Stony Brook Young Investigators Review

Heart to Heart: An Interview with Dr. Wei Yin

Social Networking and Politics

Our Journey to Mars Hinges on Human Factors

Volume 7 Fall 2016

Stony Brook Young Investigators Review Staff 2016 - 2017 Editor-in-Chief Amanda Ng ’17

Layout Chief Samuel Lederer ’17

President Aaron Gochman ’17

Managing Editors Jenna Mallon ’18 Sahil Rawal ’19

Assistant Layout Editor Dana Espine ’18

Cabinet Peter Alsaloum ’19 Benjamin Kerner ’18 Kyle Pacia ’19

Associate Editors Christin Abraham ’19 Samara Khan ’19 Rachel Kogan ’19 Julia Newman ’19 Nicole Olakkengil ’19 Anna Tarasova ’19 Copy Editors Taylor Ha ’18 Aaradhana Natarajan ’20 Lillian Pao ’18 Daniel Walocha ‘19

Layout Editors Dahae Jun ’19 Sarah Lynch ’17 Arun Nallainathan ’18 Abrar Taseen ’19 Webmasters Arslan Shahid ’17 Ronak Kenia ’18

Photographerc Evelyn Kandov ’17 Jerin Thomas ’19 Advisors Dr. Peter Gergen Dr. Giancarlo la Camera Dr. Laura Lindenfeld

Writers Jalwa Afroz ’17 Shannon Bohman ’19 Yasmine Brown-Williams ’18 Brandon Cuadrado ’17 Michael D’Agati ’18 Richard Liang ’18 Katherine Lo ’19 Hannah Mieczkowski ’17 Rideeta Raquib ’19 Yael Romero ’17 Lee Ann Santore ’19 Caleb Sooknanan ’20 Megan Tan ’19 Anna Tarasova ’19 Lukas Vasadi ’16 Patrick Yang ’19

Letter From the Staff Dear Reader, Stony Brook Young Investigators Review (SBYIR) was founded in 2008 by a small group of undergraduates to promote and foster undergraduate research at Stony Brook. In the past eight years, our publication and staff have been able to mirror the growth that research at Stony Brook has experienced. Today, SBYIR has a staff of 27 editors, cabinet members, webmasters, layout editors, and photographers, and has expanded to include all disciplines of research occurring within our university. In addition to successfully publishing six issues, SBYIR has also invited a number of prominent researchers to give lectures to the Stony Brook community, including the Queen of Carbon Science, Dr. Mildred Dresselhaus, and Hero of the Planet, Dr. Sylvia Earle. This year, we have invited a speaker that has greatly influenced the field of engineering. We are fortunate enough to host Dr. Donald Ingber, the Founding Director of the Wyss Institute for Biologically Inspired Engineering at Harvard University. In our seventh issue, you will find the most diverse discussions SBYIR has ever had the privilege of publishing, from the potential of life on Mars to the role social networking plays in politics. Inside you will also find faculty interviews with Dr. Matthew Lerner of the Psychology Department, a recognized member of the Autism research community, and Dr. Wei Yin of the Biomedical Engineering Department, whose work could lead to significant advancements in cardiovascular research. Additionally, you will read about Stony Brook’s own Brandon Cuadrado and Yael Romero, as they discuss the implementation of their learning software, MyTempo. The success of Stony Brook Young Investigators Review would have been impossible without the hard work and dedication of our staff and writers, whom have worked diligently throughout the semester. Additionally, this issue could not have been published without the help of our generous donors. We would also like to thank our faculty advisors, Dr. Peter Gergen, Dr. Giancarlo La Camera, and Dr. Laura Lindenfeld, for their guidance and advice. Welcome to SBYIR. We sincerely hope you enjoy.

Table of Contents Research Profiles and Interviews Heart to Heart: Cardiovascular Research with Dr. Wei Yin......................................6 Katherine Lo ’19

Creating Connections: An Interview with Dr. Matthew D. Lerner........................10 Lee Ann Santore ’19

Reviews Irritable Heart: Causes, Symptoms, and Treatments of Post Traumatic Stress Disorder...........................................................................................................................................12 Anna Tarasova ’19, Editor-in-Chief of Neuroscience Axis

Memory Manipulation Techniques: A Promising Path for Anxiety Therapy.....15

Yasmine Brown-Williams ’18

Social Networking and Politics.........................................................................................17 Hannah Mieczkowski ’17

Our Journey to Mars Hinges on the Human Factor...................................................19 Lukas Vasadi ’16

Humans and Algae: How Anthropogenic Environmental Changes are Affecting the Backbone of Earth’s Marine Ecosystems...........................................23

Shannon Bohman ’19

Primary Research Article MyTempo: Musical Conducting Simulation and its Role in Music Therapy...............................................................................................................27 Yael Romero’17 and Brandon Cuadrado ‘17

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Research News

Learning Quantifiers Across Different Languages

The Relationship between Asplenia and Invasive Pneumococcal Disease By Caleb Sooknanan ’20

The acquisition of number words was generally not tested, but researchers now have a better idea of how this process works in children.

By Megan Tan ‘19 Researchers understand what it takes to learn a new language, but the acquisition of numerical words is unknown. In order to test this problem, Professor Napolean Katsos from the Department of Theoretical and Applied Linguistics at the University of Cambridge and her team of researchers conducted an experiment on 768 children who spoke one of 31 languages between the ages of five and six years old. The researchers tested differences in linguistic acquisition of quantifiers. Participants were presented with five boxes and five objects; and some of these objects were inside the boxes. They then heard a description and were required to judge if the description was right or wrong. This description tested concepts of quantifiers such as “all,” “none,” “some,” and “most.” The researchers found a universal order of acquisition of number words.

Children started learning the concepts of singular, dual, and plural, despite the differences in language. This universal system was also seen in the order of acquisition of quantifiers. Children showed greater understanding with the concept of “all.” Children were more successful at attributing a property to “all” or “none” rather than to “some.” Most children were better at attributing a property for “some” than they were for “most.” In general, children who spoke different languages acquired concepts of number words and quantifiers at different ages, and the order in which they acquired these number words and quantifiers were similar across languages. References 1. N. Katsos et al., Cross-linguistic patterns in the acquisition of quantifiers. Proceedings of the National Academy of Sciences 113, 9244– 9249 (2016). doi: 10.1073/pnas.1601341113. 2. Image retrieved from: http://www.bcmgreenthreads.org/some-all-or-none/

Pneumococcal disease is a bacterial infection caused by Streptococcus pneumoniae that occurs mainly among infants and young children. Invasive pneumococcal disease (IPD) is a more serious form of the infection that can cause meningitis, or bacterial infection in the blood, inflammation of the lungs, and other conditions. Bacterial infection, also known as sepsis, is especially common among patients who have undergone spleen removal, as it is the spleen’s macrophages that remove streptococcal bacteria from the blood stream. Dr. Thomas J. Marrie and his team of researchers from Dalhousie University in Canada performed a study to determine the relationship between asplenia, the lack of a spleen, and invasive pneumococcal disease in patients. From 2000 to 2014, data was collected on all patients in Northern Alberta with IPD; each patient was asked whether they had undergone a splenectomy, and they were categorized based on their responses. The researchers studied conditions such as osteomyelitis, meningitis, septic arthritis, and acute kidney injury in asplenic patients. The researchers also performed serotyping, and the results were categorized according to the presence or absence of a

spleen in the patient. Serotyping is a method used to determine the variant strains of microorganisms in a sample. Of the 2435 patients studied, 37 were asplenic. These patients had more medical complications and were more likely to require treatment in an intensive care unit or with mechanical ventilation. The results also showed that asplenic patients had a higher occurrence of pneumococcal serotypes 23B and 22F. The researchers concluded that patients with IPD and asplenia were more likely to contract severe bacterial infections. However, the mortality rate among asplenic and nonasplenic patients did not differ significantly. Given that the number of asplenic patients in the sample was very small, the data would be difficult to generalize. Another limitation of this study is that it did not focus on nonbacterial pneumococcal infections. More work is needed to study the serotypes that are prevalent in asplenic patients. Such research can help facilitate the development of future vaccinations for IPD. References 1. Marrie, et al., Asplenic patients and invasive pneumococcal disease—how bad is it these days? International Journal of Infectious Diseases 51, 27-30 (2016). doi: 10.1016/j. ijid.2016.08.022.

Stem Cells Successfully Generate a Fully Functional Liver By Rideeta Raquib ‘19 Approximately 30 million people are affected by liver disease globally, and the quest to find donors for liver transplants is difficult. There is a lack of functional livers available

compared to the liver disease patient population. In some cases, a portion of the liver from a living donor is sufficient for regular function. Stem cells are unspecialized cells that can differentiate into a variety of cells. Researchers have been trying to

utilize stem cells to create various organs and body parts in order to aid patients who lack functional ones due to injuries or diseases. Previous strategies combatted liver disease by liver cell transplant, which required rare donors. This approach

is viable for about a year, but eventually an organ transplant has to be performed. Scientists have also tried to use humaninduced pluripotent stem (iPS) cells, but those cells were not mature enough to differentiate into functional liver cells.

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Therefore, a better treatment to eliminate liver disease is needed. The Saban Research Institute of Children’s Hospital

Stem cells are the puzzle pieces to produce a functional liver.

research team in Los Angeles produced a tissue-engineered (TELi) liver from human and mouse liver organoid units (LOU). They implanted these units into a murine, mouserelated, model and included various cell types, such as hepatocytes, bile ducts, and endothelial cells. The mouse hepatocytes present expressed albumin, a key protein required to regulate osmotic pressure in

the blood. Other components of the liver incorporated bile ducts expressing CK-19 and vascular structures that contained alpha smooth muscle actin expression. Within four weeks, there was a major development in the differentiation of albumin expressing cells in the TELi. While previous transplants required perfusion, this therapy does not, which will minimize cell loss. This therapy also does not require the use of immunosuppression or cell reprogramming. Overall, this study may be able to produce novel initiatives for cellular therapy, whereby donor liver organoid units could be transplanted into patients to generate a fully functional tissue-engineered liver. References

1. N. Mavila et al., Functional human and murine tissue-engineered liver is generated from adult stem/progenitor cells. Stem Cells Translational Medicine (2016). doi: 10.5966/ sctm.2016-0205. 2. Image acquired from: http://www.startstemcells.com/img/liver-stem-cell-therapy.jpg

New Enzyme Responsible for Cell Mediated Death Identified By Richard Liang ‘18 The human body has developed mechanisms to deal with genetically damaged cells before they can become a threat. One such mechanism occurs when DNA is damaged. Cells undergo cell death mediated by an enzyme known as poly ADPribose polymerase-1 (PARP-1). However, in certain instances like a stroke, the PARP-1 pathway is overly activated, causing mass cell death in the body. In a recent study led by Dr. Yingfei Wang at Johns Hopkins School of Medicine, the main enzyme in the PARP-1 mediated pathway was identified. The enzyme, known as Macrophage Migration Inhibitory Factor (MIF), is an endonuclease in the PARP-1 pathway that cleaves the DNA in cells. 3-D modeling was used to determine the structure of MIF, and exposing DNA to MIF tested its activity. When DNA

was exposed to MIF, the DNA became cleaved, demonstrating the enzyme’s nuclease activity. A mouse model was then exposed to an adeno-associated virus serotype 2 containing either a wild-type of MIF or an inactive version of MIF. The mice that were exposed to an inactive version of MIF retained an average of 75% more of their cortex, striatum, and hemisphere (regions of the brain) compared to the mice that were exposed to the active version of MIF. This showed that MIF was directly related to the PARP-1 pathway. With further research into the activity of MIF in different conditions, the mass cell death induced by PARP-1 in certain diseases could be mitigated. References 1. Y. Wang et al., A nuclease that mediates cell death by DNA damage and poly(ADP-ribose) polymerase-1. Science (2016).

Improved Batteries in the Human Body By Michael D’Agati ‘18 The field of bioelectronics, which produces implantable devices for sensing and therapeutics, has recently become a popular field of study. There iare many possibilities for integrating electronics into bilogy, but in order for these new innovations to work, a power source, such as implantable batteries, must be present to supply the energy needed. Currently, implantable batteries require bulky metal cases to keep the battery’s toxic electrolytes and immunogenic active materials from leaking inside the human body.

To fix the toxicity and size issues, Dr. Craig Milroy and Dr. Arumugam Manthiram from the University of Texas at Austin have developed a fabrication method using exclusively endogenous biomolecules. Endogenous biomolecules are molecules that originate from within an organism, tissue, or cell. The endogenous biomolecules allow the implantable battery to be fully biocompatible, since they are similar to molecules that already exist or are produced by the human body. These biomolecules were created using a one-step combination of dopamine (DA) to hyaluronic acid (HA). This composite still al-

lows the battery to perform well with long-term electroactivity for 400 cycles, meaning that the endogenous biomolecules are still able to exhibit electrical activity even after 400 cycles of charging and discharging the device. The biomolecule’s p(DAHA) biopolymer also exhibits stability and high pseudocapacitance, or electrochemical storage. These attributes show promise for the usage of endogenous biomolecules in a bioelectronic energy storage device, such as a supercapacitor or an implantable biobattery. The ability to create biocompatible batteries and other implantable energy storage

devices is encouraging for the future of not only energy storage devices themselves, but also new implantable medical technologies for the future. By advancing the characteristics of energy storage devices, other innovations in many medical applications can advance as well. An example of this is implantable sensors, which can now have a battery that can supply the power needed from directly inside the body. References 1. C.A. Milroy, A. Manthiram, Bioelectronic energy storage: a pseudocapacitive hydrogel composed of endogenous biomolecules. ACS Energy Letters 1, 672-677 (2016). doi: 10.1021/ acsenergylett.6b00334.

‘Super-agers’ Retain Youthful Memories By Jalwa Alfroz ‘17 As humans age, it is normal for cognitive skills, such as memory, to decline. However, some people seem to escape this fate, and are subsequently categorized as super-agers. Investigators at the Harvard-affiliated Massachusetts General Hospital, led by Dr. Bradford Dickerson, revealed that certain areas of the brains of older adults with extraordinary memory performance looked similar to those of young adults. Previously, super-aging studies had only compared the brains of people over 85 years old to those in their middle ages. The current study focused on people around the typical retirement age, mostly in their sixties and seventies, and compared their memories to those of twenty year olds. Forty adults aged 60-80 years old were enrolled. From these participants, 17 adults performed better on memory tests than 41 young

adults aged 18-32 years old. The study used a hypothesis-driven approach and focused on two large-scale intrinsic brain networks known to be important in memory. One of the networks was the default mode network, which is shown to play a role in learning and remembering new information. The network includes the salience network, which helps translate certain information as important or urgent. Whole-brain resting-state fMRI data was processed and the posterior cingulate cortex was used to identify the default mode network, while the right dorsal anterior insula was used to identify the salience network. Correlation maps of the two networks in all study participants were converted to z values, using Fischer’s r-to-z transformation, and were averaged across all subjects. Researchers have not only showed that there was no shrinkage in the default mode network, the volume of the hippocampus,

Research shows that adults past their 60s, who have resilient memories, have brains similar to adults in their 20s.

and the salience network in super-agers compared to those of typical older adults, but also that the size of these regions correlated with memory ability. In fact, the preserved cortical thickness and hippocampal volume in super-agers was statistically indistinguishable from young adults. This correlation between brain size and memory was found in the para-midcingulate cortex, an area in the brain that intersects the salience and default mode networks. Effective communication between these networks is

crucial for healthy cognitive aging. Therefore, understanding the networks in the brain that protect against memory decline could potentially lead to advances in treatment of dementia and other age-related disorders. References 1. W. Sun et al., Youthful brains in older adults: preserved neuroanatomy in the default mode and salience networks contributes to youthful memory in superaging. The Journal of Neuroscience 36, 9659-9668 (2016). doi: 10.1523/ jnuerosci.1492-16.2016. 2. Image retrieved from: http://www. huffingtonpost.com/2013/08/23/superagers_n_3804213.html

Mitigation of Sea Level Rise Due to Increased Snowfall Increased snowfall in Antarctica will hopefully begin to mitigate global sea level rise by mid-century.

By Patrick Yang ’19 Many global climate models project that anthropogenic global warming will lead to increased snowfall in Antarctica due to increased moisture in the atmosphere. However, the actual trend in Antarctica shows a discrepancy. Surface mass balance (SMB), the difference between

the amount of snow accumulated and sublimated, has not shown any significant increase, despite the rise in global temperature. This discrepancy may be caused by natural climate variability, which is characteristic of the chaotic variation in Antarctica’s climate. A recent study led by Michael Previdi, Ph.D., of Columbia University, evaluated SMB simulations from 35 coupled atmosphere-ocean climate models from the most recent Coupled Model Intercomparison Project (CMIP5), which quantified the SMB increase caused by global

warming. His team determined that from 1961 to 2005, forced SMB increase by global warming was 124 billion tons per year, which is smaller than the SMB increase by natural variability of 126 billion tons per year. Since forced SMB increase was smaller than natural SMB increase, it is possible that the forced response was completely or partially masked by natural variability. Despite the current obscurity of the effects of global warming on SMB, CMIP5 models predict that after 2015, there is a 66% chance that anthropogenic global warming will become evident in Antarctica’s surface mass balance. By 2040, these chances increase to 90%. Since the to-

tal amount of water on earth is constant, water stored as snow or ice will decrease the amount of water available to increase sea levels. CMIP5 simulations show that increased snowfall in Antarctica may mitigate rises in global sea level by up to three inches by 2100. Although three inches may not seem too significant, with recent global sea level rises at 3.2mm per year, any mitigation is welcomed. References 1. M. Previdi, L.M. Polvani, Anthropogenic impact on Antarctic surface mass balance, currently masked by natural variability, to emerge by mid-century. Environmental Research Letters 11, 1-9 (2016). doi: 10.1088/17489326/11/9/094001. 2. Image retrieved from: https://www.pexels. com/photo/ice-antarctica-blue-ocean-7495/.

HEART TO HEART:

Interview

Cardiovascular Research with Dr.Wei Yin

Katherine Lo ’19 Introduction With 17 million fatalities per year, cardiovascular disease is the leading cause of death worldwide. In 2008 alone, it represented 30% of global deaths, proving to be a pressing issue for scientists and doctors everywhere. These deaths are the results of cardiovascular problems that often begin with atherosclerosis, the buildup of plaque on arterial walls. Atherosclerosis can cause the clotting of blood in parts of the circulatory system, that can lead to strokes or heart attacks. These issues are supplementary to the effects of inherited genetic disorders and lifestyle choices, such as diets high in trans fats and sodium (1). This imminent issue has led Associate Professor Dr. Wei Yin of the Biomedical Engineering Department at Stony Brook University to conduct research on cardiovascular disease using various in vitro, in vivo, and computational strategies. Career Path Dr. Yin has been fascinated with biomedical engineering since the beginning of her career in 2001, when she received her Master’s degree in biomedical engineering from the University of Akron in Ohio. After graduating, she examined mechanisms of thromboembolism induced by mechanical heart valves. Thromboembolism is the obstruction of a blood vessel from dislodged blood clots, which is the most common complication of mechanical heart valves. For her doctoral dissertation in biomedical engineering at Stony Brook University, Dr. Yin focused on the flow-induced activation of platelets, and how the thrombin generation rates measured by flow cytometry compared with a modified prothrombinase (PAS) assay (2). She concluded that the modified prothrombinase assay was one of the most effective techniques to measure flowinduced platelet activation caused by prosthetic cardiovascular devices (3). As a Post-Doctoral Research Fellow at Weill Medical College of Cornell University, Dr. Yin worked in the Pathology Department. Using proteomics, and other wet lab standard techniques, she investigated differences in platelet protein expression in blood samples from patients with clotting disorders. She attempted to identify the “fingerprints” of the total proteome of platelets and observe the differences between normal and diseased patient patterns in thrombosis. She also

studied the role of complement activation in various vascular diseases. In 2007, she joined the School of Mechanical and Aerospace Engineering at Oklahoma State University as an Assistant Professor, where she dedicated herself to creating a biomedical engineering program in the College of Engineering and Advanced Technology. Eventually, she returned to Stony Brook to become an associate professor, avid researcher, and advisor to the Biomedical Engineering Society. She currently teaches several upper division undergraduate and graduate courses at Stony Brook, including Quantitative Human Physiology (BME 430), Biomedical Engineering Design (BME 440), and Engineering Principles of Cell Biology (BME 501) (3). Research History Dr. Yin’s work at Cornell disproved the previous idea of a gC1qR-dependent classical complement pathway activation in platelets. “gC1qR” stands for the globular head of Complement Protein 1 (C1) receptor. C1q is a protein complex that can bind to immunoglobulins and initiate an immune response to eliminate pathogens from the body. The classical complement pathway involves activating C1 and many other downstream complement proteins, which are essential in healing inflammations associated with vascular injury. In platelets, however, scientists discovered specific binding sites for C1q that could potentially initiate the C1q pathway directly. Dr. Yin’s work furthered our understanding of the roles gC1qR play in platelet and endothelial cell activation (4). At Oklahoma State University, Dr. Yin worked with Dr. David Rubenstein and Dr. Hongbin Lu to study biomedical applications of aerogels. Their research culminated in several publications including one in the International Journal of Polymeric Materials and Polymeric Biomaterials, which characterized the biocompatibility and mechanical properties of organic polymers in the vascular system. Dr. Yin also coauthored two editions of the 2012 Biofluid Mechanics textbook and contributed a chapter to the Biomedical Applications of Aerogels in the Aerogels Handbook in 2011 (3). At Stony Brook, Dr. Yin’s research focuses on cardiovascular dynamics in the vascular system, inflammatory response associated with cardiovascular disease, and platelet-endothelial cell interactions. She is also interested in identifying bio-

that oscillatory shear stress promotes atherosclerosis (5). Dr. Yin is interested in how cardiovascular disease conditions change local shear stress, and how that affects endothelial cell and platelet mechanotransduction, as well as cell surface functional protein expression. To observe this effect she measures platelet surface CD62P (a platelet activation protein), GPIb and GPIIb (important adhesion proteins), PECAM-1 (an important mechanotransducer), and endothelial cell surface ICAM-1(an endothelial-activation marker) expression. Her research has shown that low pulsatile shear stress was a greater atherogenic factor than elevated shear stress induced by stenosis, the narrowing of blood vessels. Dr. Yin also uses in vitro and in vivo models to investigate coagulation kinetics and platelet adhesion to endothelial cells. She believes that these processes play critical roles in thrombosis. Computational models are also used in Dr. Yin’s lab to understand the macroflow and microflow conditions as well as how they affect the mechanical transduction pathways.

Figure 1 Shown are the effects that the build-up of plaque has on blood flow. A shows a blood vessel under normal conditions and B shows a vessel with atherosclerosis.

markers that can predict cardiovascular diseases early on, and biomedical applications of various polymers, such as silica aerogels. By collaborating with labs in the Materials Science Department at Stony Brook and a company in Chicago, Dr. Yin works with nanoparticles as well as the biocompatibility of diamond coating in biological systems, respectively. Through these collaborations, Dr. Yin examines the properties of the materials and cellular responses are examined to see if they are biocompatible with vascular tissue, induce inflammation, and affect blood cells or endothelial cell growth. Lab Focus The Yin lab specializes in the study of platelets, diskshaped cell fragments involved in clotting, and endothelial cells (EC), which form the lining of blood vessels. More specifically, the lab studies cardiovascular dynamics and investigates how altered mechanical stress and strain in the vascular system affects the behavior of these cells. Both platelets and EC are constantly exposed to dynamic shear stress, which is the frictional force caused by blood flow. Interestingly, while unidirectional shear stress is atheroprotective, studies show

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Current Project In 2015, the Yin lab received a grant from the SUNY Research Foundation Materials and Advanced Manufacturing Network of Excellence to create a nanoparticle complex targeting activated endothelial cells, and to bring anti-inflammatory and anti-platelet drugs to a specific site (6). In collaboration with Dr. Yizhi Meng from the Materials Science Department at Stony Brook, this project focuses on analyzing the biocompatibility of hydrophobically-modified glycol chitosan (HGC) nanoparticles and observing their functionality as biomaterials. HGCs are composed of a hydrophilic shell of glycol chitosan and hydrophobic layers of bile acid analogs. They have been studied and observed as a promising therapeutic cancer drug delivery system (7). HGC will be combined with the ICAM-1 glycoprotein antibody, an intercellular adhesion molecule expressed in endothelial cells, to examine its specificity in targeting inflamed vasculature and delivering localized drugs. Then, the Yin and Meng labs plan to combine the HGC-ICAM-1 complex with aspirin and ICAM-1 inhibitor to understand the complex’s effect on endothelial cell and platelet adhesion. However, this study is preliminary, and the labs are still trying to create an optimal system for successful results. Proteomics and the Future of Preventative Medicine The human genome is widely studied due to the recognition of its significance and overarching function in controlling biochemical substances and disease development. Due to these discoveries, scientists have also started studying the

Dr. Yin believes her research in thrombosis and atherosclerosis will have a long journey. Her biggest challenge is that both these diseases are “a complex story… [followed by] a web of mystery”

”

significance of downstream proteomes in diseases and physiological conditions. Dr. Yin believes this form of biomarker investigations will allow doctors to identify potential diseases in a patient, because they provide long-term identification of the body’s cellular processes. Dr. Yin’s work is inspired by the fact that current markers are extremely ineffective: the possibility of a stroke is only identifiable 30 minutes before it occurs. However, if proteomes become better understood, a doctor could determine the likelihood of a disease by running a blood sample and examining the proteome fingerprints of the specific disease. However, little can be known for sure since Dr. Yin’s biomarker studies are still at a very early stage. In addition, many of these studies have very high data interference and variability from background proteins, and are thus extremely inconclusive. On Obstacles and Hardship Dr. Yin believes her research in thrombosis and atherosclerosis will have a long journey. Her biggest challenge is that both of these diseases are “a complex story… [followed by] a web of mystery” (8). During her career, she has only been able to study several proteins within the intricate cardiovascular system. While much knowledge has been cultivated, there is still a plethora of mechanical and environmental factors from shear stress, blood flow, pressure change, tension stretch, and interactions between cells that have yet to be discovered. Furthermore, there may be biochemical interactions that trigger downstream responses or physical contact that causes cell adhesion, which are not yet understood. With so many aspects unknown, it is hard to determine a single path for her research to follow. Dr. Yin describes the investigative process as a “big and complicated jungle with a lot

of trees and leaves, lost inside without a map… and without knowledge of which leaves come from which tree” (8). As a single principal investigator with a small group of students, her lab finds it difficult to study all of the biochemical pathways because it is time consuming and expensive to do so. Despite these challenges, Dr. Yin is still hopeful that her investigation into under-investigated mechanisms and her work on the nanoparticle drug delivery system will lead to a promising cure for atherosclerosis and thrombosis.

References 1. D. Mozaffarian et al., Heart disease and stroke statistics at-a-glance. American Heart Association, (2014). 2. D. Bluestein et al., Flow induced platelet activation in mechanical heart valves. Journal of Heart Valve Disease 13, 501-508 (2004). doi: 10.1115/ imece2004-61336. 3. Wei Yin. (n.d.). Retrieved July 28, 2016, from http://www.bme.stonybrook. edu/people/faculty/w_yin.html 4. E. Peerschke et al., Blood platelets activate the classical pathway of human complement. Journal of Thrombosis and Haemostasis 4, 2035-2042 (2006). doi: 10.1111/j.1538-7836.2006.02065. 5. W. Yin, S. Shanmugavelayudam, D. Rubenstein, The effect of physiologically relevant dynamic shear stress on platelet and endothelial cell activation. Thrombosis Research 127, 235-241 (2011). doi: 10.1016/j.thromres.2010.11.021. 6. W. Yin et al., Characterization of the biocompatibility and mechanical properties of polyurea organic aerogels with the vascular system: potential as a blood implantable material. International Journal of Polymeric Materials and Polymeric Biomaterials, 109-118 (2012). doi: 10.1080/00914037.2012.698339. 7. K. Min et al., Hydrophobically modified glycol chitosan nanoparticles-encapsulated camptothecin enhance the drug stability and tumor targeting in cancer therapy. Journal of Controlled Release 127, 208-218 (2008). doi: 10.1016/j. jconrel.2008.01.013. 8. SUNY MAM research projects. The State University of New York, (2016).

Photos Retrieved from: 1. 2. 3. Courtesy of Dr. Wei Yin

Figure 2 Experimental simulations done in Dr. Yin’s lab involve computational simulation of stenosis in vessels and how they affect the shear stress on the vessel walls. This is one of the many experiments going on in Dr. Yin’s lab.

Interview

Creating Connections: An Interview with Dr. Matthew D. Lerner Lee Ann Santore ’19

In the short time that he has been an Assistant Professor of Psychology, Psychiatry, and Pediatrics at Stony Brook University, Dr. Matthew D. Lerner has already acquired a reputation among his students as the big, quirky, eccentric teddy bear that teaches the autism class. In this time, Dr. Lerner has also established his research lab, The Social Competence and Treatment Lab (SCTL; pronounced skittle), which focuses on developing new interventions to help youth with Autism Spectrum Disorders (ASD) build friendships. One of his most exciting methods of intervention is Socio-Dramatic Affective Relational Intervention (SDARI), which employs novel activities to promote social growth in youth with ASD. He has instituted this model in several social group programs, including the Spotlight Program in Massachusetts and his lab here in Stony Brook. He is currently studying their potential impact in easing the social challenges of youth with ASD and helping them make friends. He is also dedicated to forming connections with the youths and their families. Dr. Lerner earned a B.A. in Philosophy from Wesleyan University and a Ph.D. in Child Clinical Psychology from The University of Virginia. Additionally, he has received many awards, including the Biobehavioral Research Award for Innovative New Scientists in 2016 from the National Institute of Mental Health. As accomplished as he is, Dr. Lerner also loves being a mentor and makes it a point to prioritizes building relationships with the members of his lab, whom he affectionately refers to as his SCTLers. He sat down with the Stony Brook Young Investigators Review to show readers that there can be more than one way to achieve a goal, and the importance of enjoying the journey. How did you first develop an interest in youth with autism spectrum disorders? When I was 12 or 13 years old, I went to a friend of my sister’s house for dinner. I noticed that my sister’s friend had a little brother who was not at the dinner table with us. I asked their

mother why he wasn’t sitting with the rest of us. She said that he wasn’t with us because “he had this thing, it’s sort of like autism, and he doesn’t really talk to people.” She also explained that he was hyperlexic, or able to read far beyond the average child his age, and shared that one night she found him sitting with the refrigerator open, having read the boxes of every item in it. I asked if I could go play with him, and his mom responded with “you can go but you’re going to come right back because you’ll get very bored very quickly.” I found the child playing with some cars and decided to grab one, copying what he was doing. I stayed and continued playing with him for a few hours. I was later told that when I left, the child said “goodbye Matt,” and his mother began to cry out of happiness because her son didn’t normally speak to anyone. She asked me when I could come back, and from then on, I became his “buddy.” What did you do in between undergrad and grad school? After I graduated from Wesleyan with my degree in Philosophy, I realized that I had no “marketable” skills. I took a position at a social skills camp because I figured I had been making this up for ten years with my buddy, and wanted to see how the professionals did it. It was the same camp that my buddy was going to, so I had an in. At this time, I lived with a couple of friends who were aspiring actors. One night, my friends and I brainstormed ideas for an alternative program for children like my buddy. We came up with a program in which we would follow the child’s lead, just as I had been doing with my buddy, and allow them to dictate the content, while we provided the form for social interactions. We tried this out at the camp I worked in, and the kids seemed to like it. So, I wrote a proposal and received a grant to start a camp that consisted of nine kids on the spectrum and some peers that I hired as counselors. I planned on making it a one-and-done type of program, and to get my masters in Philosophy after it ended. I had even been accepted into a program in New York, but received

a call stating that 100% of the families in my program loved it and wanted to do it year round. They asked me to stay and I did, turning my one-off into the Spotlight Program, which has grown exponentially, and currently serves hundreds of families each year while doubling as the site of some of my current studies. Why did you decide to switch from Philosophy to Psychology? While running Spotlight, I experienced a sort of “crisis of science.” While many dozens of families and schools told me that they appreciated what I was doing, I realized that I had no way to measure what was really happening, or to identify how or for whom we could make the program work best. Since I wanted to make sure that what we were doing really helped – and that the participants would not be better served by doing something else – I became extremely focused on acquiring the tools to ask these questions. I spent several years taking night classes and volunteering in a psychiatric research lab at Harvard, while still running Spotlight by day. The first time I applied to graduate school in Clinical Psychology, I didn’t get in anywhere. Learning from my rejections the first time, I built my resume in several ways, including publishing a paper, earning a grant, and becoming more versed in the current research literature before I applied a second time. With this focus and experience, I was accepted into several PhD programs, and decided to go to The University of Virginia where I earned my Ph.D. in Clinical Psychology. How did you meet your wife? I met my wife, Chelsea, while I was volunteering at the child psychiatry research clinic. She was one of the staff members, and I was the only volunteer. I started off making copies and trying to figure out what research was. Our friendship developed quickly and we started going out after about a year. I would visit her during work to bring her mix tapes that I burned for her and from there it was history. She was way more qualified than I was to get into a Ph.D. She had a psychology degree from an Ivy League university, had been involved in research for years and had published several papers, and was working in a worldrenowned child psychiatry research clinic. She originally was interested in research in clinical psychology, but realized she was especially passionate about clinical care. She decided to re-specialize and become an ER nurse, and she currently works at the Stony Brook Hospital ER. Having far more energy than I have, she has been continuing her education, and recently graduated from Stony Brook as a pediatric nurse practitioner. Even more exciting, Chelsea and I have a preschool-age son named Everett (born at Stony Brook!), who is the most fun person you’ll ever meet. He also gets along great with our dog, Westley. What do you do in your spare time? Mostly, I love to spend time with my family; given Chelsea and my work schedules, we try extremely hard to carve out family downtime together with Everett as often as possible. When I’m not doing research, I love music. At Wesleyan, I was surrounded by friends who were also interested in music, and I majored in music through most of college. I played the saxophone in many bands over the years. I first fell in love with music because I thought it was the purest means of connection between people. In college, I lived in a dorm that was known to be filled with many musicians and artists, so I formed a couple of bands

with other students from my dorm. One band, a ska band called Andy, had an album produced by one of Aerosmith’s producers. Another one, The Contingency Plan, was a jazz funk band that had a residency at The Knitting Factory. The bass players in my band ended up leaving to create their own group, MGMT, and they now headline at places like Coachella. It’s pretty neat to see! What is your favorite thing about Stony Brook? I came to Stony Brook three years ago, and my favorite thing about the university is the academic culture. Generally in academics, you sometimes have to trade off between having a highly productive environment in which folks might be more competitive at the expense of being supportive, or the opposite. Stony Brook is the very rare institution that hits the “sweet spot,” where I feel inspired every day by the brilliance and productivity of my colleagues, but also feel entirely supported by – and feel welcome to likewise support – them. This is especially true within the psychology department. Because of this, I try to create the same environment – working hard, but also supporting each others’ challenges and successes – within my own lab. What is it like to have a relatively large amount of students in your lab? I recently learned (in fact, it was during this interview!) that I have one of the largest labs in the department, with several doctoral students, full-time staff, master’s students, volunteers, and a few dozen undergraduate research assistants. I am surprised to hear that my lab is considered big, as I figure most labs doing a wide array of studies require a lot of person-power; however I guess it makes sense, considering we have had to move our meetings to my observation room because we don’t all fit at the conference table anymore. When my lab first started it was really small (just a couple of undergrad RAs), but it has grown exponentially. I’m happy that it has grown to keep up with the needs all our studies and the many families who visit us in the lab, and everyone is certainly keeping very busy! But, I don’t like that I have less opportunity to really know each of my students personally, because there are so many now, and only so many hours in the day. As successful and talented as he is, the best way to describe Dr. Lerner is as an inspiring individual. He does not just focus on the research, but also on the families. He takes the time to meet and ease the fears of each parent he encounters. He gives them hope and makes them feel like their daily struggles are important, and that there are people working hard to find ways to help them. He connects with the kids, most of who consider “Dr. Matt” a friend. He treats his research assistants and other lab members like family, and pours everything he has into mentoring them. He is one of the most passionate and altruistic humans one could hope to meet, and we are very fortunate to have him here at Stony Brook.

References 1. M.D. Lerner, Personal Interview with Matthew D. Lerner. Rec. 30 Jun 2016. MP3. Photos Retrieved from: 1. Courtesy of Evelyn Kandov ’17 2.http://www.stonybrook.edu/commcms/psychology/images/faculty_images/ mlerner.jpg

Science Review

Irritable Heart: Causes, Symptoms, and Treatments of Post-Traumatic Stress Disorder Anna Tarasova ‘19

Editor-in-Chief of Neuroscience Axis

Photos Retrieved From: 1. https://upload.wikimedia.org/wikipedia/commons/d/d2/Van_Gogh_-_Trauernder_alter_Mann.jpeg

Introduction Post-traumatic stress disorder (PTSD) is the fourth most common psychiatric disorder in the United States, with a lifetime prevalence of 5-6% in men and 10-14% in women (1). Lifetime prevalence refers to the proportion of people in a population that will experience a certain illness within their lifetime. PTSD’s pervasiveness and paralyzing consequences are strong incentives to conduct research, provide accessible and effective treatment, and educate individuals about its aftermath. Because it is difficult to prevent PTSD, the majority of research associated with the illness focuses on patient recuperation. However, the effects of the illness still need to be better addressed by policy-makers, medical practitioners, counselors, and the victims’ families. History Although vague descriptions of the clinical effects of combat have long pervaded historical accounts, a disorder akin to PTSD was first officially reported in Civil War soldiers. Jacob Mendez da Costa, a physician at the time, noted the appearance of certain symptoms in the soldiers during times of stress. In his honor, the illness became known as “Da Costa’s syndrome” (2). World War I brought about new terms such as “shell shock” and “combat neurosis” to describe the effect of serving in the military on returning veterans. Immediately following World War II, neurologist R. R. Grinker and psychiatrist J.P. Spiegel utilized psychiatric terminology in order to present the disorder and its associated symptoms. During the late 1970s and early 1980s, the self-reported symptoms of Vietnam War veterans were found to parallel symptoms found in victims of other traumas, such as rape and natural disaster. In the mid-1980s, doubt spread through the scientific community with regard to the existence of PTSD as a distinct psychiatric entity. However, analyses of proposed symptoms using psychophysiological and psychometric measures provided strong evidence for its unique nature. This solidified the place of the illness in the Diagnostic and Statistical Manual of Mental Disorders (DSM) from the third edition onwards (3). Signs and Symptoms According to the current version of the DSM, in order to be diagnosed with PTSD, an individual must have been exposed to a traumatizing event or stressor that induced fear, helplessness, or horror. Furthermore, patients must have been experiencing three types of symptoms for at least one month. These symptoms include re-experiencing the event, avoiding reminders of the event, and hyperarousal. The term “unwanted recollections” is frequently used to describe stressful re-experiencing of the event, and manifests in the form of nightmares and flashbacks. Reminders of the events can include physical people, places, objects, and thoughts. Hyperarousal consists of physiological symptoms such as irritability, sleep disruptions, and inability to concentrate. These symptoms are frequently noticed by primary care physicians. Because most patients are unwilling to share traumatic experiences, a practitioner may diagnose the patient with a physical condition, such as low blood sugar. Similarly, in a counseling or psychological evaluation setting, unless the trauma victim discloses the occurrence of a traumatic event, the therapist may prescribe treatment for depression or a different anxiety disorder because of their similar manifestations (1). Disturbed sleep, irritability, and other physiological and mood symptoms are also listed in the current DSM as diagnostic

criteria for Major Depressive Disorder (MDD) and Generalized Anxiety Disorder (GAD). This explains why practitioners unaware of a traumatic event may misdiagnose PTSD differently. The two main factors distinguishing PTSD from other disorders are the occurrence of a traumatic event and the combination of the aforementioned psychosomatic – that is, both psychological and physiological – symptoms. Additionally, physiological studies have demonstrated that the biological changes brought on by PTSD are distinct from those in other types of stress-induced disorders. For instance, people experiencing major depression typically have elevated stress hormone levels whereas people with PTSD exhibit reduced levels of the same hormone (1). Causes of PTSD One of the current leading hypotheses on the development of PTSD involves a maladaptive pathway that begins with a failure to contain the normal biological stress response. Patients developing PTSD following a traumatic event have been shown to have smaller increases in cortisol than those who do not develop the disorder. The lack of cortisol may strengthen memory consolidation and encoding, meaning that the person would remember the traumatic event extremely well. The sympathetic nervous system is responsible for responding to stressful situations. When this system is activated by lowered cortisol levels, the victim’s memory of the trauma may become linked to strong distress. This change in cognitive processes could lead to distorted fear responses, continuous re-experiencing, and avoidance symptoms (1). Considering that some physiological symptoms do not manifest until at least one month after trauma, it is possible that there are other steps to be discovered in the maladaptive stress response sequence. PTSD cannot be diagnosed immediately following a traumatic event because of the month-long symptom requirement of the DSM. However, the trauma victim may be diagnosed with acute stress disorder (ASD), which is associated with a higher risk of developing PTSD in the future (1). Another major hypothesis c introduces the concepts of allostasis and heterostasis as pertaining to stress perception. Allostasis refers to the recovery or maintenance of an organism’s state in response to a stressful stimulus. Heterostasis is defined as the overload on an organism’s stress-recovery capacity. The allostatic hypothesis attributes the psychosomatic symptoms of PTSD to the individual’s perception of stress. The individual’s ability to deal with stress is determined by their ability to return to his “set points,” which is a biological norm maintained through homeostasis. Set points are affected by two types of allostatic load. Allostatic load is the amount of psychosomatic resources an organism requires to successfully cope with stressful stimuli. Type I allostatic load uses stress responses to strengthen coping and adaptation mechanisms. Type II overwhelms allostatic regulation by encouraging nonstop allostasis. This model can be applied to PTSD: in this particular disorder, both psychological and biological responses to normal stressors cannot be brought back under full control (2). This hypothesis provides a new framework for exploring the differences in the expression of PTSD. Minor variations may result from different types of trauma. Age group, gender, and other factors may also have an effect on the ability to return to set points. For example, some age groups may be particularly sensitive to stress resulting from specific types of trauma, while others may be more resilient. Understanding allostatic capabilities in in-

dividuals may allow practitioners to formulate specific treatment combinations based on the patient’s unique history. Treatment Since PTSD is understood primarily as a disruption of cognitive processes, the first step in providing treatment is to establish a feeling of security and support. Another component of the treatment is to help the trauma victim understand the psychological changes they are experiencing. It is common for a traumatized individual to be unwilling to seek help because of the social stigma surrounding both the survival of a traumatic experience and the use of therapeutic services (1). An accommodating environment can also facilitate the therapeutic process. The most common treatment for PTSD involves a combination of pharmacology and psychotherapy (1, 2). Medications are mostly used to treat physiological and mood symptoms, while psychotherapy focuses on treating avoidance behaviors and reexperiences of the event. The main medications used to treat PTSD are serotonin-reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), and tricyclic antidepressants. SSRIs are frequently used as the first-line treatment because of their relative lack of side effects. Benzodiazepines, commonly used antidepressants, are usually avoided because of the associated risks of dependency and addiction. There have been few randomized controlled trials exploring the effectiveness of different medications in treating PTSD. However, the existing research has shown placebos to be ineffective in treatment, indicating a biological etiology. Studies have also shown medication to be almost entirely ineffective in treating avoidance symptoms of PTSD. Thus, further research must be conducted to establish treatments specific to the disorder, as opposed to using pre-existing medications designed for other illnesses (4). Psychotherapeutic approaches to treating PTSD have been shown to be better at controlling all aspects of the illness. According to the International Consensus Group on Depression and Anxiety, exposure therapy is the most viable option (2). This is a type of behavioral therapy that assumes a disorder is the result of learning to associate a particular stimulus with negative emotions. Therefore, the goal of exposure therapy is to sever this cognitive association by demonstrating the harmlessness of the stimulus. This is done through a continual activation of the fear response that results in eventual habituation. There are two main types of exposure therapy: systematic desensitization and flooding. The former involves a gradual increase in exposure to the stressor, and the latter involves an extended period of pervasive exposure. Flooding has been shown to greatly reduce fear and anxiety, as well as improving veterans’ civilian life. However, the main issue with flooding is the possibility that the intensity of the exposure may cause aggravation and relapse of PTSD symptoms. For this reason, flooding is mainly recommended as a complementary treatment to other forms of psychotherapy (4). The second type of therapy used in PTSD treatment is cognitive therapy, which is meant to teach patients to control their fear responses through cognitive restructuring. Stress inoculation training (SIT) is a form of cognitive therapy that combines relaxation techniques with changing the client’s perspective on the event. Guided self-dialogue is a major part of SIT that trauma victims are prompted to use outside of therapy. However, in randomized controlled trials, SIT did not show the same long-term healing effects as flooding. The ebbing effect of the treatment is

likely due to the client abandoning the techniques after completing therapy. Flooding, on the other hand, is thought to be a more effective long-term treatment since it causes permanent changes in the memory and perception of past trauma (4). Cognitivebehavioral therapy (CBT) combines both of the approaches described above and is seen as the most effective therapeutic treatment currently available (2). Psychodynamic therapy may also be used to treat PTSD. Psychodynamic theory proposes that the disorder is the result of a disparity between what occurred during the traumatic event and the client’s perception. This disconnect is what leads to avoidant and intrusive symptoms. The goal of psychodynamic therapy is to merge reality and perception through the release and integration of unconscious thought processes. Hypnotherapy has been shown to have a positive effect on reducing avoidant symptoms and on increasing awareness of the event (4). However, the most recent studies have been inconclusive. A major factor complicating PTSD treatment and research is the high rate of co-occurrence of PTSD and other illnesses, especially substance abuse disorders, major depression, and generalized anxiety. This is particularly associated with combat-caused PTSD; one study found that 57-62% of Croatian Balkan war veterans were diagnosed with PTSD and at least one other disorder (2). Future treatments may take into account this high rate of illness co-occurrence. Novel Approaches Blueberries have been proposed as a potential treatment for PTSD. Dr. Philip J. Ebenezer of Louisiana State University and his team have recently been focusing on the antioxidant properties of this common food. They argue that a novel non-medicinal option is necessary due to pharmacological agents’ harmful side effects. Dr. Ebenezer’s group investigated how the chemical content of blueberries can interact with the neurological damage associated with PTSD, which includes tissue inflammation and cell stress. This damage can be propagated by the presence of free radicals and could be potentially prevented by free-radical-eliminating antioxidants. Blueberries have a high content of anthocyanin, a chemical that has anti-inflammatory and antioxidant properties. The researchers analyzed free radical, neurotransmitter, and inflammatory protein content using an animal model. Oxidative stress occurs due to the body’s inability to maintain homeostasis because of a high free radical concentration that results in neuronal damage. Damage on the level of individual cells can affect larger portions of brain tissue, causing behavioral changes. The scientists induced PTSD in rats through interaction with cats and a continual change in environment via cage rotation; both forms of stress were introduced daily for 31 days. Using a total of 12 rats, the researchers provided one experimental group with normal feed and a second experimental group with feed containing 2% powdered freeze-dried blueberries for one week prior to and after stress exposure. A third group was not exposed to any environmental stressors. After 31 days, the team removed the rats’ hippocampi and took chemical measures. The proteins 5-hydroxytryptamine (5HT) and norepinephrine (NE) are the primary neurotransmitters associated with excitatory responses in the central nervous system. Thus, hippocampal inflammation and traumatic conditions would affect their levels. Overall, exposure to stress was associated with higher NE levels and lower 5-HT levels, implying inflammation in the hippocampus and other brain areas. The blueberry-

consuming rats experienced a reduction in neuroinflammation, which was evident in decreased NE levels and increased 5-HT levels. The lower concentration of inflammatory proteins in the hippocampus was also seen as an indicator of improvement. The researchers also found that free radical levels were significantly elevated in the PTSD group compared to the non-stressed group. However, these levels were reduced in the group fed blueberries as compared to the stressed group fed normally. These results imply that the blueberries’ high antioxidant content plays a major role in helping the body respond to oxidative stress (5). Future studies are necessary to determine both the sequence of molecular events and the utility of blueberries as a treatment for PTSD in humans. Directions for Future Research Despite advances in PTSD treatment, further research may establish a more medicinal approach to controlling the disorder. Dr. Ebenezer’s innovative proposed solution represents one of many possible directions that remain to be tested for effectiveness. Additionally, statistics suggest varying trauma response capacities in different groups, implying that individually-based treatments may be necessary. For instance, although women are about ten times more likely to be raped than men, the prevalence of PTSD after rape is 65% in men and 46% in women (1). Traumatic event recency, gender, and type of trauma are all possible confounding variables for existing PTSD treatment studies (4). Another vital research area that remains to be addressed is the treatment of PTSD in children, since an early onset of PTSD can have a longstanding effect on an individual’s life. Some of the current treatment options may not be appropriate or available for children. More randomized, well-controlled trials may help remove the controversy and uncertainty surrounding some types of therapy. Studies examining multiple treatments are few, meaning that the scientific and medical communities are unsure of what treatment combination is most effective. Reviews of existing studies have been suggested to combat this problem, but many argue that there has not been enough research in PTSD treatment to conduct a mass review. More studies may be conducted and more reviews compiled to build upon the currently available PTSD knowledge. Ongoing wars and incidences of terrorism increase the likelihood that the amount of PTSD cases will surge upward (2). If traumatic events cannot be prevented outright, at least their negative impacts on the population can be managed. This requires educating the public to recognize the disorder, improving practitioner-client relationships, and reevaluating treatment methods. Social and scientific advances may improve the quality of care for PTSD patients and allow many to lead more fulfilling lives.

References 1. R. Yehuda, Post-traumatic stress disorder. New England Journal of Medicine 346, 108-114 (2002). doi: 10.1056/NEJMra012941. 2. J. Iribarren et al., Post-traumatic stress disorder: evidence-based research for the third millennium. Evidence-Based Complementary and Alternative Medicine 2, 503512 (2005). doi: 10.1093/ecam/neh127. 3. T. Keane, J. Wolfe, K. Taylor, Post-traumatic stress disorder: evidence for diagnostic validity and methods of psychological assessment. Journal of Clinical Psychology 43, 32-43 (1987). doi: 10.1002/1097-4679(198701)43:1<32::AIDJCLP2270430106>3.0.CO;2-X. 4. S. Solomon, E. Gerrity, A. Muff, Efficacy of treatments for posttraumatic stress disorder: an empirical review. The Journal of the American Medical Association 268, 633-638 (1992). doi: 10.1001/jama.1992.03490050081031. 5. P. Ebenezer et al., The anti-inflammatory effects of blueberries in an animal model of post-traumatic stress disorder (PTSD). PLoS ONE 11, (2016). doi: 10.1371/journal. pone.0160923.

Science Review

Social Networking and Politics Hannah Mieczkowski ’17

Introduction The imminence of any presidential election means that the general public often finds itself in the midst of political discussions. Although these interactions can certainly be found in face-to-face communication, the prevalence of social media offers another outlet for these exchanges. As of summer 2016, Facebook reported 1.71 billion monthly active users (approximately 24% of the total global population), and Twitter reported a fewer but still consequential 313 million monthly active users. Additionally, the number of smartphone users worldwide is predicted to grow to approximately two billion by the end of the year, therefore expanding social media use. Social media usage has been correlated with a decrease in the usage of traditional news media, such as television, radio, and newspapers (1). Overall, the rise in social media use and fall in traditional news media has resulted in the shift of politics to the online sphere. In turn, this has led scientists to become more interested in the effects of social media usage as it relates to political participation, activism, and election results, both in the United States and around the world. Political Participation Although political decisions are generally visible on a national scale, lower-level discussions about worldly affairs among friends and acquaintances have more of an influence on political behavior than one may originally assume. As previously mentioned, these talks have a greater tendency to occur online now than in the past because of increased social media usage. More than a quarter of young adults claim that they receive information about candidates and their respective campaigns from online sources (1). This quality also makes them more likely to engage in internet activities that relate to politics such as posting comments, creating original posts, or liking pages and accounts of partisan groups. Many researchers have found that overall Internet usage directly correlates with factors such as political knowledge and involvement (2). These findings are presumably related to the internalization of one’s surroundings. Because users are inundated with many opinions over a wide range of topics, they feel the need to add their own. However, most participatory research has focused on two subsects: group formation online and the size of one’s social network (2,3). Generally, people who share similar viewpoints tend to prefer to interact with each other as opposed to people who are not like-minded, whether online or offline (4). Scholars some-

times refer to this as the “echo box” or “echo chamber phenomenon,” and it is widely regarded by the general public as something undesirable. Nevertheless, this concept can be seen on Twitter through hashtag usage. Left-wing and right-wing individuals utilize hashtags at similar frequencies, but the ones they choose to tweet have almost no overlap. For example, popular far left-wing hashtags are “#healthcare” and “#capitalism,” while “#foxnews” and “#patriots” are more favorable for far right-wing Twitter users. Moreover, as people with shared political ideologies tend to exclusively retweet each other, there is little cross-ideology retweeting (5). There have also been reports of individuals using Facebook in order to “build group identity” or form communities. For example, one study participant stated: “In my previous school, students protested against the food because it was too bad and we had to pay for it, and then we protested. No one had lunch at school one day and we made sandwiches, and it worked. It was organized through Facebook” (3). This instance showcases a way in which social media can be used to bring people together for a cause. Despite this general sense of homogeneity, there are also many instances of interaction between groups in the form of disagreements, which can have an effect on offline behavior. Whereas retweets are highly consistent, a user’s mentions are far more likely to include opposing viewpoints – 97% of the users studied have “politically heterogeneous” mentions (4). Although exposure to different ideas would be thought to promote learning and understanding, the reality is that it leads to a reluctance to participate in online discussions (2). Klofstad finds that social media users who notice “general disagreements” in their network are 13% less likely to be “extremely certain” about their voting choices, yet they are more likely to cast a vote (3). This might occur because interacting with dissenting opinions often makes one’s own opinion weaker, but seeing the myriad of attitudes present in the world may reinforce the need to make whatever difference they can. However, studies have shown that mobilizing one’s network of friends and acquaintances may play an even bigger role in political involvement. Internet users with a larger circle of friends or followers tend to engage in political activities more than users with a smaller number of “online discussants” (3). This supports the theory that the number of people someone knows has more of an effect on their political participation than on how well they know them (3). It is possible that a large network has a bigger influence on offline behavior than a smaller, but more densely connected one. Despite these results, social

Figure 1 Mapping of nodes (circles) with relation to one another (lines) is an important way to relate users’ personal data. media frequenters should not discount the influence of close friends. A recent study showed that when Facebook provided users with an “I Voted” clickable button, pictures of friends who had already voted, locations of nearby polling places, and sharing the post with close friends resulted in at least 559,000 votes in the election (6). Activism For some, simply discussing the current political atmosphere is not enough, since people want to elicit tangible change. Seeing as protests are a singularly offline experience, one might assume that online occurrences have very little impact. However, current research has shown that, although internet-based activism is no substitute for the face-to-face events, the activism has a measurable influence both here and abroad. For example, Facebook users who visit the site “several times a day” scored 35% higher on a measure of protest behavior than users who only logged on once a week (7). It has been shown that the most notable facet of online protest culture is its ability to incentivize a greater number of participants (8). When enough social media users are interested in a cause, mainstream media decides to report on the incident, spreading the information beyond its initial scope. University of Pennsylvania professor and researcher Sandra Gonzalez-Bailon reports that when users are “exposed to sudden rates of activation,” or discussing the same topic, it is often followed by their decision to join a cause, such as the protest for new forms of democratic representation in Spain during May 2011 (9). A more recent study, also completed by Gonza-lez-Bailon, emphasizes the importance of bridging “structural holes,” or ideological differences between individuals so that many groups can rally together for the same purpose, much like in offline communication (6). In addition to studying protest involvement after the event has already occurred, researchers have also been predicting future offline activities based on Internet word usage. Utilizing Google Trends, scientists have noticed that there have been “rises in the volumes and momenta [of certain words] around the same time as bursts of actual on-street protests” (9). This study was conducted regarding activism in Chile, so relevant words were protesta (protest), huelga (strike), manifestacion (demonstration), marcha (march), and paro (stoppage). Election Results Due to the logistical difficulties required to check whether a social media user participated in voting, there is a dearth in the amount of research regarding voting behavior and its online equivalent. Instead, studies have focused on politicians’ internet usage, and the influence elections have on political engagement due to the notable ease of obtaining data regarding these subjects. In a recent Colombian election, it was found that the candidate who received the most retweets on his posts, and posted the most on Twitter, received the most votes. This finding is unexpected, as the same study also showed that the Colombian politicians

“convey[ed] a rather homogenous message ”suggesting that the election result would prove difficult to ascertain (10). A similar Twitter-based model was used in Canada to accurately predict election results, both overall and within each province (11). In regards to commitment to voting, social media use seems to have a positive effect. In various countries, there have been “higher than expected turnouts among 18 – 24 year olds” at polls, which has been at least partially credited to the perusal of social media. More than 80% of this demographic also reported feeling engaged in respective elections and one in four confirmed that they had shared election related comments on their Facebook or Twitter accounts. These sites have also increasingly been used as primary sources of news: when an individual has had difficulty voting, he is likely to post about it on Youtube and other sites. Mainstream news outlets then featured these posts in their own articles. In this way, the relationship between traditional sources and newer ones is becoming symbiotic, with parties relying on each other to spread the news about worldly affairs (12). Conclusion Since politics can be such a ubiquitous topic, and social media sites are beginning to share that universality, research on the intersection between politics and social media is becoming even more crucial. Strong correlations between online and offline behavior, whether in regards to political discussion, protests and activism, or a candidate’s likelihood to win an election, could be used as powerful tools to make predictions about future events. Future research should focus on how other sites and apps, such as Instagram or Snapchat, may play a role in political elements current affairs. Additionally, researchers may inquire if certain demographics use social media in a certain way, and whether that has any connection with their ideologies. Ideally, there will be a way to easily match lists of voters to their online presences so that relationships about voting behavior can be further be studied. References 1. M. Kushin, M. Yamamoto, Did Social Media Really Matter? College Students Use of Online Media and Political Decision Making in the 2008 Election. Mass Communication and Society 13, 608–630 (2010). 2. S. Valenzuela, K. Yonghwan, H. Gil de Zúñiga, Social Networks that Matter: Exploring the Role of Political Discussion for Online Political Participation. International Journal of Public Opinion Research 24, 163-184 (2012). 3. N. Gustafsson et al., The subtle nature of Facebook politics: Swedish social network site users and political participation. New Media & Society 14, 1111-1127 (2012). 4. D. Byrne, An Overview (and Underview) of Research and Theory within the Attraction Paradigm. Journal of Social and Personal Relationships 14, 417-431 (1997). 5. J. Ratkiewicz et al., Political Polarization on Twitter. Association for the Advancement of Artificial Intelligence, (2010). 6. J. Folwer et al., A 61-million-person experiment in social influence and political mobilization. Nature 289, 295-298 (2012). 7. S. Valenzuela, A. Arriagada, A. Scherman, The Social Media Basis of Youth Protest Behavior: The Case of Chile. Journal of Communication 62, 299-314 (2012). 8. S. González-Bailón et al., The Dynamics of Protest Recruitment Through an Online Network. Nature Scientific Reports 1, 1-7 (2012). 9. H. Qi et al., Open source data reveals connection between online and on-street protest activity. EPJ Data Science 5, 1-12 (2016). 10. J. Correa, J. Camargo, Ideological Consumerism in Colombian Elections 2015: Links between Political Ideology, Twitter Activity and Electoral Results. CoRR, (2016). doi: abs/1608.01552. 11. K. White, Forecasting Canadian Elections Using Twitter. Advances in Artificial Intelligence, (2016). doi: 9673: 186-191. 12. N. Newman, W. Dutton, G. Blank, Social Media in the Changing Ecology of News: The Fourth and Fifth Estates in Britain. International Journal Internet Science 7, 6-22 (2012). Photos Retrieved from: 1. https://static.pexels.com/photos/129208/pexels-photo-129208.jpeg

Memory Manipulation Techniques: A Promising Path for Anxiety Therapy

Science Review

Yasmine Brown-Williamsâ&#x20AC;&#x2122;18

Memory is defined as the ability to recover information about past events or knowledge. Episodic memories are associated with incidents, while semantic memories are associated with knowledge. The formation and storage of memory adheres to a specific pathway that begins with learning, followed by encoding, storage, retention, and lastly, recollection. The storage phase of the pathway can be further subdivided into two phases known as consolidation and reconsolidation. Consolidation is the process of acquiring sensory information and securing it as a memory in the hippocampus, a brain structure that controls memory and emotion. Reconsolidation takes previously consolidated memories, re-encodes them, and restores them in the hippocampus. It is during this re-encoding stage that a previously stored memory is altered. Research surrounding memory storage is currently focused on understanding the mechanism behind reconsolidation, and the role it can play in memory manipulation. The majority of current memory manipulation research focuses on erasing negative episodic memories. Episodic memories provide us with the understanding of how to react during situations that we have previously been exposed to. However, episodic memories associated with traumatic experiences can often lead to generalized anxiety, as randomly recalling these memories results in a sense of heightened awareness of oneâ&#x20AC;&#x2122;s surroundings. This process is the basis for the sin of persistence. The sin of persistence is the inability to forget an episodic memory, such as one from a distressing event (1). It was previously believed that extinction, programmed memory loss, erases classically conditioned fear memories. However, it was identified that only memories manipulated during

the reconsolidation phase can be deleted (2). Thus, it is possible to relieve individuals suffering from the sin of persistence through purposeful memory erasure. Identifying the particular neurons that encode specific information and deleting those cells can allow us to manipulate and erase memories. The common neurological belief is that memories are encoded into bundles of biochemically altered neurons, which fire in specific sequences called engrams (3). Cyclic adenosine monophosphate response elementbinding protein (CREB) is a transcription factor that can bind toDNA and regulate gene expression. Neurons are recruited into a particular engram based on their levels of CREB activity during the learning stages of memory formation; high CREB activity indicates neuron participation in memory processing (3). After incoming information has been successfully encoded and stored, it can be retrieved through a process known as recollection. If a particularly pleasant or aversive incident is recalled, several neuromodulators such as acetylcholine are released, which activate widely distributed neuronal networks throughout the brain (4). Increased knowledge of these mechanisms has allowed researchers to further explore memory manipulation. CREB hyperactivity and the acetylcholine pathway have been analyzed in relation to fear memory extinction. A recent study, conducted by Dr. Lorna Role in the Department of Neurobiology and Behavior at Stony Brook University, discusses the utilization of the acetylcholine signaling pathway in the acquisition and extinction of fear memory. In this research the focus is placed on the amygdala, a brain structure associated with memory encoding, and not on the engram. The amygdalla,

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...memories can be artificially induced, erased, and reassociated if done so at a precise phase in memory formation. located posterior to the hippocampus, is made up of three groups of neurons or nuclei, jointly called the basolateral complex (BLA). The BLA is composed of the lateral, basal, and accessory basal nuclei, which are all responsible for stimulating the fear response. Fear memory expression has also been found to activate neurons of the lateral nucleus of the amygdala, which expresses increased CREB (3). Signaling from the acetylcholine pathway is required for normal fear learning and the retention of extinction. The reduction of acetylcholine signaling in the BLA during the initial training period results in increased loss of memory. Neurons that display high levels of CREB activity have been found to participate in fear memory engrams. By stimulating apoptosis in these particular neurons post-learning, fear memory expression can be disrupted. A study conducted at the University of Toronto by Dr. Sheena Josselyn has been able to successfully erase a memory by destroying the specific neurons associated with an engram. These neurons have high CREB expression and are prone to infection by the diphtheria toxin (DT), which induces apoptosis. In the study, transgenic mice that contain the CREB-recombinase(cre)-inducible form of the receptors that bind DT (DTR) were initially classically conditioned to develop a fear memory. This was done through auditory fear training, a process in which a sound is coupled with an electrical shock to encode a fear memory. The mice were subsequently infected with DT, which caused the neurons to conduct apoptosis. After the mice were injected with DT, the researchers observed that only the subjects who had both high expression of CREB and the presence of the cre-recombinase-inducible form of DTR exhibited fear memory loss (3). Because the cre-DTR and overexpressed CREB were present in cells induced for apoptosis, and their elimination caused the deletion of fear memories, it was concluded that neurons containing these specific receptors and molecules participate in storing fear memories. Successful eradication of fear memory has inspired research in other areas of memory manipulation, particularly memory implantation. For example, Xu Liu and Steve Ramirez of the Biology and Brain Cognitive Sciences Departments at the Massachusetts Institute of Technology have learned to utilize optogenetics to control neuron activity. Optogenetics is a biological technique that involves using light to stimulate specific brain cells. The researchers genetically altered a subpopulation of dentate gyrus neurons associated with the fear memory formed and made them light sensitive. An optic fiber was implanted in the cranium of the mouse, creating a pathway for light to enter the neurons. The mouse was placed into either Box A or Box B. In Box A, the mouse was allowed to form a

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non-fear memory while in Box B, it experienced a foot shock that caused it to form a fear memory. After being re-inserted into Box A, the mouse’s neurons were stimulated by a laser, which used optic fiber to reactivate the previously encoded fear response. The mouse froze more readily in anticipation of a foot shock every time it was re-introduced to Box A, but not when it was introduced to Box B (5). These observations indicate that the fear memory was manipulated to become active in an environment separate from where it was formed. Evidence from this study supports the notion that memories can be artificially induced, erased, and re-associated if done so at a precise phase in memory formation. One of the standardized treatments for anxiety disorders is cognitive behavioral therapy (CBT). In this treatment method, emphasis is placed on changing the individual’s thought patterns and understanding of events. The positive effects of CBT may not be seen for up to 16 weeks, and treatment involves the patient’s active participation in the form of homework assignments and daily logs (7). In addition to behavioral therapy, individuals suffering from anxiety disorders are often prescribed psychiatric medications. One in 10 Americans is prescribed antidepressants, making them the most commonly administered medications for the treatment of anxiety disorders (8). A novel neurological therapy for depression and anxiety is Repetitive Transcranial Magnetic Stimulation (rTMS). The treatment requires an electromagnetic coil to be placed against the forehead, near the brain’s mood regulatory area. The coil fires electromagnetic pulses that stimulate neurons in the brain area, altering the individual’s mood to focus on pleasant thoughts. It is unclear whether this technique is more effective alone or when paired with other behavioral therapies (9). References 1. D.L. Schacter, The seven sins of memory: how the mind forgets and remembers. Houghton Mifflin Company, (2001). 2. G. J. Quirk et al., Erasing fear memories with extinction training. The Journal of Neuroscience 30, 14993–14997 (2010). doi: 10.1523/JNEUROSCI.4268-10.2010. 3. S.A. Josselyn et al., Selective erasure of a fear memory. Science 323, 1492-1496 (2009). doi: 10.1126/science.1164139. 4. L.W. Role et al., Cholinergic signaling controls conditioned fear behaviors and enhances plasticity of cortical-amygdala circuits. Neuron 90, 1057-1070 (2016). doi: 10.1016/j.neuron.2016.04.028. 5. X. Liu et al., Optogenetic stimulation of a hippocampal engram activates fear memory recall. Nature 484, 381–385 (2012). doi: 10.1038/nature11028. 6. R. J. Mcnally, Memory and anxiety disorders. Philosophical Transactions of the Royal Society B: Biological Sciences 352, 1755–1759 (1997). doi: 10.1098/ rstb.1997.0158. 7. Therapy. Anxiety and Depression Association of America, (2016). 8. Medication. Anxiety and Depression Association of America, (2016). 9. Transcranial Magnetic Stimulation (TMS). Anxiety and Depression Association of America. (2016). Photos Retrieved from: 1. http://www.favorite-banned-books.com/images/iStock_000003711102XSmall.

Science Review

Our Journey to Mars Hinges on the Human Factor Lukas J. Vasadi â&#x20AC;&#x2122;16

Humans have both visited the moon during the Apollo program and explored low Earth orbit onboard the International Space Station (ISS), but now the National Aeronautics and Space Administration (NASA) has turned its attention toward exploration-class missions to Mars (1). Why Mars as opposed to other planets in the solar system? Aside from being in close proximity to Earth, Mars has demonstrated potential for supporting primitive microbial life forms. Satellites and rovers have gathered evidence that our red neighbor may have had liquid water on its surface as well as complex organic compounds (2,3). Although such information has been available since the 1970s, space agencies and commercial industries have only recently developed the technology capable of transporting humans to the Martian surface. So what is still hindering our journey to Mars? Despite advancements in space transport technology, there are many concerns regarding human health in a mission of such duration. A round-trip transit to Mars using the Orion capsule and Space Launch System would require a minimum of 520 days, assuming a one-month stay on the planetâ&#x20AC;&#x2122;s surface (1). Studying human health in space has proven challenging, especially considering the small sample size that makes generating conclusive data impossible. There are less than 50 U.S. astronauts who have served on long-duration missions of at least six months (4). Furthermore, spaceflight adaptation and recovery are functions of mission duration and vary significantly between individuals (5). Although the adverse effects of spaceflight on the human system have been studied for years onboard the Skylab, Mir, and ISS, there remains a list of human risk factors that must be addressed before visiting Mars. Modern spaceflight countermeasures have achieved marginal success at mitigating these risk factors, which include skeletal deconditioning, immunodeficiency, vision impairment, increased risk for cardiovascular disease, and neurological degeneration (6).

Skeletal Deconditioning Throughout long-duration missions, astronauts lose significant bone mass at load-bearing skeletal regions, such as the hip and lumbar spine. Loss of mineralized tissue compromises bone microstructure, increasing the risk for fragility fractures during re-ambulation in normal gravitational conditions on Earth (7,8). Spaceflight-induced bone loss has been attributed to skeletal unloading, or weightlessness, which causes an imbalance in bone remodeling that favors a net decrease in bone formation (7). From early on in the space program, astronaut bone health has been monitored triennially using dual-energy Xray absorptiometry to measure bone mineral density (BMD). One study reported declines in BMD at rates of approximately 1.5 percent per month in the hip and 1.0 percent per month in the lumbar spine (9). However, it is important to note that bone loss is highly variable across individuals. Losses in lumbar vertebrae occur at twelve times the rate of elderly persons with age-related bone loss, which ranges from 0.5-1.0% per year (7). Although many astronauts recover BMD during postflight rehabilitation, computational estimates of bone strength remain significantly lower than preflight values, suggesting that bone microstructure is permanently compromised (10). In order to protect the astronaut skeleton, NASA has implemented strength-training routines on the ISS with the Advanced Resistive Exercise Device (ARED), which simulates free-weight exercises in normal gravity (11). Each astronaut exercises for about two hours every day, rotating between the ARED, treadmill, and stationary bicycle. Recent data suggest that exercise on the ARED, combined with optimal nutrition and antiresorptive bisphosphonates, may mitigate bone loss (11,12). However, this machine is a massive payload that cannot be brought to Mars onboard the Orion capsule, which is about 50 times smaller than the ISS. Thus, NASA scientists

Figure 1 On the ISS, astronauts exercise using the ARED to protect against musculoskeletal deconditioning. This machine weighs about one ton and thus, will not be included on the Orion capsule for deep space missions. A special engineering team in the NASA Human Research Program is working to design a more compact exercise device that provides similar protection.

and engineers are developing a compact exercise device that weighs significantly less and fits the dimensions of a large shoebox. Immuno-Dysregulation Spaceflight may cause immune system dysregulation and increase the reactivation of latent viruses relative to terrestrial norms (13). Although many astronauts have demonstrated increased vulnerability to infection (14), it is important to note that their immune responses are not always impaired. Some astronauts actually exhibit immune hyperactivity, which may lead to hypersensitivity or autoimmunity (13). While this research is still ongoing, these changes in immune function have been attributed to increased stress and internal fluid shifts (15). The stress experienced by astronauts is mostly due to high performance expectations, sleep disruption, and confinement in the vessel. Performance expectations refers to the pressure that astronauts place on themselves to complete tasks assigned by Mission Control. Radiation exposure has also been shown to lower immune activity (16). Short-duration spaceflight during the shuttle missions affected leukocyte, white blood cells that eliminate infectious agents through phagocytosis, distribution and function, which resumed to normal preflight activity after return to Earth (17). Although white blood cell count was not altered during spaceflight, abnormal functioning of T cell populations may hinder B cell maturation and activation of macrophages, which are our first line of pathogenic defense. Traveling to Mars may inflict unprecedented levels of stress due to not only extreme performance expectations, but also isolation. On Marsâ&#x20AC;&#x2122;s surface, communications with Mission Control can be delayed up to 40 minutes depending on the relative positioning of Earth and Mars, which can make astronauts feel especially sequestered (1). Crew confinement in a spacecraft increases the transfer of microorganisms (18,19), but the risk of pathological

infection remains low since astronauts are quarantined for several days before launch. Still, some studies have reported inflight cross-contamination with pathogenic bacteria (20,21), which grow more rapidly in microgravity (15). Bacteria also exhibit higher mutation frequencies in microgravity, which may explain their increased resistance to antibiotics (22, 23). Researchers have offered speculation on these phenomena, but the underlying cause remains unclear. Altogether, this increased bacterial activity provides the ideal environment to breed infection, but antioxidants and dietary supplements have been effective in mitigating this risk (15). Therefore, more research is needed to determine whether infection poses a serious threat to deep space missions. Vision Impairment In 2011, NASA investigators published a finding that explained how some astronauts on the ISS experienced impaired distant and near visual acuity (24). The causes of these vision changes were inconsistent across subjects. MRI scans revealed posterior globe flattening, optic nerve thickening, and choroidal folds (24). This odd condition has been termed Vision Impairment and Intracranial Pressure (VIIP) syndrome ,due to the current hypothesis, which attributes loss of visual acuity to the increased intracranial pressure that results from internal fluid shifts. Studies during the shuttle program demonstrated that cerebral arteries dilate in microgravity, causing fluid equilibrium to shift upward (25). These pressure fluxes are easily noticeable in astronauts during the first few days of spaceflight when they experience â&#x20AC;&#x153;puffy face syndrome.â&#x20AC;? Over time, the buildup of intracranial pressure can actually alter the anatomical shape of the eyeball and surrounding soft tissues (26). Currently, there are no countermeasures for VIIP, and it is unclear how vision changes will perpetuate as mission duration increases. Long-Term Cardiovascular Effects A recent study has shown that deep space missions may

put astronauts at risk for cardiovascular disease. Researchers from several institutions, including NASA, compared the health status of astronauts who never flew, those who only flew in low Earth orbit, and the Apollo astronauts who landed on the moon (27). To this day, the Apollo astronauts are the only humans to fly beyond the Earthâ&#x20AC;&#x2122;s magnetosphere, which shields us from harmful space radiation. Without this protection, astronauts may be exposed to destructive protons and heavy ion particles that could damage DNA and disrupt normal cellular repair and reproduction. The researchers discovered that cardiovascular disease was much more prevalent in the lunar Apollo astronauts compared to the other groups. Mortality related to cardiovascular disease was at 43% in Apollo lunar astronauts, which is four times greater than in those who exclusively flew in low Earth orbit. This difference was even more pronounced between Apollo astronauts and astronauts who have never flown, since the latter showed only 9% mortality due to cardiovascular disease. Animal studies were conducted to further investigate the physiological effects of radiation and microgravity on cardiovascular function. Vascular activity in mice was evaluated 6-7 months following hind-limb tail suspension (a common method used to simulate weightlessness in microgravity), 56Fe irradiation treatment, or a combination that represented spaceflight (27). The researchers concluded that weightlessness had no significant effect on long-term cardiovascular health in the mice, whereas constant radiation exposure impaired normal vasodilation (27). Through a metabolic analysis, they found that 56Fe irradiation disrupted nitric oxide signaling, which impaired endothelium-dependent vasodilation. This may eventually lead to occlusive arterial disease, in which blocked arteries restrict blood flow and typically cause serious cardiovascular events, such as heart attack or stroke. Despite these powerful findings, the researchers emphasize that caution should be exercised in

spaceflight biomedical studies because the sample size tends to be small due to the relatively small population of astronauts. In addition, although the radiation in animal studies represents the total amount of radiation encountered by astronauts, it is administered at a higher dose.. Neurological and Sensorimotor Effects Microgravity causes changes in neurological functions related to sleep, motor control, and cognition. However, normal neurological function is usually restored after acclimation to microgravity. Still, upon return to Earth, long-duration astronauts show significant neurological deconditioning as demonstrated by obstacle course time trials. In one study, ISS astronauts showed a median 48% increase in their time to complete a functional mobility test compared to preflight values (28). The researchers also created a mathematical model to track locomotive recovery and determined that it took an average of over two weeks for normal function to reach 95% of preflight levels. Recent studies have shown that long-duration spaceflight may cause quantifiable structural changes in the brain. In particular, one head-down tilt bed rest study found that resting state functional connectivity changes in the motor, somatosensory, and vestibular regions (29,30). Interestingly, the majority of energy expenditure in the brain supports spontaneous neural activity during rest (31), which is the reason this index was used to assess astronaut neurological adaptation. This study only simulated the effects of weightlessness, ignoring potential contributions of spaceflight radiation. While these changes were associated with altered sensorimotor and memory performance, the result was not always a loss of function. Rather, the researchers attributed some of these structural changes to neuroplasticity mechanisms that allow astronauts to adapt to microgravity (29). Despite these findings, the researchers are unsure whether these structural changes result in any long-

Figure 2 NASA is building the Space Launch System to propel the Orion beyond Earthâ&#x20AC;&#x2122;s atmosphere for deep space missions. This will be the most powerful rocket ever built by the US space agency.

Another recent study discovered that astronauts exhibit significantly greater white matter hypersensitivities than previously expected (32). White matter hypersensitivities are lesions where insulating grey matter degrades, exposing the underlying white matter in the brain. These lesions have been associated with age, dementia, and other neurological conditions (33). The U.S. Air Force also found an increased prevalence of white matter hypersensitivities in high-altitude U2 pilots (32). Due to occupational differences related to hypobaric training, it was expected that these lesions would occur less frequently in astronauts. However, MRI scans revealed instead that white matter hypersensitivities were even more pronounced in astronauts compared to both the U.S. population and U2 pilots. These findings are alarming because of the implications of white matter lesions in the progression of neurological diseases. There are no countermeasures, currently used to prevent or reverse neurological changes in space. Artificial Gravity as a Possible Solution When considering deep space missions, the ultimate countermeasure for mitigating the adverse effects of microgravity may be artificial gravity (31). Ideally, artificial gravity would eliminate the need for all other countermeasures except those concerning radiation exposure. It would provide mechanical loading to prevent bone deterioration and maintain normal internal fluid distributions, which may alleviate immunosuppression, vision impairment, cardiovascular dysregulation, and neurological impairment. This concept was introduced by Russian scientists who proposed creating artificial gravity through centripetal motion, in which two or more partitions of the spacecraft rotate about a common central axis (31,32). This approach has been portrayed in science fiction novels and films, such as “A Space Odyssey” (2001), since the mid-1900s. The proper rotational velocity would generate a normal force equal in magnitude to the gravity on Earth’s surface. However, despite having a logical foundation in physics, developing such a spacecraft would be expensive and exceedingly complex (31). Thus, artificial gravity is still being explored, but is unlikely to be implemented before the first human sets foot on Mars. Conclusion Deep space missions to Mars and other celestial bodies have become the focus of both the government and private space industries. The technology needed to transport humans to Mars is available, but there are still many health concerns associated with long-duration spaceflight that may jeopardize crew safety and mission success. All of these risk factors are related to microgravity, radiation exposure, or a combination of both, and modern countermeasures may not be sufficient to protect astronauts. While the best solution to weightlessness may be artificial gravity, the engineering constraints associated with the construction of a rotating spacecraft will likely prevent this design from being implemented in the near future. Linear artificial gravity has also been proposed, but this would require sustained thrust with an immense fuel consumption rate. For the time being, it seems that most spaceflight countermeasures will focus on exercise, pharmaceutical intervention, and physical shielding from space radiation. However, the aluminum shielding on the Orion capsule may not offer enough protection against high-energy solar events or heavy-ion interceptions

from galactic cosmic rays that are likely to be encountered in a transit to Mars (36). Thus, NASA scientists and engineers still have many issues to address, and the journey to Mars remains a milestone just out of reach. References 1. M. Heppener M, Spaceward ho! the future of humans in space. EMBO Reports 9, S4-S12 (2008). doi: 10.1038/embor.2008.98. 2. C. Gallagher, M.R. Balme, New insights on the roles of ice, water and climate change in recent landscape development on mars. Geography 100, 84-93 (2015). 3. E. Hand, Mars rover finds long-chain organic compounds. Planetary Science 347, 1402-1403 (2015). doi: 10.1126/science.347.6229.1402. 4. J.D. Sibonga, Spaceflight-induced bone loss: is there an osteoporosis risk? Current Osteoporosis Reports 11, 92-98 (2013). doi: 10.1007/s11914-013-0136-5. 5. S.J. Wood, J.A. Loehr, M.E. Guilliams. Sensorimotor reconditioning during and after spaceflight. NeuroRehabilitation 29, 185-195 (2011). doi: 10.3233/NRE2011-0694. 6. D.R. Williams, A historical overview of space medicine. McGill Journal of Medicine 6, 62-65 (2001). 7. E.S. Orwoll et al., Skeletal health in long-duration astronauts: nature, assessment, and management recommendations from the nasa bone summit. Journal of Bone and Mineral Research 28, 1243-1255 (2013). doi: 10.1002/jbmr.1948. 8. A. LeBlanc et al., Bone mineral and lean tissue loss after long duration space flight. Journal of Musculoskeletal and Neuronal Interactions 1, 157-160 (2000). 9. T. Lang et al., Cortical and trabecular bone mineral loss from the spine and hip in long-duration spaceflight. Journal of Bone and Mineral Research 19, 1006-1012 (2004). doi: 10.1359/JBMR.040307. 10. T.F. Lang et al., Adaptation of the proximal femur to skeletal reloading after long-duration spaceflight. Journal of Bone and Mineral Research 21, 1224-1230 (2006). doi: 10.1359/JBMR.060509. 11. S.M. Smith et al., Benefits for bone from resistance exercise and nutrition in long-duration spaceflight: evidence from biochemistry and densitometry. Journal of Bone and Mineral Research 27, 1896-1906 (2012). doi: 10.1002/jbmr.1647. 12. A. Leblanc, et al., Bisphosphonates as a supplement to exercise to protect bone during long-duration spaceflight. Osteoporosis International 24, 2105-2114 (2013). doi: 10.1007/s00198-012-2243-z. 13. B. Crucian, C. Sams, Immune system dysregulation during spaceflight: clinical risk for exploration-class missions. Journal of Leukocyte Biology 86, 1017-1018 (2009). doi: 10.1189/jlb.0709500, 14. S.L Kimzey, Biomedical Results from Skylab. Washington, DC, NASA (1977). 15. N. Guéguinou et al., Could spaceflight-associated immune system weakening preclude the expansion of human presence beyond earth’s orbit? Journal of Leukocyte Biology 86, 1027-1038 (2009). doi: doi:10.1189/jlb.0309167. 16. G. Sonnenfeld, Extreme environments and the immune system: effects of spaceflight on immune responses. Journal of Allergy and Clinical Immunology 107, 19-20 (2001). doi: 10.1067/mai.2001.112034. 17. B. Crucian et al., Immune system dysregulation occurs during short duration spaceflight on board the space shuttle. Journal of Clinical Immunology 33, 456465 (2013). doi: 10.1007/s10875-012-9824-7. 18. D.L. Pierson et al., Person-to-person transfer of candida albicans in the spacecraft environment. Journal of Medical and Veterinary Mycology 33, 145-150 (1995). 19. D.L. Pierson et al., Epidemiology of staphylococcus aureus during space flight. FEMS Immunology and Medical Microbiology 16, 273-281 (1996). doi:10.1016/ S0928-8244(96)00094-6. 20. J.G. Decelle, G.R. Taylor, Autoflora in the upper respiratory tract of Apollo astronauts. Applied and Environmental Microbiology 32, 659-665 (1976). 21. D.L. Pierson. Microbial contamination of spacecraft. Gravitational and Space Biology Bulletin 14, 1-6 (2001). 22. T. Fukuda et al., Analysis of deletion mutations of the rpsl gene in the yeast saccharomyces cerevisiae detected after long-term flight on the russian space station Mir. Mutation Research 470, 125-132 (2000). doi: 10.1016/S13835742(00)00054-5. 23. N.M. Leys et al., Space flight effects on bacterial physiology. Journal of Biological Regulators and Homeostatic Agents 18,193-199 (2004). 24. T.H. Mader et al., Optic disc edema, globe flattening, choroidal folds, and hyperopic shifts observed in astronauts after long-duration space flight. Ophthalmology 118, 2058-2069 (2011). doi: 10.1016/j.ophtha.2011.06.021. 25. C.R. Taylor et al., Spaceflight-induced alterations in cerebral artery vasoconstrictor, mechanical, and structural properties: implications for elevated cerebral perfusion and intracranial pressure. The Official Journal of the Federation of American Societies for Experimental Biology 27, 2282-2292 (2013). doi: 10.1096/ fj.12-222687. 26. L.A. Kramer et al., Orbital and intracranial effects of microgravity: findings at 3-t mr imaging. Radiology 263, 819-827 (2012). doi: 10.1148/radiol.12111986. 27. M.D. Delp et al., Apollo lunar astronauts show higher cardiovascular disease mortality: possible deep space radiation effects on the vascular endothelium. Scientific Reports 6, 1-11 (2016). doi: doi:10.1038/srep29901. 28. L.C. Simonsen et al., Radiation exposure for human mars exploration. Health Physics Journal 79, 515-525 (2000). 29. J. Norcross et al., Initial incidence of white matter hyperintensities on mri in astronauts. NASA Technical Reports Server, (2016). 30. N.D. Prins, P. Scheltens et al., White matter hyperintensities, cognitive impairment and dementia: an update. Natures Reviews Neurology 11, 157-165 (2015). doi: 10.1038/nrneurol.2015.10. 31. L.R. Young, Artificial gravity considerations for a mars exploration mission. Annals of the New York Academy of Sciences 871, 367-378 (1999). 32. R.R. Burton, A human-use centrifuge for space stations: proposed groundbased studies. Aviation, Space, and Environmental Medicine 59, 579-582 (1988). Photos Retrieved from: 1. http://taka-style.net/wp-content/uploads/2016/05/gahag-0028326360.jpg 2. https://upload.wikimedia.org/wikipedia/commons/thumb/3/3a/ISS24_Shannon_Walker_exercises_using_the_aRED.jpg/1024px-ISS-24_Shannon_Walker_exercises_using_the_aRED.jpg 3. http://imagesbase.ru/uploads/posts/2015-11/1447597815_imagesbase.ru2749.jpg

Science Review

Humans and Algae: How anthropogenic environmental changes are affecting the backbone of

Earth’s marine ecosystems

Shannon Bohman ‘19

Introduction: What Are Algae and Why Are They Important? Algae encompass a broad spectrum of some of the most important photosynthetic marine organisms on Earth. There exists a great deal of genetic and morphological diversity within the algae community - thirty thousand to one million algae species exist (1). All algae are autotrophic, and they comprise the base of the food chain, which make them a key part in the carbon and oxygen cycles on Earth. Algae not only produce much of the Earth’s oxygen, but also lie at the base of the marine food web (2). Any change to the physical environment could spell disaster to the algal community and the fragile biological balance it supports. At one end of the spectrum are multiple types of microalgae, organisms that are too small to be seen with the naked eye. Diatoms are a type of microalgae that are composed of silica skeletons and are present almost anywhere water is found. Streams, lakes, ponds, oceans, and even fish tanks are full of these tiny, glasslike algae, which can exist individually as free-floating cells or linked together by silica spines, creating long chains and more complex shapes (3). Though tiny, diatoms contain a great deal of information about the environments in which they live in. Certain species can only form under very specific pH and salinity levels, and in general ,are very sensitive to flow patterns, sediment disruption, and nutrient concentration. By studying the preserved silica skeletons of ancient diatoms, scientists have been able to determine the chemical and physical environmental conditions of the past, providing a good measure of how waterways are changing today. It is clear that nutrient levels, dissolved organic carbon,

light, and temperature all influence diatom population, and changes in these levels are most pronounced in the Northern Hemisphere, where most bodies of water are subject to sediment disruption and nutrient enrichment from overdeveloped land (4). Dinoflagellates are another type of microscopic algae that significantly influence the environment they inhabit. These single-cell protists are able to propel their way through the water with two flagella composed of proteins and microtubules (1). Sometimes dinoflagellate populations can grow uncontrollably, causing what is known as a “red tide.” When the red tide consisting of dinoflagellates that secrete neurotoxins, nearby fish and shellfish that eat the dinoflagellates suffer nerve damage and may die. For example, the ciguatera toxin, a specific type of dinoflagellate-secreted neurotoxin, becomes stored and concentrated in the organs of fish that consume it. Humans who consume seafood containing ciguatera can contract ciguatera disease, which is characterized by nausea, heart pain, and adverse neurological symptoms (5). On the opposite end of the algae spectrum are macroalgae, which include millimeter-wide seaweed and kelp stalks up to 30 meters long. Macroalgae, such as red and green algae, comprise the most recognizable types of seaweed. Red algae, also known as rhodophyta, are multicellular marine organisms that include a majority of the world’s seaweed. Phycoerythrin is the pigment responsible for its red hue. In some shallow, sunny waters, rhodophyta are integral to coral reef construction. These reef-building algae are deemed “coralline” because their hard shells of calcium carbonate aid their neighboring corals in providing structure for the reef (2).

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Unfortunately, humans are responsible for a number of drastic environmental changes that are wreaking havoc on many of these algae populations. -teria, are not technically algae. Rather, they are a type of bacteria that display many of the characteristics of the filamentous green algae (1). Both blue-green algae and cyanobacteria are found in freshwater systems, but unlike their algal doppelganger, cyanobacteria exist in marine environments as well (6). Like dinoflagellates, cyanobacteria are particularly sensitive to the nutrient concentrations of the water they inhabit. Runoff from nearby farm or residential land can cause harmful algal blooms (HABs) that damage the health of both the surrounding ecosystems and economies. Unfortunately, humans are responsible for a number of drastic environmental changes that are harming many of these algae populations. Increased levels of carbon dioxide, ocean temperature, and nutrient enrichment have complex and generally negative impacts on different algal communities (7). Such anthropogenic problems, however, can have anthropogenic solutions. Working to ensure the stability of algae populations is an important first step in maintaining marine ecosystems around the world. Red Algae and Ocean Acidification Ocean acidification, which occurs when too much carbon dioxide dissolves in the ocean, threatens the ability of red algae to successfully calcify. One may initially think that increased carbon dioxide levels bode well for algae because these organisms require carbon dioxide in order to photosyn-

Figure 1 Cyanobacteria blooms tint the water a greenblue color and pose potential health risks to marine and terrestrial life.

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thesize. However, when the CO2 dissolves in water, carbonate ion levels decrease while bicarbonate levels increase, thereby decreasing the pH of the water and harming the algae. Since the Industrial Revolution, the ocean has absorbed approximately one-third of the carbon dioxide released into the atmosphere by human activity. Coralline rhodophyta are composed of a magnesium-rich calcite skeleton, and aragonite crystals deposited throughout their cell walls create an organic matrix ideal for calcification. When this matrix is exposed to acidified seawater, the calcite skeleton begins to dissolve. One recent study from the University of Bremen in Germany analyzed how calcifying rhodophyte Corallina officinalis responded toward increased carbon dioxide levels. While calcification abilities were diminished and photosynthesis increased as expected, a wide array of other metabolic processes, such as inorganic nutrient uptake and assimilation, came under flux as well (7). Changes in the behavior of algae like C. officinalis due to elevated carbon dioxide levels pose a huge threat to the health of coral reefs, which rely on calcified algae for structure and support. By disrupting the physical structure of the coral reef, elevated carbon dioxide levels also disrupt the competitive interactions between all marine life in the reef. The ability to cope with a loss of habitat and maintain competitive dominance varies between even closely related species. Some species will come to monopolize the degraded coral reef, while

others will dwindle in number (8). The effects of ocean acidification due to increased carbon dioxide dissolution are broad and pervasive, and this situation is especially evident in the case of coral reefs. Blue-Green Algae and Eutrophication Algal blooms occur when there is a sudden and extreme increase in population of certain types of algae. Freshwater blue-green algal blooms are the most common type of harmful algal bloom in New York. During periods of rain, residuals from farmland, over-fertilized lawns, septic tanks, and sewage treatment plants leak into natural bodies of water. Runoff like this brings a flush of unwanted nutrients, such as nitrogen and phosphorous, which can spark a sudden overpopulation of algae on the water surface. Like clouds on a rainy day, the dense layer of algae prevents sunlight from penetrating far into the body of water, therefore depriving the plants at the bottom of the energy they need to photosynthesize. This leads to low levels of oxygen within the body of water, a situation known as hypoxia. Oxygen-dependent animals in the water are essentially suffocated by nutrient-supported algae as well as oxygen-hogging bacterial decomposers, which thrive on the dead plants that litter the floor. When the water becomes completely devoid of oxygen, it is deemed anoxic. Oxygen deprivation is a side effect of both red and blue-green algal blooms, but an added danger is that certain cyanobacteria produce neurotoxins that poison the marine life that feed on them (6). Due to prolonged and intense nutrient enrichment from farmland along the Mississippi River, the Gulf of Mexico has an expansive anoxic zone aptly dubbed the “Dead Zone.” While dead zones occur naturally, anthropogenic dead zones, like the one in the Gulf, are increasing in abundance and severity around the world. In a 2014 study, Dr. S. S. Rabotyagov and his team used a simple statistical model to estimate the relationship between nutrient load and the size of the Gulf of Mexico’s dead zone. They found that both immediate and past levels of nutrient runoff, as it occurs on a seasonal basis, determine the size and extent of the hypoxia. Aside from the biological toll of nutrient enrichment, the researchers examined the economic damage inflicted on areas that depend on hypoxic fisheries and other ecosystem services. It was estimated that restoring wetlands on just one hectare of land along the southern Mississippi River would save between $900 and $1,900. The wetlands are a natural means of nitrogen mitigation, but have diminished in size and health dramatically in recent years due to over-development of nearby land (9). Varying projections of climate change for specific areas complicate mitigation of harmful algal blooms, especially HABs of cyanobacteria (CyanoHABs) (9). With climate change comes changing rainfall patterns. Some areas are going to experience wetter rainy seasons, leading to increased storm water runoff and nutrient enrichment. In between these wetter wet seasons are going to be drier dry seasons. The increased intensity of wet and dry seasons is expected to accelerate the eutrophication process (5). Anthropogenic Solutions Coral reefs are often the center of any conversation involving anthropogenic impacts on algae. Given their reliance on microscopic calcifying algae, these complex ecosystems are

especially sensitive to ocean warming and acidification. One method of restoring coral reefs is the “gardening concept,” which is a low-cost operation that involves growing coral polyps in a controlled environment and then cultivating them in a designated location. First, small groups of coral nubbins are grown in special mid-water nurseries. Once these corals reach a mature size, they are transported to coral colonies that have been carefully primed as “reef areas.” Applying such a high degree of control over the rearing and the implantation of new coral colonies has proved successful for the 86 coral species that have been farmed worldwide (10). Dead zones are another anthropological issue that drain both the biodiversity and economic health of communities that rely on marine life for commerce. One way of controlling water quality and reducing the occurrence of harmful algal blooms is biomanipulation. This involves altering the food web in order to restore ecosystem health. In one study conducted in the Netherlands, the quagga mussel was introduced into an urban pond containing an excessive amount of cyanobacteria. The quagga mussel is a planktivorous bivalve: meaning it feeds on the phytoplankton that cause CyanoHABs. Compared to the control groups where no mussels were present, the enclosures containing quagga mussels displayed lower concentrations of cyanobacteria and phosphorus, along with higher levels of transparency. Therefore, biomanipulation can be a successful means of controlling algal blooms. However before employing biomanipulation, it is imperative that environmental managers consider the possible dangers of introducing alien and invasive species into an ecosystem, as doing so could have negative effects that outweigh the positives (10). Sediment disruption and eutrophication pose huge risks to coral reefs and marine and freshwater ecosystems. Moreover, it is estimated that nearly 50% of today’s water pollution stems from nonpoint sources, such as communities of well-manicured suburban homes (12). Naturally, the issue of who should pay for nonpoint source degradation is complex, and it is important that economists work in tandem with ecologists and other natural scientists in order to formulate successful solutions. The Environmental Protection Agency (EPA) has promoted and enforced government policies that safeguard water quality since its inception in 1970. The 1987 Water Quality Act is an example of these efforts. By establishing and monitoring a program of federal subsidies that incentivize farmers to utilize management practices, designed to

Figure 2 The quagga mussel is, a plankivorous bivalve apt at controlling algal blooms.

Figure 3 Crustose coralline algae, shown above, is an important part of coral reef structure.

minimize agricultural runoff into nearby water, the EPA has been able to tackle the issue of nonpoint source pollution directly. Providing cost-effective solutions has proven to be a successful way to incentivize individuals to adopt environmentally sound habits (13). Conclusion Algae, albeit tiny, have an enormous impact on the environments they inhabit. At the same time, the environment can have a large impact on the algae it supports. As humans pollute and degrade the environment, algae are among the first organisms to suffer, setting off a grave chain of events in their ecosystems. Red algae, an important staple of coral reefs, find difficulty calcifying under increased acidity (6). This deprives the coral reefs of the structure they require to sustain their complex ecosystems. In an effort to restore the coral reefs already ravaged by ocean acidification, some environmental managers are using the “gardening system” to rear and implant new coral colonies in barren reef areas (10). Green and blue-green algae populations are also destabilized due to anthropogenic environmental interference. When runoff from farmlands rich with nitrogen and phosphorous fertilizer makes its way into local waterways, eutrophication causes algal blooms (9). At best, these blooms hurt nothing but the aesthetic of the water. At worst, hypoxic conditions can turn that habitat into a dead zone, such as the one found in the Gulf of Mexico. Algal blooms can poison marine life and terrestrial life that come in contact with them, making them doubly dangerous. In some bodies of water at risk for hypoxia, researchers employ “biomanipulation,” a technique that skews the food web in order to control algal populations that may grow uncontrollably (11). There is still work to be done to understand the full effects of human-induced climate and habitat disruption on algae. As of now, policymakers are most concerned with mitigating the damage already inflicted on algae populations by anthropogenic environmental changes. It is imperative, however, that policymakers take action to curb the roots of

the issues, such as fossil fuel combustion and the overuse of fertilizers and pesticides. Without such proactive action, algae and all those organisms that depend on them will experience significant, if not devastating, changes in the near future. Humans have already demonstrated their incredible capacity to control the natural world via science, technology, and international collaboration. All it may take is a coordinated effort to channel that power toward safeguarding the health of organisms at risk, and algae is a good place to start. References 1. M.D. Guiry, How many species of algae are there? Phycological Society of America 48, 1057-1063 (2012). doi: 10.1111/j.1529-8817.2012.01222.x. 2. M. Edwards et al., Macroalgae Fact-sheets. Irish Seaweed Research Group, (2012). 3. L. C. Hofmann, S. Straub, K. Bischof, Elevated CO2 levels affect the activity of nitrate reductase and carbonic anhydrase in the calcifying rhodophyte corallina officinalis. Oxford Journals: Journal of Experimental Botany 64, 899-908 (2013). doi: 10.1093/jxb/ers369. 4. S. S. Rabotyagov et al., The economics of dead zones: causes, impacts, policy challenges, and a model of the Gulf of Mexico hypoxic zone. Review of Environmental Economics & Policy 8, 58-79 (2014). doi: 10.1093/reep/ret024. 5. Diatoms. Microfossil Image Recovery and Circulation for Learning and Education, (2016). 6. J. E. Saros, N. J. Anderson, The ecology of the planktonic diatom cyclotella and its implications for global environmental change studies. Biological Reviews 90, 522-541 (2015). doi: 10.1111/brv.12120. 7. H.W. Paerl et al., Mitigating cyanobacterial harmful algal blooms in aquatic ecosystems impacted by climate change and anthropogenic nutrients. Harmful Algae 54, 213-222 (2016). doi: 10.1016/j.hal.2015.09.009. 8. M.I. McCormick, S. Watson, P.L. Munday, Ocean acidification reverses competition for space as habitats degrade. Scientific Reports 3, (2013). doi: 10.1038/ srep03280. 9. B. Rinkevich, Rebuilding coral reefs: does active reef restoration lead to sustainable reefs?. Current Opinion in Environmental Sustainability 7, 28–36 (2014). doi: 10.1016/j.cosust.2013.11.018. 10. T. C. Arnold, Ciguatera Toxicity. Medscape (2015). 11. C. D’Angelo, J. Wiedenmann, Impacts of nutrient enrichment on coral reefs: new perspectives and implications for coastal management and reef survival. Current Opinion in Environmental Sustainability 7, 82–93 (2014). doi: 10.1016/j. cosust.2013.11.029. 12. B. C. Field, M. K. Field, Environmental Economics: An Introduction. McGrawHill (2013). 13. G. Waajena et al., Biomanipulation with quagga mussels (dreissena rostriformis bugensis) to control harmful algal blooms in eutrophic urban ponds. Ecological Engineering 90,141-150 (2016). doi: 10.1016/j.ecoleng.2016.01.036. Photos retrieved from: 1. https://commons.wikimedia.org/wiki/File:Coral_planting_and_reef_restoration_may_11_-2.jpg 2. https://commons.wikimedia.org/wiki/File:Cyanobacteria_Aggregation1.jpg 3. https://commons.wikimedia.org/wiki/File:Quagga_mussel_(8741974730).jpg 4. https://commons.wikimedia.org/wiki/File:Crustose_coralline_algae,_South_ East_Bay,_Three_Kings_Islands_PA121443.JPG

MyTempo: Musical Conducting Simulation and Its Role in Music Therapy Yael Romero ‘171, Brandon Cuadrado ‘171 1 Stony Brook University College of Engineering and Applied Sciences

Abstract MyTempo is a desktop application for Windows and MAC OS X machines designed to teach its users about the proper forms of conducting music. It incorporates a novel interface – a gesture-controlled armband known as Myo – to track user movements. Educators who wish to teach the elements of conducting and students who want to improve their conducting may utilize this novel application to do so. MyTempo also serves to connect musical learning with language development. Children with language impairment can integrate MyTempo’s music training into their therapies to improve their grammatical skills.

Introduction In recent years, developers have attempted to integrate technology into musical learning in an intuitive and helpful way. The purpose of this integration is to introduce software that can be adapted to formal training. In the area of musical conducting, the majority of students learn techniques through individual practice. Thus, they often lack feedback on how their conducting can be improved. Increasing this feedback has been the premise for previous implementations of musical conducting technology. For example, MAES:TRO is a different conducting practice room in which users can alter the tempo and dynamics of an automated musical piece. Prior knowledge of proper hand gestures, body orientation, and eye gaze directions are necessary to initiate these changes (1). The system then presents the user with auditory and visual feedback on his/her performance. Similarly, other musical conducting platforms aim to build a robust system for accurately teaching conducting and providing feedback, primarily focusing on helping student conductors. Unlike MAES:TRO, MyTempo serves as an introduction to conducting: highlighting the potential for learning music actively through interaction. In the past, many music teachers have been hesitant about shifting to technological means for education. However, recent developments in the field of interactive technology allow for real-time visual representation of

Figure 1 Schematic for the how MyTempo interacts with the Myo.

movement and sound. This visualization helps improve the technical components involved in most areas of musical training (2). Visual feedback, when employed correctly, positively reinforces and motivates children as they learn. This feedback, in the form of dynamic graphics, encourages children to become interested in a subject and set their own musical goals. In a group environment, the ability to witness another user’s progress can promote constructive competition. These two opposing incentives emphasize the role of visuals in collaborative versus individual settings (2). Additionally, visuals enhance young students’ attention when working towards an assigned goal. The feedback provided by MyTempo serves to track the user’s progress, allowing for self-improvement when used in both individual and competitive settings. Musical training has also been effective in improving language development. Prior research has demonstrated a strong positive correlation between rhythm perception and expressive grammatical skills in children with typical development (3). Further research is being conducted to test this correlation in children with language impairment, which is commonly linked to rhythm discrimination. MyTempo provides a variety of rhythms for the user to detect and comprehend, a feature useful for improving language competency through musical therapy. Materials & Methods Keyboard MyTempo was developed on Adobe Director utilizing Lingo code. Adobe Director is a multimedia authoring platform that allows users to create executable applications for desktops. The starting menu of the application was developed such that the user is able to choose the piece he/she would like to play. The user is then free to select any difficulty level for the piece. MyTempo was designed to feature a selection of eight musical works, ranging in difficulty based on various aspects of musical conducting. Works that are classified as easy include common time signatures and follow a consistent tempo throughout the piece. Medium-level pieces include common, yet more complex time signatures in which each beat is subdivided into smaller beats. Hard musical works include unique time signatures, more fluid rhythms, and a tempo that varies in different interpretations. The interface of each piece includes a conducting pattern, a visual representation of its time signature. Adobe Audition was used to place beats, or cue points, at precise moments of the musical work. Markers along the conducting pattern represent targets for the user to hit at the appropriate

Figure 2 (left) Myo armband positioned on developer Yael Romero’s forearm. The armband senses an individual’s arm movement as he or she conducts. (right) The Myo armband, shown with its packaging, collects gestural data and sends it to a computer via bluetooth when a participant utilizes MyTempo. beat. The code confirms that the user’s position corresponds with the target at the cue point. If achieved, ten points are awarded to the user, and the marker is enlarged as visual confirmation. The displayed score is a quantitative measure of the user’s progress in learning to conduct music. Levels were constructed such that the user’s main objective is to follow the conducting pattern accurately and pass through the beats at the correct times. Myo Armband MyTempo initially accepted input from a traditional mouse and keyboard. Once the application was fully functioning, Myo was introduced as the gestural component, simulating actual musical conducting. Myo is an armband, positioned on the user’s forearm, that utilizes built-in sensors to detect both movement and gestures. The acquired movement data is transferred to a computer via Bluetooth with an adapter connected through USB. Prior to usage, the user places the Myo armband on his/her forearm and waits for it to vibrate. The vibration indicates to the user that the armband has initialized calibration. At this point, the user is instructed to wave his/ her hand to the right to complete the process. This gesture was chosen because it is arbitrary compared to conducting movements and would not be misread during the simulation. Calibration is necessary each time the Myo armband is switched between users. The Myo armband controls the mouse via arm movements. By default, Myo makes this option available through a hidden toolbar. The user is not aware of this toolbar if he/she has not interacted with Myo before. Keyboard Mapper, a utility built into the Myo software, eliminates the need to access this toolbar. A clenched fist is mapped to toggle the mouse on or off. This allows the user to utilize his/her arm as the cursor, which provided a means to simulate conducting movements. Once the user takes control of the cursor, the calibration and setup processes are completed after the user controls the cursor. MyTempo was tested on the general public in two trials. The first, implemented at Stony Brook’s 2016 URECA Celebration, included roughly 40 individuals, and the second, at the Eastern Long Island Maker Faire, included roughly 60 individuals. Users ages 6 to 60 participated in both trials. The test subjects also ranged in their knowledge of music from limited to experienced. Results Participants who tested MyTempo at Stony Brook’s 2016 URECA Celebration provided data regarding MyTempo’s conducting simulation. The test subjects input varied depending on the individual’s demographic. Young users between the ages of six and thirteen used a computer mouse and keyboard to conduct, while users ages fourteen and older used the Myo

armband. Due to its large size, the Myo armband was unable to calibrate to the younger demographic. Users with limited knowledge of music prior to using MyTempo offered data in regards to the learning aspect of the program. These individuals experienced initial difficulty in grasping the basics of music conducting, despite receiving instructions at the onset of the simulation. However, these users were able to grasp the conducting patterns approximately four to eight measures into a musical work. Additionally, most of these participants progressed in musical conducting after roughly two or three attempts. Adult users with limited knowledge of music generally took between six and eight measures to adjust to the pattern. Most young users, however, were able to follow the musical conducting patterns after only four measures in a given piece. Users with formal musical experience provided data on the effectiveness of MyTempo in simulating conducting techniques. Those who fell under this demographic did not find issues with understanding the concepts of musical conducting. However, some individuals did experience difficulties adapting to the application’s controls. Discussion The data collected at the URECA Celebration and the Eastern Long Island Maker Faire provided insight for MyTempo’s role in the classroom. The Myo armband was unable to effectively calibrate to younger users. As seen at the Eastern Long Island Maker Faire, children are able to interact effectively with MyTempo through alternate input devices. Children using a Nintendo Wii remote, as opposed to a computer mouse, would be able to simulate conducting music with a baton. Added instructions prior to the Maker Faire helped children adapt to the conducting patterns more quickly. Future versions of MyTempo will include additional device functionality in order to broaden the demographics that can utilize the simulation. Users who were inexperienced provided data for determining how MyTempo can further develop in its educational aspects. Although an instruction screen provided testers with information to follow along with a musical piece, users often skipped past this screen regardless of musical experience. Users who had access to interactive guidance on the gameplay screen were able to grasp the basic elements of musical conducting earlier in a piece, relative to those who did not have access to interactive guidance on the gameplay screen. Though previous instruction screens were meant to guide inexperienced users, helpful information during play would further enhance the learning process. As work on MyTempo continues, the gameplay screen will continue to provide assistive steps and guidance for users who know less about conducting.

Figure 3 (top) Associate Dean of Students, Mr. Jeffrey Barnett, tests MyTempo as Associate Provost for Academic Success, Dr. Richard Gatteau, and developers, Brandon Cuadrado and Yael Romero, look on. Photo Credit: Professor Anthony Scarlatos. (left) MyTempo screen that allows you to interact with the program and conduct a given time signiture. Shown is 4/4 time. (right) The ending screen that shows you your score and allows you to either retry the piece of music or choose another piece. Participants with musical experience offered insight into accurately emulating the nuances of musical conducting. Field testers included music teachers, choral directors, and others who have conducted in real ensembles. These users conducted in a MyTempo setting in which the beats in a time signature were denoted by specific targets on the screen that must be hit at the appropriate time. This, however, caused experienced testers to be less immersed in the simulation. They observed that musical conducting does not typically concern itself with specific points on a plane. In conducting, a relative downward motion, for example, would denote the first beat in a measure. In MyTempo, however, there is a target towards the bottom of the conducting pattern that indicates the first beat. In order to fully immerse users with the conducting experience, this idea of relative positioning is essential for teaching conducting with more accuracy and better understanding. As MyTempo continues to develope, it will address this relative positioning issue in order to enhance the conducting simulation for people with varying musical experience. Many involved in the field testing saw potential in MyTempo for demographics not originally anticipated. Multiple users recognized the link between MyTempo’s interactive usability and physical rehabilitation. This relationship has precedence in motor learning research and its role in clinical practice. Additionally, in younger users’ experience with the software, friendly competition motivated them to learn and achieve scores that rivaled their peers’. This form of collaborative learning leads to further engagement and progress with MyTempo. Users with experience in education similarly found commonalities between MyTempo’s interactive learning

and assistive technology in the classroom. Students with cognitive and motor challenges can find treatment with musical therapy through engagement in musical techniques. MyTempo uses interactive technology that could play a role in strengthening this beneficial immersion in music. With further direction to becoming a more accurate and engaging interactive conducting simulator, MyTempo is finding new potential in music therapy as a field of study. Research and implementation continues to form MyTempo into a system that properly emulates true musical conducting. Music therapy’s place in clinical practice is ever evolving to include interactive technologies. Research involving MyTempo and music therapy patients is currently being conducted. The implementation of MyTempo will continue to be true to the real conducting experience and will further highlight References 1. E. Ivanova et al., MAES:TRO: a practice system to track, record, and observe for novice orchestral conductors. CHI ‘14 Extended Abstracts on Human Factors in Computing Systems, 203-208 (2014). doi: 10.1145/2559206.2580929. 2. L. Nijs et al., Interactive technologies in the instrumental music classroom: a longitudinal study with the Music Paint Machine. Computers and Education 73, 40-59 (2014). doi: 10.1016/j. compedu.2013.11.008http://dx.doi.org/10.1016/j.compedu.2013.11.008 3. R. Gordon et al., Does music training enhance literacy skills? A meta-analysis. Frontiers in Psychology 6, (2015). doi: 10.3389/fpsyg.2015.01777. Photos Retrieved from: Courtesy of Yael Romero ’17

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