural events climate change such as hurricanes events such as that are likely to droughts or floods increase with a could have on the changing climate. rivers in the future “If you monitor Figure 3. A map showing the locations of the sampling stations that [1]. something day Brent McKee and other researchers visit every month to collect data. This project to day to day, but Image courtesy of the UNC-Chapel Hill Smith Foundation Project. is unique in that you miss these it is funded by a events, you are private foundation, the Smith Foundation, named probably missing most of the story.” [1]. after the Eddie and Jo Allison Smith family took a References special interest in the recent decline of water quality 1. Interview with Brent McKee, Ph.D. 9/20/11. in the Tar-Pamlico and Neuse rivers. The family wants 2. The UNC-Chapel Hill Smith Foundation Project. Black this study to be used as a tool to inform educators, water, white water, blue water: Understanding the Fate students, policy makers and other researchers about of Organic Matter Within North Carolina Rivers and its this serious environmental issue in the hopes that Consequences for Water Quality in Coastal North Carolina. funding and support will be extended for the Tar- 2009, <http://uncsmithfoundrivers.web.unc.edu/>.

Cyanobacteria Like It Hot Kelsey Ellis, Staff Writer

or people living near the shores of Lake Taihu, China, May 2007 was not a good month. Unseasonably warm weather in the region caused a massive algal bloom of the cyanobacteria Microcystis on Taihu’s northern shore (Figure 1). In the city of Wuxi, the bloom was so large that more than 2 million people were left without water for a week when the local water treatment plant could no longer handle the algae load [1]. While overwhelming algal blooms like the one in Lake Taihu are still uncommon, they are increasing in frequency due to a number of factors that Dr. Hans Paerl, distinguished professor at UNC-Chapel Hill’s Institute of Marine Sciences, has spent years researching. As part of that research, Dr. Paerl has studied cyanobacterial blooms in such diverse places as the Baltic Sea, Lake Victoria, polar regions and, finally, Lake Taihu [2]. According to Dr. Paerl, “Taihu is a looking glass for how bad things can get if we let nutrient loading continue in an uncontrolled manner” [2]. Nutrient Figure 1. A view of loading, which is the excess Microcystis aeruginosa input of nutrients such as under a microscope. Image nitrogen and phosphorus by Kristian Peters, [CC-BYinto watersheds through SA-3.0]. human activity, leads to lakes such as Taihu reaching a nutrient-saturated, eutrophic state that provides plenty of food that algae such as Microcystis can use to grow explosively (Figure 2) [3]. This uncontrolled growth causes the familiar neon-green pond scum seen in so many local ponds and lakes during summer months (Figure 3). Such large quantities of algae consume tremendous amounts of the oxygen in the water, causing problems for other aquatic organisms such as fish and mollusks. Furthermore, cyanobacterial blooms can be toxic to humans and “represent a serious threat to drinking water supplies and the ecological and economic sustainability of our largest freshwater systems” [4]. In the United States, over two billion dollars are lost annually from cyanobacteria-related problems in our

water sources [3]. In order to better understand the interaction between nutrient loading and cyanobacterial growth, Dr. Paerl traveled to Lake Taihu and measured the amounts of nitrogen and phosphorus that were being discharged into the Dr. Hans W. Paerl lake throughout the year. This data led Dr. Paerl to recommend that both phosphorus and nitrogen inputs should be limited in shallow lakes like Taihu in order to decrease the frequency and intensity of algal blooms [4]. Restrictions on phosphorus inputs have existed since the 1960s and have helped to slow rates of eutrophication, but Dr. Paerl’s research posits that nitrogen inputs may also need to be controlled. “With the explosion of chemical fertilizers in agriculture … the role of nitrogen has become much more prominent in these systems,” says Dr. Paerl. “Because [Taihu] is so shallow and the nutrients can be exchanged so readily between the sediments and the water column, it’s difficult to control nutrients in there” [2]. Authorities in Taihu are removing the nutrient inputs that cause the blooms in the first place to reverse the effect. Many small factories near Taihu that previously dumped nutrients into the watershed have been forced to close or relocate, and those businesses that have stayed have been forced to follow strict guidelines for what effluents can get into the water [1]. According to Dr. Paerl, Taihu “needs to undergo a very radical initial reduction in nutrients, probably around 50 percent of both nitrogen and phosphorus” [2]. While nutrient loading in bodies of water plays a large role in cyanobacterial development, “changing climatic conditions, including global warming” also encourage algal growth [3]. “Cyanobacteria like it hot,” says Dr. Paerl. “They can take advantage of sudden events like storms that can dump a lot of nutrients into a lake in a short period of time … lastly, drought conditions tend to favor them too because that causes residence time of a water body to increase” [2]. As the climate warms and patterns of storms and droughts become more commonplace, cyanobacteria are well-

Carolina Scientific put these systems out of whack,” argues Dr. Paerl. “They’ve been able to take advantage of human exploitation of systems rather well” [2]. The problem is not the existence of the cyanobacteria themselves but rather the way in which our misuse of resources has led them to upset the balance of the ecosystems of which they are a part. Dr. Paerl argues that “we’ve exploited and benefited from these systems, and people have gotten rich from them … people are going to have to pay up to Figure 2. Algal blooms in Lake Daichi, China, have become so severe that the compensate for the exploitation lake has been deemed unfit for industrial and agricultural uses. Image courtesy of that has occurred.” The problem Greenpeace China. of algal blooms is tied up in the larger issues of climate change adapted to take advantage of the changing climate. and the unsustainable way many communities With the wide coverage of “red tides” and huge, approach resource use. Until those problems are costly algal blooms in the media, it is easy to forget addressed, we will continue to be plagued by these that cyanobacteria are an integral part of earth’s blooms. As Dr. Paerl says, “It’s a classic example of how carbon cycle. Through photosynthesis, they are able to we need to be more in tune with our environment” [2]. take carbon dioxide from the atmosphere and convert it into organic matter. Cyanobacteria have been References around for over two billion years and are significant 1. R. Stone. Science 2011, 6047, 1210-1211. contributors to the production of the oxygen we 2. Interview with Hans W. Paerl, Ph.D. 09/16/11. breathe today. “They’re only terrible because we’ve 3. H. W. Paerl, et al. Sci. Total Environ. 2011, 10, 1739-1745. 4. H. W. Paerl, et al. Water Res. 2011, 5, 1973-1983.

Figure 3. A diagram illustrating eutrophication, the process through which a water body acquires a high concentration of nutrients. Image by Northern Beaches Marine Studies Wikispace, [CC-BY-SA-3.0].

Investigating the Role of Symbiotic Bacteria in Mediating GI Toxicity Makani Dollinger, Staff Writer

here are a number of bacteria living in the human gastrointestinal (GI) tract that are essential to our nutrition and metabolic processes. A significant number of symbiotic bacteria convert digested food into vitamins and minerals and aid in the removal of toxic substances [1]. However, they also cause the harsh side effects of an important colon cancer treatment. Bret Wallace, a graduate student in Dr. Matthew Redinbo’s laboratory, has been investigating a ground-breaking tactic to alleviate the toxic side effects of a colon cancer chemotherapeutic, CPT-11. By using an inhibitor that targets the symbiotic bacteria that cause the side effects, Dr. Redinbo’s group aims to alleviate the toxicity of CPT-11 and increase survival rate of colon cancer patients. Camptothecin was added to the National Cancer Institute natural products screening set in 1966 [2]. A derivative of camptothecin,

Figure 1. Metabolism of CPT-11. Image courtesy of Dr. Matthew Redinbo.

CPT-11, is currently used as a chemotherapeutic to fight colon cancer. It functions by inhibiting the human enzyme topoisomerase I, which is crucial to cell replication [2]. Once topoisomerase I is inhibited by an activated form of CPT-11, replication of colon cancer cells is halted, and cell death occurs. After this process, CPT-11’s active form is converted to an inactive form in the liver by undergoing a process known as glucuronidation. Special enzymes in the liver add a glucuronide group to active CPT-11, deactivating it, before it is secreted into the large intestine. No longer inhibiting topoisomerase I and subsequently killing cells, the drug is now safe to digest [2]. Once the inactivated form of CPT-11 reaches the large intestine, symbiotic bacteria cause an unfortunate reaction to occur. Symbiotic bacteria typically live in a mutually beneficial association with humans. However a bacterial enzyme, known as ß-glucuronidase, removes the glucuronide group from deactivated CPT-11 to use as a food source, reactivating the drug (Figure 1). This reactivation causes diarrhea and inflammation of the intestines. Scientists and doctors had previously been unable to prevent the toxic side effects caused by the drug. A simple resolution to alleviate CPT-11 toxicity would be to kill the intestinal bacteria with broadspectrum antibiotics. However, the symbiotic bacteria in the large intestine are essential to human health, and long-term usage of antibiotics can be harmful [1]. Instead, Wallace sought to inhibit the function of bacterial ß-glucuronidase.

Both human and bacterial cells contain ß-glucuronidase, and any inhibitor would ideally prevent bacterial Dr. Matthew ß-glucuronidase Redinbo activity without affecting the human version of the enzyme. Wallace solved a 3-D structure of Escherichia coli ß-glucuronidase that illustrated some of the structural differences between the two enzymes (Figure 2), which were useful in identifying inhibitors of bacterial ß-glucuronidase. Potent bacterial ß-glucuronidase inhibitors were identified using a new strategy for toxicological testing, known as high-throughput screening [3]. This strategy uses in vitro biochemical and cell-based assays and non-rodent animal models to prioritize substances

Figure 2. Protein structure of the E. coli β-glucuronidase tetramer. Image courtesy of Dr. Matthew Redinbo.

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Figure 3. Inhibitor-bound crystal structure: Bacterial loop confers specificity. Image courtesy of Dr. Matthew Redinbo.

for further biochemical experiments [4]. The crystal structures of an inhibitor bound to the bacterial enzyme established that selectivity of the inhibitors was based on a loop unique to bacterial ß-glucuronidases (Figure 3). The fact that bacterial ß-glucuronidases have this loop and the human enzyme does not allows for specific targeting of the bacterial orthologue of the enzyme, leaving the human enzymes unaffected. Wallace’s discovery is the first known instance of an enzyme from symbiotic bacteria being targeted, and his results were published in Science in November of 2010. The ability of the inhibitors to impede bacterial ß-glucuronidase activity was tested in E. coli cells, and it was found that the compounds were effective inhibitors of the bacterial ß-glucuronidase. The inhibitors were then tested for their ability to prevent the diarrhea and intestinal damage caused by CPT-11. In a preliminary mouse study, mice were divided into four groups and

administered a vehicle (a control solution without effector compounds), inhibitor, CPT-11, or CPT-11 with the inhibitor. After about ten days, mice in the group receiving CPT-11 suffered severe diarrhea and intestinal inflammation, while those receiving CPT-11 in addition to the inhibitor did not [2] (Figure 4). This experiment demonstrated that in mice, the use of an inhibitor with CPT-11 prevents diarrhea and protects the intestine from damage. Further research is currently being performed on other bacterial strains such as Streptococcus agalactiae and Bacteroides fragilis. Key regions of the unique loop on the bacterial ß-glucuronidase are found in 98 percent of other such bacterial strains in the human GI tract. For the most effective inhibition of bacterial ß-glucuronidase and thus the toxic side effects of CPT-11 treatment, these other strains of bacteria must be examined and targeted as well. The initial results may lead to pharmacokinetic studies that will help us learn how to administer the drug to human patients with colon cancer in order to prevent the harsh side effects of CPT-11. Wallace’s results show that drugs may be designed to inhibit undesirable enzyme activities in microbial symbiotes to enhance chemotherapeutic efficacy. This novel approach may improve the lives of colon cancer patients and increase their survival rates.

References

1. A. M. Prater. Gut Bacteria: Healthy or Unhealthy? 2011, <http://www.interesting-health-facts.com/2010/03/gutbacteria-healthy-or-unhealthy.html>. 2. B. D. Wallace, et al. Science 2010, 330, 831-835. 3. Presentation by Adam Roberts, 05/19/2011. 4. National Toxicology Program. High Throughput Screening Initiative. 2011, <http://ntp.niehs. nih.gov/?objectid=05F80E15-F1F6-975E-77DDEDBDF3B941CD>.

Figure 4. Alleviation of CPT-11 toxicity in mice. Image courtesy of Dr. Matthew Redinbo.

Fundamental yet Elusive Dimensions of Dementia Sarayu Kumar, Staff Writer

emory is an integral part of life. Good and bad memories shape our everyday outlooks. The disintegration of memory to any degree is extremely frustrating, whether it be misplacing car keys or forgetting whole conversations. Dementia is a “decline in mental functions that affects daily living,” and it can have a traumatizing effect on both its patients and their caregivers [1]. Dr. Daniel Kaufer is an associate professor in the department of neurology at the UNC-Chapel Hill School of Medicine, and he deals with patients showing symptoms of Alzheimer’s disease, Lewy body dementia (LBD) and frontotemporal dementia (FTD). He is interested in the social cognition and translational neuroscience behind these brain disorders (Figure 1). Dr. Kaufer’s holy grail consists of developing measures to test fundamental but elusive aspects of dementia such as changes in personality and behavior. In other words, Dr. Kaufer is trying to “develop ways to measure personhood in a clinical context” [2]. He feels that many physicians largely ignore this aspect of dementia even though they are very significant components of the mental disease. For example, measuring changes in a dementia patient’s personality is hard to do in a laboratory setting but

it is an important part of the treatment. Dr. Kaufer often works with patients who exhibit frontotemporal degeneration. In frontotemporal degeneration (FTD), “damage to the brain’s frontal and temporal lobes affect complex thinking and reasoning abilities,” which results Dr. Daniel Kaufer in inappropriate social behavior, problems with expressing language and word meaning and problems with motor skills (Figure 2) [2]. In patients with FTD, it is easy to measure their language function, but it is challenging to measure their ability to have a conversation [3]. Dr. Kaufer gave the example of a party or family get-together as an example of a setting that poses significant challenges to FTD patients in terms of integrating memory and language abilities in a social context. “How we act in diverse social circumstances plays a large role in defining who we are, yet it is very challenging to measure such fundamentally human characteristics with clinical metrics,” he said. Dr. Kaufer is interested in translating information from the realm of research to

Figure 1. A normally aged brain (left) and the brain of a person with Alzheimer’s (right).

Carolina Scientific create a practical and clinical tool, thereby facilitating diagnosis and monitoring treatment effects in a way that is more “ecologically valid” [3]. During his fellowship at the University of California, Los Angles, Dr. Kaufer worked with Dr. Jeffrey Cummings, who developed a scale called the Neuropsychiatric Inventory (NPI), which explores “various dimensions of behavior abnormality associated with Alzheimer’s” [3]. Dr. Kaufer, in turn, developed a short questionnaire to be used with the NPI called the Neuropsychiatric Inventory (NPI-Q), which is used at 30 Alzheimer research centers funded Figure 2. Human brain showing frontotemporal lobar degeneration, which causes FTD. Image by by the National Institute of Health. [3]. Efficiency is Wikimedia Commons, [CC-BY-SA-3.0]. extremely important is clinical practice; the use of the NPI-Q saves time for the doctor, the patient and the patient is requested to repeat as many words as she can remember from the recited list. After that, Dr. Kaufer caregiver. Dr. Cummings and Dr. Kaufer identified that reads from a larger list comprising of some of the old caregivers are an extremely important part of the words and some completely new ones. Then he asks treatment of dementia because they are able to report the patient if each word is new or from the original list. what the patient has been going through. Therefore, In addition to this binary response, he asks the patient, the NPI-Q includes a portion to be filled out from the on a scale of one to four, how sure the patient is of her caregiver’s perspective. The questionnaire consists answer. From this clever addition, Dr. Kaufer is able of 12 symptoms, each of which includes a section for to determine how far along an Alzheimer’s patient how severely a patient suffers from that particular is. Patients who are more certain about their wrong answers demonstrate symptom and a section awareness of their for how distressing “How we act in diverse social circumstances impairment problem. that particular Alzheimer’s symptom is to the plays a large role in defining who we are, yet it is Since caregiver. For example, very challenging to measure such fundamentally patients are generally unaware of their one of the symptoms human characteristics with clinical metrics.” memory problems, on the questionnaire this test can potentially is “delusions,” and the caregiver, on a scale of one to three, has to rate how indicate the onset of Alzheimer’s disease. [3]. Dr. Kaufer strives for “ecological validity” by using severely the patient expresses this symptom. Then the caregiver, on a scale from zero to five, rates how research-backed information as a practical clinical tool with his patients. Many significant components of distressed they are because of that symptom [3]. According to Dr. Kaufer, 25 percent of the dementia go unmeasured in a clinical sense because patients who displayed mild cognitive impairment, a they are too abstract. He has already breached possible early symptom of dementia, were reported this domain with the development of his NPI-Q to suffer from moderate to severe depression [2]. questionnaire and his enhancement of the standard The questionnaire is potentially helpful in assessing memory recall test. Dr. Kaufer’s ultimate goal is to people for depression and in helping caregivers translate clinical research into practical clinical tools manage the neuropsychiatric symptoms displayed that make the diagnosis and treatment of dementia by patients. This entire process individualizes the more relevant and robust. treatment of dementia depending on the severity of the symptoms exhibited by the patient and the References 1. An Introduction to Lewy Body Dementia. Lewy Body emotional state of the caregiver [3]. Dementia Association. Flyer. In addition to the NPI-Q, Dr. Kaufer has revised 2. Frontotemporal Degeneration. Association for Frontoa standard binary memory test in patients starting temporal Degeneration. Flyer. to exhibit memory impairment symptoms. He starts 3. Interview with Daniel I. Kaufer, M.D. 9/22/11. by reading a list of words and asking the patient to 4. E. D. Roberson, in Alzheimer’s Disease and Frontotemporepeat as many as she can remember. After a delay, the ral Dementia: Methods and Protocols (Humana Press, 2011).

A Very Bright Future Indeed Braden Zahora, Staff Writer

to various carbohydrates” [3]. However, in order to do this artificially, there is a key half-reaction that must occur: the splitting of water to give oxygen. This is a difficult reaction to carry out because it is very complicated, and in order for it proceed at an optimal reaction speed, Dr. Thomas Meyer a catalyst must be introduced. Dr. Meyer has discovered a group of molecules, ruthenium complexes (Figure 1), that can be manipulated to help oxidize water and split it into its substituents by means of an electrochemical reaction or the addition of chemical oxidizing agents. The ruthenium complex catalysts that help with this step are crucial to the overall process of producing solar fuels. In order to accomplish artificial photosynthesis, a number of reactions and processes must be performed to accommodate all of what needs to occur. This is known as the modular approach. This specific approach “allows individual elements for each function to be investigated separately and integrated into molecular assemblies or nanoscale arrays” [3]. In other words, there are many different procedures that are performed and analyzed individually; they are then all put together and analyzed as a whole. In this method of performing artificial photosynthesis, energy in the form of light is used to convert molecules into excited states. Electrons are transferred from the excited state to catalysts where the reaction can occur [1]. The diagram in Figure 3 reveals the basic steps taken for the net process to occur from the oxidation of water and production of hydrogen, all the way to the use of this hydrogen to produce solar fuels. Figure 1. A molecular model of one of the ruthenium comUsing naturally abundant materials, such as

ociety’s need for an efficient and powerful alternative source of energy has slowly become an extremely critical topic as our civilization progresses and our natural resources dwindle. Right now, most of the world’s energy supply is dependent on fossil fuels, which cause pollution to the earth and an economic dependence on oil [1]. In the search for alternative energy, many scientists are turning to the ultimate source of energy — the sun — to create solar fuels. Professor Thomas Meyer at UNC-Chapel Hill states that the sun’s “daily input to the earth is 10,000 times current energy use, [and] it is free of greenhouse gases and pollutants” [2]. If the switch is made to solar energy and the production of solar fuels, the negative impact of these pollutants on our global climate will diminish. Dr. Meyer has been quite successful in this area, especially with regards to his research in artificial photosynthesis. In natural photosynthesis, a process plants have been utilizing for a few billion years, “light [is used] to … reduce carbon dioxide

plex catalysts. Image courtesy of Dr. Thomas Meyer.

Carolina Scientific sunlight and carbon dioxide, and converting them into solar fuels, is a huge improvement from the energy sources we have at our disposal now. Unfortunately, with the production of solar fuels, there are still limitations. One of these limitations is that the sun is not out all of the time, so there needs to be a way to store the massive amount of energy received so that it can be tapped at any time. Another limitation is the diffuse nature of the sun, necessitating an area greater than the state of North Carolina in order to meet Americaâ&#x20AC;&#x2122;s huge power needs [2]. In spite of these limitations, the potential benefits of this energy source are immense. Having an unlimited source of energy that is clean for the environment and sustainable will be a huge step forward in the evolution of our society. As seen in Figure 2, a closed cycle could be created in the future where part of the energy that is produced could be used to

A Closed Cycle with Solar Fuels CH4 + O2

CO2 + H2O 9/19/2011 - 4

Figure 2. A proposed model where the products created could be used to fuel further reactions, allowing for a closed energy cycle.

fuel more energy collection and production of solar fuels. Simultaneously, the rest of the energy and fuel could then be sent to homes and businesses across the country. If future research continues that is as successful as Professor Meyerâ&#x20AC;&#x2122;s, it sure seems as though we have a bright future ahead of us!

References

1. Interview with Thomas Meyer, Ph.D. 09/19/2011. 2. T. J. Meyer, et al. Catal. Lett. 2010, 141, 1-7. 3. J. J. Concepcion, et al. Accounts Chem. Res. 2009, 42, 1954-1965.

Figure 3. A diagram of artificial photosynthesis, where water is split and fuel is produced. Image courtesy of Dr. Thomas Meyer.

The Big, Fat Truth About Anxiety Bianca Desai, Staff Writer

any people worry about the kinds of foods they eat and how it will affect their cardiovascular systems in the future. Surprisingly, however, large amounts of saturated fats in American diets may also put many at a higher risk for Alzheimer’s. Alzheimer’s disease is a neurodegenerative disease that has plagued the elderly for years. One large component of Alzheimer’s disease is the feeling of anxiety, which is also common in those who are obese [1]. Recently, nutrition experts have taught us the horrible effects that fat has on the body, which may be why obese individuals have anxiety disorders. However, it is not known whether the cause is psychological Dr. Patricia Sheridan or biological. Herpes simplex virus 1 (HSV-1) mimics how Alzheimer’s affects the brain and is being used to better understand the biological and psychological causes of these effects. At Dr. Melinda Beck’s laboratory in the nutrition department of the Gillings School of Global Public Health at UNCChapel Hill, Dr. Patricia Sheridan is looking at the interplay between obesity and HSV-1 and how they affect anxiety levels in the brain. Studies from other labs have showed that obesity at mid-life is a high predictor for Alzheimer’s, and 25 percent of obese individuals have an increased risk for anxiety [1]. There is clearly a correlation between obesity and anxiety. HSV1 is relevant to the study of Alzheimer’s because both the virus and aging cause inflammation in the brain, specifically with the activation of microglia [1]. Microglia are macrophage-like cells in the

central nervous system; they destroy infectious agents that may have infected the brain or spinal cord (Figure 1). In Alzheimer’s disease and HSV-1, many believe that once microglia are activated, they participate in an inflammatory response that contributes to damaged brain tissue and neurodegeneration [2]. Continuous, uncontrolled activation of the microglia results in degeneration

Figure 1. A confocal image of microglia. Image courtesy of Dr. Patricia Sheridan.

that may damage neurons and allow infectious agents to invade the brain. Just about everyone becomes infected with HSV-1 at some point in his or her life. After a person becomes exposed to HSV-1, though, the virus becomes latent and sits in the semilunar ganglion, which is composed of neurons that are just below the brain (Figure 2). “By age 20, 80 percent of humans have the latent virus [in this area],” Dr. Sheridan explained [1]. To test how obesity and HSV-1 affects anxiety, Dr. Sheridan used four groups of mice. Mice were either infected with HSV-1 or mock-infected with saline. The mice remained in controlled conditions for nine months in order to recover from the infection, and the virus became latent in the semilunar ganglion. Then, mice from the HSV-1 and saline-treated groups were placed on either a high-fat or low-fat diet. Dr. Sheridan’s collaborator, Dr. Sheryl Moy in the department of psychiatry,

Carolina Scientific performed four behavioral tests on each group, testing for locomotion and anxiety, motor coordination and motor memory, sensorimotor gating and anxiety, and learning and memory. Dr. Sheridan found that the mice did not have any learning and memory problems; they were all able to find their way around a Morris water maze (Figure 3). In this maze, mice are put into a small pool of water with a hidden platform. The mice are taught how to get to the platform, and then this learning ability is tested. Though there was no change in the mice’s learning and memory ability, there were a number of issues when looking at motor-coordination and anxiety. As expected, the mice that were fed with the high-fat diet had many Figure 3. A mouse in a Morris water maze. The animals should remember the position of the below surface platform. Image by Samuel John, [CCmotor-coordination issues and fell off BY-SA-3.0]. of a rotarod, a rotating rod that tests for motor coordination. What is interesting, though, that were not obese had lower inflammation in is that the obese mice injected with HSV-1 had the same regions. This shows that the anxiety high levels of anxiety. Obese mice had increased associated with obesity may not be completely inflammation in regions of the brain that are psychological but rather biological [1]. This could important for controlling anxiety, whereas mice contribute to studies of Alzheimer’s disease. Since anxiety is a component of the disease, it could be improved with treatments, including different medicines. In the future, scientists could manipulate certain regions of the brain with different medications or surgeries to ease the anxiety of obese individuals. This research is important to public health because it can lead to advancements toward finding a cure for Alzheimer’s disease. The experiment was not a perfect model for a cure of Alzheimer’s disease because there was no change in learning or memory ability, both of which degenerate with the onset of Alzheimer’s. However, because anxiety is also a large component of the disease, Dr. Sheridan’s research helps scientists understand how obesity could be a risk factor for Alzheimer’s.

Figure 2. Semilunar ganglion.

References

1. Interview with Patricia Sheridan, Ph.D. 09/22/11. 2. D. W. Dickson, et al. Glia 1993, 1, 75-83.

The Telltale Heart: Uncovering the Genetics of Cardiac Development Kristen Rosano, Staff Writer

magine waking up every day wondering whether your newborn was going to live. For children with congenital heart disease, it’s a struggle just to survive. Congenital heart disease, which includes any of the broad range of structural defects of the heart that can be present at birth, affects 1 percent of newborns and is the cause of 10 percent of stillbirths [1]. It is the most common type of birth defect and results in more deaths in the first year of life than any other [2]. Symptoms depend on the defect and may either be present at birth or Dr. Frank Conlon take years to develop. Currently, the available treatments for congenital heart disease are heart transplantation and drugs improving the ability of the heart to contract. Heart transplantation is risky and “any drug for heart disease lasts only five to ten years,” says Dr. Frank Conlon, associate professor of genetics and adjunct associate professor of biology at UNC-Chapel Hill [3]. Dr. Conlon studied early vertebrate development for his Ph.D. and from there decided to pursue heart development research. His laboratory is helping reveal the causes of heart disease by studying the relationship between the proliferation of cardiac progenitor cells — the precursors to mature, fully differentiated cardiac cells — and cardiac differentiation [1]. While cell differentiation as a general mechanism has been studied extensively, relatively little is known about this process on a tissue-specific basis [4]. Dr. Conlon is studying cell differentiation in the heart with the hopes that the information will improve diagnoses by more clearly defining the subtypes of heart disease [3]. This specificity allows doctors to apply the right treatment to the right case and see the

best possible outcome. “If you can diagnose a disease and you can do an operation early in life,” you can greatly improve a patient’s chances, Dr. Conlon explains. It has also been suggested that a better understanding of cell proliferation and differentiation in heart development could lead to a new and exciting form of treatment, one in which cardiac progenitor cells are injected into a patient’s heart to replenish the damaged tissue. This solution, if made a reality, could be safer than transplantation and longer-lasting than medication. In vertebrates, the heart is one of the first organs to form, and the process of cardiac development is highly conserved among species [4]. The heart grows by the continuous addition of cells and the rapid proliferation that goes along with it. It was previously thought that after heart development was completed, nearly all of the heart muscle cells exit the cell cycle, both stopping proliferation and

Figure 1. The developing heart of a Xenopus laevis. Image courtesy of Dr. Frank Conlon.

Carolina Scientific leaving the heart without regenerative power. including T-box genes (especially TBX5), which But to the surprise of many, recent studies have have been extensively studied by the Conlon identified small populations of Laboratory [1]. In addition to progenitor cells still present in TBX5, Dr. Conlonâ&#x20AC;&#x2122;s laboratory adult heart tissue, suggesting has identified two other that the adult heart may still genes critical to cardiac have some renewing power. development: SHP-2 and The regulation of these cells CASTOR (CST). TBX5 and remains unknown. SHP-2 are known to function in the same pathway, but Xenopus, the African clawed frog, has been used their relationship is still to identify many of the unknown. One study by genes involved in heart the Conlon Laboratory [6] showed that without SHP-2, development [5]. Xenopus is an ideal model organism genes associated with heart development and the onset because it develops externally, of differentiation are downunlike the mouse, and its Figure 2. A developing mouse, with the heart embryo is relatively large and in pink. Image courtesy of Dr. Frank Conlon. regulated and thus lose some of their function in promoting thus easily visualized. The developing heart of a Xenopus embryo can even development of the heart. be imaged in real time to record the process. Its The third gene, CST, has been shown by genetics and anatomy are very similar to those the laboratory to play a critical role in cardiac of humans, making it a good model for studying differentiation. The Conlon Laboratory was the human disease. Mutations in many genes have first to identify it in vertebrates and to show that been identified with the help of Xenopus studies it is expressed in the developing heart [1,3]. In its as the causes of a variety of human heart defects. absence, cardiac cell differentiation is blocked. One Heart development depends on the study [7] showed that without CST, some cardiac expression of cardiac transcription factors, cells arrest and therefore never differentiate into mature cells. This can result in cardia bifida, a disease defined by improper heart development The future of Dr. Conlonâ&#x20AC;&#x2122;s research includes using Xenopus to identify other genes involved in heart development [1] and proteomics to elucidate involved pathways by mass spectroscopy [3]. All of these clues are giving researchers a more complete picture of cardiac development, an understanding critical to diagnosing and treating congenital heart disease. References

Figure 3. The stages of vertebrate heart development [4]. Image courtesy of S. C. Goetz et al.

1. Frank Conlon. Research Overview. 2011, <http://www. unc.edu/~fconlon/Synopsis.htm>. 2. Kurt R. Schumacher. Congenital Heart Disease. 2009, <http://www.ncbi.nlm.nih.gov/pubmedhealth/ PMH0002103/>. 3. Interview with Frank Conlon, Ph.D. 9/16/11. 4. S. C. Goetz, et al. Cell Cycle 2007, 6:16, 1974-1981. 5. C. Showell, et al. PLoS One 2011, 6, e22392. 6. Y. G. Langdon, et al. Development 2007, 134, 4119-4130. 7. K. S. Christine, et al. Dev. Cell 2008, 14, 616-623.

A Magnetizing Find Apurva Oza, Staff Writer

t just got Sirius. Known as Sopdet to the Ancient theoretical models have not been Egyptians and later as Seirios, meaning “glowing” able to predict the structure or the or “scorcher,” in Ancient Greek, Sirius is indisputably power of these magnetic fields. the most ancient and well known star to man. Sirius We experience stellar is the brightest star in the night sky, about 23 times magnetism every day in brighter than our north star Polaris. Sirius is actually unusual ways. Examples include a binary star system in the constellation Canis Major, communication disruptions, radio consisting of Sirius A, the brighter main sequence signal perturbation, blackouts star, and Sirius B, a smaller white dwarf. and finally — on the bright side — Dr. Pascal Petit French astrophysicists have found a previously aurorae, due to the interaction of unknown weak surface magnetic field on Sirius the sun’s magnetic field with Earth. A star’s magnetic A after analyzing polarized radiation from the field is essentially created by the convective star. Dr. Pascal Petit, my research mentor, working movement of conductive plasma inside the star. This at the Laboratoire d’Astrophysique de Toulouse- magnetic field generation is coined “Solar Dynamo Tarbes with the Centre National de la Recherche Theory.” This theory is based on conducting gases Scientifique (CNRS) and the Université de Toulouse, and liquids that generate self-amplifying currents led the research that resulted in this finding. which in turn induce magnetic fields. This magnetic Dr. Petit is a researcher in the subfield of stellar field is powered by the differential rotation of the astrophysics. The study of stars and their structure, star, induction and other forces. These currents travel formation and evolution has branched off of one around the sun in loops and eventually get tangled of the most ancient sciences — observational in what astronomers call “flux ropes.” This results astronomy. Astro, the in a twisting resembling Greek word for star, has a toroidal magnetic field been the genesis of [1]. This primordial field modern astrophysics. is eventually annihilated, That is what makes this leaving only a net dipolar new finding particularly magnetic field. For this bewildering — Sirius has reason, only certain stars been observed for over were thought to possess 4000 years, and yet we are this remaining surface still discovering unknown magnetic field [2]. In the properties about it. past decade, these certain Magnetism in stars stars were thought to be can get very convoluted. chemically peculiar Ap From basic physics, we and Bp stars, white dwarfs expect a star to have some and magnetars — highly sort of magnetic field dense magnetic neutron like Earth has due to the stars [3]. Now, with the oscillation of a charged invention of an extremely particle. However, when Figure 1. A visualization of the magnetic field topology sensitive detector, we can observing more massive in Vega. This was constructed using a technique called detect more faint fields. stars like Sirius, past Zeeman-Doppler Imaging. Image courtesy of D. Alina et al. The first instrument

Carolina Scientific built for the study of stellar magnetic fields is NARVAL, housed at the Pic du Midi de Bigorre Observatory in the French Pyrénées Mountains. NARVAL is a spectropolarimeter, which is a fusion of a polarimeter and a spectrograph that collects light and outputs intensity in Stokes I (linear polarization) and Stokes V (circular polarization) profiles [3]. In order to visualize the magnetic field, a plot of the Stokes V intensity as a function of the star’s radial velocity must be created. If there is a magnetic field present, a pattern is seen in the profile due to the Zeeman Effect, which physicists call the Zeeman signature. In general, magnetic field detection is due to the magnetic movement of atoms and molecules in a star’s atmosphere. Flips and transitions between atomic energy levels cause the polarization of spectral lines that allows us see the Zeeman Signature. The next step is to quantitatively determine the probability of a magnetic field detection using an X2 statistic, which is a function of

the wavelengths that the Stokes V intensity was measured in, as well as the error of detection. A magnetic field is detected when a value is obtained that has an X2 value greater than 0.99. After finalizing all of the data, the magnetic field is measured using a “center-of-gravity” technique. For Sirius, the value was 0.2 ± 0.1 G. This astounding result demonstrates that a star that is twice as massive as the sun can output a magnetic field that is five times as feeble. In fact, Sirius’s magnetic field resembles that of Earth’s, which is close to 0.3-0.5 G. These net dipole fields are usually weak for normal stars and planets. To put these field strengths in perspective, a simple refrigerator magnetic field is 50 G; the sun’s net field is approximately 1 G, with sunspots being 1,000 times stronger; and finally, a truly magnetic neutron star (magnetar) can be up to 1015 G! Due to NARVAL’s extreme sensitivity and the analysis done by Dr. Petit’s team, astrophysicists have a new classification of weak magnetic stars, which are

Figure 2. The [averaged] Zeeman signature of Sirius A. Note the characteristic central peak. Image courtesy of Apurva Oza.

called “Vega-like” due to the initial breakthrough discovery of the rapidly rotating star Vega possessing a weak magnetic field [2] (Figure 1). Furthermore, when Sirius was scrutinized further, no net magnetic variability was detected for the star. Since we expect the magnetic field to change periodically for a star, this implies a different field generation mechanism, which was most likely conceived in the deeper layers of the star and not in the convective zone. The search continues. Beta Uma is another star that has been found to possess Vega-like magnetism. This is a liftoff point not only for stellar magnetism and stellar evolution but also for the perpetual discoveries of exoplanets. With NARVAL detecting the weakest fields, the study could be broadened to planets like our own.

References

1. P. Petit. The Magnetic Field of Sirius: Exploration of a New Class of Magnetic Stars Among Intermediate-Mass Stars. 2011, CFHT Proposal,11AF0122011. 2. Donati J.-F, et al. Annu. Rev. Astron. Astrophys. 2009, 47, 333-370. 3. F. Lignieres, et al. Astron. Astrophys. 2009, 500, 3, L41-L44. 4. Donati et al. 2007, ESPaDOns: An Echelle SpectroPolarimetric Device for the Observation of Stars at CFHT. < http://www.cfht.hawaii.edu/Reference/Proceedings/index.html>. 5. O. Kochukhov, et al. Astron. Astrophys. 2010,524, A5. 6. J-F. Donati, et al. Astron. Astrophys. 1997, 326, 1135-1142. 7. C. Stütz, et al. Astron. Astrophys. 2009, 505, 3, 1233-1235. 8. J.D. Landstreet, et al. Astron. Astrophys. 2011, 528, A132. 9. R. R. Britt. Mystery of Magnetic Stars Solved. 2004, <http://www. space.com/507-mystery-magneticstars-solved.html>.

Of Mice

Men

Insights into Glaucoma from Mouse Genetics Keith Funkhouser, Staff Writer

ore than 3 million Americans suffer from glaucoma, and another 100,000 are diagnosed each year [1]. Dr. Gareth Howell, a research scientist at the Jackson L aborator y in Bar Harbor, Maine, is making an impact on Dr. Gareth Howell this terrible disease with the help of some fuzzy little rodents: blind mice. Glaucoma encompasses a group of eye diseases that collectively affect nearly 70 million people worldwide. These diseases are characterized by elevated pressure within the eye, which leads to the death of retinal ganglion cells (RGCs), atrophy of the optic nerve and eventual blindness (Figure 1). Glaucoma is the second leading cause of blindness worldwide, yet 90 percent of cases proceed with no noticeable pain or symptoms. It is thus a major clinical problem, with known risk factors including increasing age, high intraocular pressure (IOP) and a family history of glaucoma [1]. Over time, it causes a unique “tunnel vision” effect in patients due to the peripheral loss of RGCs and vision (Figure 2). The most common forms

of glaucoma do not exhibit classical Mendelian inheritance. They are complex, multifactorial diseases that are likely affected by a number of environmental and genetic factors. Because experimentation on humans is extremely limited by factors such as government regulation, sample size, and maturity time (glaucoma often does not develop until late in life), animal models are used extensively for genetic studies of human retinal diseases. The house mouse, Mus musculus, is the most widely used animal model, particularly because its ocular structures are essentially the same as human ones, lacking only the macula and fovea. The drainage structures, which regulate normal pressure in the inner

eye, are highly similar between mice and humans. Furthermore, blockage of these drainage structures seems to result in the same problems in mice and humans — elevated IOP and glaucoma. Therefore, the mouse is a very powerful model for studying the mechanisms of glaucoma risk and development [2]. At the Jackson Laboratory, mice allow researchers to investigate human disease at the genetic level. Founded in 1929 as a nonprofit biomedical research institution, its mission is “to discover the genetic basis for preventing, treating and curing human disease, and to enable research and education for the global biomedical community.” It is the world’s

Normal

Advanced Glaucoma Figure 1 (above). Glaucoma causes the death of retinal ganglion cells (RGCs) in the optic nerve and eventual blindness. Image by Ignacio Icke, [CC-BY-SA-3.0]. Figure 2 (left). “Tunnel vision” develops due to peripheral loss of retinal ganglion cells (RGCs) in the eye. Image courtesy of the National Eye Institute, Bethesda, MD.

Carolina Scientific

Figure 3. Molecular clustering techniques were used on the microarray data in order to group the mice into stages based on their gene expression profiles. This resulted in the discovery of two stages that preceded any morphological damage, providing opportunities for the discovery of novel therapeutics. Image courtesy of the Jackson Laboratory, Bar Harbor, ME.

primary source for more than 5,000 inbred strains of mice. Dr. Howell has been working under the auspices of Dr. Simon John, who over the last decade was responsible for identifying and characterizing the DBA/2J mouse as a model for human glaucoma (Figure 3). DBA/2J mice are ideal for modeling the human disease, displaying the same hallmarks such as death of RGCs, excavation of the optic nerve, high IOP, and eventual blindness. The molecular progression of glaucoma and the genetics underlying it are not fully understood. In order to more fully understand the early stages of glaucoma, Dr. Howell studied DBA/2J mice with varying degrees of glaucomatous damage. Some were healthy and had very little optic nerve degeneration, while others had lost nearly 90 percent of their RGCs. Using a tool called

a microarray, Dr. Howell was able to measure expression levels of tens of thousands of genes simultaneously and compare the healthy mice to the diseased ones. Using clustering techniques that group the most similar samples based on gene expression, he identified five distinct molecular stages of glaucoma. Incredibly, there were two distinct stages that preceded any morphological damage [3]. Dr. Howell explains that â&#x20AC;&#x153;what we were able to do in this study was identify genes that were changing in tissue that essentially had no obvious signs of glaucomatous damageâ&#x20AC;? [4]. The significance of these molecular stages is two-fold. By identifying molecular signatures of the early events in glaucoma progression, the team has identified thousands of genes that can be studied further in order to understand their specific

importance and role in the disease. Furthermore, this work may lead to the development of novel therapeutics targeting genes that are involved in the early stages of the disease. Through the use of the DBA/2J mouse as an animal model for human glaucoma, Dr. Howell and his team have paved the way for future research into new neuroprotective strategies that can eventually be used to reduce the effect of this terrible disease on the world. Their work gives new hope to the millions who suffer from glaucoma.

References

1. R. T. Libby, et al. Visual Neurosci. 2005, 22, 637-648. 2. G. R. Howell; S. W. M. John. Neuromethods 2010, 46, 25-49. 3. G. R. Howell, et al. J. Clin. Invest. 2011, 121, 1429-1444. 4. Interview with Gareth Howell, Ph.D. 6/1/11.

Forever Young?

Germ Cell Immortality and Telomere Replication Olivia Wayne, Staff Writer

he quest for immortality is the stuff of legend. Heroes of old traveled to the ends of the earth to find it. Early scientists spent entire lifetimes trying to synthesize elixirs that would grant everlasting life. Today, few individuals know that immortality, in a sense, lives in their very cells. In the case of germ lines, immortality is simply a fact of life. Unlike somatic, or body, cells, which divide by mitosis and are eventually discarded after a single generation, germ cells possess hereditary information that could potentially be passed on an infinite number of times [1]. Thus, their ability to transfer genetic information to successive generations is crucial. This process is not perfect. As females age, the chromosomes in their germ cells are 35 times more likely to suffer non-disjunction during meiosis [1]. The number of mutations in the gametes of older males causes their offspring to be 5-30 times more susceptible to such diseases as acondroplasia, a type of dwarfism, and Apert’s syndrome, a disorder characterized by skeletal deformities in the skull, hands and feet [1,2]. The accumulated damage in germ cells can, in some cases, be attributed to the wearing down of the cap-like ends of chromosomes, called telomeres. One of the main reasons somatic cells do not share germ cells’ “immortal” reputation is because the telomeres of somatic cells shorten with replication, limiting the somatic cells’ lifespan. Without such a mechanism, tumors might develop

far more often [3]. In addition to protecting against cancer, it may also be that natural selection “favor[s] allocating greater energy resources for maintenance and repair of the germ line rather than the soma” because “higher levels of DNA repair in the germ line might result in a lower rate of spontaneous mutation in Dr. Shawn Ahmed germ versus somatic cells” [1]. In normal germ cells, the protein telomerase sustains telomere length over several generations using RNA as a template [1]. However, in mutants defective for telomerase, germ cells grow increasingly sterile over time. This is the case for the mutant organisms currently under investigation here at UNC-Chapel Hill. Working in conjunction with the department of genetics, Dr. Shawn Ahmed of the biology department is investigating the nature of germ line immortality and telomere replication using the nematode Caenorhabditis elegans. After studying telomeres as a graduate student for six years, Dr. Ahmed entered his post-doctoral training with the intention of studying an organism in which he would easily be able to identify mutant genes that would correspond to telomere replication [3]. The genetics of this model organism also had to be capable of manipulation. Once he and his team identified a worm with that particular mutation,

Figure 1. Caenorhabditis elegans are either male or hermaphrodites, having both male and female anatomy. Image by Gyll, [CC-BY-SA-3.0].

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Figure 2. The fecundity of mortal germ line mutants decreases with time. Image courtesy of Dr. Shawn Ahmed.

the genome using a chemical reagent, and we find one that causes the effects that we’re interested in. Then we track down those mutations to identify the genes,” he explains [3]. It has been a time-consuming process with only a few major discoveries in the past couple of years. The more information scientists gather on the mechanisms by which chromosomes erode and pass on hereditary information, the greater the hope they have to one day cure such diseases as cancer, pulmonary fibrosis and aplastic anemia [4]. While it may be some time before these discoveries can be put to practical use, the task does seem less daunting than searching the ends of the earth. The key to unlocking the secret of “immortality” may turn out to be a small round worm.

it was propagated for several generations, with interesting results. “The telomeres were getting shorter and shorter and finally malfunctioning, resulting in chromosome fusion and sterility,” states Dr. Ahmed [3]. The telomerase mutation was identified as recessive. To confirm this, it was necessary to propagate several heterozygous generations of C. elegans. The recessive mutation showed no effect on telomere replication when present in heterozygous individuals because alternate copies of the gene were present. This is not the case for humans for whom one defective copy of a telomerase gene is enough to disrupt telomerase activity [3]. The reason for this is unknown. However, once telomerase mutants were isolated, it is interesting to note that the mutations did not cause immediate sterility in C. elegans. According to Dr. Ahmed, “There is some selection to keep them going. One of the interesting Figure 3. The number of chromosomes decreases (top), suggesting fusion. things about this project is that Shortened telomere length of C. elegans mutants (bottom). Image courtesy of these genes remain dispensable Dr. Shawn Ahmed. for a number of generations” [3]. The exact reason as to why this occurs gradually References 1. C. Smelick, et al. Ageing Res. Rev. 2005, 4, 67-82. has yet to be discovered. 2. A.D.A.M., Inc. Apert Syndrome. 2011, <http://www.ncbi. Dr. Ahmed’s laboratory uses a genetics-based nlm.nih.gov/pubmedhealth/PMH0002548/>. approach to study mutations in C. elegans. “We 3. Interview with Shawn Ahmed, Ph.D. 9/23/11. basically induce spontaneous mutations around 4. Ahmed Laboratory. Telomeres and Telomerase. <http:// www.bio.unc.edu/ahmed/lab/Telomerereplication.html>.

Investigating Two Key Pathways Linking Fat Consumption and Health Risk Hannah Gavin, Staff Writer

eople generally give little thought to their digestive tract until they have the unfortunate luck of eating a bad oyster or catching a stomach bug. However, gastrointestinal (GI) health and disease are everyday topics in UNC-Chapel Hill’s Medical Biomolecular Research Building. On the sixth floor, in the cell and molecular physiology laboratory of Dr. P. Kay Lund, a variety of ongoing projects investigate two cellular signaling pathways and their roles in the regulation of proper digestive function. The insulin and insulinlike growth factor 1 (IGF-1) pathways under study are “linked to health, disease and aging,” playing key roles in obesity, diabetes and cancer development, explains Dr. Lund [1].

diets are typically low in fiber and high in fat as compared to other global diets, and the high-fat content is exaggerated in many states of the American South, including North Carolina. One of the high-fat diet projects is led by postdoctoral fellow Dr. Shengli Ding. Dr. Ding Dr. P. Kay Lund has found that diets high in fat interact with naturally occurring bacteria in the gut to promote inflammation of intestinal tissues. Until recently, inflammation was viewed as a result of obesity, which plays a role in risk of insulin resistance and diabetes. Insulin resistance, a condition preceding the onset of full-blown diabetes, is low-fat diet high-fat diet already indicative of a problem in the insulin signaling pathway. Under insulinresistant conditions, insulin present in the body becomes less effective at regulating blood glucose levels. Dr. Ding’s research suggests that the traditionally accepted cause-and-effect sequence may actually work in the Figure 1. Fluorescent imaging of the intestine of a mouse on high-fat opposite direction. Interaction between diet (left) and low-fat diet (right) showing areas of inflammation in the fats and bacteria “is necessary for obesity high-fat diet mouse. Image courtesy of Dr. Shengli Ding. to occur,” and the inflammation caused The Lund Laboratory operates on the by such interactions “contributes to, and is not combined efforts of full professors, junior faculty, a result of, obesity and insulin resistance,” says research associates, postdoctoral researchers, Dr. Ding [2]. Dr. Ding has demonstrated that graduate and undergraduate students, and even the intestine is one of the first organs to exhibit high school interns. As emphasized by Dr. Lund, inflammation due to fat-bacteria interaction prior the laboratory works on “meaningful projects to to the onset of obesity. Fluorescent images reveal which scientists at all these levels can contribute” areas of inflammation in a mouse fed high-fat diet [1]. The study of GI growth, health and disease and the lack of inflammation in a mouse on lowimpacts everyone because all people need proper fat diet (Figure 1). In the future, health programs digestive function to remain healthy and happy. can use this information to design “interventions A subgroup of Lund Laboratory projects that which limit intestinal inflammation induced by focuses on consequences of high-fat diet holds high-fat diet and bacteria” to “protect against particular relevance for local citizens. Western obesity and insulin resistance” [3].

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Figure 2. Measuring intestinal traits such as circumference, as in the cross section of proximal intestine shown here, may reveal physiological impacts of high-fat diets. Image courtesy of Hannah Gavin.

Figure 3. Fluorescence microscopy can be used to distinguish and identify intestinal epithelial cell populations, as in this photo expressing a Sox9-EGFP transgene to give cells their glowing green properties. Image courtesy of Hannah Gavin.

A graduate student in the UNC-Chapel Hill Gillings School of Global Public Health’s nutrition program, Amanda Mah studies the effects of changes in energy balance on the intestine. By restricting the caloric intake of one group of mice and allowing another group to consume a high-fat diet and become obese, Mah can test the effects of both calorie restriction and excess calorie availability. The two conditions represent the experiences of dieting or situations of overconsumption in humans. Since obesity is a known risk factor in the development of cancers, including colon cancer, the laboratory is especially interested in exploring “the ways the intestine adapts to excess calorie intake and how this might be linked to cancer risk” [4]. Many of the beneficial metabolic consequences of energy restriction result from the lowering of insulin and IGF-1 levels [5]. Conversely, excess signaling in either the insulin or IGF-1 pathways can lead to inappropriate cell growth and survival — characteristics associated with cancer cells. Thus, the insulin and IGF-1 pathways are likely involved in the adaptive changes of the intestine to excess calorie availability. Within Mah’s overall studies of energy balance, effects on the intestinal epithelial stem cells (IESC) are of special interest. Cancer is characterized by the dysregulated growth and/or survival of cells, and it is abnormal IESC that are thought to initiate colon cancer. The constant renewal of the entire intestinal epithelium depends on IESC division, coordinated with cell differentiation and programmed cell death (apoptosis). Aberrant division or reduced apoptosis in a single

abnormal stem cell has the potential to initiate intestinal cancer. As an undergraduate researcher in the Lund Laboratory, Hannah Gavin is examining the impacts of high-fat diet consumption on physiological properties of the gut such as intestinal circumference (Figure 2). Additionally, she investigates the number of IESC present using new reporter mice with green glowing stem cells (Figure 3) [6]. On the molecular level, the amount of IGF1 receptor in the IESC population is being investigated. An increase in either number of IESC or their expression of the receptor for IGF1 could potentially promote tumor development by initiating excess or dysregulated growth of intestinal tissues. The above are just a few of the exciting projects in progress under the supervision of Dr. Lund. The Lund Laboratory, working with collaborators including the Gastrointestinal Stem Cell group, the Gillings School of Global Public Health and UNC Hospitals, increases the scientific community’s knowledge of signaling pathways mediated by insulin and IGF-1. Understanding these key pathways furthers researchers’ effort to diagnose and prevent obesity, diabetes, and cancer — an effort that will potentially impact the lives of millions of people worldwide. References

1. Interview with P. Kay Lund, Ph.D. 10/7/11. 2. Written research statement of Shengli Ding, Ph.D. 10/9/11. 3. S. Ding, et al. PLoS ONE 2010, 5, e12191. 4. Written research statement of Amanda Mah. 10/5/11. 5. E. Giovannucci. J. Nutr. 2001, 131, 3109S-3120S. 6. A. D. Gracz, et al. Am. J. Physiol. Gastrointest. Liver Physiol. 2010, 298, G590-G600.

FRUITS, VEGETABLES AND FOOD DESERTS:

The Case for Going Beyond Availability Hetali Lodaya, Staff Writer

to solve this problem has been to change the landscape — to limit the permits available to fast food restaurants and to increase the number of grocery stores in any particular region [3]. A team of researchers, including Dr. Penny Gordon-Larsen of UNC-Chapel Hill’s Gillings School Dr. Penny GordonLarsen of Global Public Health, set out to analyze changes in environmental factors and associated impacts on health. They looked at the CARDIA (Coronary Artery Risk Development in Young Adults) data set, a longitudinal study following young adults ages 18-30 and tracking the development of cardiovascular health over time, environmental changes and food consumption habits. The researchers were able to monitor fast food consumption, diet quality and adherence to dietary guidelines related to fruit and vegetable intake as a function of fast food chain, grocery or supermarket availability. Their analysis controlled for socioeconomic status and was sex-stratified to examine the differences in food consumption based on access to different types of neighborhood food resources between men and women. The study’s first conclusion is hardly a surprise: The presence of a fast food chain within 1-2.55 km of an individual’s home increases the likelihood of fast food consumption, especially among lowerincome men. Lack of access to public transportation or a car is thought to perhaps contribute to this finding. The study did not monitor what participants ate at fast food chains, only how often they visited such establishments. Figure 1. More than 30 percent of adults in the United States today are obese. Image This finding provides some courtesy of the Centers for Disease Control and Prevention.

merica is getting fat. It’s a sobering but undeniable statistic: Approximately 33 percent of adults and 17 percent of adolescents in the United States are obese, proportions that are rising every day [1]. Experts have been debating the potential causes of this apparent epidemic for years. Changes in American lifestyles including irregular dinner times, more leisure time spent on the couch instead of outside and poor eating habits have all been cited as culprits. Most of us see food choice as simply that, a choice — but what if nutritious, healthy food wasn’t readily available to you? This is the problem of food deserts, defined as “areas that lack access to affordable fruits, vegetables, whole grains, low-fat milk and other foods that make up the full range of a healthy diet” [2]. The term was coined in the early 1990s to describe areas of the United Kingdom that lacked access to social services and fresh foods and has since migrated to other parts of the world to describe many urban environments where nutritious food is simply not available. More often than not, the most readily available substitute for residents of these communities is fast food — cheap but full of extra fats and salts. Thus far, the most widely accepted policy strategy

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Figure 2. Food deserts (left) are environments that cut residents off from healthy, affordable food. First Lady Michelle Obama (right) and Walmart CEO Bill Simon announced an initiative to make healthier, fresher foods available to more consumers. Images courtesy of HowStuffWorks.com and WhiteHouse.gov/Joyce Boghosian.

support for the policy strategy of zoning that restricts good eating habits through a public information construction of fast food restaurants. campaign and the next generation food pyramid, is A surprising result, however, was that no clear link an example of the growing awareness of the need appeared to exist between grocery store availability to make American consumers informed about their and either diet quality as recommended by the food choices [5]. Additionally, alternative policy American Dietary Association (ADA) or consumption options such as cost-shifting toward healthier food of fruit and vegetables. There are several key points items through subsidies could create food options that could account for this, according to Dr. Gordon- more accessible to underserved individuals. Larsen [4]. Supermarkets offer a choice just like any Ideally, according to Dr. Gordon-Larsen, further restaurant — it is possible that participants bought work would study the effects of natural experiments, foods just as unhealthy as or introduction of policies “Food deserts: areas that lack they would at a fast food or local initiatives on eating chain even if a grocery access to affordable fruits, habits. Perhaps the inclusion store was readily available. vegetables, whole grains, low- of particular types of foods Additionally, every grocery and price structures in grocery store is different, possibly fat milk and other foods that stores would encourage better resulting in disparities in food make up the full range of a eating habits. It is evident, quality and availability. however, that education, healthy diet.” The most important policy economic incentives and implication, however, is that this study suggests that outreach are key aspects of this initiative. As policy location is not enough. In order to make adding makers consider the problem of food deserts, they grocery stores a viable strategy for addressing the food would be wise to realize that you can give people a desert problem, education and outreach programs grocery store, but you can’t make them eat their fruits must go hand in hand with access to healthier foods. and vegetables. It is not enough to simply make healthier foods available to residents and take away their fast food References 1. Center for Disease Control and Prevention. U. S. Obesity restaurants — rather, such efforts must be combined Trends. 2011, <http://www.cdc.gov/obesity/data/trends. with education about the healthy food choices they html>. can make, guidance regarding the incorporation of 2. Center for Disease Control and Prevention. Food Deserts. 2010, <http://www.cdc.gov/features/fooddeserts/>. those choices into their lifestyles and attention to 3. J. Boone-Heinonen, et al. Arch. Intern. Med. 2011, 171, budget constraints in order to complete the equation. 1162-1170. First Lady Michelle Obama’s Let’s Move campaign, a 4. Interview with Penny Gordon-Larsen, Ph.D. 9/15/11. 5. Office of the First Lady. First Lady Michelle Obama comprehensive program designed to supplement Launches Let’s Move. 2010, <http://www.whitehouse.gov/ access to healthier foods with information about briefing-room/statements-and-releases>.

The Office for Undergraduate Research

Summer Undergraduate Research Fellowships Interviews conducted by Hema Chagarlamudi While the typical undergraduate would spend their summer taking classes, working, or lounging in the sun, SURF scholars are representing the Tarheels as lead investigators of their own research. Applicants are mentored by a faculty research advisor and the SURF Advising Program to propose the goal, significance and methodology of their work. Selected students are awarded $3,000 to $4,000 to carry out their projects over the course of at least 9 weeks for a minimum of 20 hours each. To learn more about the program, visit the Office of Undergraduate Research website. Applications are due by February 23, 2012. Here’s what three SURF scholars had to say about their experiences.

Melissa Wrzesien

Class of 2013, Environmental Science and Applied Mathematics double major, Geology minor Please briefly describe your SURF project. How did you come up with the research question? My SURF project was titled “The Climate Network: Analyzing the Complex Connections of Earth’s Climate.” I did a network analysis on temperature data from a climate model, which included working with the programming software Matlab. During the first half of the summer, I worked on replicating a 2009 study by Donges et al : “Complex Networks in Climate Dynamics — Comparing Linear and Nonlinear Network Construction Methods.” Once the recreation was complete, my adviser, Dr. Peter Mucha of the mathematics department, and I worked on tweaking some of the techniques to see if we still ended up with the same results. I also spent time creating multiple visual analyses of the data in order to better communicate the outcome of my network analysis to those outside the field. Dr. Mucha and I thought of the idea for the project when he found the Donges et al paper. It was perfect because it combined his field of networks with my interest in climate change. Overall, how was your research experience and what did you gain from the summer? The whole experience was fantastic. The work was difficult at times when I struggled to get my Matlab code correct. At one point, Dr. Mucha and I realized that we had interpreted a part of the Donges paper incorrectly, which required some time to go back and redo many calculations. However, it was definitely a positive experience. I am pleased that I am now much more comfortable with programming, especially since prior to this project I had little experience. It was fulfilling to look back once the summer was over and to see how much I really did accomplish. Overall, though, I would have to say that the best part of the SURF experience was growing a strong relationship with my adviser. I highly recommend everyone to get involved in research because you’ll make connections that will greatly help you in life after undergrad. What are your future career plans? How did your summer project help prepare you for your career? Currently, my career goal is to work for the National Oceanic and Atmospheric Administration (NOAA) and to do research on the interaction between glaciology and hydroclimatology. I hope to go to graduate school at University of Washington to study mountain hydrology. My SURF made me familiar with climate models and their data output, which will be useful when studying climate change. I know that the programming skills I gained over the summer will also be beneficial.

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Jase Gehring

Class of 2012, Biochemistry and Biology double major Please briefly describe your SURF project. How did you come up with the research question? Our group is working to describe the community of microbes that live in close association with the roots of plants. We have defined three regions of biological significance: bulk soil, soil immediately surrounding the root (the rhizosphere), and the root itself. We use 454 pyrosequencing of the 16S ribosomal subunit to estimate the abundance of bacterial phyla in our samples. While sequencing is currently the best method for simultaneous multiplex analysis of an entire bacterial community, its expense, inherent biases, and associated technological difficulties necessitate alternative techniques for quantification of bacteria found in soil and roots. My work this summer was devoted to developing such a technique, and we are currently testing a method combining flow cytometry and fluorescence in situ hybridization (FLOW-FISH) to quantify bacterial phyla of interest. Overall, how was your research experience and what did you gain from the summer? I work in the same lab during the school year but at significantly reduced hours due to time conflicts. During the summer, I had time to think critically about our project while also being more productive in the lab. I also enjoyed designing new techniques for our group, something that is much more difficult during the semester. I was able to really devote myself to our study, and the extra time made a huge difference in my contribution to our experiments. What are your future career plans? How did your summer project help prepare you for your career? Next year, I plan to begin doctoral study in biochemistry. My summer experience gave me a feel for the life of a bench scientist. In preparation for graduate school, there is no replacement for spending time in a research lab. Because of the SURF program, I feel more assured in my career choices, and I canâ&#x20AC;&#x2122;t wait to start my graduate studies!

Dillon Cockrell

Class of 2013, Psychology major, Chemistry minor Please briefly describe your SURF project. How did you come up with the research question? The focus of my SURF project was to use psychophysiological methods to examine the effects of cognitive strategies in the assessment of emotional dysregulation in individuals with autism spectrum disorders. I had been volunteering in Dr. Gabriel Dichterâ&#x20AC;&#x2122;s autism research lab for two semesters before beginning my SURF. This was a project we pursued in hopes of determining whether the emotional struggles of autistic individuals could be improved using a cognitive approach. In order to test our hypothesis, we measured the emotional responses of autistic participants to certain stimuli with and without an auditory command directing them to think positively or negatively. Although analysis is ongoing, preliminary results support the hypothesis that the dysregulated emotional responses may be consciously modulated to be closer to those of control participants. Overall, how was your research experience and what did you gain from the summer? The time I have spent doing research at UNC-Chapel Hill has given me a great opportunity not only to better understand the current topics and scientific methods of todayâ&#x20AC;&#x2122;s academic society but also to have a chance to meet and learn from many great people. From interacting with participants in the lab to getting to know a number of the great professors and graduate students researching here, it has been a very rewarding experience. What are your future career plans? How did your summer project help prepare you for your career? This summer, I plan to begin applying to and preparing for medical school following graduation. Participating in research through the SURF program this past summer has allowed me gain a much higher understanding of the processes and key features of the scientific community, and such knowledge will certainly be valuable for me in the next stage of my life.

“If at first, the idea is not absurd, then there is no hope for it.” – Albert Einstein

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Image by Ildar Sagdejev, [CC-BY-SA-3.0].

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Fall 2011 | Volume 4 | Issue 1

This publication was funded at least in part by Student Fees which were appropriated and dispersed by the Student Government at UNC-Chapel Hill.