Fall 2016 -- Designing the Cure

Carolina Scientific

Carolina

scıentıfic Fall 2016 | Volume 9 | Issue 1

DESIGNING THE CURE one scientist’s endeavor to combat antimicrobial resistance full story on page 34 1

Carolina

scÄąentific 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 UNC-Chapel Hill, and to educate and inform readers while promoting interest in science and research.

Letter from the Editor: Scientific research benefits our society in the most important of ways. It uncovers pasts, improves the present, and promises futures. For eight years, Carolina Scientific has written on research at the forefront of science. This semester, we continue to discuss compelling discoveries made at UNC-Chapel Hill. Read about the earliest forms of terrestrial life (page 6), superheroinspiring materials (page 28), and Peruvians’ complicated relationship with anemia (page 44). We hope you enjoy!

- Ben Penley

on the cover Dr. Kristy Ainslie is a molecular pharmacologist at the UNC Eshelman Scool of Pharmacy.

Her research seeks to suppress immune response specifically. Full story on page 34.

Monoprint by Isys Hennigar.

carolina_scientific@unc.edu carolinascientific.org facebook.com/CarolinaScientific @uncsci

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Executive Board Editor-in-Chief Ben Penley Managing Editor Karthika Kandala Associate & Design Editor Ami Shiddapur Associate Editors Aakash Mehta Akshay Sankar Lynde Wangler Design Editor Nirja Sutaria Copy Editor Patrick Truesdell Treasurer Elizabeth Smith Publicity & Fundraising Chair Allie Piselli Online Content Manager Tirthna Badhiwala Faculty Advisor Gidi Shemer, Ph.D. Contributors Staff Writers Copy Staff Anna Arlan Aditi Adhikari Jesse Barnes Toby Bader Alexandra Corbett Holly Bullis Jason Gershgorn Annie Chen Patrick Gorman Haley Clapper Saster He Alexandra Corbett Esther Lin Kristi Dixon Grant Masini Patrick Gorman Saif Mehyar Madison Hoke Carrington Merritt Hannah Jaggers Emily Pak Alina Joseph Alexander Payne Esther Kwon Gerardo Perez Saif Mehyar Rachel Phillips Carrington Merritt Adesh Ranganna Jack Moody Akshay Sankar Rachel Phillips Wilfred Wong Mackenzie Price Adesh Ranganna Illustrators Kevin Ruoff Andrew Bauer Christine Son Nim Breitenfeld Janet Yan Alexandra Corbett Jeffrey Young Claire Drysdale Isys Hennigar Designers Rachel Howard Alexandra Corbett Maddy Howell Sydney Didonato Esther Lin Stephanie Dong Tatihana Moreno Anna Hattle Kelsey Winchester Esther Kwon Julianne Yuziuk Alex Yankalunas

Carolina Scientific

contents Life Science

4 6 8

28

Planting New Ideas Holly Bullis

Patrick Gorman

Know Your Roots Kristi Dixon

Macrophages

Esther Kwon

Neuroscience and Psychology

10 14 16 18

Treating Epilepsy

Teaching Computers to Reason

32

Living on a Trampoline

Jeffrey Young Jack Moody

34

The Macrophage’s Bouncer

38

A Moment of Trauma

Mackenzie Price

40

Inducing Infant Immunity

Teenagers Might Not Be Listening - But Their Brains Are

42

Testing a Test

Racial Differences in Disordered Eating

44

Anemia: A Blessing and a Curse

46

Local Food for All

Christine Son

Nourishing Your Neurons Haley Clapper

An End to the Ultimate Hangover

Carrington Merritt

22

Rich or Poor

24

Reset Your Alarm with Glasses

Saif Mehyar

Madison Hoke Toby Bader

Janet Yan

Adesh Ranganna

Alexandra Corbett Annie Chen

Special Topics

Rachel Phillips

Physical Science

26

30

Health and Medicine

Hannah Jaggers

20

Supernova Inside a Meteorite, Billions of Years Ago

Two Dimensions: Endless Possibilities Kevin Ruoff

3

48

The Ethics of Genomics

50

No Scientist Left Behind

52

Meet the Maddoxes

Aditi Adhikari Alina Joseph

Clara Williams and Allie Brindle

life science

PLANTING NEW IDEAS

RIGOROUS PROCESS OF DISCOVERING NEW PL ANT BY: HOLLY BULLIS

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classified over 50 species using this system.1 It was not until the idea of evolution became widely accepted that the plant classification system began to seek out and showcase genetic relationships between plants, thus producing the widely-known phylogenetic tree. Recent advancements in technology have allowed for the classification of species based on genetic Dr. Alan Weakley markers, with some hypotheses relying solely on genetic markers to make their case.2 The process of discovering and documenting new plants has been standardized since Linnaeus’ time.

The International Code of Botanical Nomenclature dictates that the plant must be given a Latin name; the plant description must be written in either Latin or English; the name and paper Derick Poindexter describing the plant must be submitted to a peer reviewed botanical journal, and the hypothesis must be accepted by the scientific community.3 Dr. Alan Weakley, Derick Poindexter, and Cassie Carlyson are setting out not only to discover a new species, but also to influence the scientific process by which new species are documented.

The whole venture started when a colleague of Dr. Weakley’s found something odd about a population of eryngium plants. Eryngium, eryngo for short, is commonly called ‘sea holly.’ Native to Central and Southeastern Europe, it is a coarse, clump-forming plant, with thistle-like blue flowers that sprout from a dense mound of green leaves.4 It is just as tough-looking as the dry sandy soil that supports its growth (Figure 1,2). Dr. Weakley’s colleague observed that this population of eryngo flowered at a different time and looked a little different than other populations. Soon after these anomalies were noticed, specimens of the plant were sent to Dr. Weakley so he could see for himself. Dr. Weakley was then able to press some eryngo plants onto paper to preserve them while grow-

he difference between an oak tree and a pine tree is pretty apparent – one has leaves and the other needles.

The difference between a red oak and a white oak requires some closer inspection. These minute differences prove to be very important when discovering a new species.

Dr. Alan Weakley, an adjunct professor at UNC-Chapel Hill and director of the UNC Herbarium, is surrounded by plants. His office, on the fourth floor of Coker Hall, is situated among numerous metal cases of plants belonging to the Herbarium. The office itself boasts books, desks, and even more plants. Stacks of paper and cardboard are fixed together with ropes that press plant clippings to paper. Fresh clippings sit in mugs by the window. One might call Dr. Weakley a plant enthusiast. His latest project: discovering and naming his twelfth new species.

The process of species discovery, classification, and naming is not as fixed as one might assume. Like the plants they describe, the process of plant discovery has also evolved.

Carl Linnaeus, who established the framework for the current naming system, classified and named his own plants. However, his criteria were purely based on physical structures. Linnaeus developed a sexual system whereby he classified plants based on their reproductive parts, number of petals, stamens that release pollen, and pistons that receive it. He named and

Figure 1. Sea Holly (Eryngium maritimum). Photo courtesy of: Colin-47, CCBY-nd-nc-3.0.

Figure 2. Eryngium Planum Photo courtesy of FCIT.

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life science

THE PROCESS OF SPECIES DISCOVERY, CLASSIFICATION AND NAMING IS NOT AS FIXED AS ONE MIGHT ASSUME

lished in a peer-reviewed journal as they wait for the community to accept their idea. “It’s a process that plays out over time,” said Weakley.2 The idea could be accepted or refuted. In fact, it could be refuted immediately or ten years from now.

Additionally, their hypothesis could be rearranged to include other variations of eryngo.

“You don’t plug the data into a machine and then, ‘ding,’ it decides you have a new species,” Derik said.5 The process is a little more subjective than that. Their goal is to create a reputable body of support for their argument. Although the naming and describing of the plant is regulated by the ICBN, the type of data needed to back up a species hypothesis is not strictly dictated. Weakley and his team could publish a paper featuring any one of the three methods they used. The hypothesis might be refuted quickly if they only mention slight differences, such as flowering time and leaf length. Thus, increasing supportive data to their paper bolsters their argument. “Why go through all this work?” Weakley said. The goal is to create and uphold a high standard of what a species proposal should look like. They want to lead by example, putting in place the ideals of the Carolina way.

illustration by Stephanie Dong ing his own plant specimen to observe the plant flowering.

After almost a year of observation, Dr. Weakley suspected a new species. Then the real work began.

The team created a three-pronged attack strategy, which began by comparing the pressed specimens of both the established eryngo species and the suspected new species. They measured morphological characteristics, such as leaf length, stem length, and petal color of many individual plants to see if a statistical difference was evident. Next, they examined DNA samples, looking for distinct DNA sequences at certain points. Examining the entire genome of the plant would not be an effective use of time, so they picked specific coding regions to see if the suspected new species differed from other eryngo species. They further observed differences between the live plants, such as flowering, pollination, and germination timing.

Over the course of the year, the team amassed data on the new species and its close relatives to ensure that it is a distinct species. Once they feel satisfied with their findings, they will rerun all of the data to ensure accuracy and then commence the second phase of their species discovery process—writing the paper.

Proposing a new species requires researchers to follow the scientific method; Weakley and his team have hypothesized that this peculiar eryngo is a new species, and they have conducted experiments to prove this. Soon they will write a paper proposing to the scientific community that the eryngo in question is a new species. The paper will be pub-

References

1.Carl Von Linné; Species Plantarum, Dehra Dun : Bishen Singh Mahendra Pal Singh, v 2 2001.

2.Division 2. In International Code of Botanical Nomenclature, International Association for Plant Taxonomy: Austria, 2006.

3.Missouri Botanical Garden Plant Finder. http://www.missouribotanicalgarden.org/PlantFinder/PlantFinderDetails. aspx?kempercode=h810 (accessed September 30th, 2016).

4.Interview with Alan Weakley, Ph.D. 09/28/16.

5.Lars W. Chatrou, Michael D. Pirie, Bot J Linn Soc. 2012, 169.

6.Linnaeus Sexual System, http://www.ucmp.berkeley.edu/ history/linnaeus.html (Accessed October 10th, 2016).

7.Alan S. Weakley, http://bio.unc.edu/people/faculty/ weakley/.

8.Derik Poindexter, http://www.herbarium.unc. edu/2013internMohr.htm.

9.Eryngium Planum, http://etc.usf.edu/clipart/81900/81962/81962_eryngium_pla.htm (Accessed September 28th, 2016).

10.Sea Holly Photo, http://garden.org/plants/photo/303300/ (Accessed September 28th, 2016).

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Figure 1. Devonian age carbon compression. Photo by James St. John - Chaleuria cirrosa fossil land plant (Lower Devonian; New Brunswick, southeastern Canada) 1, CC BY 2.0.

life science

KNOW YOUR ROOTS

How the Devonian Age Shaped the Present

By Kristi Dixon

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00 million years ago, a centipede-like arthropod scurries along the damp ground surrounding a hot spring in search of decaying matter to feast on. It scampers through the pathways provided by the diverse cover of flora surrounding the area. Suddenly a geyser erupts nearby and the living ecosystem is slowly covered in dissolved silica, trapping plants and animals alike to be mineralized and preserved.

Near the village of Rhynie in Aberdeenshire, Scotland is a sedimentary deposit, known as the Rhynie Chert. Here one can find an almost complete ecosystem of fossils, due to the eruption of geysers millions of years ago. This is the golden standard of finding fossils. The fossils recovered there are some of the first land plants and earliest insect fossils known, and are preserved in such great detail that the internal structures of the organisms can be identified.1 Dr. Patricia Gensel, University of North Carolina at Chapel Hill professor and paleobotanist, shared a story from a colleague in Germany about a vertical section of fossils they had obtained. The vertical section of fossils showed chert (the sedimentary silica deposit) alternating with sandstone. This indicated successive eruptions of the geysers over time. “Until they had done this [and] they could see everything in place, they realized that they had been viewing certain specimens upside down for some time!”

She laughed over her decaf coffee. “And you just don’t know that until you’ve done enough work to figure it out.”2 There are hundreds of other fossil sites located all around the world that are preserved from this same time period as carbon compressions, petrified wood, casts, and molds (Figure 1). Researchers who are adept in identification of these organisms allow us to track their evolution throughout history.

This is important knowledge in many fields of science. For example, Dr. Patricia Gensel if a researcher were to find a plant

Figure 2. Vascular wood tissue in a 407 million year old fossil. Photo courtesy of Dr. Patricia Gensel. containing a chemical compound successful in fighting cancer, knowing the evolutionary pathway that plant took could point to other closely related plants that also have similar, useful compounds. A wide variety of characteristics developed during this time period, including more advanced root systems, vascular tissues, and relationships with the surrounding environment.

Dr. Gensel specializes in plant fossils from the Devonian age, a time period which spans from 400 to 300 million years ago. Her most prominent research came from northern Maine, the Gaspé Formation in Quebec, and the Campbellton Formation in New Brunswick, Canada. She goes to these areas asking, “What’s here? What is it telling us?”2 Dr. Gensel is skilled in the identification of these organisms and her research is often used as a reference for other researchers at these sites.

Most of the fossils discovered from this time period were found in waterways, leading paleobotanists like Dr. Gensel to infer that there was not much vegetation in mountainous regions. These early plants did not have the characteristics that would allow them to grow further inland.2 Dr. Gensel has collaborated with other researchers in learning about the evolu-

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tion of rhizomatous (root) growth forms. Roots serve several functions in plants, such as uptake of nutrients and anchoring into the soil for plants that are in danger of flooding or heavy winds. It is hypothesized that rhizomatous development at this time was also encouraged by the necessity of mechanisms against desiccation, such as root systems that could reach deeper water sources.3 Deposits of fossils, like the Rhynie Chert or Campbellton Formation, also show the differences in plant species. It was discovered that some plants were specific to certain soil and temperature conditions. They were also varying sizes, from 6 centimeters to 6 feet tall. The development of these larger plants didn’t come until later in the Devonian age due Figure 4. Quarry outline of preserved tree trunks. Image courtesy of Dr. Patricia Gensel. to the lack of structural support.2 “One of the biggest discoveries for me in recent years oped present day Earth is in the relationships established beis finding the presence of wood in a tiny plant (Figure 2).” tween the flora and fauna. Most fossilized animals found from Dr. Gensel shared. “We always thought that the acquisition the time period appear to be detritivores, feeding on decaying of wood was something that let plants get bigger, but if we organic matter. There is no direct evidence of herbivory found see it in a tiny plant, then there must be another reason.”2 ‘An in places like the Rhynie Chert, but Dr. Gensel has worked with Unexpected Debut for Wood’ in American Scientist explains fossils from Canada that expressed damage that ‘could potenthat Dr. Gensel found vascular wood tissue in a small plant as tially be produced by animals.’1,3 old as 407 million years, 10 million years Symbiotic relationships formed earlier than the previously thought ap“We always thought that between fungi and plants in this time pepearance of wood. If the wood wasn’t which is a major success story conthe acquisition of wood riod, developed in plants for increased strucsidering that over 95% of today’s plants was something that let ture support, the next best explanation still have symbiotic relationships with by paleobotanists is that the vascular plants get bigger, but if we fungi. For example, mycorrhizae are a tissue is involved in assisting the moveof fungi that attaches to plant roots see it in a tiny plant, then type ment of water from the roots throughand increases water uptake for the plant there must be another out the plant (Figure 3).5 Wood was host, which then provides the fungi with certainly a successful evolutionary trait food. reason.”2 within the plants because by middle to Earth’s surface, atmosphere, and late Devonian age (350 – 300 mya) evidence of massive forests inhabitants were all evolved from the initial developmental can be found in quarries and coal mines, where you can see steps that began in the early Devonian age. Dr. Gensel hopes preserved tree trunks showing accurate spacing, outlines, and to continue her research in Belgium next fall to compare 14 diversity of trees (Figure 4).3 species of fossilized plants that are believed to belong to the The development of large forests was not only a signifi- Psilophyton genus of extinct vascular plants.2 This research cant development in the evolution of plants, but it was also will help classify and create the evolutionary pathways dean important contribu- rived by these ancient plants. While it’s not exactly necessary tor to the creation of a for one to know about the first appearance of seed plants in habitable environment the late Devonian age to take an Advil, researchers can draw on Earth. There were parallels between different plants based on their taxonomic massive amounts of car- groupings and use that information to make better medicines bon dioxide in the atmo- and tools for life. Dare I say, it’s good to know your roots. sphere before the Devonian age plants really References took off in biodiversity. 1. University of Aberdeen. The Biota of Early Terrestrial Their success changed Ecosystems: The Rhynie Chert. http://www.abdn.ac.uk/ the concentrations of rhynie/intro.htm (accessed 21 September 2016). gases in the atmosphere, 2. Interview with Dr. Patricia Gensel, Ph.D. 09/21/16. giving oxygen a more 3. Kennedy, Kristen L. Gensel, Patricia G. Gibling, Martin prominent role. This had R. Palaios. 2012, 27(6), 424-438. a large impact on the cli- 4. Gensel, Patricia, Ph.D. “Fossil Forests.” PowerPoint mate and wildlife evolv- presentation. University of North Carolina at Chapel Hill.

Chapel Hill, NC. 2016.

2 Figure 3. Recreation of Devonian ing simultaneously.

Other ways in 5. Clabby, Catherine: An Unexpected Debut for Wood. forests from present day New American Scientist 99.6 (2011): 464. Web. 21 September York. Photo courtesy of Dr. Patri- which the evolution of 2016.

Devonian plants develcia Gensel.

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life science

Figure 1. Danio rerio embryonic development.

Photo by Ed Hendel.

MACROPHAGES A Possible Answer to Immune System Illness

BY ESTHER KWON

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henever students are snotty and sick with the flu, or bleeding with an open wound, they need forms of defense that can prevent them from a worst-case scenario. That defense is the human body’s immune system, which fights pesky pathogens to maintain health. Immune cells are present throughout the body, so when a pathogen manages to make its way into the body and gets recognized by the immune system, the immune cells act quickly to isolate the attacker and coordinate to fight it off.

The first line of defense against invaders is macrophages; large immune cells that clear away toxic chemicals in our bodies.1 Billions of macrophages patrol our bloodstream and our tissues for foreign substances. To isolate pathogens and remove dying cells, they engulf and digest these substances. Macrophages are also very versatile and can adapt in response to their environment.

For example, macrophages that travel to the brain during early development adapt to become microglia, the brain’s immune cells that protect the central nervous system.2,3 However, despite their well-known importance to our immunity, many aspects of macrophage

operation are still not well understood.

Assistant Professor Celia Shiau, one of the newest faculty to join the Biology department at UNC Chapel-Hill, attempts to address these unanswered questions of macrophage development and operation in the body. Currently, her lab focuses on two main areas of macrophages: 1) how they become resident cells of almost all of organs—including the brain, skin, liver and gut, and 2) how they are regulated and what triggers the inflammatory state.1 Ultimately, Dr. Shiau hopes her findings will contribute to the creation of new technologies to treat people who struggle with immune system diseases. Dr. Shiau explains that “the important connection [between my research and its implications]…is to see that our efforts lead to a deeper understanding of autoimmune and autoinflammatory diseases…and therefore be able to better diagnose, treat, and perhaps cure them. These diseases arise because the immune system activates itself in an unwarranted manner”.1 Dr. Shiau uses an in vivo, or live organism, approach to observe the interactions between the macrophages and the body using a small tropical freshwater fish called the zebrafish.1 Ze-

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Dr. Celia Shiau brafish are an effective model because more than 70% of human genes are represented in the zebrafish genome, and their structure and function are similar to that of humans.4 She informs, “[the zebrafish model] allows us to…study gene mutations as well as introduce transgenes [genes from another organism] that allow us to label a specific cell type or a specific protein, often in real time and space, in order to image these process in vivo and in great detail”.1 The zebrafish embryo is also an ideal model because of its transparency and rapid development—she can observe changes occurring within the embryo as the embryo itself grows. Her lab modifies genes in zebrafish to understand how certain genetic factors normally prevent

Carolina Scientific unwarranted inflammation, and uses various fluorescent tags to label macrophages and their processes. With these tags, Dr. Shiau can observe how deleting specific gene factors affect macrophage development and function, and its migration in the body.1 In her postdoctoral research, Dr. Shiau discovered a harmful mutation in the nlrc3-like receptor. A deleterious mutation in the nlrc3-like receptor inappropriately prompts macrophage activation during normal development and subsequent inflammation throughout the body,1,3 leading to the loss of microglia, the brain’s immune cells.3 Dr. Shiau’s research focus is to figure out how this receptor prevents inappropriate activation and consequent cell death, which may be important to human inflammatory diseases.1,3 In her recently established laboratory, Dr. Shiau and her group are creating new ways to investigate immune system receptors and genetic factors that protect macrophages from being abnormally activated and dying prematurely.1 She uses live imaging and cellular and genome-wide procedures to look at genes that are expressed between the normal and the mutant macropages.1,6 From these results, she can test to see which genes interact with the NLRs that normally keep macrophages inactive.1 She then uses a genome editing procedure to study these genes’ functions and their interactions with the NLRs.1,7 What Dr. Shiau enjoys the most about her life in the sciences is that her research is always expanding in new directions. “[The research] is always changing and growing, no days are ever the same. There is so much freedom and room for creativity to continuously create new methods and techniques and to ask new questions. [The lab and I] feel that we are always pivoting based on emerging new data, and we feel the excitement every new piece of knowledge brings.”1 Dr. Shiau is currently continuing her studies to understand the factors that control macrophage activation and is also investigating the connections between macrophage function and the nervous system in both the brain and the gut.1

life science

References

1.Interview with Celia Shiau, Ph.D. 09/21/16.

2.Mosser, D.M; Edwards, J.P. Nat Rev Immunol. 2008, 12, 958-969.

3.Shiau, C.E; Monk, K.R, Joo, W.; Talbot, W.S. Cell Rep. 2013, 5, 1342-1352.

4.Howe, K.; Clark, M.D.; Torroja, C.F.; Torrance, J.; Berthelot, C.; Muffato, M.; Collins, J.E.; Humphray, S.; McLaren, K.; Matthews, L.; et al. Nature. 2013, 496, 498-503.

5.Franchi L.; MMcDonald, C.; Kanneganti, T.; Amer, A.; Nunez, G. J Immunol, 2006, 177, 3507-3513.

6.Transcriptome. https://www.genome.gov/13014330/transcriptome-fact-sheet/ (accessed September 30th, 2016).

7.Sander, J.D; Joung, J.K; Nat Biotechnol. 2014, 32, 347-355.

Figure 2. Colorized scanning electron micrograph of a macrophage. Photo by NIAID.

Figure 3. The effect of an inactive NLRC3-like receptor, a type of NOD-like receptor, on microglial presence. Image courtesy of Dr. Celia Shiau.

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Illustration by Alexandra Corbett

neuroscience

TREATING EPILEPSY

Discovering the Mechanisms of Periodic Brain Stimulation

By Christine Son

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veryone has a different day. While one person may be fully reenergized from a nice, relaxing vacation, another person may be having an awful experience from a long, stressful day of work. Depending on how your day is going and how you feel, your brain may respond differently to what it is being asked for. The brain response’s dependency on its state has been overlooked in the past with plain emphasis on the means of brain stimulation.

Dr. Flavio Frohlich, assistant professor in the Department of Psychiatry, Cell Biology and Physiology, and Biomedical Engineering, is interested in studying brain network dynamics and aims to develop treatments for neurological and psychological illness using a non-invasive brain stimulation.

“Who we are, how we behave and how we perceive the world and interact in the world—at the end of the day, this is all result of the electric activity of the brain,” Dr. Frohlich said.

While other disciplines of science may be interested in underlying molecular and biological processes of

the brain functions, the Frohlich lab specifically engages in targeting abnormal electric activities of the brain using various techniques including high density scalp encephalography (hdEEG) and intracranial electroencephalography (iEEG). Both hdEEG and iEEG are electrophysiological methods of monitoring brain activity; hdEEG measures activity from the electrodes placed outside the skull whereas iEEG measures activity from the electrodes placed directly on the exposed brain surface.

The electric activity of the brain has a rhythmic structure, often referred to as cortical oscillations. These cortical oscillations are interacting with each other in the most efficient way—a structured and synchronized pattern of activity.2 “The temporal structure and synchronization is the fundamental language of the neurons and what our brain does all the time,” Dr. Frohlich said.

Not only do the neurons of the brain have synchronous electrical activity but also a specific temporal sequence, bursting at different times. The

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Dr. Flavio Frolich

Dr. Sankar Alagapan

alteration and disruption of these brain rhythms are associated with numerous neuropsychiatric disorders including schizophrenia, autism, depression, and epilepsy.1 While ideally brain stimulation can be used to target and restore these impaired brain rhythms using a weak electric current, a primary problem in humans is accessibility.2 “In collaboration with Dr. Hae Won Shin, we leveraged this unique access to the human brain,” Dr. Frohlich said. “The fundamental question was then can we really alter brain rhythm with such periodic stimulation, and the brief answer was yes.”

Carolina Scientific This “unique access” refers to difficulty of approaching human brain in research field, which was possible in this study through collaboration between basic science and clinical investigation with the UNC School of Medicine’s new annual award cycle. With the Translational Team Science (TTS) Award, the School of Medicine brings two related yet distinct disciplines—research and clinical practice—together in support of fluid translation across two fields. Dr. Frohlich and Dr. Shin were amongst the

ing of the relationship between brain stimulation and cortical oscillations was investigated and analyzed by Dr. Sankar Alagapan, a postdoctoral researcher at Frohlich lab and the first author of the paper.

“Typically to understand the functional and behavioral role of the given activity pattern, what historically have been done is correlation,” Dr. Frohlich said. “However, this correlation does not show causality.”

A common methodology used

neuroscience closed state, stimulation induced stronger response or amplification of endogenous oscillations (brain activity on its own) in the eye-open state.1 In a taskengaged state, stimulation resulted in entrainment.1 Entrainment refers to the alignment brain activity, following the rhythm provided externally by stimulation.2 Such modulation of naturally-occurring brain oscillations by 10 Hz stimulation according to its different states was demonstrated in three epileptic patients. Despite some deviation from the

"In order to develop an effective non-invasive paradigm, we need to measure the state of the brain and electric activity patterns before and during stimulation"

- Dr. Flavio Frohlich first round of recipients of this award in 2014, producing an interdisciplinary relationship between Psychiatry and Neurology.

Dr. Shin, a medical doctor in the Department of Neurology at UNC Hospitals specialized in epilepsy, has led the temporary implantation of subdural (below dura, the outermost membrane of brain) electrodes for patients with pharmacoresistant epilepsy. Pharmacoresistant epilepsy refers to a chronic condition in which seizures are nonresponsive to antiepileptic drugs (AEDs).

Patients who are diagnosed as pharmacoresistant are then often treated with surgical therapies. A direct cortical stimulation of 50 Hz is clinically used during invasive surgical procedures. In this case, stimulation frequency was adapted to 10 Hz to understand the mechanism by which periodic brain stimulation alters endogenous (naturally-occurring) brain oscillations.1 The patients underwent temporary implantation of subdural (on the surface of the brain cortex) electrodes in the Epilepsy Monitoring Unit at the UNC Neurosciences Hospital. Once the necessary clinical data was collected during the course of a week, electric stimulation was applied and, the electrocorticography (ECoG) data was collected. Using ECoG data and a computational model of population-scale neural oscillator network, a mechanistic understand-

in the past was to record brain activity while participants performed a particular task. This method showed how certain behavioral features were correlated with brain activity patterns, but did not show if those brain activity patterns were necessary for the behavioral features. In addition, the assumption has always been that the change in activity pattern is dependent only on how one applies the stimulation. However, how one applies the stimulation was not the only thing that brought about the change in the brain activity. A revolutionary finding of the study was that the effect of stimulation depended on the state of the brain.

In the study, three different stimulated states were considered: eye-closed state, eye-open state, and task-engaged state.1 These three states were specifically chosen in order to learn about a particular type of brain wave called alpha oscillations. Alpha oscillations are known to be impaired in depression, and the three conditions chosen differ in this pattern specifically.2 The eye-closed state had oscillations of large amplitude, the eye-open state had oscillations of intermediate amplitude, and the taskengaged state of low to no amplitude.1 The state-dependence of cortical oscillations is evident from different changes in power observed when induced with the same stimulation. While little changes were detected in the eye-

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prediction of the network model in one of the patients, a general agreement was found in overall enhancement in power of endogenous oscillations.1 “I think what this paper teaches us is that in order to develop an effective non-invasive paradigm, we need to measure the state of the brain and elec-

Figure 1. In the eye-closed state, the phases of change by stimulation are minimal, while in the task-engaged state, stimulation produced change at all phases, crossing the threshold level.

Figure provided by PLoS Biology.

neuroscience

Figure 2. Membrane potential of the excitatory neurons demonstrates task-dependency in the stimulation effect. Image provided by PLoS Biology.

"I think what this paper teaches us is that in order to develop an effective non-invasive paradigm we need to measure the state of the brain, electric activity patterns, before and during stimulation," Dr. Frohlich said.

The role of alpha oscillations in cognition and behavior is implicated in fundamental mechanisms by which brain signals are routed.2 In essence, alpha oscillations reflect how the brain selectively turns on or off different regions in order to accomplish a certain task more efficiently.2 For instance, in order to pay attention to one thing on a piece of paper, brain would turn off every oth-

er stimuli that is unnecessary to encode the interested information.

The new mechanism of modulating cortical oscillations by periodic brain stimulation has an important clinical implication for targeting alpha oscillations.

With this new knowledge in mind, brain stimulation studies must now consider the state of the patient before interpreting the response to the stimulator. For instance, stimulating the brain during the eye-open state is recommended if one wants to enhance endogenous alpha oscillations for clinical purposes.1

"By bringing together computational modeling and innovative ex-

perimental paradigms like this, we can understand the mechanisms underlying these oscillations and thereby develop better stimulation strategies", Dr. Alagapan said.

References

1. Alagapan, S.; Schmidt, S.L.; Lefebvre, J.; Hader, E.; Shin, H.W.; Frohlich, F. PLoS Biol. 2016, 14(3): e1002424. doi:10.1371/journal. pbio.1002424.

2. Interview with Flavio Frohlich, Ph.D. 09/21/2016.

Figure 3. A surface model of a brain with locations of electrodes over the parietal regions of three epilepsy patients, P001, P005, and P008. Image provided by PLoS Biology.

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neuroscience

Nourishing Your Neurons

By Haley Clapper Illustration by Rachel Howard

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magine running through a field of soft grass, the blades gliding glides away from you with each stride.

Now imagine running through a forest with tangled branches springing out toward you as you weave around each tree. This illustrates the difference between your brain with and without docosahexaenoic acid (DHA), an omega-3 fatty acid that is essential to brain development and Dr. Carol L. Cheatham function.1 Every human cell, including the neuron, is comprised of subcellular structures called organelles that perform different functions to keep the body in equilibrium. A double-layered membrane made of phospholipids and proteins, known as the phospholipid bilayer, holds the organelles within the cell (Figure 1). The phospholipids have polar heads made of phosphate groups that can function in water, whereas the tails, made of nonpolar lipids, cannot function in water.2 Dispersed randomly within the outermost layer of the cell membrane are various proteins, including receptor proteins that allow materials to enter and exit the cell.

However, the cell membrane requires lipids other than phospholipids to accommodate receptor proteins.1 Dr. Carol Cheatham, a researcher at the UNC Nutrition Research Institute (NRI) and Associate Professor of Psychology at the University of North Carolina at Chapel Hill, researches the effects of fatty acids such as DHA on communication between neurons, especially in infants and children (Figure 2).

Dr. Cheatham also explores how different nutrients work together to help the brain function optimally, and how to educate individuals in underdeveloped regions about proper nutrition.

Without additional fatty acids, the stiff phospholipids of the cell membrane cannot move as fluidly and allow receptor proteins to embed in the membrane.1 “It is like the difference between running through a forest and a grass field. The grass moves out of the way—that is the DHA,” Dr. Cheatham explains. “If you do not have enough DHA, other fatty acids will fill in for it, but their tails are stiffer and they do not move out of the way. It is like you are running through a bunch of trees.”1 In the brain, fatty acids are required to release synaptic vesicles, small membranous sacs filled with neurotransmitters that allow communication between neurons. The transfer of information is a critical function of the brain that allows humans to think, act, respond, and function in general.

In recent years, Dr. Cheatham has researched how different nutrients work together for optimal brain function, a concept she calls the “synergy of nutrients.” To explain, she describes an orange: “It is not just a blob of vitamin C. It has fiber, moisture, and other vitamins and minerals that are probably working together—they are there together for a reason.”1 At the NRI, Dr. Cheatham and her team study choline, a vitamin found in eggs and meat. Choline works in the liver, where DHA is stored. When the brain needs DHA for neuron activity, choline packages and sends DHA to the brain. In the Cheatham Lab, infant brain activity is measured with an electroencephalograph (EEG). This technique measures brain activity as the infants respond to stimuli.1 In EEG testing, metal electrodes are attached to the scalp, measuring small electrical pulses created by neuron activity (Figure 3). Dr. Cheatham found that when infants who drink breastmilk were tested with only the presence of high DHA or only the presence of high choline, the difference in brain wave activity when viewing novel vs. familiar pictures was minimal. However, when the infants were exposed to both high DHA and high choline at the same time, their brain wave activity indicated that they readily dif-

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Carolina Scientific ferentiated between unfamiliar and familiar pictures, indicating that the two nutrients work most effectively in synergy to improve brain function.1 Another part of Dr. Cheatham’s research explores how genes affect a person’s responses to DHA. If the body lacks exogenous, or externally-sourced, DHA from food, most people have the ability to convert an omega-3 fatty acid from plants, known as alpha-linolenic acid (LNA), to animal DHA for cell function.4 In fact, about 93% of the U.S. population has the gene mutation that allows the conversion from LNA to DHA.1 In some populations, however, people may carry a gene that prevents them from creating their own DHA. For example, on the eastern coast of China, where the average diet consists largely of fish, about 60% of the population cannot make its own DHA because it has relied on animal DHA consumption for several generations.1 “When those people move away from the coast and stop having a predominantly fish diet, they are in trouble because they cannot make their own DHA,” says Dr. Cheatham.1 Similarly, Inuit populations of Canada, Russia, Alaska, and Greenland obtain DHA from a high-fat diet of meat, blubber, and fish.1 However, climate change has threatened Inuit culture in the Arctic regions, making hunting more difficult.5 As a result, some Inuit have transitioned to a high-carb Western diet.1 Unfortunately, 100% of Inuit populations carry the gene mutation that prevents self-production of DHA, and they too may not make up the difference with DHA from food.1 Although the neurological implications of low DHA levels in some individuals must be further researched, Dr. Cheatham predicts that those who cannot convert LNA to DHA may experience slowed processing and impaired memory due to inefficient communication between neurons.1 While conducting research is important to Dr. Cheatham, she believes that the social impact of her research defines her purpose. As a graduate student, Dr. Cheatham once discussed her doctoral dissertation with her aunt over lunch and began to wonder, “so, what?” At the time, she was unsure of how her passionate work in cognition would be of any consequence. In response to her own uncertainty, she added nutrition to her research in the hope that the study of nutrition’s neurological effects could make a significant impact on society. Today, her purpose is clear: “My main goal is to help kids.

That is all I want to do. I want to make sure that every kid has

Figure 2: A young girl plays a gong for Dr. Cheatham. Courtesy of Chad W. Mitchell.

Figure 3: An infant’s brain activity is measured in eventrelated potentials using electroecephalography. Courtesy of Jon Lakey, Salisbury Post. a fighting chance of being successful, and that is only going to come through making sure that their brains are working optimally.”1 Every year, Dr. Cheatham works with health care professionals from Africa, Southeast Asia, and the Middle East to educate locals about the importance of maternal and infant nutrition so that children receive the proper nutrients for prime brain development. In the future, Dr. Cheatham plans to explore the relationship between gut microbes and the brain, and to continue helping mothers and children worldwide.1

References

Figure 1. A phospholipid bilayer, with phospholipids in yellow

and proteins in purple. Image courtesy of Suncana.

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1. Interview with Carol L. Cheatham, Ph.D. 09/26/2016.

2. University of Washington. Phospholipid Bilayers. https://courses.washington.edu/conj/membrane/bilayer. htm (accessed September 29, 2016).

3. Oregon State University. 2016. Essential Fatty Acids. http://lpi.oregonstate.edu/mic/other-nutrients/essentialfatty-acids (accessed September 29, 2016).

4. Welch, A.A.; Shakya-Shrestha, S.; Lentjes, M.A.H.; Wareham, N.J.; Khaw, K.; American Journal of Clinical Nutrition 2010, 92, 1040-51.

5.Nunavut Climate Change Center. Climate Change Impact. http://climatechangenunavut.ca/en/understanding-climate-change/climate-change-impact (accessed September 29, 2016).

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neuroscience

An End to the Ultimate Hangover

By Mackenzie Price

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lcohol is often perceived to be the perfect addition to any night out, but what starts as innocent and occasional use may lead to deadly consequences. Peyton Bohnsack, a graduate research assistant for the Bowles Center for Alcohol Studies at UNC-Chapel Hill recounts, “[Alcohol dependency] is a leading cause of preventable Peyton Bohnsack deaths in the United States. Yet there are only three medications sanctioned by the US Department of Food and Drug Association (FDA) to treat [alcohol use disorders]”.1 This is what drives Bohnsack in his studies of alcohol dependency. His current research delves into the neurological effects of excessive alcohol intake and what causes dependency-driven behavior. He plans to discover new and efficient medications for treating the side effects of the legal drug that ails Americans.

In the United States 10-15

Illustration by Rachel Howard

percent of the population suffers from alcohol use disorders.2 Of those who seek treatment, 40-60 percent relapse.1 This leads to approximately 235 billion dollars in economic losses each year.1 Bohnsack believes that more effective drug therapies could improve these statistics. For his study, Bohnsack defines alcohol dependency as “a force that is out of your control and [causes] you personal and/or psychological harm […] having the symptoms of withdrawal that come with chronic exposure”.1 Although the amount of alcohol required to reach dependency varies from person to person, the results of withdrawal are the same. In mild cases, symptoms include upset stomach, tremors, and restlessness. Severe symptoms include insomnia, anxiety, and seizures.1 Instead of curing the cause of withdrawal symptoms, current medications focus on managing cravings until the body no longer relies on alcohol to function.

Many of the physiological symptoms associated with alcoholic disorders are secondary reactions to a greater, underlying problem in the brain. According to Bohnsack, the symptoms originate from the decrease in a certain gamma-aminobutyric acid receptor (GABAA-R) located in

Many of the physiological symptoms associated with alcoholic disorders are secondary reactions to a greater underlying problem in the brain.

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Figure 1. With acute use, alcohol adversely floods the GABAA receptor. After chronic use, the receptor responds by narrowing the amount allowed, rendering it useless to future responses. Figure courtesy of Payton Bohnsack. the brain.1 GABA supplies a calming effect in situations where anxiety and neuronal over-excitability occur. A decrease in the number of receptors leads to more anxiety and dysphoria. As seen in Figure 1, alcohol increases the effectiveness of GABAA-Rs. “Long-term ethanol decreases the number of GABAA-Rs present. Thus, GABA does not have an effect during alcohol use disorders because there are less receptors”.1 Understanding the role that GABAA-Rs play in the symptoms of alcohol use disorders and withdrawal lead Bohnsack to investigating potential therapeutic interventions that would prevent changes to these receptors.

The first therapy uses a drug that affects the structure of DNA on an epigenetic level. Epigenetics may be defined as “changes in gene function that are not due to the basic building blocks (nucleotides) present in the gene, but are instead, how the cell goes about expressing these genes”.1 Bohnsack’s lab uses an experimental drug called Trichostatin A (Trichostatin A’s chemical analog, Vorinostat, is FDA approved and

neuroscience

is currently used to treat a type of lymphoma). Bohnsack believes rehabilitation clinics will be more likely to use medications that have already been FDA approved in treatment of alcohol disorders because of the lower risk of side effects.1 To observe the effects of the medication on withdrawal symptoms, the lab gives high doses of ethanol to rats on a prescribed schedule in order to achieve alcohol dependency.

Trichostatin A is then administered to these rats to see if this prevents some of their withdrawal symptoms and changes in GABAA receptor gene expression. Bohnsack observed that after receiving the medication, some symptoms were alleviated to a certain degree. The most noticeable improvement was in the rats’ improved response to anesthetics, benzodiazepines, and neurosteroids.

For the second part of his research, Bohnsack will use the CRISPR-Cas9 technology to remedy the decreased function of GABA in the brain. The CRISPR-Cas9 is a tool that allows for specific regions of DNA to be targeted and edited. It is most recognized as the tool that could allow for genetically modified “designer” babies. Now CRISPR-Cas-9 is being utilized in some studies to target specific sequences of DNA that are linked to diseases.

Normally, Cas9 works by targeting a section of DNA and making cuts along the strands. Bohnsack uses a modified version of Cas9 that does not cut DNA sequence itself, but rather modifies it at the epigenetic level. To achieve this, he will attach a second protein to Cas9 to induce changes in the structure of the DNA specifically and locally at GABAA-R genes that have been affected by alcohol. Bohnsack states “this approach is preferential because it does not have ‘off-target’ effects on genes that have not been affected by alcohol”.1 Bohnsack states that with their current success rate, he does not foresee any hurdles they cannot overcome in the next year. Bohnsack explains the greatest obstacle as “finding effective ways of delivering the Cas9 to the neurons and fine tuning its response, in both the lab and in humans”.1 He has addressed this problem in-lab by using a lentivirus system.

Lentiviruses integrate into the genome allowing for long-term stable expression of the transgene.3 Bohnsack says, “we are still a long way off from using viruses/Cas9 in a widespread manner in people”.1 He looks forward to finding solutions as they continue to explore the world of GABAA-Rs. Once concluded, Bohnsack’s contributions will have a tremendous impact on alcohol use disorders and other GABA related disorders. Patients will be able to use FDA approved drugs that have been proven to work, as well as limit or eradicate the effects of withdrawal. Bohnsack is motivated by the idea that “eventually [this research] can give people hope and the chance to overcome addiction”.1

References

1. Interview with Peyton Bohnsack. 09/19/2016.

2. Bardi, J.S. “One Night in San Diego: Tragedy of Alcohol Abuse Drives TSRI Researcher’s Work” [online]. The Scripps Research Institute. 2002.

3. Nayerossadat, N.; et al. Advanced BioMed Research. 2012, E2579-E2586.

Figure 2. CRISPR-Cas9, the gene-editing tool, and its added protein introducing change. Figure courtesy of Payton Bohnsack.

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neuroscience

By Hannah Jaggers

Illustration by Maddy Howell

Dr. Eva Telzer Dr. Jorien Van Hoorn arents, who often have no idea why their children make certain choices, might have a chance to see in detail what is really going on in their teenagers’ heads.

Dr. Eva Telzer, UNC-Chapel Hill researcher and assistant professor in the psychology department, aims to examine the importance of peers and parents on neurobiological development during adolescence. Her research study, Project NeuroTeen, will follow 150 middle school students in the Chapel Hill area for three years to observe how their brains change during this very important developmental phase.

Dr. Telzer and her team will examine brain activation in three primary networks: the reward network, which helps shape our motivations and desires, the cognitive control network, which helps us perform executive functions like memory and problem solving, and the social brain network, which helps us perceive other people’s intentions and feelings.1 Dr. Telzer will use MRI, functional MRI (fMRI), and resting state fMRI techniques to observe brain activation in these three networks. fMRI studies reveal which brain regions are used when a person performs a certain task. Dr. Telzer will specifically look at how brain regions are stimulated in adolescents when mak-

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ing decisions. “We’re interested in how these regions are activated during different decision-making processing and how connectivity between these regions supports both adaptive and maladaptive decision-making.”1 In order to gauge how peers and parents influence adolescent decision-making, Dr. Telzer and her team have designed a series of tasks that carefully examine how adolescents make decisions in different social contexts. Participants will play “games” designed to elicit real-world behaviors while Dr. Telzer views their brain activity. For example, in a previous study conducted by Dr. Telzer, adolescents completed a stimulated driving game in the presence of their mother and alone to determine the factors that influence teen risk-taking behind the wheel. By imaging the brain using fMRI, Dr. Telzer hopes to reveal what brain regions are involved when adolescents make decisions to engage in behaviors, especially when receiving competing advice from peers and parents. She also hopes to shed light on how adolescents make decisions when the outcome of their behavior can directly affect more than just themselves.1 Unlike fMRI, resting state fMRI studies denote which areas of the brain are active while the student is at rest and not performing a task. These studies can be used to reveal the specific connections that occur between brain regions.2 Dr. Telzer explains that adolescence is marked by tremendous changes in the brain that increase the salience of socioemo-

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Project NeuroTeen could change the way society views adolescence as a period of turmoil that is largely unalterable.

Carolina Scientific tional contexts. In other words, during adolescence, peers can become more important and risks can seem more rewarding.1 Dr. Telzer anticipates seeing differences in brain structure and activation over the course of the experiment. “Greater influence is expected to be associated with differential neural processes,” Dr. Telzer said.1 Adolescents who change their behavior more to conform to the ideals of their parents or peers are expected to show heightened activation in brain regions involved in social cognition, reward processing, and cognitive control.1 “This heightened activation may then predict longitudinal changes in their real-life behaviors, such as substance use initiation – either engaging in more or less substance use depending on the direction of the conformity.”1 Dr. Jorien Van Hoorn, a postdoctoral researcher in Dr. Telzer’s lab, said that Project NeuroTeen differs from other studies by seeking to compare peer and parental influences on adolescent brain development. “Most studies until now have really looked at what these peer influences do and they assume that parents don’t really have any influence on adolescents anymore,” Dr. Van Hoorn said. “They’ve never really compared the two.”3 Project NeuroTeen will examine how the brain processes social influence from parents and peers and determine if the neural signatures of peer and parental influence differ within one person. While the students perform a task, Dr. Telzer will observe how peer versus parental presence impacts decision-making and how this corresponds to neural circuitry.

Dr. Telzer will also be testing for individual differences: for example, her team might question if parental influence is more detrimental for adolescents from high family conflict homes.

neuroscience

Rather than assuming that parental and peer influence is always positive or negative, Dr. Telzer will examine when and why parent and peer influence may be either good or bad.1 Middle school students will be chosen at random without selecting for characteristics de- Figure 1. Project NeuroTeen. Image termining the level provided by Dr. Eva Telzer. of peer and parental influence in their lives. Dr. Van Hoorn believes that brain imaging techniques, rather than questionnaires, should better reveal these factors. “It’s really hard to ask teenagers ‘Are you influenced by your peers?’ It’s not really something people like to talk about,” Dr. Van Hoorn said. “[This] is why it’s more interesting to look at the brain. Sometimes the brain is a better predictor of these things than when people have to report it themselves.”3 Current models of adolescent brain development show that reward systems in the brain are hyperactive during adolescence and control networks are not fully developed. These models explain why adolescence is a period where teenagers sometimes engage in risky behavior though they are capable of making good decisions. Dr. Van Hoorn believes that including a social context is integral to fully understanding these brain systems. “Usually research studies look at these reward versus control systems and what we are trying to integrate here is the social context,” Dr. Van Hoorn said. “Most of the time, you don’t make your decisions in a social vacuum so it’s really important to include social context in how people make decisions.”3 By revealing how peer and parental influences can directly affect adolescent brain development, Dr. Van Hoorn said Project NeuroTeen could help make parents more aware of their influence on their child. “Sometimes, I think the general opinion is that parents don’t have much influence anymore on teenagers,” Dr. Van Hoorn said. “With this study, we can hopefully provide parents with a sense of ‘Hey, what I do does influence my child and so I can still steer them in the right direction’.”3 Dr. Van Hoorn also said Project NeuroTeen could change the way society views adolescence as a period of turmoil that is largely unalterable. “People look at the adolescent period as a period during which kids are very vulnerable, but it’s also a period of opportunity if you shape and adapt in a right way rather than a wrong way.”3

References

1.Email with Eva Telzer, Ph.D. 2.Van Den Heuvel, M. P.; Hulshoff Pol, H. E. European Neuropsychopharmacology. 2010. 519–534.

3.Interview with Jorien Van Hoorn, Ph.D. 09/23/16.

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psychology

RACIAL DIFFERENCES IN

DISORDERED EATING R A C I A L D I F F E R E N C E S I N B U L I M I C B E H AV I O R R I S K FA C T O R S

BY: CARRINGTON MERRITT

ental health ailments, such as eating disorders, can be a delicate and traumatic subject for those who suffer from them. Research on mental health is needed to facilitate an understanding of disease processes as well as create treatments for these diseases. Dr. Anna Bardone-Cone’s clinical psychology laboratory at UNC-Chapel Hill explores how racial and cultural factors influence the formation of eating disorders.1 In the past, few studies have investigated eating disorders in minority populations due to a pervasive myth that it was exclusively an ailment of Caucasian females.2 However, it is now known that “within the U.S., racial and ethnic minorities are getting eating disorders at similar rates to Caucasians”.1 Considering the similarities in prevalence of eating disorders among racial minorities and the few studies examining minorities and their experiences with eating disorders, Dr.Bardone-Cone seeks to fill this niche with her research.

To add to the literature regarding minorities and their experiences with disordered eating, Dr. Bardone-Cone and her graduate students, including Ph.D. candidate, Stacy L. Lin, conducted a study investigating the relationship between body shame, impulsivity, and bulimic symptoms (e.g., binge eating, purging, and negative attitudes toward body weight and shape) and how this relationship differs between Caucasian and African-American females. Lin clarified that impulsivity was selected as a factor of the study because it is understood to be a “classic risk factor for bulimic behavior”.1 Furthermore, body shame was a factor of interest, as disordered eating behavior is usually linked to dissatisfaction with one’s own body. It was hypothesized that impulsivity and body shame would positively correlate with bulimic symptoms, such that as an individual’s scores for impulsivity and body shame increased, bulimic symptoms would also increase. It was also predicted that impulsivity would serve as moderator for the relationship between body shame and bulimic symptoms, meaning that increased impulsivity would strengthen the predicted positive correlation between body shame and bulimic symptoms.

Undergraduate Caucasian and African Americans fe-

males in this study completed questionnaires that were used to calculate individuals’ scores for impulsivity (see figure 1), body shame (see figure 2), and bulimic symptoms (see figure 3). Statistical analysis of these scores was conducted in order to determine how the different factors were related.

The results of such analysis revealed that for both African-American and Caucasian females, body shame was positively correlated with bulimic symptoms, including binge eating. However, the results between the two racial groups diverged when examining the relations between impulsivity and bulimic symptoms. While impulsivity and overall bulimic symptoms were positively correlated for African-American females, impulsivity was only positively correlated specifically with binge eating frequency in Caucasian females. In this group, impulsivity was not positively associated with overall bulimic symptomology. The most interesting finding, however, indicated that impulsivity acts as a moderator of the relationship between body shame and bulimic symptoms in African-Americans, but not in Caucasian females. These results ultimately suggest that the interaction of impulsivity and body shame may not operate in the same manner for Caucasian and African-American females. For African-American women, it appears that high levels of both impulsivity and body shame are working together in some way that is uniquely associated with increased bulimic behavior.

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illustration by Stephanie Dong

EATING DISORDERS ARE A VERY RELEVANT ISSUE TO RACIAL/ETHNIC MINORITY WOMEN

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These observed differences in risk factor relationships between races have several possible explanations. For example, it is possible that Caucasians who exhibit both high body shame and high impulsivity simply have other methods to “escape” stress beyond bulimic behavior.2 Other escapes for these females may include activities such as excessive alcohol consumption or self-harm behaviors, which have been found to be more common in white communities compared to black ones.2 Additionally, it is possible that increased stressors related to being a minority (i.e. prejudice or discrimination) may combine with body shame stress to interact more substantially with impulsivity, thus leading to bulimic behavior. Lin also suggests that “body shame to African-Americans may not be experienced in the same way that it is experienced in Caucasians,”1 meaning that African-Americans may incorporate broader aspects of body shame that are not relevant to Caucasians.3 With this understanding, Lin proposed the need to investigate more raciallysalient physical features, such as skin tone or hair texture, and how attitudes toward these features may be incorporated into measuring body shame in minority women.

Overall, this study, contrary to past assumptions, demonstrates that eating disorders are a very relevant issue to racial/ethnic minority women.

Moreover, it demonstrates variances in the relationships between risk factors for disordered eating behaviors among different races. This knowledge contributes to the clinical literature due to its examination of racial and cultural factors that are relevant to mental health.

Considering the widespread racial disparities in mental health care, research of this nature is imperative to developing universally effective care and treatment for such serious disorders.

References Figure 1. (Top) This figure displays some of the items included on the Barratt Impulsivity Scale (BIS), which was used to measure each participant’s level of impulsivity. (Middle) This figure includes some of the items found in the Objectified Body Consciousness Scale (OBCS), which was used to assess participants’ body shame. (Bottom) This figure displays some of the questions of the Bulimia Test- Revised (BULIT-R), which was one of the measures used to assess bulimic symptoms of the study participants.

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1. Interview with Stacy L. Lin, M.A; Ph.D. Candidate, 10/04/16.

2. Higgins, M., Lin, S. L; Alvarez, A; Bardone-Cone, A. M. Body Image, 2015. 39-46.

3. Buchanan, T. S; Fischer, A. R; Tokar, D. M; Yoder, J. D. The Counseling Psychologist. 2007. 697-718.

psychology

RICH OR POOR THE NEURAL LINKS BETWEEN SOCIOECONOMIC STATUS AND HEALTH OUTCOMES

By Saif Mehyar

Illustration by Maddy Howell

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t’s finals week. Students check their schedules and think of all the readings they failed to finish in the early weeks of school. This is followed by a realization that the exams for one’s hardest subjects are on the same day – a Saturday. Panic ensues, and depending on which stage of stress one is in, the body’s immune system may eventually become affected by this heightened sense of anxiety.

It comes as no surprise that a person’s socioeconomic status may affect the likelihood of experiencing stress and how well they cope with it. Wealthier individuals are likely to be better at dealing with stress because of the greater resources afforded to them and the lack of encumbering external stressors (financial uncertainty, food insecurity, etc.).

The topic of stress has been studied extensively over the years, and one of UNC-Chapel Hill’s newest professors is interested in the neuroscience of stress and how it relates to socioeconomic status and health outcomes. Dr. Keely Muscatell is a social neuroscientist starting her first semester at UNC. Social neuroscience is a relatively novel field that combines neuroimaging technology, like functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) scans, to study a broad range of social-psychological experiences from the empathy one feels from seeing a loved one suffer, to the

curious phenomenon of schadenfreude (the pleasure derived from seeing another’s pain). Social neuroscientists are interested in how people’s brains react to these varying situations by looking at how different regions in the brain “light up,” or are activated, as well as looking at firing patterns of neurons and the functioning of neurotransmitters.

Stress contributes to the functionality of our immune system. Highly stressful situations can lead to hyperor hypo-reactive immune responses, which cause the body to function less effectively. Dr. Muscatell finds this interesting given that “the immune system is sensitive to and hears signals from the social environment”.1 Even though stress has been studied in a wide variety of circumstances, it has not been extensively examined on a neural level. Even less data has been collected regarding stress induced by social situations. But how can scientists study people’s reactions to stress in a social context when their brain is being analyzed in an fMRI scanner (Figure 1)?

Dr. Muscatell recognizes this challenge, but explained, “one of the most fun things about my job is dealing with the challenge of [taking] tasks and experimental paradigms that we usually do in the laboratory and translat[ing] them into being done in an MRI scanner”.1 To accomplish this challenging task, Dr. Muscatell explained, “they had

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Dr. Keely Muscatell to get creative,” and they did so by coming up with a design that would help answer the question: do wealthier people who undergo social stress experience less inflammation than poorer individuals? To measure this, Dr. Muscatell and her colleagues measured immune responses to stress by assessing “inflammatory markers” found in blood plasma as well as brain activity in regions they believe are implicated in stress processing.

Dr. Muscatell and other experimenters recruited 31 female participants from the University of California at Los Angeles (UCLA) and invited them to participate in their study. At the beginning, the participants were told that they were going to be interviewed while being videotaped. The questions were rather personal because of the study’s purpose and included questions like “what are you most afraid of in life?” and “tell me about a time you really disappointed someone”.1 In addition to the

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Carolina Scientific interview, participants were asked to rate their subjective socioeconomic status (SES) in relation to other Americans.

These young women were told that in the next session of the study, they would meet and be paired with another participant who had to go through the interview as well. However, this was a cover story, and the “other participant” was actually a confederate: someone who is “in on the experiment” and assists the researchers by temporarily deceiving the subject for the purpose of the experiment to gather accurate scientific data.

At the next session, the participants met their partners (the confederates) and were told that the experimenters would randomly assign one member of each pair to watch the other member’s videotaped interview and form an overall impression of their character.

The experimenters always chose the participant to be the one who would not watch the other person’s video and instead would go into the fMRI scanner.

Inside the scanner, each of the 31 female participants saw a grid of adjectives along with a mouse cursor that was “allegedly” controlled by the confederate who would choose an adjective every 10-12 seconds to describe the participant while watching their video. But before the participant entered the scanner, the experimenters took blood samples from them; this was done in order to see how the participant’s immune system reacts to stress over time. Blood plasma contains two “inflammatory markers,” which code for inflammatory responses in the body. With greater stress comes greater inflammation. The participants who experience greater social stress will show greater inflammation.

While in the scanner, participants believed they were seeing the confederate choose adjectives to describe how they viewed the participant. Adjectives were either negative (e.g. annoying), neutral (e.g. sensible), or positive (e.g. intelligent). The idea is that social stress would be induced because participants’ self-esteem would be reduced from seeing someone judge their personality – especially when that other person chose negative words. Each time an adjective was chosen, participants responded to the question “how do you feel?” and

gave their answer on a scale of 1 (really bad) to 4 (really good). Blood samples were taken again at 30, 60, and 90 minutes after the social evaluation stressor to measure inflammation over time.

The results indicated that there was a division in biological outcomes between people who identified as high SES (wealthier) versus people who identified with lower SES (poorer). People with lower SES showed greater inflammation in response to being socially evaluated by another person than wealthier individuals. Furthermore, it was clear from the brain scans that people reporting lower SES showed greater activity in a brain region known as the dorsomedial prefrontal cortex (dmPFC) which is involved in mentalizing, or thinking about the feelings and mental states of others. This result makes sense intuitively; people who show higher mentalizing will be more affected by social evaluations and will thus show more acute biological responses (i.e. inflammation) to stress. Dr. Muscatell explained how dmPFC activity seems to mediate the relationship between SES and immune outcomes. She described, “a mediator is a sort of mechanism or intervening variable or condition that is causing or contributing to the link between two other variables”.1 In this study, the researchers found a link between social status and inflammation, and wondered, “what in the brain is causing that link to happen?”1 Essentially, they were looking for a neural mediator. This is the first study of its kind to examine social stress on a neural level and to find a fascinating association between SES and corresponding health outcomes.

Dr. Muscatell is also interested in

how findings procured from her studies are related to diseases like cancer, arthritis, and depression. She focused on recruiting female participants for her study because “women are at greater risk for experiencing depression and both social stress and inflammation are implicated in the etiology of depression”.1 This study’s significance contributes to the “overarching framing of the project,” which was to “try and understand neural and immune processes that might put people at risk for depression”.1 Dr. Muscatell reasons that females’ immune systems are more reactive to social stressors because of how women are socialized into being more interpersonally sensitive and empathetic to the thoughts and feelings of others. However, she thinks that “times are changing” and it “would be interesting to contrast that with something like an achievement-oriented stressor” since women are now more encouraged to be achievement-oriented like men, while men are encouraged to be more interpersonal.1 Dr. Muscatell’s research gives scientists and lay-readers the chance to understand health outcomes in the context of socioeconomic status and gender, which makes it all the more fascinating and important.

References

1. Interview with Keely Muscatell, Ph.D. 09/27/16.

2. Muscatell, K. A.; Dedovic, K.; Slavich, G. M.; Jarcho, M. R.; Breen, E. C.; Bower, J. E.; Eisenberger, N. I. 2016, 11(6), 915-922.

Figure 1: A participant in an fMRI brain scanner. Photo by Center for Cognitive Brain Imaging at Carnegie Mellon University.

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psychology

Reset Your Alarm

By Rachel Phillips

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Illustration by Rachel Howard

ake a minute to look around you and you will likely notice that you are surrounded by artificial light. It comes from nearby lamps, television and computer screens, not to mention your phone or tablet. Artificial light can trick our brain into believing it is still daytime. This can be detrimental to sleep quality and holds major implications for mental health and wellness. Dr. Youngstrom explains, “Our immune system does the hard work of fighting infections and cleaning damaged and precancerous cells. All that’s happening during deep sleep,” so it stands to reason that improving sleep can improve many other areas of function.1 In an effort to explore the possibility of improving sleep, the Mood, Emotions, and Clinical Child Assessment (MECCA) lab in the Department of Psychology and Neuroscience at UNC-Chapel Hill is currently studying the manipulation of light. Their goal is to enhance sleep quality in patients suffering from mood disorders like depression and bipolar disorder. The lab is led by Dr. Eric A. Youngstrom, who developed an interest in light therapy after travelling to Norway in 2014.

It was there that he heard about new research findings on the biological mechanism of our bodies’ natural alarm clock.

Despite decades of research on the human eye, a new group of cells was recently discovered to perform a crucial role in regulating our body’s circadian rhythm. These cells “function like antennae” in the sense that they do not talk to the visual part of our brain.1 Instead, they connect to our body’s

alarm clock, the suprachiasmatic nucleus (SCN). The SCN (Figure 1) is responsible for communicating with the pineal gland in the brain to produce melatonin – a hormone that helps us sleep. Thus, the main function of these previously unknown cells is to communicate with other regions of the brain to tell us if it is day or night. It turns out that day versus night is decided based on a specific wavelength of light. It is the wavelength of light from the sun in Carolina blue skies during the day and it is also the same wavelength that is artificially created by our handheld electronics.

Dr. Youngstrom describes that, “the theory is if we block that particular light [those cells] are looking for, they will think it is virtually dark and they will tell the brain it is nighttime even if other light is coming in.”1 To test this hypothesis, he set out to find a pair of glasses that would block the precise wavelength of light being emitted by artificial sources. He tried the right pair (Figure 1) for himself on a trip to South Korea and realized that the potential benefits were endless. Suddenly, Dr. Youngstrom, a self-proclaimed night-owl, was able to fall asleep and wake up without an alarm. Youngstrom’s natural circadian rhythm had been restored, and even the usual jetlag experienced after international travel was mostly gone.1 This individual observation was corroborated when he measured improved sleep quality and heightened energy levels amongst colleagues who wore the artificial light-blocking glasses on their trips home from South Korea and compared

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Carolina Scientific their experiences with those who had not worn the glasses.2 Once back on campus, Youngstrom’s findings were of great interest to the undergraduate students in the MECCA lab. His observation led to multiple new studies on the impact of artificial-light blocking glasses, including several Summer Undergraduate Research Fellowship (SURF) projects and honors theses.

Dr. Eric From these studies, we know with Youngstrom more certainty that changing the light that enters our eyes tricks our brains into thinking it is nighttime, which results in the same benefits Youngstrom and his colleagues experienced. Such benefits included heightened energy and improved mood and attention.

In a recent sleep study (Figure 1) conducted by the MECCA lab, the biological mechanism behind better sleep was illuminated. Melatonin levels were measured through saliva, and oxygen levels in the blood were gathered to form a picture of brain activity during sleep. Here, the researchers found that the artificial light-blocking glasses appeared to be tricking the body into better sleep by producing more melatonin. Youngstrom realized that this mechanism held implications for bipolar disorder (BPD), and that he could use these findings to advance treatment.

Scientists have understood for some time now that sleep is closely related to mood, yet it has taken time for this knowledge to be translated into the clinical field. There have been studies in the past few years that examined the impact of artificial-light blocking glasses in populations with symptoms of mania.3 Mania is a characteristic of bipolar disorder, and the MECCA lab is using this knowledge to explore light therapy as a treatment for bipolar disorder, depression, and other affective disorders. Clinically, these glasses could best be used to augment existing treatment.3 In some cases, traditional treatment for BPD through medication or behavioral therapy is insufficient. Incorporating artificial light-blocking glasses may be beneficial for those in the position to try something new.

As a clinical psychologist, Youngstrom is one of the first clinicians to introduce these findings in his own practice. In most instances, he recommends that individuals receiving treatment for mood disorders wear the glasses a few hours before bedtime.1 Along with colleagues across the country, he has seen that the potential benefits of light therapy seem to far outweigh any risks. One of the likely benign risks associated with artificial-light blocking glasses, seen in few individuals, is heightened intensity of dreams. This may be a direct result of increased melatonin, and sometimes goes unnoticed unless a patient is experiencing nightmares. It is important to recognize that the potential pharmacological harm from drug side effects far surpasses minute risks such as these associated with treatment glasses. As it turns out, the benefits go much further to include better memory, attention, academic and athletic performance, and overall health.

MECCA lab findings, paired with researchers’ current understanding of the importance of sleep have led Dr. Young-

psychology

strom to explore other populations that may benefit from light therapy. Specifically, he looked to athletes who are constantly seeking to boost performance. What better way than through getting a good night’s rest? Dr. Youngstrom has reported his findings to student athletes across UNC’s campus as a low-cost method for decreasing recovery time after workouts and improved alertness to play sharp. The available benefits from light therapy are for anyone, and the MECCA lab’s ultimate goal is to enhance other areas of functioning by first improving sleep.

Light-blocking glasses at night may actually help buffer our brain from all the artificial light now blurring the distinction between night and day. This can help restore a natural rhythm while living in a modern environment, letting us have our screens and our sleep, too.

References

1. Interview with Eric A. Youngstrom, M.D. Ph.D. 09/14/16.

2. Youngstrom, E. “Preliminary Test of Amber Glasses as a Way of Resetting Circadian Melatonin Release: Randomized Trial During Travel from Asia.” 2016.

3. Henriksen, T.E; Skrede, S; Fasmer, O.B; Schoeyen, H; Leskauskaite, I. Bjorke-Bertheussen, J; Assmus, J; Hamre, B; Gronli, J; Lund, A. Bipolar Disord 2016, 221-32.

Figure 1. From top to bottom: a. Flowchart by Rachel Phillips. b. Youngstrom family’s dog, Greatsy, showing off a pair of light-therapy glasses. c. Dr. Youngstrom and MECCA researcher prepare to run participants in their sleep study.

Images courtesy of MECCA Lab.

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physical science

Two Dimensions: Endless Possibilities

Illustration by Nim Breitenfield

BY KEVIN RUOFF

S

cience fiction inspires young kids to believe they can grow up to be superheroes - for instance, Iron Man. While the idea may be discounted as ludicrous and unrealistic, kids may have their ambitious dreams come true someday.

In Marvel Comics’ Superior Iron Man #2 Tony Stark is shot in the face, but what protects him is his transparent face shield made of graphene. Graphene was the first material created to be two dimensional, essentially having the minimum width possible, one atom. It was found to be significantly stronger than steel, a discovery that astounded the scientific world.1 The other unique feature about this protective shield is its transparency. Transparency is something extremely important when it comes to solar cells (and surprising your enemies) and is the result of 2D materials like calcium nitride.2 These are just two examples of materials shaped into two dimensions; there are many other 2D materials with many more endless applications.

Electronic, energy, and science fields will soon see exponential growth in development, in part from the research being conducted at UNC Chapel-Hill. In Dr. Scott Warren’s lab, cutting edge research is happening in the extremely promising field of two dimensional materials. They work on creating new 2D materials, looking at their unique electrical and opti-

Dr. Warren’s group asks two questions: “Can we make something new? And what can it do?” The possibilities are endless.

cal properties, integrating them into devices like transistors, solar cells, and biosensors.

2D materials were only recently discovered in 2004 and research did not go beyond graphene until 2008, so this is a very new, exciting, and somewhat unpredictable field. Dr. Warren’s group asks two questions: “Can we make something new? And what can Dr. Scott Warren it do?”2 The possibilities are endless. Dr. Warren is currently testing materials for use in motor vehicles, but the applications extend to batteries, sensors, new kinds of optical lenses, and photodetectors. They can make materials that nobody else can, with properties like no others known, making them a very desirable research group to get involved with.

Dr. Warren’s group works on both experiment and theory. Their biggest challenge is understanding how and why 2D materials work, not in getting them to work. What makes 2D materials so difficult to understand is the fact that they are hard to even visualize, let alone create. Dr. Warren explains 2D materials with Scotch tape: “Take a piece of scotch tape and peel it back and you get thin flakes [of the surface you stuck it to]. You can then take another piece of tape, lay it across [the first piece], peel it apart, and now whatever is left is about half as thick. It takes about ten or twenty peels back and forth before you get down to a single atomic layer.”2 This analogy emphasizes how thin these materials are! While repeatedly peeling pieces of tape from one another can be very

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Carolina Scientific tedious, Dr. Warren’s lab is able to produce these materials in bulk. Dr. Warren said, “What distinguishes our group are our choices of materials we choose to [work with].” He is “driven by trying to do things that haven’t been done before” and if he knows that somebody has done something before, he doesn’t want to do it.2 He wants to go out and make a material that has never been made before and once it’s been made he worries about what is it good for. Applications of these materials are seemingly endless. Not only can 2D materials help protect Tony Stark from a point blank bullet but they can do so much more, like make more efficient computer chips.

A transistor is the building block of computer chips and thus a lot of the technology we use every day. It is a gate that opens and closes to allow negatively charged particles (electrons) to pass through to create a current of electricity. For an effective transistor a material is needed that can both allow electrons to pass and prevent electrons from passing. 2D materials are extremely good at bending into different shapes, absorbing energy (like that coming from a bullet), and absorbing light. Because every unit (atom) of a 2D material is on the surface, it is very easy to control the passage of electrons. With the element silicon, the usual material in computer chips, gadgets are limited by decreased electron motility and overheating. 2D materials are currently the best possible replacement for silicon, to increase technology efficacy and efficiency.3 The Warren lab was the first to produce 2D materials with the element phosphorus. It was discovered that as phosphorus gets thinner it changes color and function, meaning it has different applications than the 3D material. Another challenge for Warren’s field is to build solar cells that can operate efficiently with different wavelengths of light As a material that partially allows electron flow, 2D phosphorous material can be used in solar cells to absorb any color of light. Most recently, the Warren lab received a grant to build a new kind

Figure 1. A unique look at a unique material.

Photo courtesy of Dr. Scott Warren.

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of lens to detect single molecules. Their aim is to create a material capable of detecting changes in protein or DNA structure in a cell. For instance, a diseased cell with altered protein structure could be seen with this lens for targeted treatment.

Research in a multitude of fields would be greatly impacted by this kind of technology.

When the full potential of 2D materials is realized, future generations may even see superheroes outside of comic books.

“Our research is so exploratory it’s often difficult to see that far ahead.”2 3D structures from 2D materials, semiconductors with any optical property desired, these advances are just beginning to be understood. When the full potential of 2D materials is realized, future generations may even see superheroes outside of comic books.

References: 1.Kakalios, J. “The Magical Bulletproof Material That Made Iron Man Give Up Iron.” Wired.com. Conde Nast Digital, 14 Jan. 2015.

2.Interview with Scott Warren, Ph.D. 09/29/2016.

3.Hopkinson, M. “With Silicon Pushed to Its Limits, What Will Power the next Electronics Revolution?” N.p., 27 Aug. 2015.

Figure 2. Artistic rendering of graphene. Photo courtesy of Flickr Creative Commons.

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By Firstname Lastname

Supernova Inside a Meteorite, Billions of Years Ago

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By Patrick Gorman

whe physics that defines the flow of water in your toilet can be applied to model what space looked like billions of years ago. This is what Matthew Goodson, a UNC Chapel Hill graduate student studying Physics and Astronomy under Dr. Fabian Heitsch in the Fluids Lab, does every day.

Many might think of a Fluids Lab as a kind of massive scientific swimming pool, but in actuality, the lab is a spacious room of desks and computers connected to a central supercomputer.1 The supercomputer is used to calculate and store massive amounts of data at rates that make a simple laptop seem like a 2GB flash drive. Goodson uses this supercomputer to run three-dimensional simulations that investigate how a sun may have gone supernova during the early formation of our solar system. His work is based around using everyday fluid dynamics, such as the stirring of a cup of coffee—on an astronomical scale.

When our solar system was first forming, there was a large dust cloud collecting together through its motion in space.1 It was suggested that there was a supernova, an exploding star, near this cloud of gas as the solar system was forming. The initial cloud of gas and the possible nearby supernova is what Goodson uses fluid dynamics to model. Evidence of the supernova theory is found in specific Matthew Goodson wtypes of meteorites that have not undergone aqueous alteration, the “nerdy term,” for change by heat and water.1 Analyses have revealed that there was an abundance of radioisotopes, or decaying radioactive material, in the meteorites that were primarily created in supernovae.

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illustration by Tatihana Moreno

Carolina Scientific The most notable example was the Allende meteorite, discovered in Mexico in 1969, containing essentially chemically unaltered substances from 4.5 billion years ago at the creation of the solar system.2 The chemical analyses done on the meteorite suggested an unusually high concentration of shortlived radioisotopes (SLRs), radioactive material that decays in a short amount of time, especially Aluminium-26 (Al-26), an isotope with a relatively short half-life of 760 thousand years.

Al-26 is known to be made in supernovae, which sparked the initial investigation.3 If there was a supernova close to the early solar system during its formation, certain parameters for its distance from our forming system had to be met. When a dying sun goes supernova, there is a massive shockwave and ejection of particles and dust, including the SLRs that were detected in the meteorites.5 The supernova would have had to occur close enough to the gas cloud that the SLRs could reach us before decaying, but not so close that the shockwave destroys the building blocks of our solar system.1 The primary issue with this approach was the “injection” of the SLRs from the supernova into the gas cloud. As Goodson describes, “the problem is that the supernova materials simply do not want to mix with the star forming gas”.1 He goes on to explain that, due to heat generated by the supernova, the remains of the shockwave are significantly hotter than the cold gaseous materials in the pre-stellar cloud. Because of this temperature discrepancy, the two are essentially incompatible, hence there must be more to the injection of the SLRs to mix the two substances.1 Alternate, more probable solutions, like the ones Goodson has proposed, use fluid dynamics to model how the SLRs could have entered the pre-stellar cloud.

The foundational idea behind why the simulations work is the universality of fluid dynamics; the dynamics of fluids over a few meters on Earth are closely relatable over lightyears in space. It should be noted that fluids are not strictly considered to be liquid – gaseous substances are also fluids and adhere to the same laws as liquid fluids. This notion is fundamental to Goodson’s research because space is not a vacuum, but rather a low-density fluid. The density of space is approximately one atom per cubic centimeter, while on Earth, a cubic centimeter has 10¬19 to 1020 atoms.1 This may appear insignificantly small on a local scale; however, as you widen the field of view to several light-years, space begins to act as any other fluid would since the relative densities are relatable.

Goodson noted the extent of this application: “I can model anything from the movement of galaxies to the formation of stars to the flow of air around an airplane to the atmosphere...It all obeys the same principles.”1 These dynamics are the reason the supernova-heated particulates could not mix with the cold gas cloud; the difference in temperature made the particulates disperse around the cloud of gas rather than disperse through it and mix together.1 Simulations were run on different sizes of dust that came from the supernovae. This dust is smaller than the other pieces of debris and the lesser mass gave it a greater velocity. Rather than diffusing around the gas cloud, the smaller, higher speed particles “shoot through the cloud like bullets,” dispersing and mixing into the cloud with the stellar gas.1 Through simulating the injection of

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Figure 1. (Top) Projection of the simulated data from the experiment. Image courtesy of Matthew Goodson. (Bottom) A cut of the Allende meteorite with CA1 deposits. Image courtesy of Wikimedia Commons. varied sizes, Goodson was able to approximate how much of the SLRs could come from the supernova, and the results were more promising than previous experiments yielded.

Knowing more about this supposed supernova could suggest more behind the basis of how the solar system was constructed. In its elementary form, there is a generally accepted understanding, but specifics are only partially understood. Additionally, present knowledge on supernovae remains is limited; there is a basic understanding, but anything beyond that is mere theory. Having physical evidence of SLR that came from a supposed supernova supports theories on supernova ejecta, or what comes from super nova, and its qualities. Perhaps the most interesting implicated theory is that the heat created by the SRLs as they decayed could have melted water into liquid form during the early formation of Earth. While unlikely, this would have promoted the construction of amino acids, which in turn could be the basis of all organic life on the planet.4

References

1. Interview with Matthew D. Goodson, M.Sc. 10/03/2016.

2. Smithsonian Institution. Allende Meteorite. http://naturalhistory.si.edu/onehundredyears/featured_objects/AllendeMeteorite.html (accessed Oct 4, 2016).

3. Laurent, Philippe. (2014). Gamma-ray astronomy. In AccessScience. McGraw-Hill Education. http://dx.doi. org/10.1036/1097-8542.279300.

4. Goodson, M. D.; Luebbers, I.; Heitsch, F.; Frazer, C. C. MNRAS. 2016, 462(3), 2777-2791.

5. Berkeley Multiverse. Type II Supernova. http://cse.ssl. berkeley.edu/bmendez/ay10/2000/cycle/snII.html.

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physical science

Illustration by Julianne Yuziuk

Teaching Computers to Reason: How Computers are Helping Mathematicians

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By Jeffrey Young

book written by Maurice Lecat in 1935 included 130 pages of errors made by major mathematicians up to 1900.1 Yet think, today it is easy to take for granted that the theorems we find printed today in textbooks are correct.

Most of them have hundreds of years of mathematical foundation to stand upon. However, this necessarily cannot be the case with modern day research in mathematics. As mathematicians tackle increasingly difficult subjects and come up with theorems describing them, it becomes increasingly difficult to prove that these theorems are correct. One small mistake in the logic can lead to the downfall of a proof, and when these proofs are hundreds of pages long, as is sometimes the case, spotting these errors within incredibly complex mathematics can be exceedingly difficult, even for an expert. Even eminent mathematicians such as J.E. Littlewood have published faulty proofs. As an example, the first purported proof of the fourcolor theorem in 1879 stood for a decade before a flaw was pointed out. Andrew Wiles’ first proof of Fermat’s Last Theorem contained a mistake, and it took Wiles and a former student, Richard Taylor, close to a year to find a way to circumvent it. Clearly there is a need for some sort of toolset to aid in our pursuit of finding proofs and verifying their correctness.

Automated theorem proving was born out of a desire to use computers to solve this problem and help verify

the work of mathematicians. For example, the original proof of the oddorder theorem by Walter Feit and John Thompson, published in 1963, filled 255 journal pages.2 This proof was eventually verified by a computer and had approximately 150,000 lines of code, or formal proof scripts, including 4,000 definitions and 13,000 lemmas and theorems.

Dr. David Plaisted, a professor in the Department of Computer Science Dr. David Plaisted at UNC-Chapel Hill, has spent his career researching and developing methods used in automated theorem proving. He was originally interested in formal reasoning and mathematics, but after taking a course in theorem proving at Stanford during his graduate studies he became interested in automated theorem proving and decided to move his research in that direction.

Automated theorem proving is a field which attempts to leverage the power of computers in order to prove mathematical theorems. The basic idea is simple: give a computer a set of simple axioms, also known as rules, and allow it to combine those axioms in an attempt to come up with more

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Carolina Scientific complex statements that help to prove the theorem at hand.

The power of automated theorem proving lies in the power of computers, which are able to perform billions of calculations per second. This speed allows computers to attempt vastly more solutions than any human could ever hope to do. One disadvantage of computers however, is that they lack creativity and insight that humans have. They cannot discern meaningful statements and conclusions that may be especially interesting from ones that are trivial.

Propositional logic is one area of theorem proving where computers are especially efficient, as Dr. Plaisted confirms, “Now you can verify theorems with tens of thousands or even millions of variables”.3 This kind of logic is important for hardware verification and for combinatorial search problems.

Here is an example of a formula in propositional logic: First-order logic is a more powerful logic that includes variables and quantifiers such as “for all” and “there exists.”

Here is an example of a formula in first-order logic: Other logics can be even more expressive than firstorder logic.

Translating the intricacies and expressiveness of mathematical language into something a computer can understand is still a facet of automated theorem proving that continues to be an active area of research. The general strategy for accomplishing this is to take a complex statement and break it down into many smaller parts. Next, one must assign a binary value (true or false) to these simpler statements. Computers can then take these simple statements and combine or manipulate them in various ways to determine the validity of a proposed theorem. There are many different ways to synthesize these mathematical statements into terms computers can understand and process, each with their own advantages and disadvantages in terms of complexity and runtime.4

“Now you can verify Theorems with tens of thousands or even millions of variables.”

A fundamental concept in the field of automated theorem proving is the idea of decidability. For most logic systems, it is impossible to know whether or not a theorem proving program will “halt” after given any particular input. That is, even with the best theorem prover it is not guaranteed that the program will ever cease execution and even if it does eventually cease there is no way of knowing how long it might take.

“There is no recursive bound on how long it will take to prove the theorem…as the theorem increases in length the time to solve it increases faster than any mathematical function,” said Dr. Plaisted.3 Recursive functions include exponentiation and many more functions that grow even faster.

Computers have a key advantage over their human counterparts in this field; they never get tired. Humans are prone to mistakes and can only spend so long working on

physical science

the same problem. A computer, on the other hand, will never make a mistake or lose focus when trying to solve a problem.

However, humans cannot completely be eliminated from the picture, and the programs that do this theorem proving will always be limited by the humans who coded them.

Computers have a key advantage over their human counterparts in this field; they never get tired.

Since the early days of computers, researchers have been investigating ways to use computers for the purpose of theorem proving. However, some of the limitations researchers encountered in the 1960s are still being wrestled with today. One fundamental issue is the fact that people still do not understand exactly how people prove things. “Human intelligence is much smarter than people think,” said Dr. Plaisted.3 Programming theorem provers is difficult because people are not sure what exactly the steps in proving a theorem are and it is a process that is not easily reducible into a set of welldefined steps. In addition, while computers are great at parsing syntax, the structure of words and phrases, they struggle mightily when trying to discern or make use of the semantics of a statement, the actual meaning behind the words. Programming theorem provers to understand semantics is one of the most difficult aspects of automated theorem proving.

The applications of automated theorem proving are widespread and not just related to the field of mathematics.

“There’s tremendous interest in [this field],” said Dr. Plaisted.1 Artificial intelligence (AI) is one such example. AI like IBM’s Watson (of Jeopardy! fame) are good at coming up with associations but not with proving them. Essentially, they do not use logic very well. AI systems are often developed to be “experts” in one particular area and are very brittle when taken outside of their area of expertise. Methods developed in automated theorem proving could help drive the development of more general AI systems that can be applied to a wide variety of problems.

Dr. Plaisted is optimistic about the future of the field of automated theorem proving. “I think tremendous progress is being made. I don’t know when we’re going to achieve a critical mass, but I think the field is beginning to reach maturity.”3 In the future, Dr. Plaisted believes it will be much easier to verify conjectures made in mathematics, with theoreticians working side by side with computers to create new theorems. More broadly, Dr. Plaisted believes the applications for automated theorem proving will only continue to grow as the methods improve. “Anywhere people use reasoning there are applications for automated theorem proving.”3

References

1.Lecat, M. Erreurs de mathematiciens des origines a nos jours. 1935.

2.Feit, W; Thompson, J.G. Pacific Journal of Mathematics.

1963, 13, 775–1029.

3.Interview with David Plaisted, Ph.D. 09/22/16.

4.Plaisted, D.A. Automated Deduction - CADE-25, Proceedings. 2015. 3–28.

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physical science

Figure 1. Author’s concept of matter flowing into black hole. Photo by NASA/JPL-Caltech [CC BY 4.0 via Wikimedia Commons

Living on a Trampoline: Black Holes and Still Light

BY JACK MOODY

A

ccording to theoretical science, black holes can have halos. While black holes are not a new scientific discovery, the extremely strong gravitational pull of black holes prevents exploration of these curious phenomena. No explorer would be able to escape the gravity of a black hole if sufficiently close to its center. With recent discoveries of gravitational waves by the Laser Interferometer Gravitational-Wave Observatory (LIGO), a laser detector, knowledge of black hole behavior continues to expand and support the theoretical work previously done by mathematicians and scientists.1 The laser’s detection of two black holes colliding over one billion light years away highlights the immense power of these massive objects, and the great value which theoretical math can add to scientific understanding. Dr. Jason Metcalfe, assistant professor at UNC-Chapel Hill, has been studying how light decays when trapped in black holes in order to understand how light acts when orbiting a black hole.

Dr. Metcalfe explains that to understand a black hole, we must first understand the space that surrounds us through Einstein’s theory of relativity. According to the theory, “...gravity isn’t this external force, time isn’t this independent object... the universe is actually four dimensional. Time and space are tied together and gravity corresponds to curvature.”2 Think of a trampoline. If you put a bowling ball in the middle of the trampoline, and there are lots of golf balls on the side of the trampoline, “the golf balls on the trampoline will flow along the trampoline towards that heavier object [the bowling ball]

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and that,” Dr. Metcalfe explains, “is gravity.”2 A black hole is like an extremely dense bowling ball. This enormous density causes the trampoline fabric of space time to sink so rapidly, the escape velocity necessary to leave the gravitational pull of a black hole exceeds the speed of light. However, since the speed of light is known to be the fastest speed an object can travel, this makes escaping a Dr. Jason Metcalfe black hole impossible once an object is close enough to its center. This means that if an object enters a black hole’s event horizon (where the gravity of the black hole sucks all other objects in), the object no longer has a chance of escaping.

For objects with mass, there are two fates when it comes to black holes: they are either sucked into the black hole’s event horizon, never to be seen again, or they remain safely outside the reach of the black hole.3 While this applies to objects with mass, there are slight differences when it comes to light.

Light can be sucked into a black hole, remain outside of a black hole, or be trapped in between being sucked in and escaping. While two objects with mass exert their gravity on one

Carolina Scientific

physical science

Figure 2. Left: Black hole in Centaurus A Galaxy. Photo by ESO/WFI. Right: llustration of growing black hole.

Photo by Dmytro Ivashchenko. Images courtesy of Wikepedia Commons.

another, light is merely bent by the bend in the trampoline fabric of spacetime due to the black hole’s gravity.4 This allows light to have the third option of getting trapped in between going into a black hole and escaping. We call the place where light is trapped the photon sphere. The photon sphere is very sensitive to the change in the trampoline fabric of spacetime, which makes studying the way which light waves decay very difficult.

This sensitivity of light has motivated Dr. Metcalfe’s research on how light waves decay in a black hole. Proving that a system is stable is a very complex problem. Dr. Metcalfe explains, “If you wrote the stability problem down, it becomes an equation where the solution depends on the geometry, but the geometry, in turn, depends on the solution. So you get a gnarly coupling.”2 Because both the solution and the geometry rely on each other, these physical characteristics can only be approximated to a certain level of accuracy.

While the work done by Dr. Jason Metcalfe may seem esoteric to some, there exists a long history of mathematics being well ahead of its time. Einstein’s theory of relativity has

“...gravity isn’t this external force, time isn’t this independent object...the universe is actually four dimentsional. Time and Space are tied together and gravity corresponds to curvature.” been used to explain double stars (when one star appears to be two identical stars), Joseph Fourier’s complex mathematical wave transformations allow us to communicate thousands of miles apart through cell phones, and Alan Turing’s ideas led to the computers we use today, which have gone far beyond what we ever expected.

The recent discovery of gravitational waves by LIGO

supports the necessity for the theoretical work behind black holes. Due to difficulties in studying black holes, most of our current understanding of black holes comes from mathematical theory, but to further our understanding, it has become necessary to use mathematical tools. Dr. Metcalfe has extended his work in three dimensions to higher dimensions in order to solve for interesting and more complex cases of black holes. He has began to ask, “If a black hole is rotating, how will light decay be affected?”2 While Dr. Metcalfe’s research on wave decay in three dimensions for stationary black holes has advanced scientists’ understanding of wave decay under large gravitational forces, he states that he is “never done with [his] research. There is always some other interesting scenario to explore.”2 For Dr. Metcalfe, it’s about “researching whatever fascinates [him] at the time,” but for scientific discovery there may be more to the usefulness of this subject than fascination.2 Taking the problem of light decay in black holes to higher dimensions allows mathematicians to understand how light is bent by gravity, a very important concept when determining how our vision of far away objects may be skewed by gravitational effects. Work done in higher dimensions not only simplifies problems in three dimensional space, but it can also provide insight into new ways of how the world truly works, not just from the human perspective. While general relativity allows us to consider the effect of gravity on light and the implications this has in the field of optics, Dr. Metcalfe believes that the expansion of human knowledge itself is a worthy motivation for research of black holes; to Dr. Metcalfe, “...it’s about finding interesting phenomena in the math.”2

References

1.Caltech; MIT. LIGO Lab. https://www.ligo.caltech.edu/ (accessed 2016 September 30).

2.Interview with Jason Metcalfe, Ph.D., 09/23/26.

3.NASA. Black Holes. https://science.nasa.gov/astrophysics/focus-areas/black-holes (accessed 2016 Sep 30).

4.Stephen Hawking. A Brief History of Time. 1998. 103-105.

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The Macrophage’s Bouncer

By Madison Hoke

Illustration by Rachel Howard

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he pathogens are evolving, and we are struggling to keep up. Antimicrobial resistance (AMR) has surreptitiously become one of the greatest threats to global health. Since the discovery of penicillin in the mid-twentieth century, the use and misuse of antimicrobials has lead to the evolution of drug-resistant and multidrug-resistant pathogens.1 Increasingly, common infections are becoming resistant to the antimicrobial therapeutics previously used to treat them, a cause for great concern among world health leaders and policy-makers. This well-founded concern has lead to a number of initiatives and goals, like the development of drug ‘cocktails’ to combat multiple-resistant strains; the placement of greater emphasis on hand-washing and hygiene in hospitals and treatment centers; the education of health care providers and the general public on the importance of finishingthe course of an antimicrobial prescription; and the discovery of new and less broadly-acting antibiotics.2

Dr. Kristy Ainslie and her lab have carved a niche within the field of drug delivery to address this problem. “Ninety percent of drug delivery scientists— maybe ninety-five percent— study cancer. And that’s great. And cancer might kill us all, but what might perhaps kill us faster would be having drug-resistant diseases,” she points out.3 As with cancer therapeutics, the drugs that the Ainslie Lab is developing are immunomodulatory, meaning they modify the body’s immune response.

Her lab is working to target macrophages, white blood cells that engulf and digest anything and everything that deviates from a healthy body cell.

This feature simplifies the drug delivery process: when a foreign element (i.e. the drug) in the microparticle size range is introduced to the body, it is too large to be picked up by any cells other than the macrophages. Thus, the drug simply waits for the macrophage to recognize its foreignness and engulfs it. Once inside, the drug can begin to act upon the

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Dr. Kristy Ainslie macrophage.

Because these compounds are often toxic to other cells in the body, they are encapsulated and hidden to protect the non-targeted cells. As Figure 1 shows, these drug-transporting vehicles include biopolymers, liposomes, and micelles; all of which contain the drug at the center of the vehicle. These also allow the often-hydrophobic (water-hating) compounds to travel through the body’s hydrophilic (water-loving) envi-

Carolina Scientific ronment to reach the targeted cells.2 These drugs, called host-directed therapeutics, do not target the pathogen itself, but rather the cells in which they reside—the macrophages. This is the crucial link to combatting antimicrobial resistance. The drugs’ targeting of the host cell, rather than the pathogen, removes selective pressure on the pathogen to evolve and develop resistance. Therefore, this decreases the likelihood of antibiotic resistance as the pathogen itself is not being attacked or modified.

Because the majority of pathogens reside outside of the cell, current therapeutics focus on extracellular pathogens. The Ainslie Lab, however, is working to indirectly target intracellular pathogens—those that multiply and live within a host cell. These pathogens usurp the cell and use its machinery to survive. In the minority, intracellular pathogens still contribute to a large proportion of illness and death in the world including typhoid fever-causing bacterium, Salmonella enterica serovar Typhi, which is responsible for 200,000 deaths annually; and the protozoa Leishmania, which causes 50,000 deaths a year. Additionally, the group can target the intracellular bacterium, Mycobacterium tuberculosis, which is responsible for approximately 1.4 million deaths a year - more than a tenth of which are coinfected with HIV. The host-directed therapeutic acts on the macrophage to overcome the cell signaling from the pathogen that wants to live there. In essence, the drug works to kick the intracellular pathogen out of the cell. Dr. Ainslie likes to think of the drug as a bouncer.

“It helps the macrophage recognize that the pathogen shouldn’t be there.”3 Some pathogens need to live within a host cell in order to survive; in these instances, expulsion alone results in their death.

For others that can live both intracellularly and extracellularly, expulsion makes the pathogens more susceptible to antimicrobials. Indeed, these host-directed therapeutics are meant to sensitize pathogens to antimicrobials and be used in conjunction with classic therapy.

One common misconception about these host-directed therapeutics is that the drugs are working to attack

and kill the macrophages instead of the pathogen. Harming healthy macrophages, which are an important component of the body’s immune system, would make an individual immune-compromised, thus resulting in even more issues and susceptibility to microbes.

To be clear, the drug is modulating the signaling between the macrophage and the pathogen. It is not harming either the pathogen or the macrophage itself.

Dr. Ainslie’s lab has tested a drug that is currently being evaluated in

health and medicine clinical trials as an anti-cancer agent but also shows a host-directed, broadspectrum clearance of bacteria. While the drug has been shown to effectively “bounce” several types of bacteria from macrophages in mice studies, it does not prevent the mice from dying. Ainslie’s group has clearance of bacteria.

While the drug has been shown to effectively “bounce” several types of bacteria from macrophages in mice studies, it does not prevent the mice from dying.

Figure 1. (Top) Deaths attributed to antimicrobial resistance (AMR) each year. Figure by Jim O’Neill. (Bottom) Host directed therapeutic delivery systems. Photo coutesy of Dr. Ainslie.

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Figure 3. Photo of Macrophages (blue), Salmonella enterica serovar Typhi(green), and Ace-DEX Microparticles (red). Both microparticles and bacteria can be taken up together by macrophages.

Ainslie’s group has worked to encapsulate the drug in a biodegradable polymer, acetalated dextran (Ace-DEX), and has demonstrated that the macrophages are able to engulf the microparticle (made of the Ace-Dex and the drug) and rid the white blood cell of the bacteria without killing the mice. These results are novel in their use of this new biopolymer. Ace-DEX is acid-sensitive, allowing it to degrade as the macrophage shifts pH while working to digest foreign particles. Compared to other common drug delivery biopolymers that take months to degrade, Ace-DEX has been shown to degrade within a few days, making it more advantageous for fighting microbes. The Ainslie Lab’s studies also indicate that encapsulating hostdirected therapeutic drugs in Ace-DEX can not only control intracellular bacteria but also reduce potent drug’s toxicity.

In the fight against the pathogens, pencillin was once thought to be the panacea. Now, however, researchers are relying upon more combinatorial approaches. The delivery of host-directed therapeutics to clear intracellular pathogens represents one method of combatting antimicrobial resistance.

References

1. World Health Organization. Global Action Plan on Antimicrobial Resistance. 2015.

2. Hoang, K.V; Borteh, H.M; Rajaram, M.V; Peine, K.J; Curry, H; Collier, M.A; Homsy, M.L; Bachelder, E.M; Gunn, J.S; Schlesinger, L.S; Ainslie, K.M; Int J Pharm. 2014. 334-43.

3. Interview with Kristy M. Ainslie, Ph.D. 09/23/16.

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Illustration by Rachel Howard

A MOMENT OF TRAUMA MEANS A LIFETIME OF PAIN

BY TOBY BADER

A

brupt, alarming, and harrowing: traumatic events typically only last a few moments at most, but can impact a person for the rest of their life. Generally speaking, the majority of consequences following a traumatic event happen within the first month of the incident. However, suffering from these experiences can extend far longer into its victims’ lives. Post-traumatic stress disorder (PTSD) and chronic pain are two health conditions that are often largely exacerbated in people, especially women, following a traumatic event.

Chronic pain is one of the most underestimated health care issues facing the world today. Affecting more than 100 million people, chronic pain reaches more people than diabetes, heart disease, and cancer combined.1 It is one of the most prevalent adverse outcomes following a traumatic

event. Its continuous nature can easily diminish the quality of life for someone affected by chronic pain, and there currently are very few effective treatments available to combat it. All things considered, traumatic pain is a pressing problem that has not received a fair amount of research, and this is what Dr. Linnstaedt’s lab aims to explore.

Dr. Sarah Linnstaedt Dr. Sarah Linnstaedt, a post-doc in the Department of Anesthesiology at the UNCChapel Hill’s school of medicine is just one researcher in a

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Carolina Scientific group of many focusing on addressing the different factors that can influence chronic pain in individuals following a traumatic event. Bench to bedside research is what her lab focuses on; that is, the research they do is meant to directly help victims of chronic pain following a traumatic experience.

She collects data on people following a traumatic experience such as sexual assault, motor vehicle collisions, and thermal burn injury. Immediately following the traumatic event, participants are enrolled into a longitudinal study measuring the risk of developing chronic pain. Their blood is drawn directly after the event, and they are contacted at various time intervals following their traumatic event to assess the level of pain that they are experiencing. The lab uses many techniques such as in order to closely analyze the DNA and RNA present in those who suffer from chronic pain following a traumatic incident. One of the most noteworthy techniques Linnstaedt uses is in her lab is quantitative polymerase chain reaction (PCR).2 Quantitative PCR is an especially useful technique used

by Dr. Linnstaedt because it allows her to amplify, copy, and quantitatively analyze the concentrations of certain strands of DNA that could prove key to explaining the pain victims of traumatic events often suffer.3 By understanding the differences in these genetic sequences from those who do not develop chronic pain, they hope to understand the causes for it.

Once the lab identifies the biggest risk factors for developing chronic pain following a traumatic event, their next goal is to find the best form of treatment for it.1 Surprisingly, chronic pain does not affect all people equally. The Linnstaedt’s lab research has found that there are many factors that can influence the likelihood that a person will experience chronic pain following a traumatic experience.

Along with her colleague Dr. Samuel Mclean, both researchers found that race, sex, and socioeconomic status are among the leading risk factors for developing chronic pain or after a

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and men.”1 Perhaps even more shocking than the disparity in prevalence between women and men is the poor quality of treatment available to them. “First of all, there are not a lot of great treatments for pain. Second of all, when we go to treat them, women are often treated with the same treatment plan

Race, sex and socioeconomic status are among the leading risk factors for developing chronic pain after a traumatic event. that a man would be treated with, even though they have very different mechanisms that lead to pain. So why would we not have a different treatment for them?” By understanding the ways men and women react differently to chronic pain, Linnstaedt lab hopes to uncover a more direct treatment for them.1 Most current options for treating chronic pain fail to adequately address the problem at hand. “If all data is based on treating men and women as a group, then you’re taking the average of both of them. So if you take the average of two very different things, then you’re going to get something in the middle that’s not really representative of either.”1 Moving forward, Dr. Linnstaedt’s and her colleagues’ research might one day redefine the impact that traumatic events can have on their victims. With time, a traumatic event will hopefully be just that: an event, and not a lifetime of pain.

Chronic pain is one of the most underestimated health care issues facing the world today.

Affecting more people than diabetes, heart disease, and cancer combined. traumatic event.1 Their research is providing more evidence regarding the intensity and the rate of chronic pain every day for these subsets of individuals.

One personal area of emphasis that Dr. Linnstaedt finds especially rewarding regarding her work revolves around the research her lab does focusing on women in particular. Not only does chronic pain affect women more intensely than it does men, it affects women at a much higher rate.1 “It’s a huge issue,” Dr. Linnstaedt said, “For instance, fibromyalgia can affect up to 9 women per 1 man. Across all the different pain disorders, it’s a pretty striking difference between women

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References

Illustration by Esther Lin

1. Interview with Sarah Linnstaedt, Ph.D. 09/22/2016.

2. Hren, M. “Real-Time PCR Technology Basics.”

Biosistemika. Web. 10/14/2016.

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INDUCING

INFANT

IMMUNITY

E N D I N G M O T H E R-T O - C H I L D T R A N S M I S S I O N O F H I V

Illustration by Stephanie Dong

By Janet Yan

W

e are constantly looking for cures to diseases, but prevention is an equally important area for research. There has been a recent shift towards preventative health care, particularly for young infants, by building their immunity to diseases early in life. For populations with high proportions of human immunodeficiency virus (HIV) infection, a pediatric vaccine would be life-saving.

Advances in HIV treatment, such as antiretroviral therapy (ART), and increased access to these drugs have allowed more people infected with HIV to live normal lives with an average lifespan. Although ARTs have been highly successful, many populations still do not have access to these drugs, and furthermore, pregnant women may not realize that they are infected until they have given birth and are breastfeeding their children. Consequently, these infants constitute a vulnerable population known as HIV-exposed uninfected infants, infants who are uninfected themselves, but are frequently exposed to infected individuals, specifically their mothers.1 Dr. Kristina De Paris, an Associate Professor in the Department of Microbiology and Immunology at UNC-Chapel Hill, is working towards developing a pediatric vaccine to protect infants from acquiring HIV from motherto-child transmission (MTCT) through

breastfeeding. MTCT from breastfeeding is still an understudied facet of HIV/ AIDS research, making this topic important for researchers such as Dr. De Paris to study in more depth. Breastfeeding is encouraged, as not breastfeeding has been shown to increase infant mortality, and formula is often not available to individuals from the target populations.2 However, as breastfeeding is a repetitive, long-term process, the constant exposure increases the risk of the infant acquiring HIV. Additionally, it is estimated that around 25-50% of MTCT cases are due to breast-milk transmission.1 Thus, researchers are studying different ways to prevent transmission of HIV from mother-to-child.

Rhesus macaques, a species of monkey, are used as model animals to study immune development and HIV pathogenesis due to their physiological and immunological similarities with humans. Rather than infecting the rhesus macaques with HIV, Dr. De Paris studies the macaques by infecting them with simian immunodeficiency virus, or SIV, the non-human primate version of HIV.1 Dr. De Paris explains that “[one] can mostly recapitulate in the neonatal and infant macaque model is the most severe form of the HIV infection in infants.”2 Through studying how SIV affects infant rhesus macaques, researchers can translate and apply that

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Dr. Kristina De Paris information to better understand how HIV would affect human infants. Dr. De Paris acknowledges that the model “has been proven to be extremely valuable for...the design and preclinical testing of pediatric HIV vaccines,”2 but she recognizes the limitations that come with the use of an animal model. For example, although HIV is closely related to SIV, they are not identical; the outer layer of protein of the viruses, known as the envelope protein, differs, preventing different species’ immune systems from recognizing and dealing with viruses not targeted towards them. Our immune system comprises of highly specific defense proteins known as antibodies, which interact with the envelope proteins of viruses that enter the body.

Vaccines are designed to activate these antibodies in order to prevent infection.

Thus, when the two viruses differ in their

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Carolina Scientific envelope proteins, difficulties arise in creating a vaccine that can translate from immunizing rhesus macaques from SIV to immunizing human infants from HIV.2 However, researchers have been working on chimeric SIV/HIV viruses, known as SHIV, which are viruses that contain the genes of both SIV and HIV viruses.1 Using the chimeric SHIV viruses will allow researchers to better understand HIV pathogenesis in humans.

Dr. De Paris is currently focusing on two main projects; the first is to create a better understanding of the infant immune system, and the second is developing a pediatric vaccine to target HIV locally. In order to develop a vaccine, it is crucial for researchers to understand how the infant immune system operates and changes as the individual grows older. Dr. De Paris states that “vaccine efficacy is often very different for an adult versus for an infant.”2 The infant’s immune system is functionally immature, which often results in the “disease [being] more accelerated and severe.”2 As a fetus, a child is in a more tolerant environment, able to share their mother’s immunity. However, after birth, Dr. De Paris explains that “[the infant’s]... [immune] response is qualitatively and

quantitatively completely different from an adult’s”2 due to having to “learn to accept the beneficial [microorganisms], while simultaneously learning to recognize pathogenic bacteria.”2 Consequently, an infant’s immune response to disease-causing organisms and viruses is suboptimal, making them highly susceptible to infections, including HIV. In addition to studying how an infant’s immune system operates and develops from birth to one year of age, Dr. De Paris is also researching a novel pediatric HIV vaccine strategy. As infants orally consume HIV-infected breast milk, an oral mucosal vaccine would specifically induce immune “responses at the sites where the virus can enter,”2 targeting the cells lining the mucus membrane of the mouth. As Dr. De Paris stated, “we rationalize that if we include a mucosal vaccination, our chances to induce immune responses at these sites will be increased,”2 thus providing a more focused local immunization of HIV infection. The pediatric oral mucosal vaccination is a promising strategy for preventing HIV infection from breastfeeding in infants.

From recognizing a lesser-known method of HIV infection to utilizing an

effective animal model to study immune development and viral pathogenesis, Dr. De Paris has been involved in many HIV research projects. She has collaborated with investigators from the Center for AIDS Research, Howard University, and Duke University, as well as physicians from UNC. To expand her current studies on the infant immune system and the pediatric HIV vaccine, her future goals include researching neurological conditions in HIV-infected infants and exploring how HIV-exposed uninfected infants are more susceptible to diseases like malaria and tuberculosis. Her multilevel research endeavors are complex and intertwined, addressing the equally complicated problem of vaccinating infants from HIV.

References

1. Abel, K. The rhesus macaque pediatric SIV infection model – a valuable tool in understanding HIV pathogenesis and for designing pediatric HIV-1 prevention strategies. Curr HIV Res. 2009, 7, 2-11.

2. Interview with Kristina De Paris, Ph.D. 09/27/16.

Figure 1. (Left) A member of the De Paris Lab processing infectious samples in the tissue culture room. Photo courtesy of Dr. De Paris. (Right) An adult rhesus macaque. Photo taken by Einar Fredriksen, distributed under a CC-BY 2.0 license.

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health and medicine

TESTING A TEST:

Can HIV Self-Testing Kits make people aware of their status?

I

By Adesh Ranganna

n the 1950s, the United States Public Health Service’s recommendation to fluoridate public water supplies helped reduce the prevalence of tooth decay in communities across the country. Around the same time, the movement toward enriching processed flour with vital nutrients made pellagra, a disease caused by niacin deficiency, virtually disappear from the United States. Clearly, innovations in public health can have dramatically positive effects on the communities they target. However, when deciding how to implement novel public health policy, as with all new public policy, the issue arises that humans are unpredictable and innovative strategies are new and untested. The combination of the unpredictability of human behavior with the uncertainty regarding a novel public health approach usually portends unexpected consequences. It is no surprise, therefore, that before implementing innovative public health programs, extensive research is necessary to investigate the effects of any proposed changes.

HIV self-testing kits are one of the public health innovations the public health community is examining. A relatively new innovation, HIV self-testing kits allow individuals to ob-

Figure 1: Prevalence of HIV/AIDS epidemic in Africa. Photo

by Louis Waweru via Wikimedia Commons.

tain their HIV status in as little as 20 minutes through a sample of fluid obtained from the mouth.1 Despite progress made in other parts of the world, the HIV/AIDS epidemic remains a pressing public health concern in sub-Saharan Africa. Of the estimated 36.7 million people living with HIV globally in 2015, 19 million resided in Eastern and Southern Africa, and 46% of all new HIV infections arose Dr. Donaldson Conserve from this region. Why are levels so high in this region? One explanation is that too many people, especially men, are simply unaware of their HIV status.

When people in HIV-inflicted communities do not know what their HIV status is, levels of HIV related illness and death rise.1 This is because a person who is unaware of his/her status is less likely to feel the need to practice safe sex. Additionally, individuals who do not know their status are less likely to go to a clinic and begin receiving the anti-retroviral treatment necessary to combat the advancement of the disease. When infected individuals are neither receiving treatment nor engaging in safe sexual behaviors, the rate of transmission rises.1 For this reason, getting people tested is critical to fighting the spread of HIV. In low resource countries, including many in Sub-Saharan Africa, self-testing kits have the potential to increase HIV status awareness. HIV self-testing kits can be cheaper than employing health workers, and self-testing can help alleviate issues related to stigma and confidentiality that prevent many from visiting traditional clinics.

Dr. Donaldson Conserve, a postdoctoral research fellow in the department of Health Behavior at the Gillings School of Global Public Health, is attempting to discern the effectiveness of HIV self-testing in combatting the HIV/AIDS epidemic.

His research focuses on men, who tend to get tested for HIV at lower rates than women.

There are many reasons why levels of HIV testing remain low amongst men in low resource countries. Dr. Conserve explains that barriers to testing in these areas include “fear of learning one’s HIV status, HIV stigma, lack of confidentiality and privacy at the clinic, and transportation costs

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vestigation that will continue until 2021. Formative research, Dr. Conserve explains, is similar to the kind of research a company like Pepsi would do before introducing a new beverage

The participants explained that selftesting offered several benefits over traditional testing services, including privacy, confidentiality, and even the convenience of not having to stand in long queues at hospitals.

Figure 2: Camps in Dar es Salaam. Photo by Dr. Donaldson Conserve. to the clinic”.2 The men in these areas know that once they are diagnosed with HIV, they will be labeled and encounter harsh discrimination and judgement.3 In interviews that were conducted with Tanzanian men in one of his previous studies, Dr. Conserve explains that a lot of the men were aware that they had engaged in risky sexual behaviors. Many suspected they were already HIV-positive, but the fear of confirmation of their status lead some to decide that “they would rather not know” for sure.2 In his study, Dr. Conserve and his team conducted qualitative interviews with 24 men in Tanzania to understand their HIV testing behaviors as well as their interest in HIV self-testing.

This formative research was the first phase of a multi-phase in-

type to all of its customers. Pepsi would conduct focus groups to explore consumers’ perceptions of the brand, their receptiveness to new beverages, their preferences in taste, etc.

Similarly, in his formative study, Dr. Conserve wanted to understand how aware Tanzanian men were of HIV self-testing, their motivations for wiling to use the self-test kits, and any challenges they may face regarding its usage.

The study obtained several important findings. When asked about potential challenges associated with HIV selftesting, multiple participants expressed a lack of confidence in the accuracy of the test as well as their ability to perform it properly. Others worried that the lack of counseling available to individuals who ascertain that they are HIV-positive could lead them to harm themselves or even commit suicide.

The majority of the men that were interviewed (71%), reported that they would be willing to try HIV self-testing.

The participants explained that self-testing offered several benefits over traditional testing services, including privacy, confidentiality, and the convenience of not having to stand in long queues at hospitals. Some of the participants that had indicated they were not willing to try HIV self-testing changed their minds after seeing a video demonstration of how the procedure worked.

Having completed the first phase of his study, Dr. Conserve is now preparing to begin the second phase of his investigation, in which 300 men in Tanzania will actually be offered the opportunity to use the HIV self-testing kits to see whether they are able to properly perform the test and interpret their results. Regarding the role of self-testing in combatting HIV, Dr. Conserve explains, “HIV self-testing has the potential to increase the number of people who test for HIV because it allows people to test themselves in the privacy of their home”.2 He also understands, however, that self-testing kits are just one of many tools that should be employed by public health programs to combat the spread of the disease. Dr. Conserve believes self-testing kits will help fill in the gaps that traditional HIV testing services cannot reach.

References

1. Martínez Pérez, G.; Cox V.; Ellman, T.; Moore, A.; Patten, G.; Shroufi, A.; et al. PLoS ONE. 2016, 11, 1-15.

2. Interview with Donaldson Conserve, Ph.D. 09/15/16.

3. Conserve, D.; Sevilla, L.; Mbwambo, J.; King, G. Am. J. Mens Health. 2013, 7, 450-460.

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San Juan de Lurigancho, Lima,Peru.

Courtesy of Achsah Dorsey

Anemia: A Blessing and a Curse

Iron deficiency protects members of Peruvian communities from other diseases

By Alexandra Corbett

I

magine feeling inexplicably fatigued regardless of how much sleep you got, and constant weakness and shortness of breath every time you tried to partake in physical activity. These are just a few of the symptoms of iron deficient anemia – and that’s if your case is minor. People that suffer from severe iron deficient anemia can face exhaustion, excessive sleeping that borders on hypersomnia, shortness of breath, difficulty doing physical activity, and frequent headaches.1 In minor cases, iron deficient anemia is only a frustrating inconvenience, but in severe cases, it can impair an individual’s daily functioning.

In industrialized countries such as the United States, approximately 18% of pregnant women, 12% of non-pregnant women, and 9% of school-aged children ages five to fourteen suffer from iron deficient anemia.2 However, in developing countries, these statistics are much more dire; 56% of women and 53% of school children have iron deficient anemia.2 Anemia is especially challenging for citizens of developing countries, who are much more likely to be employed for physical labor than citizens of industrialized countries. Despite efforts since the 1960s to improve iron deficiency in developing countries through iron supplementation, the incidence rate of this condition remains high.2 Women and children are especially susceptible to anemia. For women, this is due to biological factors such as menstruation and pregnancy, processes through which women naturally lose blood and thus iron.

Children have a greater susceptibility to anemia due to their

developing immune systems and growing bodies.1 While men can also suffer from anemia, incidence rates are less common when compared to those of women and children.

Achsah Dorsey, a Ph.D. student at UNC-Chapel Hill, is investigating iron deficient anemia in Peru.

Though she originally intended to do research on sex differences in health and wellness, she became more interested in the curiously high Achsah Dorsey, incidence of iron deficient anemia Ph.D. Student in the migrant community she was studying in San Juan de Lurigancho.1 As a result, she switched tracts and began to investigate iron deficiency. Though the incidence of iron deficiency in Peru is lower than the average for all developing countries, in American countries such as Peru, pregnant women and school-aged children have a considerably high incidence of iron deficient anemia (35% and 23% respectively).2 Dorsey’s investigation led her to develop a hypothesis about the cause of sustained anemia in this Peruvian community. Her hypothesis was inspired by other research involving anemia. In many African countries, where iron deficient anemia rates are some of the worst among children and women, children are given iron supplements to better their health and

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Carolina Scientific increase their iron levels. However, the children who took iron supplements tended to contract and die from malaria at a significantly higher rate than those who did not.3 This is due to the fact that iron helps to circulate oxygen through blood, and since bacteria rely on high levels of oxygen in the blood, it is much harder for bacterial infections to manifest in people with lower levels of iron in their blood.3 As this pattern was investigated, a theory arose about the optimal level of iron for people in these areas of high infectious disease loads. The idea is that there is a sort of ‘Goldilocks’ zone in which there is enough iron in the blood that individuals do not suffer from anemia, but little enough that it makes it difficult for bacterial infections to manifest.3 Dorsey explains, “It’s a trade-off;” lowering your iron stores can increase the chances of suffering from anemia and the many unpleasant symptoms that may entail, but it can also decrease the risk of contracting a number of bacterial infections, some of which could be deadly.3

“It’s a trade-off;” lowering your iron stores can increase the chances of suffering from anemia...but it can decrease your risk of contracting a number of bacterial infections.

Dorsey believes that something similar may be happening in this Peruvian community. Due to the role that iron plays in oxygen circulation, Dorsey is especially interested in investigating the relationship between respiratory infections and iron deficiency. This is especially important because, as of 2013, lower respiratory infections are responsible for the greatest number of years of life lost due to premature death in Peru.4 While the potential benefits of iron deficiency in developing countries with high infectious disease loads such as Peru is obvious, the causes are much less so. While national intervention to prevent iron deficiency in Peru started within the last five years, it has been a cause of concern for decades, and community-level interventions have started at different times over the past few decades.3 These interventions involve the distribution of iron supplements in the form of flakes that can be mixed into food. However, despite these measures, rates of iron deficiency still run very high.

Unfortunately, this problem is far from simple and could have social as well as biological causes. Financial status is just one example of a potential social cause. The migrant community that Dorsey works with is considered lower class, which means that many families may be unable to afford meat – which provides an ample source of iron – to feed themselves or their children. Potatoes are one of the biggest crops in Peru, being cheap and easily accessible to everyone living there. However, potatoes are iron inhibitors, preventing the body from absorbing iron.3 Additionally, for decades, parents who fed their children iron-rich foods like meat and eggs noticed that their children were more frequently ill than children whose diets contained significantly lower amounts of these foods. Thus, parents who noticed this pattern would alter their children’s diets to try to avoid sickness.3 Furthermore, considering that these dietary patterns have been observed

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Figure 1: The difference between normal and anemic blood.

Courtesy of Can Stock Photo. for decades, maybe even centuries, it is possible that people with a long ancestry of living in Peru could be less biologically capable of absorbing and retaining iron than others.

“So how do you strike this balance between what is good for you and that environmental context?”1 This is one of the most important questions that Dorsey is seeking to answer, in addition to figuring out why the members of this Peruvian community continually struggle to retain iron. Dorsey hopes that her work will be able to benefit the members of the Peruvian community she is studying, as well as others suffering from iron deficiency, by promoting this optimal level of iron that decreases the risk of contracting diseases, but does not impair daily life. This could help to make national intervention more adaptable to changing environments. It would lower the required amount of iron supplementation in times of disease outbreak and raise it in times of community health.

Additionally, it would vary between different communities according to environmental context, ultimately resulting in the optimal health of the community.

References

1. “Iron Deficiency Anemia.” American Society of Hematology. American Society of Hematology, 2016. Web. <http:// www.hematology.org/Patients/Anemia/Iron-Deficiency. aspx>.

2.Ramakrishnan, U.; Imhoff-Kunsh, B. Handbook of Nutrition and Pregnancy. Ed. Lammi-Keefe, C. J.; Couch, S. C. 2008. 337-54.

3. Interview with Achsah Dorsey, Ph.D. 09/29/16.

4.“Peru.” Institute for Health Metrics and Evaluation. University of Washington, 2013. Web. <http://www.healthdata. org/peru>.

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Figure 2: A child’s medical statistics are taken with the help of Dorsey. Courtesy of Achsah Dorsey.

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Illustration by Rachel Howard

Local Food For All A

BY ANNIE CHEN

t a barbeque, one would expect juicy brisket and glazed ribs, charred a bit black from the grill, not pulled pork with a vegetable mix of cabbage, collards, onions, and sweet potatoes on brown rice topped with vinegary barbeque sauce. But this dish is exactly what Dr. Alice Ammerman, UNCChapel Hill Nutrition Professor and the Director of the Center for Health Promotion and Disease Prevention, served at Lenoir County’s BBQ Festival in 2011. She used locally-grown, in-season vegetables to create a heart-healthy dish, much to the surprise of the festival visitors. They came for glazed ribs and smoked sausages; but, upon trying Dr. Ammerman’s recipe, patrons were amazed to discover how tasty vegetables and brown rice were with some barbeque sauce.

Some of the leading causes of death in the United States are heart disease, cancer, type-two diabetes, and obesity. All of these conditions are at least partially preventable (except in cases of genetic predisposition) by engaging in regular exercise and a healthy diet. People’s dietary habits are influenced by many factors, including environment, income, and culture. To combat chronic disease, behavioral problems such as diet and inactivity (both influenced by family, culture, and national policies) must be addressed.3 However, as Dr. Ammerman’s research on evidence-based methods indicates, many of the proven methods to prevent obesity and other chronic diseases are rarely used in public health because they are not well designed for lower income populations with limited resources.4 To combat this problem, Dr. Ammerman aims to provide communities and healthcare professionals with the

correct “tool-kits” to tackle public health problems.4 Dr. Ammerman’s work with chronic disease is focused on lower-income populations and minorities, who have a “higher risk for chronic disease”.2 This can largely be attributed to a lack of access to inexpensive healthy food. While soda and butter become cheaper and cheaper, fresh fruits and vegetables rise in price.

With the low cost of production of Dr. Alice Ammerman high fructose corn syrup, sugar has been made more widely available in almost every processed food. Ammerman’s observations are evidenced by the Stroke Belt, a region of 11 states plagued with high incidences of stroke, high blood pressure, obesity, and diabetes.

“My research mission includes taking on the Stroke Belt with good-tasting Southern food,” said Ammerman.2 Lenoir County, North Carolina, is part of the Stroke Belt, with high incidences of heart disease and obesity. One could argue that Southern food and inactivity created the Stroke Belt; however, eliminating Southern food culture is not necessarily the answer. By partaking in the local BBQ festival and transforming traditional foods into healthier alternatives, Dr. Ammerman is immersing herself in the Lenoir County and Southern barbeque culture.

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Carolina Scientific “Rather than just trying to tell people they need to put aside what they eat because it’s not healthy,” she said, “I’m working to improve the quality of food within their traditional dishes.”1 Similarly, at Kinston, NC’s 2014 BBQ festival, Dr. Ammerman promoted her heart-healthy hushpuppies enriched with more whole grains, nuts, and vegetables, all fried in vegetable or olive oil instead of lard or shortening. More recently in Robeson County, another poor county with high rates of heart disease and obesity, she participated in a chili cook-off,

‘Rather than just trying to tell people they need to put aside what they eat because it’s not healthy, I’m working to improve the quality of food within their traditional dishes.”

health and medicine

Along with pushing federal assistance programs to provide healthier food options, Dr. Ammerman is also planning nutrition education classes to improve health literacy in lower-income populations. However, she faces the challenges of inadequate grant funding and low attendance of her classes.

As the co-chair of the steering committee of UNC’s Food for All theme, Dr. Ammerman seeks to further the understanding of proper nutrition and the historic and cultural factors that influence what we eat. The importance of Dr. Ammerman’s research lies in its goal of changing public health policy by implementing research-proven methods in public health institutions. While treating diabetes and cardiovascular diseases with medicine can be effective, helping people change their lifestyles in order to prevent such diseases from occurring at all is the next step in improving public health and saving lives.

References

using sweet potatoes and beets in her chili sauce. Her “Sweet Beat” chili was served with brown rice and she sweetened the dish with sweet potatoes rather than added sugar. Again, people were astonished at how good these dishes tasted.

Rather than soda, she served these dishes with infused water and other alternatives. These “small steps” described and employed by Dr. Ammerman highlight how people can still enjoy their traditional tasty dishes, while making manageable alterations toward using whole grains, vegetables, or vegetable and olive oils instead of their less healthy alternatives.

These small changes can lead to significant improvements in public health. To address economic concerns about comparatively higher prices of healthier ingredients, Dr. Ammerman’s studies also point out small price differences between a food product and a healthier alternative for it; for example, white rice and brown rice.

With local food, “there’s the joy of community engagement, growing [food], and cooking,” said Dr. Ammerman.2 However, she recognizes that local food is often a luxury afforded only to wealthy consumers. Two federal assistance programs she is working with are the Supplemental Nutrition Assistance Program (SNAP), and Women, Infants, and Children (WIC). Ammerman takes advantage of SNAP and WIC to pursue her goal of making local food more accessible to everyone. With WIC, it was only in 2009 that families could purchase fruits and vegetables. At grocery stores, however, the $2 WIC vouchers are inconvenient for picking foods that are under or over $2. Ammerman helped create produce packs that cost exactly $2 to encourage WIC users to use their vouchers. Dr. Ammerman is also working with SNAP in corner stores and convenience stores in areas that lack grocery stores with affordable healthy options. By using North Carolina’s Healthy Corner Store Initiative grant, she and others will be able to encourage these stores to carry healthy food. In addition, she is currently working with the US Department of Agriculture (USDA) to subsidize Community Supported Agriculture (CSA), a partnership between farmers and consumers to deliver produce. By subsidizing CSA, the price of a monthly box of fresh vegetables is significantly reduced, allowing lower-income households to pursue a healthier diet.

1. Interview with Alice Ammerman, Ph.D. 09/28/16.

2. Flourish Training Talk with Alice Ammerman, Ph.D. 9/12/16.

3. Ammerman, A; Smith, T.W.; Calancie, L. Annu Rev Public Health. 2014, 35, 47-63.

4. Leeman, J; Sommers, J; Leung, M; Ammerman, A. JPHMP. 2011, 17(2), 133-140.

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Figure 1. (Top) Obesity rates in women by race.

Courtesy of Dr. Ammerman by the CDC. Figure 2.

(Bottom) Dr. Ammerman serves her Sweet Beat chilli in Roberson County. Courtesy of Catherine Rowheder.

Illustration by Rachel Howard

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The Ethics of Genomics

By Aditi Adhikari

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philosopher, a sociologist, a lawyer, and a medical geneticist walk into a room. It sounds like the beginning of a bad joke, but in fact these are the leaders bringing our attention to the most important questions surrounding scientific policy today.

Professor Rebecca Walker is just one of many people involved in the Center for Genomics and Society, an ELSI Center of Excellence at UNC funded by the National Institutes of Health. The Center for Genomics and Society is investigating the ethical, legal and social implications, hence ELSI, of implementing general population genomic screening for highly deleterious, but rare, treatable genetic conditions. Ever since the Human Genome Project began in the 1990s, the National Institutes of Health has funded such supplementary investigations that examine the ethical and legal aspects of genetic research.1 Some well-known points of contention that have arisen from research in genetics are the ethical and practical questions surrounding designer babies and genetically modified organisms, but Dr. Walker, as part of Dr. Gail Henderson’s team on a project called GeneScreen, is focused on another real-life application of genetics: screening for prevention and early treatment of medically actionable conditions.

Screenings are not new to the world of public health— newborn screenings for genetic conditions that must be urgently addressed are already the norm, where parents are simply informed of the procedure.1 In some places, however, parents are still in charge of deciding whether or not they

want to screen their child for deleterious genetic mutations or other health problems. In older demographics, mammograms and colonoscopies are standard measures in preventative healthcare.2 Although at first glance screenings seem like an entirely beneficial procedure, the ELSI team at UNC explores the darker questions behind implementing them as standard Dr. Rebecca Walker policy. Since these genes are rare and do not account for the vast majority of the disease burden in society, does screening benefit the population as a whole in any significant way?2 Is it justified to cause people unnecessary stress when the tests may not reveal anything important or concerning?1 “[We are in our] second iteration of a 5-year NIH grant to think about the ethical, legal, and social implications of human genomics,” explains Dr. Walker.1 The Preventative Genomic Sequencing (PGS) tests the team is examining can identify people at risk of inheritable health issues such as certain types of breast cancer, colon cancer, arrhythmia, and iron overload disease (hemochromatosis).2 All of these conditions have potentially fatal effects that can be mitigated with early identification and treatment, but often times the chance of finding

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Carolina Scientific medically actionable genes that cause these disorders is so low that researchers wonder if PGS will have a significant impact on society while being cost-effective.

Questions abound when it comes to the ethics of implementing such a procedure. Should providers make sure people have healthcare in place before doing the screening? Or is it better to screen independently of insurance status so they might seek insurance? Should these kinds of screenings only be offered to people who are old enough to consent themselves? The “right not to know” allows patients to opt out of knowing the results of their screening, but is it ever appropriate to tell them anyway?2 These questions are all important to consider when crafting effective health policy, so in order to answer them, Drs. Walker and Henderson and the rest of the ELSI team are piloting a screening and surveying people about their perspectives, feelings, and opinions surrounding the procedure.1 Although the screening has clear health benefits—such as the early identification of the BRCA 1 or 2 genes that cause breast and ovarian cancer or the HFE gene that causes hereditary hemochromatosis, a disease that causes the body to absorb too much iron and leads to severe organ and joint damage—this pilot screening could reveal whether or not PGS also has adverse sociological effects. After all, a policy is inadequate when it implements a procedure that has significant negative psychosocial effects on the population.

“Genetics is obviously very hard for people to understand, and so if you tell them, ‘you’re going to get this screening,’ and they [get the results back but] don’t have any of these mutations that we’re looking for… Are they then going to think ‘okay, I’m not going to get breast or ovarian cancer because I don’t have the BRCA 1 or 2 gene’?” muses Dr. Walker. “And that, of course, is not true,” she adds.1 Thus, screening could cause patients to alter their previously healthy habits and behaviors in detrimental ways simply because they’re not at risk of acquiring certain health problems, which ultimately harms them more than it helps.

Genomics is by no means the only scientific field that has created a partnership with philosophy and ethics. The fields of ethics and neuroscience have Illustration by Claire Drysdale also combined to give rise to the relatively new field of neuroethics, which directs attention at the implications of utilizing brain imaging and lie detectors in court cases. Is it okay to effectively read a criminal’s mind to prove them guilty of a heinous crime, or should the biological functions of your brain remain private? This type of question creates a clear bridge between science, ethics, and criminal justice. The connections between ethics and science continue in the field of animal research ethics—if we make research policies based on individual cognitive ability of an animal, then does that mean researchers can use severely cognitively impaired humans in place of “cognitively sophisticated nonhuman animals”?4 Of course, just the idea makes people balk, so researchers wonder why the lesser protection of cognitively inferior animals is justified.

These are just some of the questions Dr. Walker continues to ask herself as she explores the reach of ELSI as well as her own personal interest in animal research ethics. By immersing herself in the scientific research happening on campus and examining it through the lens of a professional philosopher, she seeks to find the answers necessary to move research and health policy forward in a way that is ethically sound and effective.

References

Figure 1. The BRCA gene affects several different areas of the body. Image courtesy of Wikimedia Commons.

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1. Interview with Rebecca Walker, Ph.D. 09/21/2016.

2. Morrissey, Clair; Walker, Rebecca L. J Med Philos. In Publication 3. https://www.genome.gov/10001214/learning-about-hereditary-hemochromatosis/ 4. Walker, Rebecca L. Hastings Center Report. 2016, 46, 28-30.

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No Scientist Left Behind In order to increase diversity in STEM, education must be accessible to all

By Alina Joseph

Photo by Chung Ho Leung, CC BY-ND 2.0

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ika virus, the iPhone 7, and genetic engineering -- these are just some of the topics you see in the news each day.

Almost every aspect of our daily lives involves the disciplines of science and technology. The world is bombarded with the need for technological and scientific advancements as we move towards the future, and we need to be prepared to keep up with this fast-paced world. With STEM, this can be accomplished.

STEM programs focus on providing a well-rounded education in the four subject areas of science, technology, engineering, and math. From curing diseases that claim millions of lives, to developing everyday technologies that rival our smartphones, many of the things with which we move towards tomorrow involve STEM. It becomes increasingly important to involve everyone in STEM so that all students are united in tackling new obstacles. Unfortunately, our journey towards STEM immersion in education too often results in leaving an important part of the population behind – minority students.

As a nation with people from a range of backgrounds, we should strive to reflect this diversity in all aspects of our culture, especially in the scientific community. However, white and Asian engineers and scientists make up eighty-seven percent of the STEM workforce.1 This means only twelve percent of engineers include underrepresented minorities, such as African Americans, Hispanics, and Native Americans.1 The numbers are just as low for other STEM fields, such as scientific research and data analysis. How is it that with this much influence of STEM in our day to day lives that minorities are largely underrepresented?

One of the biggest issues that prevents diversity in STEM is unequal access to academic funding.2 Across the

country, schools that receive the least funding are usually in areas of lower socioeconomic status with a higher density of minority students.2 With the inability to support all facets of education due to budget cuts, the impact of various programs is minimized or even removed entirely by school districts. Since STEM education has various costs associated with equipment and technology, these subjects are affected most by these decisions. As a result, minority students’ chances of exposure to quality STEM education decreases, and these students lack the opportunity to truly consider this as an option for their future. This has a tremendous impact on our nation’s involvement with STEM as a whole. In order to develop solutions to the many challenges that arise in the world, we must have diverse perspectives. This remains unattainable if it is difficult to provide the education every youth in America needs to excel in STEM. To increase minority participation in STEM fields, UNCChapel Hill has implemented a variety of programs. One of these is the Summer of Learning and Research program, also known as SOLAR. This ten week program , targeted towards rising juniors and seniors from undergraduate universities across the country, aims to provide minority students with a chance to perform independent research in preparation for a career in biomolecular research.3 Another program out of the many that UNC offers, designed with the intention of increasing minority participation in STEM, is the IDEA (Increasing Diversity and Enhancing Academia) Carolina Undergraduate Research Experience. The program exposes minority students to the field of geosciences.4 Participants work with UNC faculty to perform lab and field research and showcase their research at regional and even national conferences.4 Students interested in continu-

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ing research after graduation can also attend graduate school preparation seminars through IDEA.4 UNC also offers a number of scholarships to minority students. The most well-known is the Chancellor’s Science Scholar’s program, which provides students with research experience, guidance for professional school, and a scholarship of $10,000 a year.5 This opportunity also involves a six week program prior to beginning freshman year during which students take courses which will acclimate them to the intensity of college coursework.5 The University of Maryland – Baltimore County’s Meyerhoff Scholar’s program and the Howard Hughes Medical Institute partnered with Carolina to develop the Chancellor’s Science Scholar’s program in 2011.6 This program, which began in 1993, has had much success with increasing diversity in STEM.7 As of today, the program has had 1000 graduates, 478 of which have gone on to achieve Ph.D.’s or master’s degrees.7 Currently, another 300 graduates are enrolled in graduate programs.7 Overall, graduates of this program were more than 5.3 times more likely to currently be attending or have graduated from a masters or doctorate program than students who had declined joining the program.7The success of the Meyerhoff Scholars program displays the importance of diversity programs in increasing minority participation in STEM. UNC’s programs, which were modelled after Maryland’s, are expected to replicate these results.

Although diversity programs play a significant role in increasing minority participation in STEM, we still have much to achieve. With the continued development of STEM scholarFigure 1. As we move towards a more STEM based world, there is a need for more diversity in this field. Image by Bill Shrout, Public Domain. ships and mentoring programs directed toward minorities at universities we will soon be able to include individuals from all backgrounds on this journey forward.

References

1. Bidwell, A. STEM Workforce No More Diverse Than 14 Years Ago. http://www.usnews.com/news/stem-solutions/ articles/2015/02/24/stem-workforce-no-more-diversethan-14-years-ago. (Accessed September 24th, 2016).

2. Rogers-Chapman, M.F. “Education and Urban Society.”

2014, 716-737.

3. “Welcome to UNC’s SOLAR Program.” https://www.med. unc.edu/oge/stad/solar (Accessed October 6th, 2016).

4. Undergraduate Research Programs at UNC-Chapel Hill. http://our.unc.edu/resources/undergraduate-research-programs-at-unc-chapel-hill/ (Accessed October 6th, 2016).

5. Chancellor’s Science Scholars. http://admissions.unc. edu/chancellors-science-scholars/ (Accessed October 6th, 2016).

6. Chancellor’s Science Scholars at UNC. http://chancellorssciencescholars.web.unc.edu/ (Accessed October 13th, 2016).

7. Results – Meyerhoff by the Numbers. http://meyerhoff. umbc.edu/about/results/ (Accessed October 13th, 2016).

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Meet the Maddoxes

By Clara Williams and Allie Brindle

Illustration by Rachel Howard

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night out on the town, a dinner date for two, and a quaint discussion about the next big discovery in cell biology --UNC’ s Maddox duo excel in their field because of their support for each other and the passion they share for cell biology. Of course there is more to it than nerdy romanticism and intellectual conversations over a candlelit dinner; maintaining a balance between professional life, self care, and spending time with family and friends only gets more difficult in the higher levels of academia, particularly for dual-career families: couples where both members are lecturers or researchers. However, with the rate of hiring academic couples growing steadily (rising from 3% at the end of the 70s to 13% thirty years later)1,understanding and supporting the needs of these couples is increasingly important. This is particularly true in STEM subjects, where the number of women earning Ph.Ds is growing.1 These ‘ power couples’ offer up a great well of experience and knowledge, as they are able to combine

Through teaching, the Maddoxes feel they are achieving something far greater than praise for unearthing the unknown.

two different perspectives and backgrounds.

UNC’ s own Drs. Amy and Paul Maddox are a fantastic example of just what universities have to gain by opening themselves up to dual hires.

Dr. Paul Maddox Drs. Amy and Paul Maddox began his career in the sciences as a UNC undergraduate. The morning after attending a double-overtime Carolina vs. Duke basketball game, he flunked an 8:00 am differential equations midterm. He said this discouraged him from physics, which was just as well, because it allowed him to discover his love for biology. Dr. Amy Maddox, on the other hand, said that she had been interested in science for years. She entered and left college a biology major, but initially was unsure of what she wanted to do with her degree. On the recommendation of an academic advisor, she found a position at a lab investigating how hormones affect behavior in crabs and lobsters at Woods Hole Marine Biological Laboratory located on Cape Cod. The center, which is affiliated with the University of Chicago, is a major research hub

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Carolina Scientific for those interested in studying aquatic life. It was there that she discovered how biologists posequestions and seek out the answers through research, and realized that she adored the curiosity and energy in the scientific community. “That’ s what made it such a wonderful experience...” she said, “oh, and that summer I also met Paul.” Having changed his major, Paul realized his passion for research in Ted Salmon’ s lab at UNC, where he became a trained microscopist. It was that work which brought him to Woods Hole in the summer of 1996, where he met and fell in love with Amy. Having grown up in a time where major advancements in cell biology were commonplace, and great strides being made in the world of microscopy, the Maddox duo found themselves able to explore uncharted territory with minor limitation. As cell biologists, both are interested in the changes taking place within cells overtime, as organisms mature from a single cell into the diversity of animal life we see in the world today.

Amy’ s lab is currently seeking to uncover the mechanics of how cells change shape, stick together, move, and form groups to perform a specific task, ultimately making a whole animal.

In order to do this, the protein structure inside the cell that helps it keep its form, called the cytoskeleton, must rearrange itself.4 Paul’ s lab is studying how chromosomal matter is segregated in a cell. The chromosomes are condensed DNA material in the nucleus of the cell prior to cell division, but the roles and properties of the chromosome and the part they play in the cell division process are not very known. To better understand his lab focus and goals, a person should pretend that they are a water molecule within the cell nucleus looking at the chromosome. As a small molecule interacting with chromosomal matter, one might seek to explore the density and properties of the matter to better understand how it affects the cell at various stages of the cell cycle. Famous among biologists studying cell division is the analogy that he provided, “The chromosome is like a corpse at the funeral. It’ s the reason for the proceedings, but plays no active role.” Paul wants to identify specific roles given to the chromosomes.

Despite having a number of publications under their belts, they both agree that their greatest accomplishment is still in their future and their teaching philosophy. As Paul explained, “It’ s like [learning] a language... I crossed this threshold where I was no longer ‘ outside’ and I was able to subconsciously take the information and do something with it – synthesize it.”

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Through teaching, the Maddoxes feel they are achieving something far greater than praise for unearthing the unknown. And being a couple may give them something of an edge. Amy highlighted the fact that she and Paul hold joint lab meetings, which allows the students in both the Maddox’ s labs to benefit from the way in which their philosophies complement each other. Amy says that on a day- to-day basis, she has more specific demands for experimental outputs, and provides more guidance. Paul is more hands-off, and while happy to help students when problems crop up in their research, he expects a certain degree of independence. This allows them to mentor each other’ s lab members when one prefers a different approach, and provides a more balanced lab environment overall. Similarly, because both are searching for funding for very similar projects, they have the opportunity to support the other’ s lab when grants do not come through.

However, despite the benefits of being a dual-career academic couple, Amy and Paul say it has not always helped them. It is difficult for dual hires, particularly within the same department, to find positions, as universities often struggle to spread funding and equipment in a short period of time. Aside from this fact, the Maddoxes are able to expand on their original ideas through collaboration and experimenIllustration by tal suggestions that Isys Hennigar the other may not have considered. As Paul builds microscopes and provides imaging advice for Amy, she strategically plans how Paul can utilize his lab members to approach the problem in a different way, all while reminding the other of their successful capabilities. A day in the life is much more than heading a lab, managing a teaching job, and parenting a family, the Maddox couple aims to leave an impact on the world of science and UNC by challenging themselves and others to think scientifically and never stop questioning.

After all, two heads are better than one!

References

1. Schiebinger L, Henderson AD, Gilmartin SK. Dual-Career Academic Couples: What Universities Need to Know. 1st edition. Stanford(CA):Michelle R. Clayman Institute for Gender Research at Stanford University, 2008.

2. Interview with Paul Maddox, Ph.D. 01/20/2016.

3. Interview with Amy Maddox, Ph.D. 01/29/2016.

4. Heng, Y.; Koh, C. Int J Biochem Cell Biol. 2010, 42, 16221633.

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Allie Piselli Publicity & Fundraising Chair 54

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“Nothing in life is to be feared, it is only to be understood. Now is the time to understand more, so that we fear less.”

-Marie Curie

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

Carolina

scıentıfic Fall 2016| Volume 9 | 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 as well as the Carolina Parents Council.

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