Fall 2018 -- The Secrets of Space

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Carolina

Carolina Ca C Caro aro rolliin na a Scientific Scciien enttiifificc

scıentıfic Fall 2018 | Volume 11 | Issue 1

The Secrets of Space —USING NUCLEAR FUSION DATA TO IDENTIFY NOVA EXPLOSION PRODUCT— full story on page 26 1

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scÄąentific Mission Statement:

Executive Board

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 Editors: Scientific research, at its most fundamental level, is an endeavor that allows us to ask questions about the world around us. This unrelenting process of posing questions and seeking answers can shed light on our place in the universe, help uncover the inner workings of our minds, and reveal insights that shape future innovations in technology and medicine. At Carolina, original and exciting questions are asked every day. What could the role of massage therapy be in treating autism (pg 8)? How do different foods affect the way we feel (pg 32)? And, how do turtles find their way home (pg 34)? With this Fall 2018 edition of Carolina Scientific, we hope we inspire you to ask questions of your own. Enjoy! - Esther Kwon and Adesh Ranganna

on the cover Nuclear astrophysicists look into the formation of stardust grains from nova expolsions. Their results impact what we know of the solar system and its history. Full story on page 26. Illustration by Taylor Thomas.

Editors-in-Chief Esther Kwon Adesh Ranganna Managing Editor Akshay Sankar Design Editors Alexandra Corbett Associate Editors Janet Yan Ricky Chen Sara Edwards Marwan Hawari Andrew Se Copy Editor Aubrey Knier Treasurer Elizabeth Smith Associate Treasurer Sidharth Sirdeshmukh Publicity & Fundraising Chair Sophie Troyer Online Content Manager Rhea Jaisinghani Faculty Advisor Gidi Shemer, Ph.D.

Contributors Staff Writers Aneesh Agarwal Samantha Boeshore Peter Cheng Mehal Churiwal Lauren Glaze Harrison Jacobs Rhea Jaisinghani Rayyanoor Jawad Aubrey Knier Zhi-Wei Lin Janie Oberhauser Gracie Pearsall Kevin Ruoff Sidharth Sirdeshmukh Vaishnavi Siripurapu Praveena Somasundaram Zarin Tabassum Leo Zsembik Designers Brianna de la Houssaye Shaher Issa Taylor Thomas Jessica Tufts

carolina_scientific@unc.edu carolinascientific.org facebook.com/CarolinaScientific @uncsci 4

Illustrators Helena Ge Taylor Thomas Jessica Tufts Laura Wiser Zion Wu Copy Staff Anna Arslan Sara Bernate Coleman Cheeley Elizabeth Coletti Summer Epps Robert Fisher Jie He Shaher Issa Paige Jacky Hannah Rendulich Natalie Siegel Sophie Troyer Wilfred Wong Alex Yankalunas

Carolina Scientific

contents Medicine and Health

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The Alchemy of Healing

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Qigong Sensory Training

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Public Health

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Individualized, Data-Driven, Medicine

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Saving the Earth to Save Lives

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Understanding Your Nutritional Needs

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Genome Sequencing in Modern Medicine ย ย ย ย ย ย ย ย

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Environmental Science

Molecular Mysteries of Medulloblastoma ย ย ย ย ย ย ย ย ย ย ย

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Cortical &Qilepsies: SearD-GENE for a Cure ย ย ย ย ย ย ย ย ย ย ย ย ย

Life Science

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A Vast Unknown: The Gut Harrison Jacobs

Investigating Natural Phenomena at the Nanoscale ย ย วฆ ย ย ย ย

Is the Sun Our Last Ray of Hope?

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Light Shed on What Existed Before the Solar System

Galรกpagos Invasive Species Through the Lens of Ecohydrology

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Writing the Geological Story of Half-Dome Cliff

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Pathogen vs Host: An Evolutionary Arms Race

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Natureโ s Core Currency

Physical Science

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No Landmarks, No GPS, No Maps

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medicine & health

Illustration by Laura Wiser

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llchemy, ch hemyy the th philosophy ph hilosoph l hy that th hat d defines efi fines th the he ttransformarransfforma tion of matter, traces its roots nearly four millennia ago to ancient kingdoms. The concept of substance transmutation held great promise in early scientific and medicinal theories. While the specifics of this ancient methodology are not supported by modern research, there is an interesting parallel between primeval science and current state-of-the-art stem cell reprogramming research. Some of the latest work in stem cell oncology shows that tumor-targeting properties can be conferred onto skin cells, effectively repurposing them to work as tumor-homing stem cells. Dr. Shawn Hingtgen, investigator at the UNC-Chapel Hill Eshelman School of Pharmacy, says, “We’re trying to morph human skin into stem cells that seek out brain cancer. Ultimately, we’re trying to create a whole new way of treating cancer by harnessing these unique aspects of stem cells.”1 The current standard of care for glioblastoma, the most aggressive form of brain cancer, involves chemotherapy, surgery, and radiation therapy. However, survival is generally only Shawn Hingtgen one year from diagnosis.

there are arre few few advancements ad dvancements in sta ndar d rd d therapies h Though there standard therapies, stem cell research has seen tremendous growth in the past few decades. One of the major milestones in the early 2000s led to the unexpected discovery that stem cells are attracted to and drawn towards tumors. Yet, the process of reverting skin cells back to the pluripotent stem cell stage, and then forwards into the specialized cell type of interest, is very timeconsuming and a faster methodology is needed. “We could use [skin-derived stem cells] as this natural delivery vehicle,” said Dr. Hingtgen. “A lot of it came down to proving that the technology would work. The challenge was designing a personalized cell and making it work fast enough to treat a cancer patient.”1 This is the primary challenge Dr. Hingtgen and his lab are exploring, specifically focusing on targeting glioblastoma and other forms of brain cancer. This research involves transforming specific skin cells into tumor targeting cells. It works on the principle of directly converting one cell type into a different cell type with additional functions and avoids reversion to reduce lead time. This direct conversion process, developed by the Hingtgen lab, utilizes a virus that causes deadly disease to initiate specific transcription factors within cells to place certain receptors on the stem cell surface.2 This modifies the genome of the stem cells, giving them the homing and crawling properties needed to detect cancers. Tumor homing works through the process of chemotaxis, and stem cells sense factors that are released by the tumor. “We always say that the stem cells see the tumor as

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medicine & health

‹‰—”‡ Í?Ǥ Development of therapeutic and diagnostic induced neural stem cells (iNSCs). Photo by Shawn Hingtgen. on brain cancer or on any other indications.â€?1 So, what motivates Dr. Hingtgen and his research interests? “I’ve always wanted to work at that interface between basic science and the clinic to create something that can solve an urgent medical issue, and patients and create that translation. I think what really excites me is the innovative culture at UNC,â€? he says.1 The movement towards highly-specific and targeted cancer treatment through stem cell reprogramming is happening now, and it has the potential to unlock the medical care of the future. While terminal cancers today have no cures, using scientific research techniques in conjunction with clinicians creates a powerful combination with potential for clinical trials and movement into the clinical setting. According to Dr. Hingtgen, “Hopefully, in ten years, it will be the standard of care where patients can come in and get blood drawn or a little skin punch and in a couple days we’re able to process those into personalized cell therapy products. With a single injection, these cells can go in and they’ll be able to hunt down tumors. Then we could use the immune system to eliminate [the tumor] and keep it from ever coming back. That’s what we’re working towards.â€?1

a wound that never heals. The stem cells always want to heal and correct things, so they home towards the tumor and try to heal it,� Dr. Hingtgen said, “but they’re not strong enough to destroy the cancer. In a way, they’re like tumor-homing ‘Pac-Mans’ that want to chase tumors.�1 The newly created cells from the lab have receptors that enhance the natural properties of stem cells and carry medications directly to the tumor site. Additionally, these stem cells are engineered for each individual specifically, reducing the chance of immune rejection. Currently, this technology is being studied as a drug delivery mechanism for existing therapies. In the future, the lab is interested in investigating novel molecules that can be created for these highly specific cells to carry. The implications of patient-specific and tumor-targeting stem cell therapies are enormous. Due to the aggressive nature of cancers like glioblastoma, translation from lab research to the clinical setting is very important. A variety of factors are crucial for cancer patients, especially time and risk of undesirable side effects. The principle of translation plays a heavy role in the goals of this research, since application to patient care is critical to the viability and success of these new methodologies. As a result, utilizing this technology for other forms of cancers and diseases is an important consideration. Dr. Hingtgen says, “We can also hone to all sorts of cancers outside and below your neck, like peripheral tumors. We’re working on things like triple negative breast cancer and ovarian cancer. The same mechanism applies; we just need to make the same cell with different properties, and we can release it

References Í?Ǥ Â?–‡”˜‹‡™ ™‹–Š Šƒ™Â? ‹Â?‰–‰‡Â?ÇĄ ŠǤ Ǥ ÍœÍĽČ€ÍžÍ?Č€Í?ͤ ÍžǤ ÂƒÂ‰Ă— ǤǢ Â?‘Ž‹‡ ǤǢ —Â?‹–”— Ǥ ‡– ƒŽǤ Sci Transl Med. 2017ÇĄ ÍĽČ‹Í&#x;ÍŁÍĄČŒǤ

‹‰—”‡ ÍžǤ Č‹ Â‡ÂˆÂ–ČŒ Â?–‹–—Â?‘” ‡ƥ‡…–• ‘ˆ ‹ •Ǥ Ž‹‘„Žƒ•–‘Â?ƒ Č‹ ČŒ …ƒÂ?…‡” …‡ŽŽ •Š‘™Â? ‹Â? ‰”‡‡Â?ÇĄ ‹ • •Š‘™Â? ‹Â? ”‡†Ǥ Č‹ Â‹Â‰ÂŠÂ–ČŒ ‹‰”ƒ–‹‘Â? ƒÂ?† Š‘Â?‹Â?‰ ’”‘’‡”–‹‡• ‘ˆ ‹ • –‘™ƒ”†• …ƒÂ?…‡” …‡ŽŽ Ž‘…ƒ–‹‘Â?•Ǥ Š‘–‘• …‘—”–‡•› ‘ˆ Šƒ™Â? ‹Â?‰–‰‡Â?Ǥ

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QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST

medicine & health

QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST

ǣ A Traditional Chinese Medicine Approach to tism

QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST T QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST T QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST T QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST

QST T QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST QST

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hildren with autism characteristically have abnormal sensory experiences which may contribute to problems with communication and forming relationships with others. These different sensory experiences can elicit responses in a child that are often times perceived as socially abnormal. For example, a child with autism may feel nervous or pull away if a parent tries to hold their hand. Interactions that are typically considered affectionate are often times uncomfortable or painful to children on the spectrum. Autism is characterized as a bio-neurological developmental disability, with abnormalities in areas such as social interaction and cognitive function.1 Clinically, this disability is defined as having a delay in social and language skills and is characterized by tendencies towards abnormal and repetitive behavior.2 Autism is prevalent in the United States, with 1 in every 45 children receiving the diagnosis.3 However, little is known about the neural mechanisms that contribute to sensory ab-

normalities experienced by people on the spectrum. These neural mechanisms allow certain parts of the brain to interact with one another. Research is currently being conducted in areas such as integrative medicine and health to make life easier for people and families affected by sensory issues associated with autism. Integrative medicine and health can be described as treatment and research with a focus on holistic practices.4 This field of study focuses on therapeutic approaches that result in healing and increased overall health of an individual.4 Dr. Kristin Jerger, a licensed massage therapist and psychiatrist in UNC-Chapel Hill’s Program in Integrative Medicine, is working to improve quality of life for families affected by autism, as well as furthering the understanding of neural mechanisms involved in sensory abnormalities. Dr. Jerger conducted a feasibility study to begin investigating neural mechanisms underlying efficacy of a massage treatment program called Qigong Sen-

Dr. Jerger conducted a feasibility study to begin investigating neural mechanisms underlying efficacy of a massage treatment program called Qigong Sensory Training (QST) for children with autism. 8

Carolina Scientific sory Training (QST) for children with autism. QST, a form of massage, is a therapeutic approach to treating autism. There is extensive evidence showing that it effectively improves sensory processing in children 3-8 years old.5 The massage itself is derived from traditional Chinese medicine. The technique is similar to acupressure, following the same meridians used for acupuncture, but without needles.6 “With autism, there are certain areas of the body that are typically blocked—often around the ears and neck,� stated Dr. Jerger. “Where energy is blocked, there is typically pain or other problems.� A randomized clinical trial of elementary school-aged kids showed that by the end of a two-year period of treatment, responses to touch normalized by 73%, and the overall severity level of symptoms was reduced by 44%.5 “The intention of QST is to help children feel more comfortable in their body,� explains Dr. Jerger. Dr. Jerger’s goal is to determine the mechanisms that make this technique work so well. Currently, her work focuses on how the method affects the relationship between the central nervous system and the autonomic nervous system.1 The prefrontal cortex of the central nervous system composes part of the frontal lobe of the brain and has influence on personality and behavior.7 The amygdala takes on the role of a traffic cop, increasing or decreasing the flow of autonomic nervous system signals both to the prefrontal cortex and to the brainstem. These signals are transmitted to the heart, lungs, and the rest of the body by way of the vagus nerve, indicating arousal level.8 By calming the amygdala down through techniques such as QST, Dr. Jerger hypothesized that the flow of information and activity level in prefrontal cortex would increase.6 The feasibility study conducted at UNC involved 20 children diagnosed with autism who participated in a single visit study of QST.1 They were shown images of children displaying emotional facial expressions before and after receiving the massage treatment. Throughout the process, several measurements were taken, each within areas known to show improvement by this technique. Sound sensitivity was observed by measuring the threshold at which background noise was no longer tolerable to the child. Parasympathetic nervous system responses (part of the autonomic nervous system) were recorded by measuring changes in heart rate throughout the process. In addition, they observed activity of the prefrontal cortex by measuring cerebral oxygenation.1 Dr. Jerger’s study confirmed feasibility of the treatment protocol with 95% of the parents saying that they would bring their child back for follow-up sessions.6 Kristin Jerger The results also sup-

medicine & health

‹‰—”‡ Í?Ǥ Human body meridians used in acupuncture and acupressure. Image courtesy of Wikimedia Commons. ported the hypothesis that a substantial increase in prefrontal cortex occurs with the massage. This preliminary data can be used in designing subsequent studies to determine how the massage impacts the processing of social information as well as neural mechanisms involving the autonomic nervous system.6 In addition to the continuation of her study and the new neural mechanism hypotheses proposed, Dr. Jerger is developing a clinical outreach program with the goal of educating families affected by autism about the benefits of QST and training parents to perform the massage technique to help their own child. Dr Jerger explains that the goal of this program is to provide parents with an effective tool for reducing their child’s sensory symptoms while using touch to grow and improve their connection with their child.6

References Í?Ǥ ‡”‰‡”ǥ Ǣ —Â?Â†Â‡Â‰ÂƒÂ”Â†ÇĄ Ǣ ‹‡’Â?‡‹‡”ǥ Ǣ ÂƒÂ—Â”Â‘Â–ÇĄ Ǣ —ƼÂ?‘ǥ Ǣ ‡”‰‡”ǥ Ǣ ‡Ž‰‡”ǥ Ǥ Ž‘„ †˜ ‡ƒŽ–Š ‡†. 2018ÇĄ ͧǥ Í?njͥǤ ÍžǤ Â‹ÂŽÂ˜ÂƒÇĄ Ǣ …ŠƒŽ‘…Â?ÇĄ Ǥ J Neurol Disord. 2016ÇĄ Í ÇŁÍžǤ Í&#x;Ǥ ƒ„Ž‘–•Â?›ǥ Ǣ Žƒ…Â?ÇĄ Ǣ ƒ‡Â?Â?‡”ǥ Ǥ Ǣ Â…ÂŠÂ‹Â‡Â˜Â‡ÇĄ Ǥ Ǣ Ž—Â?ÇŚ „‡”‰ǥ Ǥ Ǥ Natl Health Stat Report. 2015ÇĄ 87ÇĄ Í?Č‚ÍžÍœǤ Í Ç¤ …ƒ†‡Â?‹… ‘Â?•‘”–‹—Â? ˆ‘” Â?–‡‰”ƒ–‹˜‡ ‡†‹…‹Â?‡ ƒÂ?† ‡ƒŽ–ŠǤ Š––’•ǣȀȀ‹Â?…‘Â?•‘”–‹—Â?ǤÂ‘Â”Â‰Č€ÂƒÂ„Â‘Â—Â–Č€Â‹Â?–”‘†—…–‹‘Â?Č€ Č‹ÂƒÂ…Â…Â‡Â•Â•Â‡Â† ‡’–‡Â?„‡” Í&#x;ÍœÂ–ÂŠÇĄ ͜͞Í?ͤČŒǤ ͥǤ Â‹ÂŽÂ˜ÂƒÇĄ Ǣ …ŠƒŽ‘…Â?ÇĄ Ǣ ƒ„”‹‡Ž•‡Â?ÇĄ Ǣ ‘”–‘Â?ÇŚ —Â?Â„ÂƒÂ”ÇĄ Ǥ The Research Institute at Western Oregon University. 2016. ͢Ǥ Â?–‡”˜‹‡™ ™‹–Š ”‹•–‹Â? ‡”‰‡”ǥ Ǥ Ǥ Í?ÍœČ€ÍžÍ&#x;Č€ÍžÍœÍ?ͤǤ ͣǤ ‹††‹“—‹ǥ Ǥ Ǣ ÂŠÂƒÂ–Â–Â‡Â”ÂŒÂ‡Â‡ÇĄ Ǣ —Â?ÂƒÂ”ÇĄ Ǣ ‹††‹“—‹Ǣ Ǣ

Â‘Â›ÂƒÂŽÇĄ Ǣ Indian J Psychiatry. 2008ÇĄ 50(3)ÇĄ ÍžÍœÍžČ‚ÍžÍœͤǤ ͤǤ Â… ‘””›ǥ Ǥ Ǥ Am J Pharm Educ. 2007ÇĄ 71(4).

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medicine & health

ČĊēĔĒĊ ĘĊĖĚĊēĈĎēČ Ďē ĒĔĉĊėē ĒĊĉĎĈĎēĊ ͝Ǥ ǡ ǡ actual onset of cancer. This can greatly improve the options and outcomes for patients. Photo courtesy of Creative Commons.

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enomic sequencing is increasingly being used in clinical settings to enhance current diagnostic approaches. With this, however, many questions regarding its use have been left unanswered. To address these issues, investigators at the UNC School of Medicine are actively studying the overall effectiveness of genomic sequencing. In the first phase of their research, the North Carolina Clinical Genomic Evaluation by Next-Generation Exome Sequencing (NCGENES) group had already encountered a miracle case. A woman with a lifelong history of issues in her leg muscles, which prevented her from participating in day-to-day activities, was admitted into their clinical study. After sequencing her DNA, the research team discovered that she had a treatable disease, and her neurologist started her on the appropriate medication. Only a couple of weeks later, she was able to walk on her own again. It is cases like hers that inspire the research team at NCGENES—led by Dr. Jonathan Berg of the University of North Carolina at Chapel Hill’s Department of Genetics, to push the boundaries of genome sequencing as a clinical application. The NCGENES research initiative aims to investigate

the effectiveness of DNA sequencing as a diagnostic tool in the clinic. Dr. Berg’s research team uses highthroughput sequencing technology to identify variants in the patient’s genetic code. During their first study, NCGENES focused on practical problems associated with clinical sequencing, specifically in sequencing results called “secondary findings.” Secondary findings are variants that are unrelated to the patient’s initial symptoms but might be relevant to a different health concern or phenotype. For example, if a patient is sequenced to check

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Carolina Scientific

‹‰—”‡ ÍžǤ Sequencing the DNA of newborns allows physicians to catch genetic †‹•‘”†‡”• ‡ƒ”Ž› ‘Â?ÇĄ ƒÂ?† ‹– ’”‘˜‹†‡• •ƒŽ‹‡Â?– „ƒ…Â?‰”‘—Â?† ‹Â?ˆ‘”Â?ƒ–‹‘Â? ˆ‘” ƒŽŽ ˆ—–—”‡ diagnoses. Image courtesy of Creative Commons. for an inherited genetic disease and their results also show that they have a genetic predisposition to breast cancer, then their breast cancer marker is a secondary finding. Accordingly, Dr. Berg’s team focused on studying the clinical relevance of secondary findings, and the best practices for reporting them to their patients. Now in their second phase of funding, the NCGENES group has a new goal in mind: to prove to health insurance companies that clinical genome sequencing can be more effective than traditional genetic tests. Dr. Berg spoke about the slow approach that insurance companies take towards supporting new diagnostic tests: “It’s a continual struggle in genetics because we’re relatively new and cutting edge, and insurance companies are relatively slow and conservative.â€?1 Before clinical sequencing can be used broadly in healthcare as a diagnostic test, insurance companies will have to support

coverage for them. As a result, Dr. Berg is setting up a randomized, controlled clinical study to compare the efficacy of genome sequencing against traditional genetic tests. The study will generate evidence about clinical outcomes and hypothesizes that genome sequencing will establish more diagnoses and improve patient care. This is in contrast to traditional tests that may only screen a few genes at a time. Additionally, while the inclusion criteria for the patients in the first phase was relatively broad, the follow-up study will enroll patients who are just beginning their diagnostic odyssey, focusing on children with suspected genetic syndromes or neurodevelopmental disorders. In a closely related project, Dr. Berg’s research team is sequencing the DNA of newborns. Regarding newborn sequencing, Dr. Berg said, “We are really excited about the use of genomic technologies not just to diagnose people who already have diseases, but for identifying diseases before they manifest. There are certain conditions where after the symptoms start, it is too late to treat it.�1 By screening for these types of genetic conditions early on, the likelihood for improved disease outcomes is greatly increased. When asked about the challenges he faces in researching clinical sequencing, Dr. Berg points to differences in the roles that genetic variation plays in different health condi-

“It’s a continual struggle in genetics because we’re relatively new and cutting edge, and insurance companies are relatively slow and conservative.�

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tions. In some cases, patients can be sequenced and a single gene disorder would definitively explain their disease. However, most health conditions are caused by a complex interplay between genes and environment, making interpretation of genetic variants more difficult. Finally, scientists are still looking for the genes that cause many health conditions. For Dr. Berg’s team, this means that they have to carefully parse through individual cases to determine what conclusions they can ultimately make from the data. Altogether, future advancements in genetics will further position clinical genome sequencing as an attractive procedure that not only diagnoses diseases in the present, but also helps prevent them in the first place.

References Í?Ǥ Â?–‡”˜‹‡™ ™‹–Š ‘Â?ƒ–ŠƒÂ? ‡”‰ǥ Ǥ Ǥ ŠǤ Ǥ ÍœÍĽČ€ÍžÍœČ€Í?ͤǤ ÍžǤ ‹ŽÂ?‘ǥ Ǥ Ǥ ‡– ƒŽǤǢ Nature. 2018ÇĄ ’‡nj …‹ƒŽ ”–‹…Ž‡Ǥ , opportunities:

, and

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medicine & health

Molecular Mysteries of Medulloblastoma

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edulloblastoma is one of the most aggressive brain tumors diagnosed in children. It accounts for 30% of all pediatric brain tumors, and there are approximately 350 new cases every year in the United States. The 10-year rate of survival for all patients is only 64.7%, and the outlook is even worse for children under the age of four.1 Researchers such as Dr. Timothy Gershon, an associate professor at the UNC-Chapel Hill School of Medicine, have dedicated their work to understanding the mechanisms behind medulloblastoma development. Dr. Gershon first realized that cancers such as medulloblastoma may arise from a disruption of

controlled brain growth when he was in medical school studying pediatric tumors. He has now discovered that the way in which cells use sugar for energy may play a crucial role in this disruption, and that further insight into this mechanism could create a better understanding of this cancer.2 Cells in our differentiated tissue, that is, tissue composed of cells that have a specific function, need large amounts of energy to conduct their many metabolic processes. This energy comes in the form of ATP. Cells produce ATP by breaking down glucose from a 6-carbon molecule from the food we eat to carbon dioxide, a 1-carbon gas molecule. This is done in a process called aerobic respiration, where the final step is called oxidative phosphorylation. As the name implies, this last process requires the presence of oxygen. However, stress and exertion lead to a lack of oxygen supply for cells, in which case they cannot maximize ATP production. Instead, cells can break down glucose to pyruvate, an intermediate in aerobic respiration, then to lactate in a process called anaerobic glycolysis. Lactic acid is responsible for the burning sensation in our muscles during continuous exercise.2 In the 1920s, German scientist, Otto Warburg, made a very surprising discovery on this topic—the implications of which are still being understood by researchers like Dr. Gershon today. Warburg found that even in the presence of large amounts of oxygen, cancer cells choose to go through ͝Ǥ ơ Ǥ Ǥ3

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Carolina Scientific anaerobic glycolysis instead of maximizing their ATP output. At the time, Warburg reasoned that these cancer cells must have lost the ability to perform oxidative phosphorylation; however, this hypothesis was soon proved incorrect.3 Dr. Gershon’s lab found that cerebellar granule neuron progenitors (CGNPs), normal cells undergoing rapid proliferation during early brain development, perform aerobic glycolysis. It is ex5 ‹�‘–Š› ‡”•Š‘� actly these cells that give rise to medulloblastoma. Just as cancer cells take advantage of the normal replication process, it seems that they are also taking advantage of a normal aerobic glycolysis processes to undergo rapid proliferation.2 But what advantage does this hold for cancerous cells? In 2013, Dr. Gershon began studying specific molecules in glycolysis to answer this question. He chose to work with Hexokinase 2 (Hk2), an enzyme that phosphorylates glucose in order to begin aerobic glycolysis in neural progenitors and cancer cells. Deletion of Hk2 in these cells leads to glucose not being able to enter aerobic glycolysis and therefore decreases tumor growth. Despite this promising discovery, scientists have faced many obstacles in developing a cancer treatment that selectively attacks Hk2. Therefore, Dr. Gershon decided to look at the other side of the aerobic glycolysis pathway for potential solutions.2 Pyruvate kinase-M (Pkm) is the primary enzyme in the last part of aerobic glycolysis, ultimately yielding pyruvate which can be used for the rest of aerobic respiration. There are two main forms of Pkm; both perform the same function, but have slightly different structures. Scientists have observed that most of the differentiated tissue of the brain uses a form of Pkm called Pkm1 that is always active, while cancer cells use the isoform Pkm2 that has the ability to turn on and off. Previous studies suggested that Pkm2 is actually not necessary for the growth of cancer cells and that its deletion can even help increase cancer cell proliferation. On the contrary, Dr. Gershon and his team argued that past experiments did not study the effect of a deletion of Pkm2 specifically in aerobic glycolysis of tumorous cells. His team’s study in 2017 aimed to identify the role of Pkm2 in CGNPs to see whether Pkm2 could possibly be a better target for medulloblastoma cancer therapy.4 To further investigate this, the researchers produced two types of medulloblastoma mice, those with heterozygous genes for Pkm2 deletion and those with homozygous genes for Pkm2 deletion. Surprisingly, the lack of Pkm2 of CGNPs in aerobic glycolysis led to less lactate production while tumor growth still increased. The mice that were homozygous for deletion of Pkm2 had the lowest lactate production and fastest tumor growth. Previous studies conducted on mouse embryonic fibroblasts (MEFs) showed that the deletion of the gene encoding Pkm2 resulted in an increased expression of Pkm1. Thus, MEFs made up for the lack of Pkm2 by increasing

medicine & health

‹‰—”‡ ÍžǤ ÍĄ –ƒ‹Â?‡† ‹Â? ”‘™Â? ƒÂ?† ͢ –ƒ‹Â?‡† ‹Â? Ž—‡ ‹Â? ‹ƥ‡”‡Â?–‹ƒ–‡† ‹••—‡Ǥ Â?ƒ‰‡ …‘—”–‡•› ‘ˆ ‡…Š ‡– ƒŽǤǥ Í˘Í ÍĄÍ§Ç¤4 production of Pkm1. Dr. Gershon’s study used CGNPs instead of MEFs, but deletion of Pkm2 did not result in any increased expression of Pkm1. In fact, even when these CGNPs had neither Pkm1 nor Pkm2, there was increased tumor cell growth.4 The combined results of the studies from 2013 and 2017 provide an astonishing conclusion. Dr. Gershon’s study from 2013 showed that deletion of Hk2 significantly suppressed tumor growth. His more recent study from 2017, which observed the effects of Pkm2 deletion, showed increased proliferation of CGNP cells and uncontrolled tumor growth. Together, it seems that cancer cells use aerobic glycolysis to make some kind of a ‘mystery’ intermediate molecule between glucose and lactate that supports rapid proliferation. Hk2 reactions occur before this, which is why its deletion stops tumor growth. Pkm2 reactions occurs after this intermediate which is why its deletion actually promotes more of this ‘mystery’ molecule and thus more proliferation. Since Pkm2 has the ability to shut down, the cells only keep Pkm2 active when it needs lactate for energy, during which time the ‘mystery’ molecule is not produced.2 This is one of those cases in which the data does not support the hypothesis, yet it could completely change the way we think about cancer cells. Dr. Gershon has helped clear up the misunderstanding that all steps of glycolysis promote tumor growth. Based on Dr. Gershon’s work, Pkm2 actually works as a tumor suppressor. Thus, cancer therapies, especially for medulloblastoma, should not be directed towards suppressing Pkm2. In the meantime, Dr. Gershon and his team of researchers are working to figure out the identity of this ‘mystery’ molecule and its secret role in cancer.2

References Í?Ǥ ÂƒÂŽÂŽÂ‘ÇĄ Ǥ ‡†—ŽŽ‘„Žƒ•–‘Â?ƒǤ Š––’•ǣȀȀ‡Â?‡†‹…‹Â?‡ǤÂ?‡†•…ƒ’‡Ǥ …‘Â?Č€ÂƒÂ”Â–Â‹Â…ÂŽÂ‡Č€Í?Í?ͤÍ?ÍžÍ?ÍĽÇŚÂ‘Â˜Â‡Â”Â˜Â‹Â‡Â™Ǥ Č‹ÂƒÂ…Â…Â‡Â•Â•Â‡Â† ƒÂ?—ƒ”› Í?ÍœÂ–ÂŠÇĄ ͜͞Í?ͤČŒǤ ÍžǤ Â?–‡”˜‹‡™ ™‹–Š ‹Â?‘–Š› ‡”•Š‘Â?ÇĄ ŠǤ Ǥ ͼȀͣ͞ȀÍ?ͤǤ Í&#x;Ǥ —Â?‰ǥ Ǥ Š‡ ƒ”ƒ†‘š ‘ˆ ƒÂ?…‡”ǯ• ƒ”„—”‰ ƥ‡…–Ǥ Š––’•ǣȀȀ Â?‡†‹—Â?Ǥ…‘Â?Č€ĚżÂ†Â”ÂŒÂƒÂ•Â‘Â?ˆ—Â?Â‰Č€Â–ÂŠÂ‡ÇŚÂ’ÂƒÂ”ÂƒÂ†Â‘ÂšÇŚÂ‘ÂˆÇŚÂ…ÂƒÂ?Â…Â‡Â”Â•ÇŚÂ™ÂƒÂ”ÇŚ „—”‰nj‡ƥ‡…–njͣĆ&#x;ÍĄÍŁÍžÍ&#x;Í˘Í Â„ͤÍ?Ǥ Č‹ÂƒÂ…Â…Â‡Â•Â•Â‡Â† ‡„”—ƒ”› ÍžÍ?•–ǥ ͜͞Í?ͤČŒǤ Í Ç¤ ‡…Šǥ Ǣ ‹Â?—Â?Â‘Â˜ÇĄ Ǥ Ǣ ÂƒÂ”Â‘Â‘Â“ÇĄ Ǣ ‘””‹••›ǥ Ǥ Ǣ ‡‹†‹Â?‰nj ‡”ǥ Ǣ ‹•Šǥ Ǥ ‡– ƒŽǤ Cancer Res. 2017ÇĄ ͧͧČ‹ͥ͢ČŒÇĄ Í&#x;ÍžÍ?ÍŁČ‚Í&#x;ÍžÍ&#x;ÍœǤ ͥǤ ‡”•Š‘Â?ÇĄ Ǥ ‡‘’Ž‡Ǥ ‰‡”•Š‘Â?Žƒ„Ǥ™‡„Ǥ—Â?Â…ǤÂ‡Â†Â—Č€ÂŽÂƒÂ„ÇŚÂ?‡Â?ÇŚ „‡”•ȀǤ Č‹ÂƒÂ…Â…Â‡Â•Â•Â‡Â† ‡„”—ƒ”› ÍžÍ?•–ǥ ͜͞Í?ͤČŒǤ

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medicine & health

Cortical Epilepsies: Searc-GENE for a Cure

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͝Ǥ A gene. Image courtesy of Pixabay.

hen the science fiction film Gattaca was released in 1997, the film’s portrayal of disease prevention at a genetic level seemed to many as implausible as colonizing Mars. Perhaps it still is. Truthfully, Gattaca’s depiction of a society dominated by libertarian eugenics, where some children are granted ideal traits and stripped of any markers for genetic disorders, raises some significant moral dilemmas and still exceeds the capabilities of modern science.1 But the treatment of human disorders via gene therapy isn’t nearly so far-fetched today. The screenplay was written in the mid-nineties, as the field of gene therapy had just emerged onto the scientific stage.1 The AAV, or adeno-associated viral vector, was developed in the 1980s and grabbed the attention of researchers in 1995.2 Those interested parties included Dr. Thomas McCown, a professor at the UNC-Chapel Hill’s School of Medicine working in the areas of pharmacology and seizure suppression. What makes the AAV viral vector a uniquely popular candidate for gene therapy is its low pathogenicity, rendering it harmless to the cells it infects, and its ability to enter both dividing and quiescent cells.3 This factor is particularly important to the McCown lab because, “as a cell divides, [the viral vector] gets split out- gets diluted… In the central nervous system, many of the most important cells, especially neurons, don’t divide.”2 Dr. McCown and his lab are currently working to develop a gene therapy treatment for patients suffering from intractable temporal lobe epilepsy, a disorder where “neurons in the cortex do not migrate appropriately,” generating a dysplasia, or abnormal cell distribution, that causes drug-resistant frontal cortical seizures.2 Currently, the only remedy for these cortical epilepsies involves a risky surgery to remove affected pieces of the cortex. This procedure is not even a viable option

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Carolina Scientific for many patients whose seizure activity is centered too close to vital parts of the brain that manage speech and basic functionality. The gene therapy route would offer such individuals a much less invasive alternative.2 Before discussing the McCown lab’s development process, it is important to understand how the AAV vector operates in non-dividing cells. The vector itself consists of two terminal repeats surrounding the AAV virus’s replication and encapsidation genes. The replication and encapsidation genes are cut out and the gene of interest is inserted between the two terminal repeats. The process of creating the infectious, recombinant AAV virus can be summarized via a “3-plasmid system,� where each plasmid is a small, circular viral DNA strand.2 The first plasmid includes the AAV vector with the gene chosen for expression inside the terminal repeats. The second holds the genes for viral replication and protein encapsidation, and the third has helper genes necessary for the process of vector rescue. This “vector rescue� process is necessary to facilitate AAV replication in vivo. When the plasmids are combined with cells in culture, the resulting recombinant vector can infect any cell that AAV can transduce, expressing the gene of interest in the process.2 So where does the AAV vector come into play? The McCown lab’s initial approach to the development of a treatment for epilepsy was “to try to reduce or take out excitatory actions in the central nervous system� that induce seizure activity.2 This was accomplished via the development of a construct to block one of the brain’s primary excitatory receptors. However, it was found that the brain’s response to treatment depended on the type of cell whose gene expression was affected. In some cases, blocking excitatory action with this method increased the system’s susceptibility to seizures rather than the opposite.2 This ‘significant therapeutic liability’ led the lab to adopt a novel method in the early 2000s that involved a protein called fiberonectin, which is excreted from nearly every cell in the human body.2 Fiberonectin was interesting to Dr. McCown in that it had no regulatory system acting upon it. If this characteristic could be incorporated into a vector including the active coding sequences of galanin and neuropeptide Y, two highly effective seizure-suppressing neuroactive peptides, perhaps a treatment method could be devised with a secure method of delivery and a high degree of efficacy in seizure prevention. Through several papers and years’ worth of studies, the lab succeeded in showing that treatment with this viral vector resulted in seizure suppression in any brain area that contained the receptors for galanin and neuropeptide Y. The injection of these viral vectors into the dysplasic cortex could result in a novel method for the treatment of epilepsy without the need to extract part of the cortex. Preclinical studies are currently ongoing at UNC with a biotech firm in the Research Triangle, an effort that will hopefully lead to the eventual movement of the McCown lab’s anti-seizure gene therapy model into the clinical stage.2 However, Dr. McCown warns that as progress with the epilepsy treatment moves forward, there will “inevitably be setbacks due to the level of unknowns with human subjects.�2 One issue involves translation from animal models

medicine & health

‹‰—”‡ ÍžǤ (Top). Protocol used to create recombinant AAV ˜‹”ƒŽ ˜‡…–‘”•Ǥ Č‹ ‘––‘Â?ČŒǤ Â? ‡šƒÂ?’Ž‡ ‘ˆ Š‘™ ”‡…‘Â?„‹Â?ƒÂ?– ˜‡…–‘”• ƒŽ–‡” ‰‡Â?‡ ‡š’”‡••‹‘Â? ™‹–Š ƪ—‘”‡•…‡Â?– ’”‘–‡‹Â? ‹Â? –Š‡ cortex of a rat. Images courtesy of Thomas McCown. to the human condition. The vector’s ability to transduce certain cells may not be the same between animal models and the human brain. This ties closely into the second obstacle: the immunological differences between tested rodent models and the primate models in which the next stage of testing needs to take place raises the possibility of new problems that might arise when the viral vector is exposed to a more complex immune system similar to that found in human subjects.2 Nevertheless, Dr. McCown remains optimistic that these potential pitfalls can be overcome “as long as we keep our focus on basic mechanisms.â€?2 Today, multiple therapies using AAV vectors have moved into human clinical trials, correcting genetic eye disorders and treating diseases from hemophilia to Parkinson’s. The McCown lab’s study is one of many ongoing investigations looking into the possibility of using gene therapy to improve function of the central nervous system, and they are confident that, with more testing and development, AAV viral vectors could represent a new and promising treatment option for individuals living with drug resistant epilepsies.2

References Í?Ǥ ƒ––ƒ…ƒǤ Š––’•ǣȀȀ‡Â?Ǥ™‹Â?‹’‡†‹ƒǤ‘”‰Ȁ™‹Â?‹Ȁ ƒ––ƒ…ƒ Č‹ÂƒÂ…Â…Â‡Â•Â•Â‡Â† ‡’ ÍžÍ?ÇĄ ͜͞Í?ͤČŒǤ ÍžǤ Â?–‡”˜‹‡™ ™‹–Š Š‘Â?ĥ Â… ‘™Â?ÇĄ ŠǤ Ǥ ÍœÍĽČ€Í?ÍŁČ€Í?ͤǤ Í&#x;Ǥ ÂƒÂ›ÂƒÇĄ ǤǢ ‡”Â?•ǥ Ǥ Ǥ Clinical Microbiology Review. 2008ÇĄ ͥ͢ǥ ͥͤÍ&#x;ÇŚÍĄÍĽÍ&#x;Ǥ

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Image courtesy of Pixabay

life science

ÂƒÂ–Â—Â”Â‡ÇŻÂ• ‘”‡ —””‡Â?…› › ‡‘ •‡Â?„‹Â?

W

hen I enrolled in Dr. Robbie Burger’s class on human ecology and evolution, I was expecting to go over a narrow range of ecological topics and how they related to prehistoric humans on the African savanna. What I got instead was a unique way to view humans and energy that was applicable to a wide range of topics. The questions we were asked to investigate were unique and relevant to human life. What makes a human different than other animals? Why do we have grandmothers? Are cities the problem or the solution to global energy use? Is space colonization a viable plan for the future of the human race? Dr. Burger’s research focuses on macroecology. In this emerging field, “energy [is the] core currency to unify aspects of ecology.�1 In practice, macroecologists apply underlying principles of thermodynamics and energy to many different systems to understand human uniqueness, health, and sustainability. They utilize information from other fields such as biology, statistics, and anthropology to create and apply laws that result in powerful facts directly relevant to the human experience. For instance, leading theories suggest that every species of mammal on earth has roughly the same number of heartbeats throughout its life (about 1.5 billion).2 This was concluded by using laws derived from the relationship between the mass, biological rates, and lifespans of animals. One of Dr. Burger’s interests involves investigating how humans deviate from other animals. For the past few years, he and three UNC undergraduates have compiled data on the brain sizes of over half of extant mammal species, in-

”Ǥ ‘„„‹‡ —”‰‡” cluding humans. By analyzing how the animals’ brain sizes compared to their body masses, the group determined that humans have the highest brain to body size ratio of any animal on the planet.3 This reinforces the idea that humans are smarter than any other creature in the world. Additionally, other studies have found that humans are one of four species of animal that have post-reproductive grandmothers. Macroecologists propose that the purpose of grandmothers and grandfathers historically was to be reservoirs of cultural knowledge and to help with child upbringing. In this way, groups of intelligent humans could build on generations of knowledge. In fact, knowledge is so vital to the way that humans have evolved that we are born with our eyes and ears

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life science

Carolina Scientific

The discussion on whether or not cities are the downfall of the environment or its savior is one of the most pressing questions that humans must answer. The principles of macroecology also reach far beyond the planetary boundaries of Earth. Dr. Burger is fascinated by what it would take for humans to colonize other planets. By examining the energy use of humans on earth and by adding in the energy that would be used for inter-planetary travel, he deduced that the energy that must be spent is massive. Therefore, whether we as a species put our efforts into colonization of other planets or preservation of the Earth, the time to act is now. The window for available energy at a time when we are running through our supply of fossil fuels is narrower than we might think. The breadth of Dr. Robbie Burger’s research spans from hundreds of thousands of years in the past to far into the future, but still remains relevant to immediate questions of sustainability, health, and the human condition. Research in macroecology is easy to get excited about with its catchy, powerful facts and powerful, wide-reaching implications. It is a line of inquiry that has changed not only how we think about science, but also about our responsibilities to the world through our lifestyles.

1& 67$7( 81,9(56,7< ,QWHUGLVFLSOLQDU\ 3K\VLRORJ\ *UDGXDWH 3URJUDP ‹‰—”‡ Í?Ǥ ”Ǥ —”‰‡” Šƒ• …‘Â?’‹Ž‡† †ƒ–ƒ ‘Â? –Š‡ „”ƒ‹Â? •‹œ‡• ‘ˆ over half of extant mammal species open so that we can immediately begin making sense of everything we can perceive. Another particularly relevant aspect of macroecology is how humans use energy. In his class, Human Evolution and Ecology, Dr. Burger uses observations of efficient energy use in hunter-gatherer societies and estimations of global net primary production—the total amount of energy that Earth can sustainably provide. This is in order to show how all large cities on Earth operate at levels above the limits of sustainability in relation to environmental productivity. This phenomenon occurs at a time when over half of the world’s population is living in cities for the first time in human history. It is our excessive use of resources and fossil fuels that is driving the sixth mass extinction (the fifth killed all of the dinosaurs) due to humanmade, physical modifications of the world. Dr. Burger also discusses how hyper-creative professions (professors, inventors, artists, engineers, etc.) scale with the size of cities. The number of the hyper-creative professions is disproportionately high in large cities. As Dr. Burger proposed, if the human race has a chance of curbing its energy use and becoming sustainable, it is these hyper-creative people who are going to lead the way.

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References Í?Ǥ Â?–‡”˜‹‡™ ™‹–Š ‘„„‹‡ —”‰‡”ǥ ŠǤ Ǥ ÍœÍĽČ€ÍžͤČ€ÍžÍœÍ?ͤǤ ÍžǤ ƒŽÂ? ‰‹˜‡Â? –‘ Â?–Š”‘’‘Ž‘‰› †‡’ƒ”–Â?‡Â?– „› ‘„„‹‡ —”‰‡”ǥ ŠǤ Ǥ ÍœÍĽČ€ÍžÍĄČ€ÍžÍœÍ?ͤǤ Í&#x;Ǥ —”‰‡”ǥ ǤǢ ‡‘”‰‡ǥ Ǥ ǤǢ Â‡ÂƒÂ†Â„Â‡Â–Â–Â‡Â”ÇĄ ǤǢ Šƒ‹Â?Šǥ Ǥ „‹‘ š‹˜ ͜͞Í?ͤǤ

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life science

PATHOGEN HOST

VS

an evolutionary arms race

͞Ǥ nies. Photo courtesy of Creative Commons.

S

ince our immune systems exercise constant vigilance, we are blissfully unaware of the vast number of dangerous environmental pathogens that we are exposed to. The immune system is the body’s defense against these types of pathogens, such as bacteria and viruses. However, the immune system is not perfect. From time to time, something manages to evade the immune system, requiring the emergence of better defenders. The immune system steps up to the challenge and evolves better mechanisms. Dr. Edward Miao, of the Department of Microbiology and Immunology at UNC-Chapel Hill, studies the nature of this evolutionary race between host and pathogen. He proposes that eventually the host (human) develops defense mechanisms that the pathogen can no longer catch up to. In this race, one could imagine that as the immune system evolves, it discards some of the defenses that pathogens have already evolved to avoid. For example, classes of bacteria, such as Salmonella and Listeria, have developed techniques to hide from the innate immune system’s inflammasomes (Figure 1). Inflammasomes are protein complexes found in the body’s cells that monitor the cytosol for foreign microbes. When they detect these microbes, they initiate a cascade of events that start with the activation of another protein called caspase-1 (or caspase-11) and end with a form of programmed cell death called pyroptosis, in which the cell bursts open.1 Thus, the cell containing the foreign microbe selfdestructs. Even though many bacteria can evade these inflammasomes, the immune system still employs them. Dr. Miao and

his lab set out to find the evolutionary basis for this process. Their investigation led them to two bacteria: Burkholderia and Chromobacterium violaceum. Both environmental bacteria are found in the soil and are harmless to people with competent immune systems. However, when mice without caspase proteins were exposed to a single B. thailandensis bacterium (Figure 2), the mice died soon after. In wild-type mice, nearly 20 million of the same bacterial strain were required to kill a single mouse.2 The lethal dose in the knockout mice was greatly reduced. These results indicate the importance of the inflammasome pathway in fighting off this strain. This observation led the lab to wonder if there are other microbes that inflammasomes protect against. To answer this question, Dr. Miao and other lab members decided to “screen for other environmental […] pathogens that primarily cause disease in immunocompromised individuals, hypothesizing that healthy individuals would competently clear them via the activity of inflammasomes.”2 During this process, they discovered the bacteria C. violaceum (Figure 3), which is commonly found in soil near bodies of water and does not cause disease in people with normal immune systems.1 They subjected C. violaceum to the same caspase knockout experiment in mice and found that fewer bacteria killed the knockout mice than the wild type. This result is similar to that of the same experiment with B. thailandensis, indicating that the inflammasome pathway is critical for defense against common environmental pathogens. These observations culmi-

“This evolutionary victory against certain pathogens is, for the most part, permanent.” 18

Carolina Scientific

͝Ǥ ƪ Ǥ Creative Commons. nate to Dr. Miao’s Red Pawn Hypothesis, which builds upon the existing Red Queen Hypothesis. The Red Queen Hypothesis proposes that the host and pathogen must each continuously evolve to remain ahead of the other. It references Alice’s race with the Red Queen in Lewis Carroll’s Through the Looking Glass and What Alice Found There, since Alice had to do all she could in order to simply keep up with the Red Queen. Here, the host is Alice, and the pathogen is the Red Queen. Essentially, “the pathogen develops a virulence factor and we develop a defense in response.”2 However, the role of inflammasomes does not exactly fit this definition. As aforementioned, many bacteria are able to avoid inflammasome detection. Thus, the question that arises is “Why would ‘Alice’ [the host] run with inflammasomes that fail to fight the ‘Red Queen’ [pathogen]?”3 The Red Pawn Hypothesis predicts that the immune system has certain components that “provide a near-permanent victory for the host in defense against a large reservoir of potentially deadly environmental pathogens, while host-adapted pathogens must evade these sensors.”3 The experiments involving B. thailandensis and C. violaceum provided Dr. Miao with the insight to form the Red Pawn Hypothesis. The evolutionary story behind B. thailandensis and C. violaceum date back to the time of primordial fish. The hosts for these bacteria back then could not have been humans so Dr. Miao posits that “microbes like Burkholderia and Chromobacterium were running this Red Queen’s race with primitive vertebrate.”2 For a time, these bacteria were on even footing with the vertebrates. However, the tide changed when inflammasomes evolved in early sharks. The strength of the inflammasome defense was too overwhelming for the two aforementioned microbes; as Dr. Miao states, “it was such a big step forward, that they couldn’t keep up with us and they essentially fell away.”2 Had there not been other eukaryotic organisms without inflammasomes that Burkholderia and Chromobacterium could infect, the bacteria could have gone extinct. While they were once Red Queens, they have been demoted to Red Pawns due to the emergence of inflammasomes, leading to our complete immunity to the bacteria. This evolutionary victory against certain pathogens

life science

͟Ǥ Chromobacterium Violaceum colonies. Photo courtesy of the CDC Public Health Library [PD US HHS CDC]. is for the most part permanent. In a game of chess, if a player’s pawn reaches the end of the board, the player can promote it to a queen. Even in a chess game, a player has to take many steps and avoid many dangers to promote a pawn to queen. The process would take a very long time. Therefore, the demotion to Red Pawn is nearly always permanent. This same principle could apply to the Red Pawn Hypothesis, in which the pathogen promoted itself back to the “queen” position, albeit rarely. For example, even though B. thailandensis is harmless to humans, there is another strain of Burkholderia called Burkholderia mallei that infects horses. Dr. Miao states that “it seems that some ancestral Burkholderia acquired multiple steps in the evolutionary tree and got to the end, and promoted itself back into the Red Queen against horses […] but it was probably very difficult.”2 At this point, the Red Pawn hypothesis is still just that—a hypothesis. It requires further support, but could one day have significant applications. The next step for the lab would be to acquire other types of bacteria and test their abilities to infect immunocompromised mice. However, the pathogens that our bodies face are Red Queens and not Red Pawns. They still have mechanisms for evading our innate immune system. Dr. Miao wonders that if the immune system does such a good job wiping out Red Pawns, will Red Queens be demoted to Red pawns?2 Such a method could reduce the severity of certain infections and may be even more effective long-term than antibiotics. For now, we must continue to run our Red Queen’s race with these pathogens and bide our time before the queen is taken out.

References

Dr. Edward Miao

͝Ǥ ǡ ǤǢ ǡ Ǥ J. Immunol. 2016ǡ 196ǡ ͥ͢͡Ǧͥ͢͞Ǥ ͞Ǥ ǡ Ǥ Ǥ ͥ͜Ȁ͜͡Ȁͤ͝Ǥ ͟Ǥ ǡ ǤǢ ǡ ǤǢ ǡ Ǥ Nat. Rev Immunol. 2017ǡ 17ǡ ͝͡͝Ǧ͢͝͠Ǥ

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͝Ǥ Ǥ Image courtesy of Pixabay.

ǣ The Gut By Harrison Jacobs

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an basic biochemistry research translate to treating complex biological systems? In Dr. Matthew Redinbo’s lab, a reductionist approach, which involves studying complex interactions in separate parts, thus simplifying the task of discovery, to the gut microbiome does just that. The human gut contains over 2 million genes, or approximately 100 times as many as the human genome.1 As such, the gut is far more complex than most biological systems that are studied. In the Redinbo Lab at UNC-Chapel Hill, hypotheses are created and tested by looking at individual enzymes, proteins, and even atomic structures. Functionality of compounds can be determined by x-ray diffraction. Then, using chemical biology methods, inhibitors are tested to determine how compound activity can be altered. If the results

are promising, such structures are made into cell-based assays and used in mouse models for further testing and proof of concept. If toxicity in mouse models is shown to be low, then applications are sent to the FDA for the approval of human clinical trials. Although Dr. Redinbo’s basic lab results were published in 2010, the FDA approval for a drug developed by his lab will likely not be until 2020.3

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Dr. Redinbo

Carolina Scientific

life science

‹‰—”‡ ͞ǣ Mechanism of substrate molecule conversion Č‹Â–Â‘Â’ČŒ ƒÂ?† ’‘••‹„Ž‡ Â?‡–Š‘† ‘ˆ ‹Â?Š‹„‹–‹‘Â? ȋ„‘––‘Â?ČŒ ‹Â? ‡Â?œ›Â?‡•Ǥ Â?ƒ‰‡ …‘—”–‡•› ‘ˆ ‡ŽŽ‘…Â? ‡– ƒŽǤǥ Í˘Í ÍĄÍ¨Ç¤ ‹‰—”‡ Í?ÇŁ ‹š ‰”‘—’‹Â?‰• ‘ˆ ‡Â?œ›Â?‡•ǣ ÍĄÇĄ Â? ÍĄÇĄ ͢ǥ Â? ͢ǥ Â?‹Â?‹njŽ‘‘’ ͥǥ͢ Č‹Â? ͥǥ͢ČŒÇĄ Â?‘ Ž‘‘’ Č‹ ČŒǤ ƒ…Š ‘Â?‡ †‹ƥ‡”• ‹Â? „‘–Š •‹œ‡ ƒÂ?† Ž‘…ƒ–‹‘Â? ™‹–Š‹Â? –Š‡ ‡Â?œ›Â?‡ǥ ƒÂ?† ĥ ƒ ”‡•—Ž– Šƒ˜‡ varying structural and chemical properties. Image courtesy ‘ˆ ‘ŽŽ‡– ‡– ƒŽǤǥ Í˘Í ÍĄÍ§Ç¤ One project in the lab focused on creating a crystal structure of gut enzymes from E. coli and Salmonella complexes.2 E. coli is a generally harmless type of bacteria commonly found in food and the intestine. By contrast, Salmonella can cause severe illness and even death if it spreads throughout the blood stream.4 In the study, they found the location of enzymatic DNA regulatory sites that are pivotal in DNA binding and the recognition of enzymes in the gut microbe environment. Following this study, the group members transferred E. coli DNA to Salmonella strands and showed that both functioned similarly. This demonstrates that at the molecular level, gut pathogens can control enzymatic activity by altering and binding to DNA receptors of normal bacteria. An ongoing project for the group involves classifying β-glucuronidase (GUS) enzymes by structure. Six categories have been determined to classify GUS enzymes and 112 of these enzymes have been discovered from a sample of 139 individuals. In doing so, the necessary steps were taken by the lab to create a more personalized technique for treatment. Structural and functional variance between classifications revealed through research provide insight for further studies as to how certain inhibitors affect each type of GUS enzyme differently. Inhibition of GUS enzymes could prove critical to medicine, as some cancer drugs are activated by these enzymes and can cause severe side effects, such as diarrhea. While “all of [the] work on the basic science side slowly

moves to the clinic,� the students in the Redinbo Lab have the opportunity to grow, learn how to research, and think scientifically.3 Dr. Redinbo has seen the importance of adaptation in research through his experiences over the years. When he first came to UNC-Chapel Hill 19 years ago, he did not plan on studying the gut microbiome. He said that, rather than plan one’s pursuits, he advises all who are interested in science to pick projects that interest them and to run with such ideas. Dr. Redinbo values the importance of diversity, especially in thought, background, and expertise. He enjoys working with undergraduates, as they often come in with a beginner’s mind and have less preconceived notions of a central dogma. By providing them a “scientific sandbox,� Dr. Redinbo enables researchers in his lab to creatively think about a subject in a novel way and study it with a multitude of devices and biological probes at their disposal. In doing so, Dr. Redinbo provides a “very tangible and gratifying experience.� He finds that the diversity of a group is its greatest strength, as brainstorming ideas with people who share interpersonal relationships creates a laboratory setting that is conducive to discovery.

Dz Â?Š‹„‹–‹‘Â? ‘ˆ ‡Â?œ›Â?‡• …‘—Ž† ’”‘˜‡ …”‹–‹…ƒŽ –‘ Â?‡†‹…‹Â?‡ǥ ĥ •‘Â?‡ …ƒÂ?…‡” †”—‰• ƒ”‡ ƒ…–‹˜ƒ–‡† „› –Š‡•‡ ‡Â?œ›Â?‡• ƒÂ?† …ƒÂ? …ƒ—•‡ •‡˜‡”‡ •‹†‡ ‡ƥ‡…–•Ǥdz References

Í?Ǥ ‡ŽŽÂ?ƒÂ?ÇĄ Ǥ —– „ƒ…–‡”‹ƒ ‰‡Â?‡ …‘Â?’Ž‡Â?‡Â?– †™ƒ”ˆ• Š—nj Â?ƒÂ? ‰‡Â?‘Â?‡Ǥ Š––’•ǣȀȀ™™™ǤÂ?ƒ–—”‡Ǥ…‘Â?Č€Â?Â‡Â™Â•Č€ÍžÍœÍ?ÍœČ€Í?͜͜Í&#x;ÍœÍ&#x;Č€ ÂˆÂ—ÂŽÂŽČ€Â?થǤ͜͞Í?ÍœǤÍ?ÍœÍ Ç¤ÂŠÂ–Â?ŽǍ•ϋÂ?‡™•̟”•• Č‹ÂƒÂ…Â…Â‡Â•Â•Â‡Â† ‡’–‡Â?„‡” ͞ͼ–Šǥ ͜͞Í?ͤČŒ ÍžǤ —– ‹…”‘„‹‘Â?‡ ‡•‡ƒ”…ŠǤ ‡’ƒ”–Â?‡Â?– ‘ˆ Š‡Â?ÇŚ istry. Í&#x;Ǥ Â?–‡”˜‹‡™ ™‹–Š ƒ––Š‡™ ‡†‹Â?„‘ǥ ŠǤ Ǥ ͼȀ͞Í?Č€Í?ͤǤ Í Ç¤ ƒÂ?‘Â?‡ŽŽƒǤ ‡Â?–‡”• ˆ‘” ‹•‡ƒ•‡ ‘Â?–”‘ŽǤ ͥǤ ‘ŽŽ‡– ÇĄ ‡– ƒŽǤ Structure. 2017ÇĄ ͢ͼǥ ͼͣ͢Č‚ͼͣͣǤ ͢Ǥ ‡ŽŽ‘…Â? ÇĄ ‡– ƒŽǤ ACS Cent. Sci. 2018ÇĄ 4ÇĄ ͤͤ͢Č‚ͤͣͼǤ

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physical science

By Zh By Zh hiii--Wei L Liin

Image courtesy of Wikimedia Commons

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magine a world so wonderfully small that a single E. coli cell is considered astronomically large. Nanoparticles as tiny as one nanometer in diameter (about a million times smaller than the diameter of a single raindrop) inhabit this magical world of endless possibilities, which we will term the nanoverse. Objects in the nanoverse come in various forms and shapes. Some are star-shaped gold particles while others are spherical platinum clusters. Other occupants include proteins and stands of DNA (remember, though, just one at a time), viruses, and sub-cellular organelles like mitochondria. At the UNC - Chapel Hill Chemistry Department, the laboratory of Dr. Jeffrey E. Dick is interested in studying the chemical and physical properties of these single objects. You might be curious as to why it’s important to study single entities. Dr. Dick used the following analogy of observing fireflies:1 Imagine you’ve never seen nor heard of fireflies. In front of you is a large jar containing millions of fireflies. Collectively, you observe that they give off a steady intensity of light. However, the reality is that fireflies don’t continuously produce light. But how were you supposed to know? What is the probability that millions of fireflies blink on and off synchronously? Because you were observing all of them at once, you failed to notice the individual fireflies blinking on and off. The analogy of observing a single firefly parallels Dr. Dick’s approach to the study of nanoparticles and individual biological

͝ǣ Schematic of water-in-oil emulsion technique cells. For example, the mechanism of an individual cancer cell may well be concealed in a sample dominated by a majority of healthy cells. Similarly, the energy conversion properties of

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Carolina Scientific

Ǥ ơ Ǥ a single nanoparticle might be drastically different from other nanoparticles and bulk metals. Being able to identify the activity and understand a single nanoparticle’s nature allows for the discovery of how we can optimize energy conversion by minimizing total cost. At the macroscopic view, scientists may neglect certain phenotypes or cellular responses occurring at the individual microscopic level. To further demonstrate the importance of studying single entities, protein fluorescence was recently discovered to be discontinuous. This discovery, in part, contributed to the invention of super-resolution microscopy, which garnered the 2014 Nobel Prize in Chemistry. As you can probably tell, it’s important to optimize parameters for energy storage and conversion. While nanoparticles hold the key to a new age of materials, one of the current challenges for the field lies in nanoparticle deposition. The traditional methods, such as drop-casting and electrodepositing from a continuous solution, are problematic due to the lack of precise controls over the properties of nanoparticles.2 Even more, these methods cannot guarantee the nanoparticles retain their full catalytic potentials when deposited onto a substrate. This is a current focus in the Dick Lab. By using a robust water-in-oil emulsion method, Dr. Dick and his colleagues demonstrated, for the first time, the ability to precisely control physical properties of nanoparticles, such as size, porosity, and coverage.3 Briefly, an emulsion is created by mixing immiscible liquids, like water and oil, to form a uniform suspension of droplets. The most well-known emulsion is milk, where fat droplets are suspended in water. Under ultrasonication, nanoparticle salts that are embedded within water droplets collide and stick to a conductor, and the conductor converts the salts to a nanoparticle.3 The use of water droplets allows for unprecedented control over size, morphology, and coverage, parameters that are difficult to control without droplets. In their recent publication, Dr. Dick and his colleagues further demonstrated the ability to coat platinum nanoparticles onto a graphite substrate and to control their “size, roughness, coverage, and overall morphology.”4 From these results, they showed that the water-in-oil emulsion method is compatible with depositing a variety of metal nanoparticles onto different substrates. In addition to the precise controls this

physical science

method offers, it also avoids the use of any ligands that might interfere with experimental analysis and measurement. This recent demonstration opens the door to an array of possibilities and applications that were once hindered by classical deposition methods. Excitingly, it allows Dr. Dick and colleagues to precisely fabricate nanoparticles at specified conditions and study their behavior at the individual level. From here, Dr. Dick and colleagues are able to design instruments and nanoprobes, such as a nanoelectrode, to probe and study a single nanoparticle and understand what makes it so special. But this is only the beginning. The techniques developed in these projects allow the group to study other single entities and fabricate a special class of alloys, termed high entropy alloy nanoparticles. Current projects in the group range from the detection and quantification of single mitochondria and understanding the electrochemistry of an exciting new anti-aging molecule, nicotinamide riboside. The group is also developing a state-of-the-art microscope capable of imaging with light and nanoelectrodes in real time. Perhaps a more appropriate job description for Dr. Dick is an interdisciplinary detective, who uses molecular tools and principles of electrochemistry, analytical chemistry, and nanoscience to investigate natural phenomena occurring at the ti-

͟ǣ Scanning electron microscope micrograph of a nanoelectrode niest scale. By truly understanding natural phenomena at this scale, whether it’s the study of a single firefly, nanoparticle, or cell, Dr. Dick and colleagues hope to develop game-changing techniques and uncover truths of nature that have been quietly awaiting discovery.

References ͝Ǥ ơ Ǥ ǡ Ǥ Ǥ ͥ͜Ȁͥ͝Ȁͤ͝ ͞Ǥ ǡ Ǥ AAPS J. 2012ǡ ͤ͡ȋ͢Ȍǡ ͤ͞͞Ǧͥ͞͡Ǥ ͟Ǥ ǡ Ǥ Ǣ ǡ Ǥ Ǥ Anal. Chem.ǡ 2018ǡ 90ǡ ͣͤ͜͠Ǧ ͣͤͤ͜Ǥ ͠Ǥ ǡ Ǥ Ǣ ǡ Ǥ Ǣ ǡ Ǥ Ǥ ACS Appl. Nano. Mater. 2018ǡ 1ǡ ͣ͜͡͞Ǧͣ͡͝​͝Ǥ

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physical science

Is the Sun Our Last Ray of Hope? By Rayyanoor Jawad

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ach semester, as a part of our tuition, we are charged four dollars for “FEE Renewable Energy.” These four dollars from each UNC student have been allocated toward green projects such as the Solar Panel Project, which aims to reduce university energy costs by one billion dollars by 2031. Additionally, the project aims to provide electricity in a more sustainable way.1 However, the main problem today is that once the sun goes down, solar panels are not able to continue generating electricity. Researchers in chemistry are trying to find sustainable mechanisms by which solar energy can be harvested and stored for later use on-demand. One such researcher is Dr. Alexander J. M. Miller, Associate Professor in the Department of Chemistry at UNC-Chapel Hill and Deputy Director of the Alliance for Molecular PhotoElectrode Design (AMPED). Dr. Miller focuses on uncovering new chemical reactions for synthesizing fuels that store chemical energy. In order to do this, the Miller Group’s primary focus is to understand how molecules interact with synthetic materials to harvest the energy in sunlight and convert that into solar fuel. Their research also seeks to investigate new ways of using sunlight to take dinitrogen from the air and convert it Ǥ Ǥ into ammonia or other forms

of nitrogen that can be used in fertilizer in a process called electrochemical nitrogen fixation. Fertilizer production is one of the most energy intensive processes on the planet, releasing enormous amounts of heat-trapping CO2. The Miller Group hopes to bring these emissions as close to zero as possible by developing more sustainable nitrogen fixation chemistry. In both areas of study, Dr. Miller and his colleagues use fundamental chemistry, which is the most mechanistic level of chemistry, in order to search for transition metal catalysts that can carry out reactions to produce sustainable solar fuels and ammonia for fertilizers. Dr. Miller is involved in the chemistry of transition metal ions. He focuses on choosing the right combination of elements, supporting ligands, and reaction conditions (such as pH and temperature) to achieve the desired chemical reaction. According to Dr. Miller, “I love the idea of making molecules that no one has ever made before and being able to do that with my own hands.” In order to create solar fuel, a chromophore, or the light absorbing part of a molecule, must be used to absorb solar photons. This excites an electron from its ground state into an excited state, therefore harvesting the energy from the solar photon. Next, a new chemical bond must be formed, namely the formation of an H2 bond derived from H2O. The formation of H2 from H2O requires a catalyst, which is a protein that lowers the energy needed to progress a reaction to form products without being consumed in the process. In the solar-hydrogen energy cycle, the newly formed hydrogen is stored by a fuel cell, which can be accessed later for electricity production without the need for sunlight. Dr. Miller’s research

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Carolina Scientific

physical science

‹‰—”‡ Í?Ǥ (Left) Three double-wide glveboxes and vacuum lines for free-air synthesis in the Miller lab. (Middle and right) ‘Ž˜‡Â?– ’—”‹Ƥ…ƒ–‹‘Â? •›•–‡Â? ƒÂ?† ˜ƒ”‹‘—• ‡Ž‡…–”‘…Š‡Â?‹…ƒŽ ƒÂ?† ƒÂ?ƒŽ›–‹…ƒŽ ‹Â?•–”—Â?‡Â?–ƒ–‹‘Â? ™‹–Š‹Â? –Š‡ Žƒ„Ǥ Â?ƒ‰‡• …‘—”–‡•› ‘ˆ Alexander J. M. Miller. focuses on the second aspect of creating solar fuels, which requires the use of a transition metal catalyst that can lower the energy needed to create the appropriate chemical bond. Synthesizing new transition metal catalysts for solar fuels requires two main steps: the formation of hydride (H-) molecules and the release of hydrogen gas.2 In the electrochemical process, electrons are added to the metal catalyst in order for it to react with water to create a metal hydride bond. The next step requires the catalyst to absorb light energy and release hydrogen. Hydrogen gas then becomes the fuel that can be used for many applications. One application would combine hydrogen gas with nitrogen gas to make ammonia, which is used in fertilizers. This method of producing ammonia would be more sustainable than the current process, which uses hydrogen produced from methane or coal and releases CO2 into the atmosphere. Dr. Miller must also characterize the transition metal catalyst of interest before and after the chemical reaction using Nuclear Magnetic Resonance (NMR) spectroscopy, UV-vis spectroscopy, and single X-ray diffraction studies. Characterization provides structural information about the catalyst that offers better insight into how the catalyst is reacting. Furthermore, under different conditions, the rate of the reaction is monitored with NMR and special electrochemical techniques. These kinetic studies can reveal the mechanism by which the catalyst reacts. After determining the mechanism and the byproducts of a reaction with a certain catalyst, that catalyst is tweaked in hopes that it will stabilize both steps of the reaction and is entered into the catalytic cycle again. Although there are two major steps associated with the production of solar fuel (or hydrogen gas, in this case), challenges arise when trying to find one system, or catalyst, that will effectively carry out both steps. The Miller Group has been able to successfully implement one distinct transition metal catalyst for each of the two steps: hydride formation and hydrogen gas release. However, the goal is to be able to carry out both steps at the same time and this requires using the same transition metal complex. Regarding the project on production of H2, the Miller

Group has utilized H2 evolution chemistry, which is the production of hydrogen from H2O using a metal. In this process, Dr. Miller and his colleagues have synthesized and exhausted about 10 iridium and rhenium catalysts, with iridium demonstrating more promising catalysis. In terms of efficiency, each catalyst molecule produces about 12 molecules of H2 per minute. One of Dr. Miller’s latest findings is in the nitrogen fixation project. He and his colleagues have discovered how rhenium metal complexes can be manipulated and how they can split N2 to produce its more usable form, metal nitride (N3). For what seems like a one-step reaction, the Miller Group’s understanding of this mechanism showed that in reality, there are 5-6 steps. Nitrogen atoms are used in many applications from drugs to fertilizers, however, the strong bond in N2 is difficult to overcome sustainably. The mechanistic insight gained in this rhenium system introduces possibilities for additional platforms for chemical and electrochemical N2 splitting, which can then be integrated in fertilizer applications.3 Dr. Miller’s research is at the core of solar fuel chemistry, concentrating on the characterization of a transition metal complex, the characterization of the products produced by the chemical reaction, and finally the understanding of the catalytic mechanism. Today, sustainable hydrogen gas production is very costly relative to its production from fossil fuels. However, Dr. Miller plans to continue collaborations with companies and labs in efforts to use a fundamental mechanistic understanding to discover transition metal complexes. This will allow for the sustainable production of hydrogen gas with a low enough cost to be competitive in the chemical industry.

References Í?Ǥ ‘†‰‡ǥ ŽƒÂ?‡Ǥ Â?˜‡‹Ž• ‡™ ‘Žƒ” Â?‡”‰› ”‘Œ‡…–Ǥ Šƒ’‡Ž„‘”‘Ǥ …–Ǥ ͜͞Í?ͥǤ ÍžǤ ”‡”‡–‘Â?ÇĄ Ǥ Ǣ ‘Â?Â?ÇĄ Ǥ Ǣ ‹ŽŽ‡”ǥ Ǥ ACS Energy Lett. 2018ÇĄ 3(5)ÇĄ Í?Í?ÍžͤnjÍ?Í?Í&#x;͢Ǥ Í&#x;Ǥ ‹Â?†Ž‡›ǥ Ǥ Ǣ Ǥ ˜ƒÂ? Ž–‡Â?ÇĄ Ǣ ‹Â?‰‡”ǥ Ǣ …Š‡Â?Â†ÂœÂ‹Â‡ÂŽÂ‘Â”ÂœÇĄ Ǣ ò”–‡Ž‡ǥ Ǣ ‹ŽŽ‡”ǥ Ǣ ‹‡™‡”–ǥ Ǣ …ŠÂ?‡‹†‡”ǥ Ǥ J. Am. Chem. Soc. 2018ÇĄ ÍĄÍ¤Í Č‹͢ͼČŒÇĄ ͣͼ͞͞njͣͼÍ&#x;ͥǤ Í Ç¤ Â?–‡”˜‹‡™ ™‹–Š Ž‡šƒÂ?†‡” Ǥ Ǥ ‹ŽŽ‡”ǥ ŠǤ Ǥ ͼȀͣ͞ȀÍ?ͤ

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physical science

Illustration by Taylor Thomas

‹‰Š– Š‡† ‘� Šƒ– š‹•–‡† ‡ˆ‘”‡ –Š‡ ‘Žƒ” ›•–‡�

› ”ƒ˜‡‡�ƒ ‘�ƒ•—�†ƒ”ƒ�

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very 10,000 to one million years, two stars orbiting each other will explode due to an accumulation of matter between the stars. This is the scene of a nova explosion (Figure 1). Nova explosions are a result of nuclear fusion reactions within a binary, or two-star, system. Two stars orbit each other because they have the same gravitational center. One star in this scene

‹‰—”‡ Í?Ǥ Artist’s concept of a nova explosion binary star system. Photo courtesy of NASA/JPL-Caltech.

is a white dwarf. Stars, like the sun, become white dwarfs after they have burned up all of their hydrogen, which is the element used for energy by conversion to helium.1 This means white dwarfs, on their own, have no source of energy. However, the second star is a companion star, a main sequence star, which can still fuse hydrogen atoms. Though both stars are very dense in this binary system, the white dwarf is so dense that it pulls matter from the main sequence star onto its surface.2 When this occurs, the matter spirals and heats up to cause nuclear reactions until an explosion occurs.2 Many scientists around the world believe that “stardust grains� originate from these nova explosions. Stardust grains are tiny pieces of matter that existed before the solar system was born.2 Some of these stardust grains survived the solar system formation process and are still present today in meteorites. They have the same composition today as when they originated, which means these stardust grains hold information about the composition materials prior to the formation of our current solar system. Research has been conducted by running large-scale computer simulations of nova explosions to investigate the origin of these stardust grains. However, the simulated abundances had to be diluted by factors of 10 with normal solar system matter, matter that is not presolar, in order to fit the

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Carolina Scientific

physical science

‡ˆ– –‘ ”‹‰Š–ǣ ”Ǥ Š”‹•–‹ƒÂ? ÂŽÂ‹ÂƒÂ†Â‹Â•ÇĄ ”Ǥ ‘™Â?‡Â?ÇĄ ”Ǥ ‘•‡ǥ ”Ǥ ‹––Ž‡”ǥ ”Ǥ –ƒ””Ƥ‡Ž†Ǥ observations of the stardust grains.2 Essentially, research measurements such as isotopic ratios, which indicate the presence of different chemical compounds, are impacted by the introduction of extra solar material in the simulation. In order to truly discover the origin of stardust grains, simulations without dilution needed to be run. Dr. Christian Iliadis recently conducted research on the stardust grains using nuclear fusion data from the Laboratory for Experimental Nuclear Astrophysics (LENA) (Figure 2), an ion accelerator facility that was completed in the early 2000s with the help of UNC-Chapel Hill faculty.2 The ion accelerators deliver atoms at energies sufficient to initiate nuclear reactions, and thus, LENA is often used for research and measurements in nuclear astrophysics. In particular, research conducted at LENA aims to explore nuclear reactions that occur in stars to answer questions about element production in the universe, stellar evolution, and explosions.

The team used the database of nuclear reaction measurements from LENA and performed new computer simulations. The simulations showed peak temperature and peak density data, characteristics of nova conditions necessary for presolar stardust grain formation. These parameters were studied using a Monte Carlo technique, meaning the parameters were selected randomly and compared with the abundances observed from the simulation. The parameters that did not match the simulations indicate that they were not characteristics of the event that formed the stardust grains. For the first time, these simulations did not require any questionable dilution with normal solar system matter, as in previous research on stardust grains. The grains that the simulations identified more than likely derived from nova explosions.2 The small pieces of matter that the team identified in the research originated in the nuclear explosions of two-star systems, explosions between a white dwarf and a main sequence star. Thus, the research identified eighteen different stardust grains for the first time that likely derived from nova explosions with simulations that did not assume any ad hoc dilution.2 These results have implications for the known history of our solar system in a nuclear astrophysical context, as well as for the current composition of the solar system because these materials from the nova explosions can be found on Earth today. Currently, there are many other astronomical research studies being done on stars and stellar explosions, particularly focused on their origin. For example, in April 2018, researchers at the University of Southampton identified 72 stellar explosions, and have not been able to explain their origin. Dr. Iliadis and his team’s research could potentially be useful in stellar research that focuses on origin of materials such as the study at Southampton because they have characterized materials that originated from stellar explosions.

‹‰—”‡ ÍžǤ The electron–cyclotron-resonance ion source with its new acceleration column at TUNL’s Laboratory for Experimental Nuclear Astrophysics (LENA). Photo courtesy of the UNC Physics Department.

References

Due to the multifaceted nature of the research, Dr. Iliadis worked with a team of four other individuals on the research. “If you have a stellar explosion, it’s not just the nuclear physics that’s important, but the atomic physics, the thermodynamics, the hydrodynamics, and essentially all physics is important so you need experts in all of these areas,� Dr. Iliadis said.2

Í?Ǥ ÂƒÂ”Â•Â–Â‘Â™ÇĄ ǤǢ Š‹–‡ ™ƒ”ˆ• ƒÂ?† –Š‡” ‰‹Â?‰ –ƒ”•Ǥ Š––’ǣȀȀ ™™™ǤÂ?ƒ–‹‘Â?ƒŽ‰‡‘‰”ƒ’Š‹…Ǥ…‘Â?Ȁ•…‹‡Â?Â…Â‡Č€Â•Â’Â…ÂƒÂ‡Č€Â—Â?Â‹Â˜Â‡Â”Â•Â‡Č€ Â™ÂŠÂ‹Â–Â‡ÇŚÂ†Â™ÂƒÂ”ÂˆÂ•Č€ Č‹ÂƒÂ…Â…Â‡Â•Â•Â‡Â† ‡’–‡Â?„‡” Ížͤ–Šǥ ͜͞Í?ͤČŒǤ ÍžǤ Â?–‡”˜‹‡™ ™‹–Š Š”‹•–‹ƒÂ? ÂŽÂ‹ÂƒÂ†Â‹Â•ÇĄ Š Ǥ ÍœÍĽČ€ÍžÍĄČ€Í?ͤǤ Í&#x;Ǥ ‡„„ǥ ǤǢ –ƒ” •Â?ƒ’’‡† „‡ˆ‘”‡ ƒÂ?† ƒˆ–‡” ‡š’Ž‘•‹‘Â?Ǥ Š––’•ǣȀȀ™™™Ǥ„„…Ǥ…‘Â?Č€Â?‡™•Ȁ•…‹‡Â?…‡nj‡Â?˜‹”‘Â?Â?‡Â?–njÍ&#x;ÍŁÍœͼͤÍ&#x;Í?ÍŁ Č‹ÂƒÂ…Â…Â‡Â•Â•Â‡Â† …–‘„‡” ͼ–Šǥ ͜͞Í?ͤČŒǤ Í Ç¤ •–”‘Â?‘Â?‡”• ƤÂ?† ÍŁÍž „”‹‰Š– ƒÂ?† ˆƒ•– ‡š’Ž‘•‹‘Â?•Ǥ ™™™Ǥ •…‹‡Â?…‡†ƒ‹Ž›Ǥ…‘Â?Č€Â”Â‡ÂŽÂ‡ÂƒÂ•Â‡Â•Č€ÍžÍœÍ?ͤČ€ÍœÍ Č€Í?ͤÍœÍ ÍœÍžÍ?ÍĽÍžͥͣ͢ǤŠ–Â? Č‹ÂƒÂ…ÇŚ …‡••‡† …–‘„‡” Í?Í&#x;–Šǥ ͜͞Í?ͤČŒǤ

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public health

Image courtesy of Wikimedia Commons

ǡ Ǧ

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atients are not similar in their physical and genetic makeup, so their progression from sickness to health often does not follow the same path over the duration of their treatment. Variations, or sources of heterogeneity, among patients are generally ignored when patients are prescribed one common therapy. Powerful and more efficient approaches have been developed over the last few years to first develop individualized treatment rules (ITRs) that recognize differences among patients, and furthermore, to develop dynamic treatment regimens (DTRs) that evolve based on patient responses and additional data along the patient treatment path. Dr. Michael Kosorok, W. R. Kenan, Jr., Distinguished Professor of Biostatistics and Professor of Statistics and Operations Research at UNC-Chapel Hill, is leading the charge to deliver real-time data driven solutions for patients with serious diseases—and thereby making significant contributions to the field of precision medicine. As a pioneering researcher in biostatistics, data science, and precision medicine, Dr. Kosorok’s scientific investigations span a wide range of applied areas Dr. Michael Kosorok

including cancer, cystic fibrosis, and depression. His research has led to methodological advances in areas such as highdimensional classification, tree-based methods, and clustering. However, several of his recent papers and publications in progress focus on the complex task of developing precise and dynamic treatment plans and demonstrating their value over traditional methods of assigning treatments to patients. Dr. Kosorok is also advising several major health IT providers, given the applied value of the methods developed by him and his co-authors. In a paper that marked a significant departure from existing methods of assigning treatments to patients, Dr. Korosok and his co-authors developed a novel “outcome weighted learning” (OWL) approach to identify optimal ITRs.1 Earlier parametric methods that focused more on reducing prediction error than on identifying ideal decision rules relied on an indirect method to estimate ITRs for patients. Instead, the OWL developed in this paper used a nonparametric method that focused on maximizing patient outcomes (value function) and thereby directly focused on developing an optimal decision rule based on patient specific factors or prognostic variables that could lead to ideal treatment outcomes. Simulations using multiple scenarios demonstrated the predictive superiority and efficiency of multiple versions (Gaussian and linear kernels) of the OWL with traditional methods including partial and ordinary least squares (PLS and OLS). The authors then compare the OWL, with a linear kernel, with PLS AND OLS

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Carolina Scientific methods to clinical trial data for patients with a depressive disorder. Patients were either assigned to Nefazodone (a synthetic antidepressant), psychotherapy, or both, and their scores on a depression rating scale were used as the outcome measure. The results showed that the OWL significantly outperformed OLS and PLS in assigning patients to optimal treatment, which in this case was the combination of drug and therapy. The OWL procedure developed by Dr. Kosorok and his co-authors led to the most superior clinical outcomes— which if applied in clinical settings, has the potential to help more patients suffering from debilitating depression achieve positive therapeutic outcomes compared to conventional approaches. In subsequent research, the authors are developing improvements in methods for developing ITRs by using residual weighted learning (RWL) and, more recently, augmented outcome-weighted learning (AOL).2 The authors note a limitation of their research being that the ITR methods fail to recognize changes in patient factors and adaptive responses over the time of a treatment. Their subsequent work addresses this limitation by developing time varying dynamic treatment regimes (DTRs). In their most recent research projects, Dr. Kosorok and his team have developed methods for not only recognizing differences between patients (heterogeneity), but also accounting for different paths of responses and other factors over the time of a treatment to developed personalized and adaptive treatment strategies for the benefit of patients. In a series of papers resulting from this research, it is evident that the authors have harnessed the availability of data, as well as modern computational developments, and applied them to the important context of patients suffering from chronic diseases and a medical community facing the challenge of choosing among complex treatment options. One paper develops a method named Augmented Outcome-Weighted Learning (AOL) which can be used to apply the earlier developed OWL models to unique clinical trials called sequential multiple assignment randomized trials (SMARTs).3 Their methods lead to minimal data (patient) loss in the analysis, and leads to more reliable (less variable) DTRs. Application of their methods to data from a multi-site, multi-stage randomized clinical trial of treatment regimes for patients with depression demonstrated its superior clinical performance over Q-learning and a one size fits all technique. In figure 1, it is clear that there is a lower mean (level of depression) for AOL, which is the desirable outcome and lower stand error for AOL both Gaussian and linear kernels. Dr. Kosorok’s most recent work encompasses a technique known as v-learning, which he describes in his paper, “Estimating Dynamic Treatment Regimes in Mobile Health Using V-Learning.� This technique allows researchers or physicians to process real time data and produce moment-to-moment diagnostics for patients with serious health conditions. V-learning is unique in that it combines two data timelines, i.e., data collection over an indefinite time horizon as well as minute-to-minute data collection, to be able to generate short-term diagnostics for patients.3 This way, sudden changes in variables like glucose level or heart rate can trigger an immediate dichotomous cascade that can produce actionable

public health

‹‰—”‡ Í?ÇŁ This plot compares the various methods (Q-learn‹Â?‰ǥ —–…‘Â?‡ ‡‹‰Š–‡† ‡ƒ”Â?‹Â?‰ǥ ƒÂ?† —‰Â?‡Â?–‡† —–…‘Â?‡ Weighted Learning) in their means and standard deviations ˆ‘” †‡’”‡••‹‘Â? ƒÂ?‘Â?‰ ’ƒ–‹‡Â?–•Ǥ Â?ƒ‰‡ …‘—”–‡•› ‘ˆ ‹— ‡– ƒŽǤǥ Í˘Í ÍĄÍ¨Ç¤ alerts for patients to actively improve their health. Dr. Kosorok is currently advising several companies focused on using mobile technologies to guide clinical decision making and patient treatment plans.5 Dr. Kosorok believes that in an outpatient setting, mHealth is the best solution for being able to record all of the data that is produced away from a physical provider of care (physician, nurse etc.), as electronic sensors can take a high volume of data constantly and significantly reduce the amount of “missedâ€? data that can accumulate even in the care of a doctor.4 Dr. Kosorok believes that the solution being developed has the potential to be useful to patients dealing with a host of other health conditions and even with those comorbidities who face the dauting challenge of managing multiple conditions at once.5 With his deep expertise across a variety of biostatistical methods and his passion for improving public health, Dr. Kosorok continues to be a leader in the field of precision medicine and in exerting a positive force in the lives of the medically afflicted for years to come.

References Í?Ǥ ÂŠÂƒÂ‘ÇĄ ǤǢ ‡Â?‰ǥ ǤǢ —•Šǥ ǤǢ ‘•‘”‘Â?ÇĄ Ǥ ǤǢ J. Am. Stat. Assoc. 2012ÇĄ 107ÇĄ Í?Í?Íœ͢njÍ?Í?Í?ͤǤ ÍžǤ Š‘—ǥ ǤǢ ‘•‘”‘Â?ÇĄ Ǥ ǤǢ arXiv. 2017. Í&#x;Ǥ ‹—ǥ ǤǢ ƒÂ?‰ǥ ǤǢ ‘•‘”‘Â?ÇĄ Ǥ ǤǢ ÂŠÂƒÂ‘ÇĄ ǤǢ ‡Â?‰ǥ ǤǢ Stat. Med. 2018ÇĄ ͣͧČ‹͌͢ČŒÇĄ Í&#x;ͣͣ͢njÍ&#x;ͣͤͤǤ Í Ç¤ —…Â?‡––ǥ Ǥ ǤǢ ÂƒÂ„Â‡Â”ÇĄ Ǥ ǤǢ ƒŠÂ?‘•Â?ÂƒÂŠÇĄ Ǥ ǤǢ ÂƒÂƒÂŠÂ•ÇĄ Ǥ ǤǢ ÂƒÂ›Â‡Â”ÇŚ ÂƒÂ˜Â‹Â•ÇĄ ǤǢ ‘•‘”‘Â?ÇĄ Ǥ ǤǢ arXiv. 2017. ͥǤ Â?–‡”˜‹‡™ ™‹–Š ‹…Šƒ‡Ž ‘•‘”‘Â?ÇĄ ŠǤ Ǥ ÍœÍĽČ€ÍžͤČ€ÍžÍœÍ?ͤǤ

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ŽŽ—•–”ƒ–‹‘Â? „› ‡Ž‡Â?ƒ ‡Ǥ

Saving the Earth to Save Lives › ‡˜‹Â? —‘ƥ

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ir pollution is responsible for one in nine deaths worldwide, including one-third of deaths caused by stroke, lung cancer, and chronic respiratory disease.1 Environmental concerns have begun to consume a large portion of our scientific and political discussions, from finding methods to save the planet and curb global warming to acknowledging humans’ destruction of Earth with the burning of fossil fuels and industrialization. Some people choose to ignore warnings, maybe because they think that they will be long gone before any consequences come to fruition. The truth is, humans will be gone a lot sooner than they think because our actions are not only poisoning the environment, but also ourselves. The same processes that cause global warming place harmful pollutants in the air that kill millions of people every year.2 Any efforts to save the environment are also efforts to save human lives. Dr. William Vizuete uses computational modeling to understand processes that pollute the atmosphere and provide policy advice to stimulate positive changes in public health. Dr. Vizuete works in the engineering department of

‹‰—”‡ Í?Ǥ Š‡ …›…Ž‡ ‘ˆ ’‘ŽŽ—–‹‘Â?Ǥ Š‘–‘ „› ‹ ‡– ƒŽǤ Í˘Í ÍĄÍ Ç¤

the Gillings School of Global Public Health at UNC-Chapel Hill with the Air Quality and Atmospheric Processes Group to develop solutions to growing public health issues. Dr. Vizuete combines chemistry and engineering to identify, quantify, and source the different kinds of chemicals that humans are exposed to when they breathe in polluted air. Computer models are another helpful aid for understanding atmospheric chemistry and how it produces air pollution. However, as Dr. Vizuete says, “science doesn’t drive change, policy does.�3 Thus, one of his most important tasks involves communicating the problems he finds to lawmakers and making recommendations as to what policies they should implement to decrease pollution. Dr. Vizuete’s current research involves work with various research groups, commercial organizations, and environmental agencies such as the Environmental Protection Agency (EPA), that are concerned with the content of the atmosphere at specific locations. His research studies the creation and effects of ozone and different types of aerosols—articles of liquid suspended in air (i.e. particulate air pollutants, fog, and dust)—at the surface level of the Earth, which have significantly different effects compared to ozone in the upper atmosphere. Ozone in the upper atmosphere protects humans from harmful solar radiation. However, ozone near the ground is toxic and can cause adverse health effects, such as poor cognitive function in older adults4 and cardiopulmonary diseases.5 Dr. Vizuete currently works with the cities of Denver and Houston through the Colorado Department of Health and Environment and the Texas Commission on Environmental Quality, respectively, to address their excess ozone levels, which are reaching the federal limit for ozone in their air. The chemistry involved in forming ozone is the same everywhere, but its source

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Carolina Scientific varies across different geographic areas. In Houston, for example, high levels of ozone are attributable to the presence of numerous oil and gas refineries. Dr. Vizuete’s group collects data from these industrial plants and attempts to determine which practices contribute to excessive ‹‰—”‡ ÍžǤ Legal marijuana sales cre- ozone creation. Once ate escalating environmental dam- they find the source, ƒ‰‡Ǥ Š‘–‘ „› ”Ǥ ‹œ—‡–‡ they recommend operational changes that can be made to decrease the harmful emissions. Meanwhile, Denver’s current levels of ozone could be worsened due to the incipient marijuana industry. To understand what is going on in Denver, Dr. Vizuete provided a comparison to the Smoky Mountains. He explained that the Smoky Mountains are “smokyâ€? because “trees release gases into the atmosphere that react with sunlight and produce aerosols that look like off white colored smoke.â€?2 This is the same process that goes on in Denver’s marijuana farms. The marijuana plants give off gases that react with sunlight to produce aerosols and ozone that pollute the air. Dr. Vizuete has sent a graduate student to Colorado to quantify and identify the gases emitted from four different strains of marijuana and then use computer models to predict their impact on Denver’s air quality. His direct measurements of marijuana farms are the first investigation of these facilities’ emissions and their ultimate effect on pollution. Dr. Vizuete’s research combines measurements of air composition with air quality models. These two practices work hand-in-hand—his measurements help to determine what information to put into his models and his models help him figure out what to look for in his measurements. The models predict the effect of pollutants, as well as inform the policy

public health

recommendations he makes. Models are valuable for further understanding complex phenomena, however, they never paint a complete picture. Dr. Vizuete says that “all models are wrong, but some are useful.�2 The greatest challenge, according to Dr. Vizuete, is not getting his models to work correctly or take accurate measurements. Rather, it is trying to communicate ‹ŽŽ‹ƒ� ‹œ—‡–‡ his scientific findings with policymakers or business leaders who often have a minimal scientific background. Research findings must be translated into layman’s terms so that the important points are clearly conveyed. Science can indicate what action should be taken, but if the intended audience does not like the idea or finds it financially unfavorable, then the advice can be ignored. Whether or not his recommendations are taken, Dr. Vizuete finds great pleasure in knowing that he is doing his part to help improve public health. In addition to his research efforts with city governments and agencies, he runs a study abroad program in the Galapagos Islands to teach environmental chemistry and has taught students to take measurements of aerosols in the marine environment. Trying to understand everything that goes on in the atmosphere is a complicated, but important task for the health of the environment and the general public. Despite its challenges, atmospheric research can make great strides towards alleviating numerous public health issues and ensuring a viable planet for future generations.

“Science can indicate what action should be taken, but if the intended audience does QRW OLNH WKDW LGHD RU ÂżQGV LW ÂżQDQFLDOO\ XQIDYRUDEOH WKHQ WKH DGYLFH FDQ EH LJQRUHG ´

References

‹‰—”‡ Í Ç¤ ”Ǥ ‹œ—‡–‡ ’‡”ˆ‘”Â?‹Â?‰ ”‡•‡ƒ”…Š ‘Â? Â?ƒ”‹Œ—ƒÂ?ƒ ’ŽƒÂ?–• ‹Â? ‘Ž‘”ƒ†‘Ǥ Š‘–‘ „› ”Ǥ ‹œ—‡––‡Ǥ

Í?Ǥ ‘”Ž† ‡ƒŽ–Š ”‰ƒÂ?‹œƒ–‹‘Â?ÇŁ ‹” ‘ŽŽ—–‹‘Â?Ǥ Š––’ǣȀȀ™™™Ǥ ™Š‘Ǥ‹Â?Â–Č€ÂƒÂ‹Â”Â’Â‘ÂŽÂŽÂ—Â–Â‹Â‘Â?Ȁ‡Â?Č€ Č‹ÂƒÂ…Â…Â‡Â•Â•Â‡Â† …–‘„‡” ÍŁÇĄ ͜͞Í?ͤČŒǤ ÍžǤ Š‹Â?‰ǥ Ǣ ƒŒ‹Â?‘ǥ Ǥ Nature. 2018. Í&#x;Ǥ Â?–‡”˜‹‡™ ™‹–Š ‹ŽŽ‹ƒÂ? Â‹ÂœÂ—Â‡Â–Â‡ÇĄ ŠǤ Ǥ ÍĽČ€ÍžÍ Č€ÍžÍœÍ?ͤǤ Í Ç¤ ƒ•ƒÂ?Â‘Â˜ÂƒÇĄ ǤǢǥ ƒÂ?‰ǥ ǤǢ ‡›‡•ǥ ǤǢ Â?Â‹Â–ÂƒÇĄ ǤǢ ‡””‡ǥ Ǥ ǤǢ Â‹ÂœÂ—Â‡Â–Â‡ÇĄ ǤǢ Š—‹ǥ Ǥ ǤǢ ”‹•…‘ŽŽǥ ǤǢǥ ‡•Â?‹…Â?ÇĄ Ǥ ǤǢ •’‡nj ŽƒÂ?†ǥ Ǥ ǤǢ ‡– ƒŽǤ ”‘Â?–Ǥ —Â?Ǥ ‡—”‘•…‹. 2016. ͥǤ ‹ǥ ǤǢǥ ‹„•‘Â?ÇĄ Ǥ ǤǢ ÂƒÂ–ÇĄ ǤǢǥ —‰‰‹‘Â?‹ǥ ǤǢ ƒ•ƒÂ?ÇĄ ǤǢ ‡•–ǥ Ǥ ǤǢ Â‹ÂœÂ—Â‡Â–Â‡ÇĄ ǤǢ ‡š–‘Â?ÇĄ ǤǢ ‡””‡ǥ ǤǢ Elsevier. 2010ÇĄ ÍĄÍŁÍ¤Í ÇŚÍĄÍŁÍĽÍ&#x;Ǥ

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Understanding Your Nutritional Needs By Lauren Glaze

Image courtesy of Pixabay

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hat foods should humans consume to feel their best? Nutrition is more personal than many people would expect. An individual’s genetic code wields significant influence over how the body responds to various sources of nutrition. For example, some individuals must seek more dietary sources of docosahexaenoic acid (DHA) because a genetic difference prevents their body from producing enough.1 The normalization of genetic testing may soon allow humans to delve into their own genetic code, uncovering variations that could provide insight into their inner workings. However, there are also simple steps which can be incorporated into daily routines and may help people become more aware of their body’s nutritional needs. Pregnant mothers should pay special attention to this information as genetic influences and environmental influences, such as nutrient availability, may impact their child’s nutrient processing ability later on in life. Alpha-linolenic acid (LNA) is an essential fatty acid that humans obtain from their diet. It is converted to DHA,

which plays a key role in cognitive development and function. DHA exists in all cells and is essential to maintaining the structural integrity of the brain cells. Over 80% of the U.S. population can make their own DHA from LNA. However, Dr. Carol Cheatham of UNC-Chapel Hill studies a mutation of the FADS2 gene, which results in a reduced ability to convert LNA to DHA. She studies this mutation in an effort to identify sources of variation in cognitive responses to DHA. Thus, she is attempting to refute hypotheses that suggest there is no connection between Carol Cheatham

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Carolina Scientific

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to make all-encompassing statements about optimal quantities of daily nutrient consumption for the average human. Choline, a nutrient found in peanuts, eggs, beef, and poultry, is essential for transporting DHA that is stored in the liver to the brain. Without choline, our bodies cannot reap the cognitive benefits from DHA. This is evident in Dr. Cheatham’s research concerning the effect of DHA on breastfed babies. Dr. Cheatham uses an electrophysiological technique known as event-related potentials (ERP) to test infant memory. While infants observe a series of familiar and unfamiliar pictures, Dr. Cheatham records their brain activity. That brain activity is then time-locked to the stimulus that was on the screen. By comparing averaged brain activity when the infant viewed the familiar picture with averaged brain activity when the infant viewed novel pictures, she can determine whether or ͝ǣ An infant’s memory is tested via ERPDHA supple- not the infants “remembered” the stimulus. ERP is a great tool Ƥ Ǥ Ǥ for testing recognition memory in preverbal infants. Previous Cheatham. studies found variable effects on babies consuming baby forDHA in the brain and improved cognitive function. Not all in- mula supplemented with DHA. However, much of this varidividuals benefit from an increased DHA intake, but individu- ability was eliminated in her study which examined recognials who are deficient in this nutrient must pay extra attention tion and memory skills in 6-month-old babies. She found that to finding sufficient dietary sources to optimize their cognitive when choline was present in the breast-milk alongside DHA, the babies consistently experienced function. Her research goal is to unimproved mental processing. derstand how nutrients are utilized Dr. Cheatham hopes to inin different ways and to different despire future research investigating grees within the body.2 which nutrients work best together In addition to genetics, anin allowing the body to best utilize other important consideration and nutrients. Additionally, she hopes potential source of variation in nutrithat such studies will control for getional studies is the mode of ingesnetic variation. Thus, in the future, tion. “You have to eat whole foods,” nutritionists might be able to avoid Cheatham explains, “an orange, making broad recommendations for example, is not just vitamin C. that may overlook important conIt also has the pulp, fiber, iron, and nections between genetics and nuall of the other wonderful propertrition. ties within the food matrix that So how can consumers move help that vitamin C to be absorbed.” Otherwise, vitamin C would move quickly and ineffectively forward in developing a nutrition plan that best suits their through the body. The synergy between nutrients allows for body’s needs? A simpler method for revealing which foods optimal nutrient absorption in the body. As such, it is difficult help humans feel their best involves an elimination diet. This strategy removes certain foods from diets one at a time to observe how it affects energy levels, mood, and overall body function. Additionally, Dr. Cheatham suggests “eating a rainbow” because a greater diversity of colors on the plate encourages greater nutritional value within a meal. In the near future, it may be possible to send one’s genetic code to a lab and receive a personalized meal plan in return. However, using one’s intuition to understand the effects of certain foods on bodily function without such testing them can also be effective. Therefore, it is important to pay attention to how the body reacts to daily food intake in order to evaluate one’s nutritional health.

Dr. Cheatham suggests “eating a rainbow” because a greater diversity of colors on the plate encourages greater nutritional value within a meal.

͞ǣ Ǥ ǡ warming ocean temperatures are reducing DHA content References Ƥ Ǧ ͝Ǥ ǡ Ǣ ǡ Ǣ ǡ Ǣ ǡ Ǣ Ƥ Ǥ ǡ Ǥ J. Nutr. ͜͞​͜͠. 134ǡ ͤ͟͝Ǧͤ͢͝Ǥ ͞Ǥ ǡ Ǥ Ǥ ͜͝Ȁ͝Ȁͤ͝ Pixabay.

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͝Ǥ Ǥ Image courtesy of Wikimedia Commons.

No Landmarks, No Gps, No Maps By Vaishnavi Siripurapu

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magine: What would you do if you were trying to get home? You would probably take a bus, car, plane, or even walk, right? Now imagine if you were trying to get home on a raft, alone and in the middle of the ocean, with no GPS or sense of direction. What would you do? I’ll tell you what you would do if you were a sea turtle: use Earth’s magnetic field! Many species of animals migrate long distances and utilize various forms of navigation during their seasonal migrations. Sea turtles migrate extremely long distances during their lifetime— they traverse the open ocean, which lacks any distinct landmarks, and return to the beaches on which they were born to lay their own eggs.1 Dr. Roger Brothers, a professor of Biology at UNC-Chapel Hill, researches how exactly turtles accomplish this feat. Dr. Brothers utilizes a three-pronged approach to test his hypothesis: Do female sea turtles use Earth’s magnetic field to return to the beach they were born at to lay their eggs? In order to answer this ques-

tion, Dr. Brothers and his research team analyzed the behavior of female sea turtles on nesting beaches, compiled years of detailed nesting behavior data from the Southeastern United States, and examined how changing magnetic field lines impacted sea turtle nesting behavior (Figure 1).1 To understand the direct impacts of magnetic signatures on the behavior of turtles, Dr. Brothers and his team intercepted female Olive Ridley sea turtles, the smallest and most abundant of all sea turtles, as they were coming out of the sea onto the beach to lay their eggs. These turtles were put into a tank large enough so that they could move around 360 degrees without touching the sides. The tank was atop a magnetic coil, which would emit a magnetic signal similar to that experienced at a beach northwest of the turtle’s birth beach. When the females were exposed to this new signal in the tank, a majority of them reacted by swimming southeast. Had the females been in the ocean and sensed the signature

“The team uncovered that turtle populations that nest on beaches with identical magnetic signals are usually genetically very similar.”

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Carolina Scientific of the northwest beach, their swimming pattern would have brought them southeast and back to their original beach of birth.1 Based on the females’ behavior as they attempted to swim back to their birth beach based on the magnetic signal information, the researchers speculated that sea turtles use Earth’s magnetic field as a compass to direct them to swim home (Figure 2). However, as is always the case in science, more evidence was needed in order to make a stronger claim. To do this, Dr. Brothers and his team looked at data collected by various other scientists over years of detailed record-tracking of Loggerhead sea turtles in order to determine a stronger correlation between magnetic field influence and turtle navigation. Earth’s magnetic field shifts and changes over time, and this shift can change the magnetic signatures of geographic locations on earth. As a result, magnetic field lines can get closer and closer together or further and further apart, which impacts sea turtle nesting behavior. Through analysis of the previously collected data, Dr. Brothers and his team discovered that it is not the geographic location of an area that attracts sea turtles, but rather the magnetic signature of the area. It was found that when magnetic field lines that were previously far apart get closer together, turtles will still nest in between the magnetic field lines, therefore causing an increased nesting density. The reverse happens as well. When magnetic field lines that were previously closer together get further apart,

͞Ǥ Ƥ Ǥ Ǥ Ǥ

environmental science

͟Ǥ Ǥ Ǥ Ǥ Ǥ turtles continue to nest between the lines, causing a lower nesting density than previously recorded.1 This correlation of turtle nesting density with the geographic location of magnetic field lines illustrated a relationship between magnetic influence and female turtles’ choice of nest sites (Figure 3). In order to further rule out the possibility that sea turtles were using geographic markers and not magnetic signals to find nesting beaches, Dr. Brothers and his team took into account additional data from nesting turtles in the southeastern United States. Female sea turtles will sometimes confuse the magnetic signals of one location for the magnetic signal of another and will nest at an alternate beach instead of their birth beach. Upon investigation, it was found that the birth beach of the turtle and the alternate beach that she had laid her eggs on produced the same magnetic signal. After data analysis, the team uncovered that turtle populations that nest on beaches with identical magnetic signals are usually genetically very similar.1 As Dr. Brothers explains, “For example, a turtle population nesting on a beach would be more genetically similar to a turtle population nesting on a beach 500 miles away but with the same magnetic signature than a turtle population only 50 miles away but with a different magnetic signature.” This genetic data provided a stronger correlation to show how turtles use magnetic fields to influence their navigation and egg-laying behavior. Altogether, Dr. Brothers and his team uncovered a certain magnetic influence behind sea turtle nesting behavior via various direct and indirect research methods. In the future, this research could have impacts on conservation efforts for sea turtles, as human development can impact magnetic field signatures. More effort should be made to minimize human impact on magnetic field signals near known turtle nesting beaches in order to encourage nesting and reproduction. According to Dr. Brothers, “In the far future, this type of research could be combined with other interdisciplinary research and used to inform new GPS and navigation tools for human use based off of the Earth’s magnetic field.” If you are lucky enough to see a baby turtle hatch, keep your eyes peeled, she may just return to the same beach in the future, using magnetic fields to guide her home!

References ͝Ǥ Ǥ ǡ Ǥ Ǥ ͜͝Ȁ͞Ȁͤ͝

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GalĂĄpagos Invasive Species Through the Lens of Ecohydrology By Aubrey Knier

Illustration by Taylor Thomas

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he Galåpagos Islands are considered to be the key that unlocked the door to evolutionary theory and biology as we know it today. The islands are famous for fostering the world’s richest biodiversity, which inspired Charles Darwin’s theories on evolution. However, a recent increase in human presence on the islands have introduced invasive species that threaten its pristine condition and the unique plants and animals that are critical to the islands’ ecological integrity. The initial disruption of the immaculate ecosystem of the Galåpagos Islands began with the arrival of humans between 1820 and 1830. With humans came plants and livestock which competed for resources with the Galåpagos’ endemic species, many of which are only found on the Galåpagos Islands.2 Invasive species are able to thrive in the ecosystems of the Galåpagos because they have adaptions that are better fit for the islands’ environment. For example, many invasive species are able to retain water for longer periods of time and at higher pressures than the native species, making them more likely to survive during periods of drought.1 Invasive species are thus able to disrupt and dominate ecosystems since they lack the same predatory checks and balances that the native species do. Although harmful to the ecosystem of the Galåpagos Islands, many invasive species provide valuable resources for food and farming, meaning that people will continue to bring invasive species to the islands for their benefit.1 Today, the introduction of these invasive species by humans continues to put the native plants of the islands in imminent danger of extinction.

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‹‰—”‡ Í?Ǥ Č‹ Â‘Â’ČŒ ÇŚ Šƒ’‡Ž ‹ŽŽnj ƒŽž’ƒ‰‘• …‹‡Â?…‡ ‡Â?–‡” ˆƒ…‹Ž‹–›Ǥ Š‘–‘ …‘—”–‡•› ‘ˆ —„”‡› Â?‹‡”Ǥ Č‹ ‘––‘Â?ČŒ ”‡•‡ƒ”…Š‡”• ƒ– ™‡ƒ–Š‡” •–ƒ–‹‘Â? ƒ– ÂŽ Â‹Â”ÂƒÂ†Â‘Â”ÇĄ ƒÂ? Â”Â‹Â•Â–Ă—Â„ÂƒÂŽÇĄ ƒŽž’ƒ‰‘• •ŽƒÂ?†•Ǥ Š‘–‘ …‘—”–‡•› ‘ˆ ‹Â?–‘Â?‰ —Ǥ

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environmental science

Guava is one of the GalĂĄpagos Islands’ most stubborn and threatening species—it’s also adored by the people and animals of the islands alike. Birds enjoy eating its sweet fruit and, in turn, disperse their various seeds across the islands, allowing this invasive species to multiply over widespread areas.1 Many people plant guava trees near their house in order to make delicious guava juice, thus further increasing their presence on the islands. Additionally, the tenfold increase in tourism over the last 20 years and its resulting economical shift have indirectly impacted the proliferation of invasive species like guava through a phenomenon called land abandonment.1 Many farmers have made the choice to abandon their land to open a restaurant or giftshop on the coast because it is more lucrative due to the shifting economy. When farmers abandon their land, invasive species have the opportunity to freely invade the area without a farmer there to fight against them.1 An example of this is illustrated by the invasion of guava onto the lands of a treasured endemic species of the GalĂĄpagos: the miconia tree. Recently, an extreme effort was made by the national park of the GalĂĄpagos Islands to reintroduce miconia trees in regions throughout the island that were taken over by guava. Unfortunately, the severe drought caused by El NiĂąo in 2016 killed the majority of the miconia plants while guava survived.1 So, why could guava survive the drought when the miconia trees could not? In the summer of 2018, a group of students at UNCChapel Hill went abroad to study at the USFQ-UNC-Chapel Hill GalĂĄpagos Science Center to answer questions like these under the instruction of Dr. Diego Riveros-Iregui, a geography professor at UNC. Through the unique lens of ecohydrology— ‹‰—”‡ ÍžǤ UNC-Chapel Hill student measuring leaf-water the study of the interaction between plants and water in eco- ’‘–‡Â?–‹ƒŽ ‹Â? —Â?Â?‡” Í˘Í ÍĄÍ¨Ç¤ Š‘–‘ …‘—”–‡•› ‘ˆ —„”‡› Â?‹‡”Ǥ systems—researchers obtain novel insights into how invasive determine how different plants are able to retain and hold species impact native species, as well as their general effect on onto water, making them more likely to survive in times of the ecosystem at large, based upon their interactions with wa- drought. Stem samples of each plant species were placed inter.1 Dr. Riveros-Iregui investigates side of a pressure chamber, which these interactions through the simulated a drought environment, study of the islands’ water budget, and were exposed to a constant which essentially is an account of high pressure which drew the how water is distributed within an water out of the plant. Plants that ecosystem, as well as how it flows were able to hold onto the water through said ecosystem.2 This for a longer amount of time were perspective can inform Dr. Riveconsidered more durable than ros-Iregui and his students about those that held onto the water how invasive species are able to for a shorter amount of time.1 The compete with native species due results imply that the invasive to how they utilize the water that species, guava, hold onto water they receive in the water budget. longer and therefore are more fit In the humid highlands of to the environment than the nathe Island of San CristĂłbal, guava tive species in periods of drought. overruns the area and often outThis is why guava was able survive competes native species like ferns, when the miconia could not durmiconia, and scalasia trees. UN C ing El NiĂąo. Information about the students investigated how these ways in which invasive species are plants use their water and what able to outcompete native species makes the guava successful in further contributes to our knowlthese environments. In order to edge about the invasive epidemic do this, the plant-water potential ‹‰—”‡ Í&#x;Ǥ —ƒ˜ƒ ‹Â? –Š‡ ƒŽž’ƒ‰‘• •ŽƒÂ?†•Ǥ Š‘–‘ in the GalĂĄpagos, and informs of each species was measured to courtesy of Creative Commons. what we can expect for the future

“Plants that were able to hold onto the water for a longer amount of time were considered more durable than those that held onto water for a shorter amount of time.�

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environmental science

‹‰—”‡ Í&#x;Ǥ ‹…‘Â?‹ƒ ’ŽƒÂ?– ‘Â? ÂŽ —Â?…‘ǥ ƒÂ? Â”Â‹Â•Â–Â‘Â„ÂƒÂŽÇĄ ƒŽž’ƒ‰‘• •ŽƒÂ?†•Ǥ Š‘–‘ …‘—”–‡•› ‘ˆ —„”‡› Â?‹‡”Ǥ of the Islands’ native species.1 Although the problem of invasive species is a multifaceted and ongoing issue, finding a solution has to begin with analyzing this simple ecohydrological data, like plantwater potential, which may help piece together more complicated questions. In order to preserve the endemic species of the GalĂĄpagos, efforts must be made as soon as possible to protect the native species. Reclaiming farmland and removing the invasive species that threaten the existence of the GalĂĄpagos Islands’ native species is essential to preserving its treasured biodiversity. However, as worldwide research and conservation efforts continue at the USFQ-UNC-Chapel Hill GalĂĄpagos Science Center, a brighter day is on the horizon for the endemic species of the GalĂĄpagos Islands.

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Dr. Diego Riveros-Iregui

References Í?Ǥ Â?–‡”˜‹‡™ ™‹–Š ‹‡‰‘ Â‹Â˜Â‡Â”Â‘Â•ÇŚ ”‡‰—‹ǥ Š Ǥ ÍœÍĽČ€ÍžͤČ€Í?ͤǤ ÍžǤ ‡”…›ǥ Ǥ Ǣ …ŠÂ?‹––ǥ Ǥ Ǣ Â‹Â˜Â‡Â”Â‘Â•ÇŚ ”‡‰—‹ǥ Ǥ Ǣ ‹”—•ǥ Ǥ Ǣ WIREs Water. 2016ÇĄ 3ÇĄ ͥͤͣnj͢͜͜Ǥ

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medicine.campbell.edu EEO/AA/Minorities/Females/Disabled/Protected Veterans http://www.campbell.edu/employment

Carolina Caro Ca rolililin ro na a Scientific Sci c een ntiific fic

environmental science

Writing the Geological Story of Half Dome Cliff

͝Ǥ ơ Ǥ Ǥ Ǥ

Y

osemite National Park, located in the Sierra Nevada mountains in California, boasts one of the most remarkable landscapes in the world. The kilometer-high cliffs of Yosemite Valley attract nearly four million visitors every year. However, most visitors fail to grasp that these impressive cliffs did not just spontaneously appear. The intricate and fascinating story of their creation is being unearthed by geologists such as Dr. Allen Glazner, a professor in the UNC-Chapel Hill Department of Geological Sciences. Through his research and field work in Yosemite, Dr. Glazner has helped write a story that is not only geological, but highly relevant to the world today. Rocks record evidence of nearly every process they undergo and express them in physical or chemical characteristics, such as mineral composition and fractures. Thus, geologists can examine rocks and use this evidence to piece together the story of their creation. Dr. Glazner is specifically investigating the formation of the granite cliffs in Yosemite. “We are kind of doing forensics,” said Dr. Glazner when describing his research, “We have these ‘corpses’—these magmatic systems—and we are trying to take them apart and see how they formed.”1 In his research, Dr. Glazner has focused on the formation

of continental crust at subduction zones and the long-term geochemical cycles associated with subduction. His research eventually led him to Yosemite, an excellent place to study these processes because the bedrock in Yosemite was formed from magma cooling in an ancient subduction zone. Subduction zones are boundaries where oceanic and continental plates converge and the denser oceanic crust sinks below the continental crust and is forced back into the mantle. As the oceanic plate subducts, magma forms by processes that are not well understood—which is another focus of Dr. Glazner’s research. New magma is less dense than the surrounding solid rock and rises toward the surface until it cools underground or erupts. If the magma cools and solidifies underground, it produces a large igneous body formation called a pluton. This type of magmatic cooling process at subduction zones usually produces granite, referred to as granitic pluton emplacement. This exact process took place in Yosemite 100 million years ago, making it a perfect place to study granitic pluton emplacement, which has been the subject of Dr. Glazner’s research for nearly 30 years.2

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environmental science

͞Ǥ ǡ Ǥ ơ ơ Ǥ Ǥ Dr. Glazner has taken an almost iconoclastic approach to his research. He says the most exciting part of science is going out and investigating “things that we think we know and discovering that those things turn out not to be true.”1 This happened in one of his early projects in Yosemite. In the mid2000s, Dr. Glazner and his UNC colleague, Dr. Drew Coleman, used radioactive dating to narrow the age of emplacement for bedrock in Yosemite. They expected to find a very narrow range of ages, since the paradigm at that time stated that plutons are emplaced quickly and concurrently. However, they found a huge spread of dates in the bedrock, which implied that the rocks were not all emplaced at the same time. After checking the data and repeating the analyses, Dr. Glazner began to think that the simple “textbook” conception of pluton emplacement was wrong. He and Dr. Coleman then published two papers asserting that plutons are emplaced incrementally. Geologists met the idea with resistance. The paper upended the field of igneous geology, a branch that studies the formation, structure, and chemical composition of igneous rocks. However, since this initial publication, Dr. Glazner and his colleagues have conducted more research which further confirms their findings. He says that now “most people have agreed that the paradigm has flipped, and what we said is now accepted as the way things are. It has been gratifying to see that shift.”1 Dr. Glazner’s current work in Yosemite is focused on the famed granite cliff known as “Half Dome.” Through his

research, he hopes to answer questions about its formation and why it stands so tall above the other features in Yosemite Valley. As with all the other cliffs in Yosemite, Half Dome formed from glaciers carving through the bedrock hundreds of thousands of years ago, but why it resisted being torn down by the glaciers, and how it attained its unique shape, are mysteries.3 Dr. Glazner believes the key to understanding Half Dome’s formation and shape lies in the structure of the rock, both on the micro and macro scale. To that end, he employs a mix of field and lab methods to analyze the rock makeup and underlying story. In the field, Glazner does a lot of hiking and observational work—using geologic mapping techniques to ascertain information about the structure of Half Dome. Field mapping includes taking direct measurements of rock characteristics such as orientation or magnetic properties. Magnetic properties are particularly relevant to the Half Dome project because magnetic properties differ between magma pulses. This allows for the identification of each individual magma pulse that contributed to the construction of the Half Dome bedrock. Measuring the magnetic properties of Half Dome required Dr. Glazner and his former graduate student, Roger Putnam, to rock climb up Half Dome. Glazner recalled how exhilarating it was to be “up in such a spectacular place clinging on the side of a rock,” while taking measurements.1 While in the field, Dr. Glazner has collected numerous samples and brought them back to his lab at UNC for microstructural and chemical analysis of the granite. His current

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Carolina Scientific

environmental science

graduate student, Justine Grabiec, uses CT-scans of rock samples to look at how tightly the crystals interlock and electron microscopes to understand how the huge feldspar crystals in the granites form. Dr. Glazner hopes to determine how these microstructural distinctive properties contribute to the overall strength of the rock. He also uses radioactive dating methods to pin down a precise time scale during which Half Dome was emplaced. The group’s work so far shows that Half Dome, ‹‰—”‡ Í&#x;Ǥ Č‹ Â‡ÂˆÂ–ČŒ ‘”Â?‡” ‰”ƒ†—ƒ–‡ •–—†‡Â?–ǥ ‘„‡”– —–Â?ƒÂ?ÇĄ –ƒÂ?‹Â?‰ Â?‡ƒ•—”‡Â?‡Â?–• and other high points in Yosemite, while scaling Half Dome. Photo by Robert Putnam. Č‹ Â‹Â‰ÂŠÂ–ČŒ ”Ǥ ŽŽ‡Â? ŽƒœÂ?‡” ”‘…Â? are supported by a dense network …Ž‹Â?„‹Â?‰ ƒÂ?† …‘ŽŽ‡…–‹Â?‰ †ƒ–ƒ ‹Â? ‘•‡Â?‹–‡Ǥ Š‘–‘ „› ”Ǥ ŽƒœÂ?‡”Ǥ of sheet-like, quartz-rich magmatic today’s smart phones on our lives, Dr. Glazner’s work continintrusions that are particularly resisues to mine the rocks of Yosemite for answers and discoveries tant to erosion by glacial ice.2 Dr. Glazner stated that he believes learning as much that shape both the cliffs as well as our modern lives. as we can about how the earth functions and why it is habitable is inherently valuable and relevant.1 He seeks to raise the public consciousness to the fact that while geological research References appears to be millions of years removed from our lives, such Í?Ǥ ‡”•‘Â?ƒŽ ‘Â?Â?—Â?‹…ƒ–‹‘Â? ™‹–Š ŽŽ‡Â? Ǥ ŽƒœÂ?‡”ǥ ŠǤ Ǥ research actually has far-reaching effects today. For example, ͼȀͣȀÍ?ͤǤ he explained that his research and the type of geochemistry ÍžǤ ÂƒÂ”Â–ÂŽÂ‡Â›ÇĄ ‘ŠÂ? ǤǢ ŽƒœÂ?‡”ǥ ŽŽ‡Â? ǤǢ ‘Ž‡Â?ƒÂ?ÇĄ ”‡™ Ǥ he conducts has significant implications in regard to the loca- ‡‘•’Š‡”‡. 2018ÇĄ 14 (3)ÇĄ Í?ÍžͤÍ&#x;Č‚Í?ÍžͼͣǤ tion of deposits of rare earth elements used to make the smart Í&#x;Ǥ ŽƒœÂ?‡”ǥ ŽŽ‡Â? ǤǢ ”‡‰ Ǥ –‘…Â?Ǥ Â? ‡‘Ž‘‰› Â?†‡”ˆ‘‘– phones and computers we use every day.1 From the seismic ‹Â? ‘•‡Â?‹–‡ ƒ–‹‘Â?ƒŽ ƒ”Â?Ǣ ‘—Â?–ƒ‹Â? ”‡•• —„Ǥǣ Â‹Â•Â•Â‘Â—ÂŽÂƒÇĄ shifts of subduction zones, to the equally impactful effect of ‘Â?–ƒÂ?ÂƒÇĄ ͜͞Í?ÍœǤ

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Carolina Scientific Excecutive Board •–Š‡” ™‘� Editor-in-Chief

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Carolina Scientific

ELEVEN YEARS OF EXCELLENCE

Check out all of our previous issues at issuu.com/ uncsci. As the organization continues to grow, we would like to thank our Faculty Advisor, Dr. Gidi Shemer, for his continued support and mentorship.

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“The art and science of asking questions is the source of all knowledge.” Ǧ

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

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Fall 2018 Volume 11 | Issue 1

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