YSM Issue 96.2
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Yale Scientific<br />
THE NATION’S OLDEST COLLEGE SCIENCE PUBLICATION • ESTABLISHED IN 1894<br />
MAY 2023<br />
VOL. 96 NO. 2 • $6.99<br />
FATAL<br />
ATTRACTION 22<br />
TRACKING CARBON’S<br />
UNDERWATER DIVE 12<br />
IT’S IN OUR BONES 14<br />
16<br />
ACNE-BIOTICS<br />
ANIMALS AGAINST<br />
19<br />
RISING TIDES
TABLE OF<br />
VOL. 96 ISSUE NO. 2<br />
COVER<br />
22<br />
A R T<br />
I C L E<br />
Fatal Attraction<br />
Cindy Mei<br />
Tsetse flies are responsible for spreading a deadly disease that leads to agricultural and medical<br />
devastation in Africa. The Carlson lab at Yale and their collaborators have identified a pheromone<br />
produced by the fly that may be able to attract and halt the activity of the flies, which holds great<br />
potential to control the tsetse fly population.<br />
12 Tracking Carbon's Underwater Dive<br />
Tori Sodeinde<br />
Many marine animals form calcium carbonate shells that deposit minerals onto the surface of the<br />
Earth, but billions of years ago, before these biotic carbonate sources evolved, what were the most<br />
important contributing sources to the precipitation of carbonate? New geological isotope data<br />
challenges previous ideas about the ancient history of the marine carbonate factory.<br />
14 It's in Our Bones<br />
Evelyn Jiang<br />
Researchers at Yale have uncovered a key molecular link between bone marrow aging and the<br />
development of atherosclerosis—which causes heart attacks, strokes, and other cardiovascular<br />
complications, which are collectively the leading cause of death worldwide. Their findings offer<br />
new hope for the treatment and prevention of the disease.<br />
16 Acne-Biotics<br />
Crystal Liu<br />
Yale structural biologists determined the structure of a promising acne-fighting antibiotic, sarecycline,<br />
in complex with the ribosome of C. acnes, the bacterium largely responsible for acne. Read about<br />
sarecycline’s mechanism, why it can be more effective than other antibiotics, and other discoveries<br />
about the C. acnes ribosome.<br />
19 Animals Against Rising Tides<br />
Abigail Jolteus<br />
Global warming is causing sea levels to rise rapidly, which imposes stress on coastal ecosystems. Researchers<br />
at the Yale School of Environment and the University of Florida have investigated the impact of mussels<br />
on salt marshes, which could help provide more insight into how to help mitigate the effects of sea level<br />
rise —one of the most urgent climate threats today.<br />
2 Yale Scientific Magazine May 2023 www.yalescientific.org
CONTENTS<br />
More articles online at www.yalescientific.org & https://medium.com/the-scope-yale-scientific-magazines-online-blog<br />
4<br />
6<br />
25<br />
34<br />
Q&A<br />
NEWS<br />
FEATURES<br />
SPECIALS<br />
What is the World's Most Efficient Form of Urination? • Victor Nguyen<br />
Who were the First Cowboys in the World? • Jamie Seu<br />
The Changing Language of Our Changing Climate • Pratiksha Bhattacharyya<br />
Saving Birds on Yale's Campus • Mia Gawith<br />
A New Approach Against an Old Foe • Johnny Yue<br />
Taking a Peek at Pandora's Cluster • Ignacio Ruiz-Sanchez<br />
Sink or Swim • Lea Papa<br />
Using Machine Learning to Produce Metallic Glass • Maya Khurana<br />
A Dynamic Duo Fighting Against Brain Cancer • Casey McGuire<br />
The Carbon Footprint of Care • Jessica Le<br />
Wooden Corkscrew Robots Plant Seeds • Madeleine Popofsky<br />
Your Unique Fingerprint • Elisa Howard<br />
The Impossible Star • Elizabeth Watson<br />
Cyborg Zebrafish • Nathan Mu<br />
How Ancient Humans Escaped the Ice Age • Matthew Blair<br />
Plant-Animal Hybrids • Samantha Liu<br />
Undergraduate Profile: Charnice Hoegnifioh (YC '24) • Emily Shang<br />
Alumni Profile: Amymarie Bartholomew (YC '13) • William Archacki<br />
Science in the Spotlight: Measure for Measure • Henry Chen<br />
Science in the Spotlight: the Darkness Manifesto • Faith Pena<br />
Counterpoint: Quantum Cryptography • Matthew Dobre<br />
Perimeter • Sophia Zhao<br />
www.yalescientific.org<br />
May 2023 Yale Scientific Magazine 3
WHO WERE THE<br />
FIRST COWBOYS IN<br />
THE WORLD?<br />
&<br />
WHAT IS THE WORLD'S<br />
MOST EFFICIENT<br />
FORM OF URINATION?<br />
By Victor Nguyen<br />
Has inspiration ever hit you while you were on the toilet? For<br />
scientists studying the potty period of the glassy-winged<br />
sharpshooter, a half-inch-long insect in the Cicadellidae<br />
family, a revelation between physics and biology was born. Known to be<br />
serious agricultural pests, sharpshooters relieve themselves by forming<br />
small droplets of urine at their anal styluses, which are appendages<br />
involved in excretion. Eventually, the droplets grow to a diameter of<br />
0.725 millimeters, and the anal styluses launches the particulates<br />
repeatedly, accelerating up to forty times the force of gravity.<br />
Sharpshooters developed this bathroom behavior due to their waterheavy<br />
diets. The leafhoppers feed on plant xylem sap, which has a small<br />
nutrient-to-liquid ratio. As a result, they drink up to three hundred<br />
times their body weight. A closer analysis of this phenomenon,<br />
published by researchers at Georgia Tech in Nature Communications,<br />
showed that sharpshooters developed this biological mechanism to<br />
conserve energy given their small size and energy output.<br />
The sharpshooter’s urinary facilities mark a notable discovery because<br />
they are the first observation of superpropulsion in a biological system,<br />
a phenomenon in which a projectile moves faster than the launcher<br />
that propelled it. Applications of the sharpshooter’s mechanisms have<br />
a future in electronics. Researchers investigating the sharpshooters<br />
foresee how the insect’s energy-efficient solution can be used to remove<br />
solvents in micro-manufacturing or to eliminate water from complex<br />
surfaces. This intersection of the physical and biological sciences sets<br />
a precedent for finding unorthodox answers. Wherever and whenever<br />
inspiration or the need to relieve strikes, innovation may soon follow. ■<br />
By Jamie Seu<br />
Stirrups. Leather boots. The Wild West. Cowboys have been<br />
a subject of fascination for centuries, appearing in every<br />
aspect of American pop culture from cliché Halloween<br />
costumes to Hollywood blockbusters. However, the modern<br />
perception of these equestrian cavaliers encapsulates only a<br />
minuscule piece of the long, intertwining history of humans<br />
and horses—a history that, according to recent archaeological<br />
findings, could date back over five thousand years.<br />
While evidence of equine domestication has been welldocumented<br />
throughout history, proof of ridership and determination<br />
of the practice’s exact origins have been difficult to establish. In a<br />
paper published in Science Advances, a team of researchers from<br />
Finland, Romania, Bulgaria, Hungary, and New York analyzed over<br />
two hundred skeletal remains to unravel these mysteries. They found<br />
the earliest bioanthropological evidence of horseback riding to date<br />
in the skeletons of five Yamnaya individuals, a people noted for their<br />
expansion across Eurasia during the Early Bronze Age in the third<br />
millennium BC. Each skeleton was analyzed according to six specific<br />
criteria indicative of “horsemanship syndrome.” The five skeletons<br />
displayed at least four of the six traits, including wear on the pelvis<br />
and femur, stress-induced vertebral degeneration, and alterations in<br />
certain bone shapes and sizes.<br />
The use of horses as a mode of transportation marked a dramatic<br />
transition in societal evolution, dictating patterns of migration and<br />
facilitating trade between previously isolated locations. So while the<br />
first cowboys were not quite the gun-toting, saloon-loving buckaroos<br />
we make them out to be, they—and their speedy, four-legged sidekicks<br />
—may have been some of the most influential figures in history. ■<br />
4 Yale Scientific Magazine May 2023 www.yalescientific.org
The Editor-in-Chief Speaks<br />
THROUGH THE LOOKING GLASS<br />
This summer, I had the immense privilege of interviewing Dr. Vivek Murthy,<br />
the 19th and 21st U.S. Surgeon General and an alumnus of the Yale School<br />
of Medicine. When asked about the role of science journalism in our society,<br />
Dr. Murthy told me, “There could not be a time in my life where I think we have<br />
needed science journalists more to be there for us explaining what people need to<br />
know in a world where we’re awash in misinformation.”<br />
Indeed, with the polarization of online forums and social media platforms,<br />
conspiracy theories are spreading like never before, while the public’s distrust in the<br />
notion of ‘experts’ has rapidly grown. How, then, can we bridge the chasm that has<br />
emerged between science and society?<br />
There is no simple or straightforward answer, but as Dr. Murthy emphasized,<br />
science journalism plays a pivotal role in connecting the two. While I would<br />
typically use this space to tell you about the articles in this issue, I found it would<br />
be fitting to re-examine the mission of the Yale Scientific itself. At its core, our<br />
work strives to highlight the relevance of recent innovations in our daily lives,<br />
spark scientific interest in youth, help communities make informed decisions, and<br />
build public trust in science. We aim to present scientific, medical, and engineering<br />
discoveries to a general audience—no matter their background—in an accessible<br />
and unbiased manner.<br />
Recently, we’ve had the privilege of poring through the archives from the <strong>YSM</strong><br />
offices in Welch Hall on Old Campus and in 305 Crown St. Flipping through the<br />
yellowing pages of our hand-bound volumes from the 19th century and learning<br />
about the history of the Yale School of Medicine, the Sheffield Scientific School,<br />
and the Yale Scientific Magazine itself has revealed that while a lot has changed,<br />
our central mission has remained steadfast. In fact, it has only been reaffirmed as<br />
science has become the center of attention in debates surrounding deeply divisive<br />
issues, ethical concerns, and public policy controversies. At <strong>YSM</strong>, we will continue<br />
to question the assumed, communicate the abstract, and weave distinctly human<br />
stories around technical scientific developments.<br />
I am honored and humbled to continue the Yale Scientific’s long legacy of<br />
science journalism alongside our incredible masthead, student contributors, and<br />
community partners. With you, our readers, let’s embark on the formidable quest<br />
to which we aspire at the Yale Scientific—to maintain objectivity without the loss of<br />
nuance, present technicality without the loss of perspective, and highlight science<br />
without the loss of humanity.<br />
About the Art<br />
Alex Dong, Editor-in-Chief<br />
Researchers have identified a<br />
pheromone that may influence the<br />
behavior of flies that spread disease<br />
in Africa. This cover illustration<br />
depicts two Tsetse flies with<br />
pheromones, represented as glowing<br />
particles, between them.<br />
Catherine Kwon, Cover Artist<br />
MASTHEAD<br />
May 2023 VOL. 96 NO. 2<br />
EDITORIAL BOARD<br />
Editor-in-Chief<br />
Managing Editors<br />
News Editor<br />
Features Editor<br />
Special Sections Editor<br />
Articles Editor<br />
Online Editors<br />
Copy Editors<br />
Scope Editors<br />
PRODUCTION & DESIGN<br />
Production Manager<br />
Layout Editors<br />
Art Editor<br />
Cover Artist<br />
Photography Editor<br />
BUSINESS<br />
Publisher<br />
Operations Managers<br />
Subscriptions Manager<br />
Outreach Manager<br />
OUTREACH<br />
Synapse Presidents<br />
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Synapse Outreach Coordinators<br />
Synapse Events Coordinator<br />
WEB<br />
Web Managers<br />
Head of Social Media Team<br />
Social Media Coordinators<br />
STAFF<br />
Sanya Abbasey<br />
Luna Aguilar<br />
Ricardo Ahumada<br />
William Archacki<br />
Dinesh Bojja<br />
Risha Chakraborty<br />
Kelly Chen<br />
Leah Dayan<br />
Steven Dong<br />
Chris Esneault<br />
Erin Foley<br />
Mia Gawith<br />
Simona Hausleitner<br />
Tamasen Hayward<br />
Katherine He<br />
Miriam Huerta<br />
Sofia Jacobson<br />
Jenna Kim<br />
Catherine Kwon<br />
Charlotte Leakey<br />
Ximena Levya Peralta<br />
Yurou Liu<br />
Samantha Liu<br />
Helena Lyng-Olsen<br />
Kaley Mafong<br />
Georgio Maroun<br />
Cindy Mei<br />
Lee Ngatia Muita<br />
Lea Papa<br />
Hiren Parekh<br />
Himani Pattisam<br />
Emily Poag<br />
Madeleine Popofsky<br />
Tony Potchernikov<br />
Zara Ranglin<br />
Yusuf Rasheed<br />
Alex Roseman<br />
Ilora Roy<br />
Ignacio Ruiz-Sanchez<br />
Noora Said<br />
Alex Dong<br />
Madison Houck<br />
Sophia Li<br />
Sophia Burick<br />
Anavi Uppal<br />
Hannah Han<br />
Kayla Yup<br />
Krishna Dasari<br />
Mia Gawith<br />
Will Archacki<br />
Matthew Blair<br />
Jamie Seu<br />
Samantha Liu<br />
Anya Razmi<br />
Malia Kuo<br />
Ann-Marie Abunyewa<br />
Sydney Scott<br />
Kara Tao<br />
Catherine Kwon<br />
Jenny Wong<br />
Lucas Loman<br />
Dinara Bolat<br />
Tori Sodeinde<br />
Georgio Maroun<br />
Yusuf Rasheed<br />
Hannah Barsouk<br />
Sofia Jacobson<br />
Jessica Le<br />
Kaley Mafong<br />
Lawrence Zhao<br />
Anjali Dhanekula<br />
Abigail Jolteus<br />
Emily Shang<br />
Elizabeth Watson<br />
Keya Bajaj<br />
Eunsoo Hyun<br />
Jamie Seu<br />
Kiera Suh<br />
Yamato Takabe<br />
Joey Tan<br />
Kara Tao<br />
Connie Tian<br />
Van Anh Tran<br />
Sheel Trivedi<br />
Robin Tsai<br />
Sherry Wang<br />
Elise Wilkins<br />
Aiden Wright<br />
Elizabeth Wu<br />
Nathan Wu<br />
Johnny Yue<br />
Iffat Zarif<br />
Hanwen Zhang<br />
Lawrence Zhao<br />
Celina Zhao<br />
Matthew Zoerb<br />
The Yale Scientific Magazine (<strong>YSM</strong>) is published four times a year by Yale<br />
Scientific Publications, Inc. Third class postage paid in New Haven, CT<br />
06520. Non-profit postage permit number 01106 paid for May 19, 1927<br />
under the act of August 1912. ISN:0091-287. We reserve the right to edit<br />
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Special thanks to Yale Science and Engineering Association.
NEWS<br />
Environmental Studies / Sustainability<br />
THE CHANGING<br />
LANGUAGE OF OUR<br />
CHANGING CLIMATE<br />
HOW WORD CHOICE AFFECTS<br />
CLIMATE CHANGE PERCEPTION<br />
BY PRATIKSHA BHATTACHARYYA<br />
FREE AS A BIRD<br />
SAVING BIRDS ON<br />
YALE’S CAMPUS<br />
BY MIA GAWITH<br />
IMAGE COURTESY OF FLICKR<br />
IMAGE COURTESY OF PXFUEL<br />
Researchers from the Yale Program on Climate Change<br />
Communication (YPCCC) are using a novel method to<br />
measure public opinion on climate change—studying how<br />
people react to different phrases used to describe emissions of<br />
carbon dioxide and methane. “Over the last few decades, there<br />
has been an increased interest in the terms ‘carbon emissions’<br />
and ‘greenhouse gasses,’” said Matthew Goldberg, an author of<br />
the study and associate research scientist at the YPCCC. The<br />
team asked study participants questions about climate change,<br />
which were identical between participants apart from the specific<br />
phrase used to describe carbon emissions—either “greenhouse<br />
gas emissions,” “carbon emissions,” or “carbon pollution.”<br />
Then, the team tracked differences in responses based on<br />
the phrases used. “We were interested in getting a holistic<br />
perspective of these terms,” Goldberg said. A key finding was<br />
that different reactions to these phrases revealed more about the<br />
general associations that participants held with each term. For<br />
example, the phrases “carbon pollution” and “carbon emissions”<br />
evoked more negative reactions and correlated with a greater<br />
understanding of the environmental harms of climate change<br />
than the phrase “greenhouse gas emissions.”<br />
These insights are crucial for policymakers and<br />
environmentalists who want to effectively communicate the<br />
urgency of addressing climate change. By paying attention to how<br />
people react to the different words used to describe these crucial<br />
issues, we can gain insight into how we can best emphasize the<br />
need for action. Experts can tailor messaging to better resonate<br />
with their audience by being cognizant of widely held associations<br />
with key scientific phrases in their communication. ■<br />
We all recognize the signs: the sickening thud on a<br />
window, the flutter of feathers hitting the ground,<br />
and the stomach-churning dread of peeking outside.<br />
As one of the top causes of bird deaths, bird-window collisions<br />
kill almost one billion birds per year. However, a new project<br />
at Yale University seeks to challenge this reality: the Yale Bird-<br />
Friendly Building Initiative, a collaboration between Yale Law<br />
School’s Law, Ethics and Animals Program, the Yale Peabody<br />
Museum of Natural History, the Yale Offices of Sustainability<br />
and Facilities, and the American Bird Conservancy.<br />
Launched in the spring of 2022, the Initiative aims to<br />
mitigate bird-window collisions and adopt bird-friendly<br />
designs on Yale’s campus and beyond. The Initiative records<br />
the location, time, and cause of all reported bird deaths,<br />
preserving the bodies for future research. “If I find a dead bird<br />
or someone else brings it to me, I want to preserve it because<br />
it gives them a second life in a way, because they become<br />
imminently useful,” said Kristoff Zyskowski, collections<br />
manager at the Yale Peabody Museum. The Initiative found<br />
that designs with highly reflective, transparent glass and<br />
nearby trees create a deadly optical illusion, luring birds to<br />
their death.<br />
“Our ultimate goal, in my view, is for Yale to be the gold<br />
standard of what it looks like to be a bird-friendly campus,”<br />
said Viveca Morris, executive director of the Law, Ethics, and<br />
Animals Program. Future developments involve retrofitting<br />
Yale buildings and implementing new design regulations on<br />
campus and beyond. By saving countless birds, this project<br />
sets its sights on a new vision of wildlife sustainability. ■<br />
6 Yale Scientific Magazine May 2023 www.yalescientific.org
Physiology / Astronomy<br />
NEWS<br />
A NEW APPROACH<br />
TO AN OLD FOE<br />
INNOVATION IN AORTIC<br />
ANEUR<strong>YSM</strong> SURGERY<br />
BY JOHNNY YUE<br />
TAKING A PEEK<br />
AT PANDORA’S<br />
CLUSTER<br />
LOOKING UP AT SPACE WITH<br />
THE JAMES WEBB SPACE<br />
TELESCOPE<br />
BY IGNACIO RUIZ-SANCHEZ<br />
IMAGE COURTESY OF NAIEM NASSIRI<br />
IMAGE COURTESY OF PIXABAY<br />
Thoracoabdominal aneurysms (TAAAs) occur when the<br />
aorta—the artery carrying blood from the heart to the rest of<br />
the body—balloons and weakens, which can lead to internal<br />
bleeding. Up until the past few years, TAAA surgery required<br />
highly invasive procedures with high chances of debilitating side<br />
effects, including paraplegia, or lower body paralysis.<br />
Endovascular Debranched Aortic Repair (EDAR), a new<br />
surgical technique performed at Yale, was first invented by<br />
Patrick Kelly of Sanford Health in South Dakota. Vascular<br />
surgeon Naiem Nassiri learned about the technology under<br />
Kelly’s guidance. “I built six prototypes on my breakfast table, and<br />
some took up to six hours to build,” Nassiri said. Together with<br />
Prashanth Vallabhajosyula, director of Yale’s Aortic Institute, the<br />
medical duo has implemented EDAR to treat the weakened aorta<br />
in a minimally-invasive manner. “TAAA surgery used to involve<br />
patients getting their entire chest, abdomen, and diaphragm split<br />
open, and the procedures were attached to high morbidity and<br />
mortality,” Vallabhajosyula said.<br />
But EDAR simply involves a stent that is inserted into the<br />
body through two small penetrations made in the groin using<br />
a needle. The stent, compressed in a tube, is delivered through<br />
blood vessels to the aorta. “We’ve done about sixteen cases and<br />
haven’t encountered any paraplegia cases (patient paralysis),”<br />
Vallabhajosyula said.<br />
EDAR shows tremendous promise to treat TAAAs. “What is<br />
wonderful about this platform is that at any time, you can decide to<br />
stop the operation and bring the patient back at a later date,” Nassiri<br />
said. “This minimizes the harm for the patient.” With the surgeons’<br />
expertise, TAAA patients now have new hope for better outcomes. ■<br />
The black background of outer space is studded with<br />
white bursts of light—some are sharp lines, while others<br />
are surrounded by a white hazy glow. In the foreground<br />
sits a star from our own galaxy, shining among a giant group<br />
of galaxies located four billion light years away from Earth:<br />
Pandora’s Cluster. After the launch of NASA’s James Webb<br />
Space Telescope, we’ve been fortunate to witness images from<br />
the distant corners of our universe, but these are the first,<br />
detailed images of Pandora itself.<br />
Scientists have been monitoring this galaxy cluster for over<br />
a decade, utilizing the most advanced technology available,<br />
mainly the Hubble Space Telescope, to get a glimpse of<br />
Pandora. However, none have achieved as much as the Webb<br />
Telescope to capture stellar pictures of the cluster, unveiling<br />
never-before-seen details. The new images were a tireless effort<br />
by the Ultradeep NIRSpec and NIRCam ObserVations before<br />
the Epoch of Reionization (UNCOVER) program, whose team<br />
of astronomers included several Yale scientists. The team<br />
captured thirty hours of data using Webb’s Near-Infrared<br />
Camera (NIRcam), with wavelengths capable of detecting the<br />
earliest stars in the process of formation and nearby galaxy<br />
populations. What’s even more exciting is that the telescope<br />
captured Pandora as a megacluster, meaning the combined<br />
mass of the four galaxies creates a powerful gravitational lens<br />
to expose other very large distant galaxies in the early Universe.<br />
While strikingly beautiful, these images are not just potential<br />
dorm-room posters or lock screens—this achievement could<br />
ultimately help us discover other hidden galaxies, further<br />
unraveling the mysteries of our Universe. ■<br />
www.yalescientific.org<br />
May 2023 Yale Scientific Magazine 7
FOCUS<br />
Ecology & Evolutionary Biology<br />
SINK OR<br />
SWIM<br />
Climate change<br />
impacting fish<br />
evolution<br />
BY LEA PAPA<br />
PHOTOGRAPHY COURTESY OF PAUL-ALEXANDER LEJAS<br />
When we think about global warming, many of us<br />
imagine melting ice caps or mass extinction events,<br />
undoing the work done by millions of years of<br />
evolution. But could climate change also threaten the forward<br />
progress of evolution? A recent study investigating the role of<br />
changes in water depth in the rapid speciation, or formation<br />
of new species, of fish in polar latitudes strongly suggests that<br />
yes, global warming can affect evolution’s progress. The study<br />
specifically points to the potential negative impact of warming<br />
waters on the ability of fish to rapidly speciate and, therefore,<br />
further their evolution.<br />
Published by Yale researchers Sarah Friedman and Martha Muñoz,<br />
the paper addresses the relationship between the remarkably rapid<br />
speciation rates of fish in polar latitudes and the ability of those<br />
fish species to move through the “depth gradient”—the intervals of<br />
water depth populated by different species in a body of water.<br />
Friedman was prompted to explore this idea after reading a<br />
paper that revealed that despite the higher biodiversity among<br />
fish in tropical regions, fish in the polar regions show faster rates<br />
of speciation. This discovery was both utterly surprising and<br />
intriguing to Friedman, who worked with Muñoz—an assistant<br />
professor of Ecology and Evolutionary Biology at Yale—to pursue<br />
research that could probe this finding. “When you look at the<br />
global scale, you’re going to see more species in the tropics,”<br />
Friedman said. “But what they found was that speciation rates are<br />
actually fastest towards the poles, which is [a] really interesting<br />
and counterintuitive result.”<br />
After intensive research into the prior literature on this<br />
phenomenon, Friedman hypothesized that shifting water depth<br />
may be the mechanism for rapid fish speciation in polar latitudes.<br />
Deep waters allow fish to move across the depth gradient, isolating<br />
fish groups from each other. This separation promotes more rapid<br />
speciation than in shallow, lower latitudes, where fish are more<br />
likely to interact and reproduce, thus slowing speciation.<br />
To investigate their hypothesis, the researchers used phylogeny,<br />
a common evolutionary biology technique that visualizes the<br />
ancestry and genetic relationships between different groups<br />
through the creation and analysis of phylogenetic trees. Because<br />
of limitations caused by the COVID-19 pandemic, Friedman<br />
and Muñoz analyzed existing data on fish evolution in this metaanalytic<br />
approach to reach their conclusions about biodiversity<br />
and speciation rates in polar-region fish.<br />
By the end of their extensive research, the team’s findings<br />
supported their hypothesis. “I think it was really reassuring to<br />
find what I hypothesized to be true,” Friedman said. “Those clades<br />
that are rapidly speciating are also those ones that are moving<br />
across the depth gradient pretty rapidly as well.” The relationship<br />
between rapid speciation rates and the ability to traverse a wider<br />
depth gradient explained the surprising speciation rates in the<br />
polar latitudes.<br />
Friedman and Muñoz also consider other findings from their<br />
study to be particularly intriguing, including one that suggested<br />
a pipeline of biodiversity exchange across latitudes, particularly<br />
from polar to tropical latitudes. “In fact, what we discovered is that<br />
speciation is faster at the poles, reflecting greater depth transitions,<br />
and that diversity is later transported to the tropics, so the polar<br />
regions are actually supplying species to the tropics,” Muñoz said.<br />
What could these findings mean for biodiversity and speciation<br />
in the era of extreme climate change and warming waters?<br />
According to Dr. Friedman, the effects will be disastrous. Because<br />
of the constant cold of the poles, there is little difference in water<br />
temperature throughout the depth gradient, meaning that the fish<br />
species through the gradient in the poles are similarly adapted<br />
for temperature, which contributes to how easily polar fish move<br />
between shallow and deep water. “As temperatures, and especially<br />
those surface temperatures, start warming up due to global<br />
warming, it’s going to increase the barriers to moving along that<br />
gradient,” Friedman said.<br />
Could global warming stall evolution? According to the<br />
researchers, this may be an extreme conclusion. Nevertheless,<br />
their research opens our eyes to a previously unknown harm of<br />
climate change, re-emphasizing the need for meaningful action. ■<br />
8 Yale Scientific Magazine May 2023 www.yalescientific.org
Computer Science<br />
FOCUS<br />
TEACHING<br />
MACHINE<br />
LEARNING<br />
PHOTOGRAPHY COURTESY OF PAUL-ALEXANDER LEJAS<br />
Machine learning is often thought of as the silver bullet<br />
for solving puzzles in science. With enough data in<br />
any given subject, a model with impressive predictive<br />
properties can be created to produce an abundance of helpful<br />
information. But sometimes, machine learning isn’t perfect. In their<br />
recent paper, Guannan Liu and his colleagues at the Schroers Lab<br />
at Yale explore the limitations of machine learning models and how<br />
we can incorporate human learning into new models to strengthen<br />
their predictive power.<br />
Liu, a Ph.D. candidate in Mechanical Engineering and Materials<br />
Science, has spent most of his time at Yale studying machine learning<br />
and its ability to solve complex materials science problems. The<br />
study of glass-forming ability is a canonical example of one of these<br />
problems. It is quantified by the minimum cooling rate required to<br />
prevent the formation of undesired crystalline structures, resulting<br />
in a glass with an amorphous atomic structure. Studying glassforming<br />
ability by performing hands-on experiments in the lab<br />
can be tedious, and this is where machine learning comes in to<br />
potentially accelerate the process. “Simply put, machine learning is<br />
trying to make inferences from data, and maybe predict something<br />
from [that] data,” Liu said.<br />
But there’s a catch—previous machine learning models designed<br />
to predict the glass-forming ability of metallic glasses have fallen<br />
short of providing useful insights on the subject. Metallic glasses<br />
are alloys, which are made by combining two or more elements.<br />
“You have to have meaningful features that describe the particular<br />
alloy after the mixing of elements,” Liu said. Liu contextualized this<br />
idea by offering an example. “For atomic size, it’s not the average<br />
[element size] that matters but the difference in size,” Liu said.<br />
“This allows space to be filled as much as possible, favorable for<br />
glass formation.” Models that lack such information and instead<br />
arbitrarily use statistical functions to construct features do not truly<br />
capture the essence of the alloy’s glass-forming ability.<br />
The other issue with the previous machine learning model for<br />
the glass-forming ability of alloys was its limited capacity to make<br />
new predictions. “[In] the previous model, usually the task was<br />
interpolation—the model was only predicting things that were<br />
www.yalescientific.org<br />
Improving a machine learning<br />
model to better predict<br />
metallic glass formation<br />
BY MAYA KHURANA<br />
similar to the dataset,” Liu said. In other words, the model could not<br />
make any predictions for new and unfamiliar data—it could only<br />
work inside the bounds of the dataset.<br />
To rectify these errors, Liu and his team worked on a new machine<br />
learning model: one that incorporated scientific insights from<br />
human learning. “Our model used extrapolation, [or] prediction<br />
into unknown space,” Liu said. This way, they were able to align their<br />
machine learning model with the reality that they have observed in<br />
the lab. Take, for instance, the property of atomic size again. Larger<br />
differences in size result in better glass-forming ability because the<br />
atoms are able to pack in more tightly. It is properties such as these<br />
that Liu and his team were better able to account for in their model,<br />
and their approach worked. “We found that our model was actually<br />
very successful in predicting glass-forming ability,” Liu said.<br />
Unlike its predecessors, this model was much better at<br />
extrapolation. “Our model can predict alloys that are more distinct<br />
from the training set,” Liu said. “We concluded that physical insights<br />
are really needed [to develop effective machine learning models].”<br />
This project is far from the end of Liu’s work with machine<br />
learning for materials science. He has three main goals moving<br />
forward. “The first is to use machine learning to test [our] current<br />
understanding of complex material science problems,” Liu said. It<br />
can be hard to quantify the efficacy of foundational rules within<br />
material science, so Liu plans to use machine learning to evaluate<br />
these guiding principles. Secondly, Liu strives to combine machine<br />
learning and high-throughput fabrication methods to discover<br />
new metallic glasses.<br />
Finally, Liu will investigate the contexts in which machine<br />
learning can be helpful. His goal is to determine what kinds of<br />
problems it can help solve and what circumstances limit its utility.<br />
“[We want to] have a viewpoint that can be meaningful for the<br />
community as to what machine learning is useful for [versus]<br />
situations where machine learning would be hard to use,” Liu said.<br />
This research will ensure that machine learning models are taking<br />
all possible human insights into account while making inferences<br />
from data. Clearly, machine learning can be an extremely valuable<br />
tool if it is wielded skillfully. ■<br />
May 2023 Yale Scientific Magazine 9
FOCUS<br />
Biomedical Engineering<br />
A DYNAMIC<br />
DUO<br />
Combining two<br />
technologies to fight<br />
brain cancer<br />
BY CASEY MCGUIRE<br />
PHOTOGRAPHY COURTESY OF YAZHE WANG<br />
It’s a diagnosis that strikes fear in the hearts of patients and their<br />
loved ones: glioblastoma, a type of brain cancer that is notoriously<br />
aggressive and difficult to treat. However, hope may be on the<br />
horizon, as researchers from Yale and the University of Connecticut<br />
(UConn) have developed a groundbreaking new therapeutic approach<br />
for those battling this devastating disease. The treatment loads tiny<br />
particles called nanoparticles, developed by Professor Mark Saltzman’s<br />
lab at Yale, with proteins that target the tumor cells, designed by<br />
Professor Raman Bahal and his team at UConn. Currently, the best<br />
treatment for glioblastoma is the removal of the bulk of the tumor<br />
during surgery, followed by radiation and chemotherapy. However, the<br />
median survival is only fifteen months. This new treatment combines<br />
two cutting-edge technologies, nanoparticles and peptide nucleic<br />
acids, to tackle this lethal disease and provide hope for future patients.<br />
Nanoparticles are particles that can infiltrate cells due to their small<br />
size. Saltzman’s lab has extensively researched nanoparticles as a vehicle<br />
to deliver drugs to specific areas of the human body. The polymerbased<br />
nanoparticle developed by his team can penetrate the brain<br />
and reach the tumor cells. Saltzman underlined the importance of the<br />
nanoparticles remaining at the tumor site and continuing to deliver<br />
the drug over time. “You can only administer the therapy after surgery<br />
directly into the brain and you cannot re-administer, but we want the<br />
therapy to last a long time,” Saltzman said. “We designed nanoparticles<br />
with certain properties to allow for this behavior.” The particles have<br />
an affinity for tumor cells due to their bioadhesive coating, and they<br />
will stick around to slowly release the drug inside the cells.<br />
The drugs encapsulated in the nanoparticles were designed<br />
by Bahal, who was a postdoctoral researcher and collaborator of<br />
Saltzman’s at Yale before moving to UConn. Bahal’s team developed<br />
peptide nucleic acids, or PNAs, to be loaded inside the nanoparticles.<br />
These proteins are synthetically constructed to be complementary<br />
to a certain sequence of microRNA, or short strands of RNA that<br />
regulate gene expression in cells. The tumor cells of glioblastomas<br />
overexpress certain microRNAs, leading to more tumor growth<br />
and decreased patient survival. Past studies suggest that two of<br />
these upregulated microRNAs, miR-10b and miR-21, are the most<br />
significant in glioblastomas. These microRNAs have been shown<br />
to exacerbate tumor growth and invasion, while decreasing the<br />
effectiveness of Temozolomide, the type of chemotherapy typically<br />
used for glioblastomas. The researchers loaded a mixture of the PNAs<br />
against miR-10b and miR-21 into the nanoparticles.<br />
After surgery, this treatment can be administered directly into<br />
the brain to target the remaining cancerous cells. Therefore, this<br />
treatment would be an addition to the current standard of care.<br />
During mouse trials, this therapy improved survival and also<br />
enhanced the efficacy of the chemotherapy. “The results are very<br />
promising, and I think there is an opportunity here,” Saltzman said.<br />
He described how the researchers are striving to move towards more<br />
extensive safety testing and eventually clinical trials.<br />
Glioblastomas account for just a fraction of cancer patients. In<br />
2022, brain and other nervous system cancers added up to 1.3<br />
percent of cancer cases in the United States, and 14.5 percent of<br />
these nervous system tumors were glioblastomas. Despite this<br />
seemingly low percentage, Saltzman has researched drug delivery<br />
systems for glioblastomas for around thirty-five years and defends<br />
its importance as a focus of research. “It’s rare, but not as rare as you<br />
would think,” Saltzman said. Even though his results were published<br />
in early February in Science Advances, he still receives one or two<br />
emails a day from people searching for new treatments for a family<br />
member suffering from a glioblastoma. Saltzman’s driving force for<br />
his glioblastoma research and this project is the hope it provides<br />
for patients. “I’ve become fascinated with this challenge and want<br />
to do something that really helps people,” Saltzman said. “Along the<br />
way, I have met a lot of individuals with glioblastoma. They are not<br />
alive anymore and that has had a huge impact on me. It feels more<br />
like a mission now than just an interesting project to work on.”<br />
Saltzman’s nanoparticles loaded with PNAs present a novel<br />
and precise approach to address the currently inadequate<br />
landscape of therapeutic options for glioblastoma. When<br />
integrated into the standard of care, this dynamic duo has the<br />
potential to improve survival rates, finally giving glioblastoma<br />
patients a fighting chance. ■<br />
10 Yale Scientific Magazine May 2023 www.yalescientific.org
Environmental Science<br />
FOCUS<br />
THE CARBON<br />
FOOTPRINT<br />
OF CARE<br />
The unexpected<br />
environmental impacts<br />
of prostate biopsies<br />
BY JESSICA LE<br />
IMAGE COURTESY OF WIKIMEDIA COMMONS<br />
When someone is planning to get a prostate biopsy—<br />
the main diagnostic test for prostate cancer—the<br />
environmental impact of their impending procedure<br />
is not usually at the forefront of their mind. However, a Yale-led<br />
study by Associate Professor of Urology Michael Leapman did just<br />
that: the team examined the environmental impacts of common<br />
screening methods like prostate magnetic resonance imaging<br />
(MRI) and prostate cancer procedures, estimating that a single<br />
transrectal prostate biopsy has the same CO 2 emissions as a roundtrip<br />
flight from New York to San Francisco.<br />
On a global scale, healthcare systems are a major source of<br />
pollution and constitute over four percent of global CO 2 emissions.<br />
Although the environmental impacts of medical procedures<br />
are not currently considered when making medical decisions,<br />
Leapman urges for a change in attitude within the medical industry<br />
to prioritize environmental stewardship that aligns with patient<br />
interest without compromising patient care. “Carbon impact comes<br />
into question when we have excessive medical care,” Leapman said.<br />
Unnecessary over-screening is a common occurrence, and<br />
invasive procedures such as prostate biopsies actually have the<br />
potential to harm certain patients. As early as fifty years old, men are<br />
advised to consider undergoing a biopsy screening to catch prostate<br />
cancer in its early stages. Overall, these procedures are shown to<br />
reduce death rates; however, for patients who are over seventy or<br />
have existing comorbidities, this invasive diagnostic procedure<br />
would risk unwarranted side effects, major hospitalization, or even<br />
death. This form of medical care is often considered low-value and<br />
may harm both the planet and the patient.<br />
“The story is more than just the carbon footprint of one<br />
procedure. It is also about making better healthcare decisions that<br />
equip patients and physicians with more reliable information for<br />
who might need what intervention,” Leapman said. Approximately<br />
one million prostate biopsies are performed per year in the United<br />
States alone, with more than half of the patients evaluated found to<br />
not have prostate cancer at all. His research found that performing<br />
one hundred thousand fewer biopsies would avoid over eight<br />
www.yalescientific.org<br />
million kilograms of CO 2 emission, the equivalent of burning 1.1<br />
million gallons of gasoline (larger procedures, such as surgeries,<br />
may easily account for more than ten times that amount).<br />
However, this issue addresses a broader problem facing healthcare<br />
management. Leapman noted that physicians are not proactive in<br />
considering the economic burden, much less the environmental<br />
burden, of expensive procedures. Introducing carbon footprint<br />
as a price to be considered when making important medical<br />
decisions should be implemented in a holistic conversation around<br />
when exactly to prescribe medical treatment. This ensures that the<br />
patient understands the broader benefits and risks of undergoing<br />
an expensive procedure, encouraging physicians and patients to be<br />
more considerate of both economic and environmental costs.<br />
Leapman emphasizes that global climate change directly<br />
influences public health. “Healthcare providers are not doing a<br />
good job if what we are doing hurts the community and our world,”<br />
Leapman said. However, the movement towards environmentally<br />
friendly healthcare is not easy and faces many barriers to<br />
progress. Leapman’s study found that energy expenditure is the<br />
largest contributor to the overall carbon footprint calculation<br />
(approximately forty percent). In general, hospitals require an<br />
immense amount of resources and energy. However, they work<br />
within a very thin financial margin for extra expenses, making<br />
it difficult for individual practitioners and hospitals to prioritize<br />
advocating for greener energy sources. “Federal regulation and<br />
oversight may need to come in if our overall goal is to improve<br />
public health,” Leapman said. “We need to make some hard<br />
decisions about the resources we allocate to ensure we are being<br />
good stewards of the environment.”<br />
Leapman hopes that generating more data to clearly illustrate the<br />
environmental impact of healthcare will help increase awareness<br />
and target areas of excessive medical care. By doing so, necessary<br />
modifications can be made to decrease superfluous resource<br />
use. Then, doctors can make better decisions when choosing<br />
appropriate patients to undergo certain procedures, in the interest<br />
of both the patient and the planet. ■<br />
May 2023 Yale Scientific Magazine 11
FOCUS<br />
Geochemistry<br />
TRACKING CARBON’S<br />
UNDERWATER<br />
DIVE<br />
ART BY LUNA AGUILAR<br />
Clearing up the history of the<br />
marine carbonate cycle<br />
BY TORI SODEINDE<br />
Carbon: it’s in the atmosphere, the<br />
oceans, the solid Earth, and even in us.<br />
This element is found all throughout<br />
Earth’s environment and exists in numerous<br />
chemical forms. One form of carbon, calcium<br />
carbonate (the major component of limestone<br />
and chalk), is the main form in which carbon<br />
in the ocean and atmosphere is returned<br />
to the earth. The precipitation pathways of<br />
carbonate minerals in the ocean are referred<br />
to as the marine carbonate factory and greatly<br />
influences abiotic and biotic geochemistry,<br />
including ocean acidity.<br />
Despite its important role in ocean<br />
chemistry, there has been little consensus<br />
on how the marine carbonate factory has<br />
changed throughout Earth’s history. It is<br />
challenging to<br />
find wellpreserved<br />
and reliable markers for its status<br />
over billions of years. However, Lidya Tarhan,<br />
an assistant professor of earth and planetary<br />
sciences, and Jiyuan Wang, an Agouron<br />
postdoctoral fellow in Tarhan’s research<br />
group, along with colleagues from Yale’s<br />
Department of Earth and Planetary Sciences,<br />
Northwestern University and University of<br />
Miami, recently developed a novel technique<br />
to trace the history of the marine carbonate<br />
factory. By measuring the ratios of different<br />
isotopes (atoms of the same element with<br />
different masses) of strontium within<br />
carbonate samples, they uncovered a more<br />
definitive history of carbonate precipitation<br />
and mineral saturation states from the ancient<br />
Precambrian to the recent Phanerozoic<br />
Eon, and published their findings in Nature.<br />
During the Precambrian, contrary to previous<br />
conjecture, a major proportion of carbonate<br />
was buried in the deep sea through abiotic<br />
processes, rather than in the shallow marine<br />
environment like reefs that dominate most of<br />
the Phanerozoic marine carbonate factory.<br />
The Marine Carbonate Cycle<br />
The marine carbonate factory is one piece<br />
of a bigger puzzle, the carbon cycle, which<br />
encompasses the cycling of carbon through<br />
nature. The carbon cycle can be divided into<br />
short-term and long-term cycles. The shortterm<br />
carbon cycle involves living organisms.<br />
Photosynthesizers, largely phytoplankton<br />
and algae, absorb carbon dioxide into their<br />
cells and use it to generate carbohydrates<br />
through photosynthesis. The carbohydrates<br />
can be broken down later to provide energy,<br />
releasing carbon dioxide back into the ocean<br />
and atmosphere.<br />
In the long-term carbon cycle, rain<br />
combines with atmospheric carbon dioxide<br />
to form carbonic acid, which falls to the earth<br />
and slowly dissolves bodies of rock. This<br />
releases ions, including calcium, that are then<br />
carried through rivers to the ocean, where they<br />
combine with dissolved carbonate ions to form<br />
calcium carbonate, a solid in water. This process<br />
is called carbonate precipitation and can occur<br />
abiotically (without living organisms).<br />
However, many marine organisms also use<br />
calcium and carbonate ions to build their<br />
shells. When they die, these shells and other<br />
sediments form rock, sequestering carbon<br />
within the ocean floor and the geologic<br />
record. Some bacteria can also facilitate<br />
precipitation of calcium carbonate in their<br />
surroundings—for instance, by taking up<br />
12 Yale Scientific Magazine May 2023 www.yalescientific.org
Geochemistry<br />
FOCUS<br />
carbon dioxide during photosynthesis.<br />
Regardless of the route, precipitation of<br />
dissolved carbonate into solid calcium<br />
carbonate incorporates other ions including<br />
strontium, an alkaline earth metal. This study<br />
exploited the incorporation of strontium into<br />
carbonate precipitates to gain insight into the<br />
history of the marine carbonate cycle.<br />
Strontium in the Marine Carbonate<br />
Factory's History<br />
The metal strontium has multiple stable<br />
isotopes, including strontium-88 and<br />
strontium-86. When carbonate precipitation<br />
occurs in the ocean, it incorporates trace<br />
amounts of strontium, but the two isotopes<br />
are incorporated at different ratios depending<br />
on environmental conditions. Strontium-88,<br />
the heavier isotope, is incorporated into<br />
carbonate minerals less often than the lighter<br />
strontium-86, but higher saturation of<br />
carbonates in the ocean leads to both faster<br />
precipitation and an even lower strontium-88<br />
to strontium-86 ratio (δ 88/86 Sr) in carbonates.<br />
The ratio of these strontium isotopes in<br />
carbonates, in particular, is a novel proxy<br />
for the history of the marine carbonate<br />
cycle because this signature is tied closely to<br />
precipitation rates, rather than—like many<br />
other isotope systems—seawater temperature<br />
or the type of carbonate mineral in which<br />
strontium is incorporated. Thus, strontium<br />
stable isotope ratios can serve as a marker<br />
for changes in the marine carbonate factory,<br />
specifically the rate of carbonate precipitation<br />
which, in turn, reflects marine carbonate<br />
saturation state at the time of precipitation.<br />
However, using stable isotope measurements<br />
has not previously been possible due to<br />
technical limitations. Luckily, with the<br />
resources of the Yale Metal Geochemistry<br />
Center, the researchers were able to develop<br />
a novel method using mass spectrometry to<br />
measure stable strontium isotope ratios with<br />
five-decimal place precision, according to<br />
Wang. “[Our work] opened the door toward<br />
using the stable strontium isotope proxy to<br />
reconstruct long-term records in Earth's<br />
history—and will, we hope, allow us and others<br />
to tackle new and exciting questions down the<br />
road,” Tarhan said.<br />
Unexpected Sources of Carbonate<br />
Precipitation<br />
While shallow regions of the ocean like<br />
reefs and carbonate platforms are commonly<br />
www.yalescientific.org<br />
thought of as hotspots for carbon deposition,<br />
which is true today, Tarhan and Wang found<br />
an unexpected phenomenon during the<br />
Precambrian, the interval preceding the<br />
explosion of organisms that created calcium<br />
carbonate shells around 540 million years<br />
ago. They found evidence of an unforeseen<br />
level of abiotic contribution to the marine<br />
carbonate cycle in deep ocean waters<br />
during this time. “A major part of carbonate<br />
was buried outside of the shallow marine<br />
environment during Earth’s early history,<br />
which is radically different than previously<br />
envisaged,” Wang said.<br />
When tracing the ratios of strontium<br />
isotopes in carbonate samples formed in<br />
shallow seafloor sediments, the researchers<br />
found a marked decrease in δ 88/86 Sr<br />
values during the transition between the<br />
Precambrian era and the Phanerozoic era (the<br />
interval in which biomineralizing animals<br />
caused skeletal carbonates to become a large<br />
contributor to the marine carbonate factory).<br />
This decrease implies slower precipitation<br />
and a lower carbonate saturation state in<br />
Phanerozoic relative to Precambrian oceans,<br />
which is consistent with the increase in<br />
precipitation due to calcifying animals in the<br />
Phanerozoic period.<br />
Additionally, the Precambrian δ 88/86 Sr<br />
record also suggests the unexpected presence<br />
of a large, non-skeletal carbonate sink within<br />
the Precambrian deep ocean—one formed<br />
as a result of the activities of bacteria living<br />
in seafloor sediments devoid of oxygen. This<br />
condition was likely characteristic of much<br />
of the Precambrian deep seafloor, leading to<br />
carbonate precipitation in the spaces between<br />
grains of previously deposited sediment.<br />
It is difficult to directly confirm the ancient<br />
history of the deep oceans, as the constant<br />
shifting of Earth’s tectonic plates leads to<br />
subduction, plates layering over each other on<br />
the deep seafloor, which would have contained<br />
this missing piece of the Precambrian<br />
ABOUT THE AUTHOR<br />
carbonate record. “The deep oceans have been<br />
something of a 'black box' for much of Earth's<br />
history, due to the continual loss of deep-sea<br />
sediments with seafloor subduction,” Tarhan<br />
said. However, this study has unveiled an<br />
aspect of this murky history. “The deep sea,<br />
among other muddy stretches of the ancient<br />
seafloor, may have been an important locus of<br />
carbonate sediment accumulation prior to the<br />
emergence of any carbonate-biomineralizing<br />
organisms, and this was the baseline state<br />
until biomineralizing animals evolved in the<br />
shallow oceans approximately 540 million<br />
years ago,” Tarhan said.<br />
Looking into the Future<br />
This new research challenges past<br />
assumptions about the main players in the<br />
marine carbonate factory and helps fill in the<br />
history of oceanic geochemistry prior to the<br />
evolution of marine calcifying animals. This<br />
research could also be used to predict the<br />
future. As humans continue to pump carbon<br />
dioxide into the atmosphere, the increased<br />
emissions alter the natural carbon cycle.<br />
While this study focused on Earth’s ancient<br />
history, the mechanisms underlying the<br />
carbon cycle remain the same, so clarifying<br />
the mechanism of past changes can help us<br />
extrapolate how human actions may now<br />
affect the carbon cycle.<br />
Tarhan’s lab is currently trying to<br />
quantify the behavior of strontium isotopes<br />
as it relates to changing seawater carbonate<br />
chemistry under ongoing climate change.<br />
“The discoveries in this study enable us<br />
to better understand how carbon cycled<br />
among Earth’s different layers and how<br />
Earth maintained its habitability under<br />
different levels of CO 2 ,” Wang said. “This<br />
is crucial information that can be used to<br />
perceive and predict the behaviors of our<br />
Earth and oceans [during] contemporary<br />
climate change.” ■<br />
TORI SODEINDE<br />
TORI SODEINDE is a sophomore MCDB major in Ezra Stiles College. In addition to writing for <strong>YSM</strong>, she<br />
is involved in telomere biology research, Danceworks, and the Downtown Evening Soup Kitchen.<br />
THE AUTHOR WOULD LIKE TO THANK Dr. Lidya Tarhan and Dr. Jiuyuan Wang for their time and<br />
enthusiasm about their research.<br />
REFERENCES:<br />
Wang, J., Tarhan, L.G., Jacobson, A.D. et al. The evolution of the marine carbonate factory. Nature 615,<br />
265–269 (2023). https://doi.org/10.1038/s41586-022-05654-5<br />
May 2023 Yale Scientific Magazine 13
FOCUS<br />
Medicine<br />
IT'S IN OUR<br />
BON<br />
E S<br />
THE LINK BETWEEN AGING<br />
AND ATHEROSCLEROSIS<br />
BY EVELYN JIANG | ART BY GIA GABRAL<br />
They lurk in your arteries, plaques that<br />
build up like hidden time bombs.<br />
These tiny fatty deposits can slowly yet<br />
steadily narrow your blood vessels, causing<br />
potentially life-threatening complications.<br />
Atherosclerosis, as it’s medically known,<br />
is a complex and often silent disease.<br />
Despite its lack of obvious warning<br />
signs, atherosclerosis is the leading<br />
cause of heart attacks, strokes, and other<br />
cardiovascular complications, which are<br />
collectively the leading cause of death<br />
worldwide. The deadly disease has earned<br />
itself the nickname the ‘silent killer’ and its<br />
prevalence has made it a central focus in<br />
cardiovascular research.<br />
Aging is the biggest risk factor for<br />
developing atherosclerosis, but the<br />
reasons for this observation have been<br />
a longstanding mystery for scientists. A<br />
team of researchers in the Greif Lab at<br />
the Yale School of Medicine has recently<br />
uncovered a crucial link between bone<br />
marrow aging and atherosclerosis that may<br />
offer part of the answer. By examining the<br />
role of bone marrow cells in the clonality<br />
of smooth muscle cells, the researchers<br />
pinpointed key molecular mechanisms<br />
that contribute to atherosclerosis.<br />
Born From Bone Marrow<br />
Smooth muscle is a type of muscle found<br />
in the walls of many organs and tissues in the<br />
body. It is called ‘smooth’ because smooth<br />
muscle cells (SMCs) lack the striations or<br />
visible bands characteristic of skeletal and<br />
cardiac muscle cells. SMCs have a spindleshaped<br />
appearance and are not under<br />
voluntary control like skeletal muscle<br />
cells. Instead, they are controlled by the<br />
autonomic nervous system and hormones.<br />
SMCs are responsible for maintaining the<br />
structural integrity of the arterial wall, but<br />
research has shown that only a select few<br />
SMCs also play a significant role in the<br />
development of atherosclerosis.<br />
When a plaque begins to form,<br />
macrophages—a type of white blood cell—<br />
are the first to arrive on the scene. They engulf<br />
oxidized low-density lipoprotein and form<br />
foam cells that, over time, accumulate to form<br />
fatty streaks and eventually develop into fullfledged<br />
plaques. Macrophages also release<br />
pro-inflammatory cytokines, chemicals that<br />
attract more immune cells, that contribute<br />
to plaque growth. Later on, rare SMCs arrive<br />
and initially attach themselves to the surface<br />
or cap of the plaque, proliferate robustly, and<br />
migrate to cover this fibrous cap. Some of the<br />
SMCs then dive into the core of the plaque.<br />
The cap stabilizes the plaque, protecting it<br />
from rupturing; if the cap becomes weak and<br />
ruptures, the contents of the plaque core are<br />
exposed to the bloodstream, triggering the<br />
formation of a clot. “When a clot blocks the<br />
artery, then blood can’t get beyond it, and the<br />
tissue that’s beyond it doesn’t get oxygen,”<br />
said Daniel Greif, professor of cardiology at<br />
the Yale School of Medicine and principal<br />
investigator. “That’s what causes the vast<br />
majority of heart attacks and strokes.”<br />
Even though up to seventy percent of cells<br />
in advanced plaques originate from SMCs,<br />
they originate from only one or a couple<br />
of SMCs that enter the plaque. In younger<br />
mice that are prone to atherosclerosis, the<br />
SMCs that contribute to plaque formation<br />
are clonally related, or monoclonal, meaning<br />
they originate from a single cell that entered<br />
the plaque. However, with aging, the number<br />
of monoclonal plaques decreases, and<br />
there is an increase in polyclonal plaques,<br />
where multiple SMCs contribute to plaque<br />
formation. Polyclonality creates a more<br />
genetically diverse and perhaps unstable<br />
population of cells that can lead to aggressive<br />
plaque formation, thereby increasing both<br />
the size of the plaque and the risk of rupture.<br />
How Does Age Impact Clonality?<br />
To study the connection between SMC<br />
clonality and aging, the research team<br />
14 Yale Scientific Magazine May 2023 www.yalescientific.org
Medicine<br />
FOCUS<br />
PHOTOGRAPH COURTESY OF THOMAS R. SHARKEY.<br />
Atherosclerosis is a disease in which plaque builds up inside the arteries, leading to a narrowing and hardening<br />
of the arteries, which can restrict blood flow.<br />
compared atherosclerotic plaques of aged<br />
and young mice. The mice carried the<br />
ROSA26R-Rainbow (Rb) Cre reporter,<br />
which is used to label cells with different<br />
fluorescent colors, allowing the researchers<br />
to track the clonal expansion of cells.<br />
Sections of aortas from the mice were<br />
stained and imaged for Rb colors, and<br />
analysis revealed that aged mice had larger<br />
plaques with increased SMC polyclonality<br />
and lipid content, implying an increased<br />
risk of plaque rupture.<br />
The researchers then transplanted bone<br />
marrow from aged mice into young mice<br />
genetically engineered to be prone to<br />
atherosclerosis to see if aged bone marrow<br />
was sufficient to induce polyclonality.<br />
They found that the mice that received<br />
the aged bone marrow transplant<br />
developed greater plaque buildup in their<br />
arteries and that their plaques exhibited<br />
increased SMC polyclonality. They also<br />
found that when liquid from cultures of<br />
macrophages of aged mice was incubated<br />
with aortic SMCs from young mice,<br />
SMC proliferation increased by about<br />
threefold, compared to incubation with<br />
the liquid from macrophage cultures of<br />
young mice. These results suggest that<br />
the age of the bone marrow, specifically<br />
the age of macrophages, is a key factor in<br />
determining the recruitment and clonality<br />
of SMC-derived plaque cells.<br />
The Molecular Mechanisms<br />
The researchers next sought to explain<br />
the molecular mechanisms underlying<br />
aging’s observed effect on how SMCs were<br />
recruited and expanded in the plaque. To do<br />
so, they isolated monocytes—precursors to<br />
macrophages—from a blood draw of young<br />
and aged humans and from the bone marrow<br />
of young and aged mice, then performed<br />
RNA and protein analysis on them. They<br />
found that a gene called integrin β3—which<br />
is essential for blood clot formation—<br />
was downregulated in aged monocytes.<br />
Decreased integrin β3 levels in mice were<br />
found to contribute to atherosclerosis.<br />
Single-cell RNA sequencing of bone<br />
marrow cells from mice with or without<br />
integrin β3 revealed that the absence of<br />
ABOUT THE AUTHOR<br />
integrin β3 leads to the upregulation of<br />
pro-inflammatory tumor necrosis factor α<br />
(TNFα) signaling pathways, and inhibition<br />
of TNFα led to a reduction of over fifty<br />
percent of SMC-derived plaque cells. It<br />
also promoted monoclonality, suggesting<br />
that integrin β3 deficiency promotes<br />
atherosclerotic plaque development by<br />
inducing inflammation through the TNFα<br />
signaling pathway. This inflammation<br />
further damages the artery walls, triggering<br />
the recruitment of more macrophages to<br />
the site and therefore the formation of more<br />
fatty streaks. Inflammatory molecules can<br />
also stimulate the proliferation of SMCs<br />
and weaken fibrous caps of plaques, making<br />
them more likely to burst.<br />
The researchers also showed that<br />
overexpression of integrin β3 in the bone<br />
marrow of aged mice led to predominantly<br />
monoclonal SMC populations and reduced<br />
the amount of plaque buildup within<br />
arteries. By increasing the levels of integrin<br />
β3, the researchers were able to prevent<br />
the recruitment and expansion of multiple<br />
SMC progenitors into the plaque, resulting<br />
in a reduced risk of plaque rupture.<br />
The study was led by Inamul Kabir, an<br />
associate research scientist in the Greif Lab.<br />
"It is gratifying to uncover the molecular<br />
mechanism of atherosclerotic disease<br />
progression at the cellular level during aging,<br />
thus informing potential novel therapy,”<br />
Kabir said. The team’s research revealed<br />
the previously unknown mechanisms<br />
of how aged macrophages induce SMC<br />
polyclonality and the development of fatty<br />
plaques in the arteries. This breakthrough<br />
marks the start of a long journey toward<br />
effective treatments for atherosclerosis.<br />
Nonetheless, these new findings represent a<br />
notable milestone in our understanding of<br />
the ‘silent killer.’ ■<br />
EVELYN JIANG<br />
EVELYN JIANG is a first-year in Morse College interested in studying neuroscience. In addition<br />
to writing for the <strong>YSM</strong>, she works at Yale’s Alzheimer’s Disease Research Unit and plays with<br />
proteins at the Koleske Lab.<br />
THE AUTHOR WOULD LIKE TO THANK Daniel Greif and Inamul Kabir for their time and<br />
enthusiasm in sharing their research.<br />
REFERENCES:<br />
Kabir, I., Zhang, X., Dave, J.M. et al. The age of bone marrow dictates the clonality of smooth<br />
muscle-derived cells in atherosclerotic plaques. Nat Aging 3, 64–81 (2023). https://doi.<br />
org/10.1038/s43587-022-00342-5<br />
www.yalescientific.org<br />
May 2023 Yale Scientific Magazine 15
FOCUS<br />
Dermatology<br />
ACNE-BIOTICS<br />
Demystifying a promising<br />
acne-fighting antibiotic<br />
BY CRYSTAL LIU<br />
ART BY HANNAH HAN<br />
16 Yale Scientific Magazine May 2023 www.yalescientific.org
Dermatology<br />
FOCUS<br />
Bumps, whiteheads, rashes, scars: acne<br />
vulgaris is the most prevalent skin<br />
disease in the world, affecting the<br />
physical and mental health of 9.4 percent of<br />
the global population. This figure includes<br />
a whopping eighty-five percent of people<br />
between twelve and twenty-four years old.<br />
Cutibacterium acnes is the major cause<br />
of acne. It is a Gram-positive bacterium,<br />
meaning it has a thicker cell wall and causes<br />
different infections than Gram-negative<br />
bacteria. C. acnes coexists with healthy skin<br />
follicles and pores, but certain strains lead<br />
to acne and other complications, such as<br />
eye inflammation after tissue implantation.<br />
To treat these infections, dermatologists<br />
often prescribe a class of antibiotics called<br />
“tetracycline,” which include doxycycline,<br />
minocycline, and sarecycline.<br />
Tetracycline-class antibiotics are a group<br />
of medications used in the treatment of<br />
bacterial infectious diseases. They target<br />
the ribosome, an organelle that translates<br />
genetic information from RNA sequences<br />
into amino acid chains, which then fold into<br />
proteins. Tetracycline is a naturally-occurring<br />
antibiotic isolated from actinomycetes, a<br />
soil bacteria, and was approved by the FDA<br />
for medical use in 1954. Doxycycline and<br />
minocycline, termed second-generation<br />
tetracyclines, were approved in 1967<br />
and 1971, respectively, thanks to their<br />
improved stability and pharmacological<br />
efficacy. Almost half a century later, in<br />
2018, sarecycline was introduced as a thirdgeneration<br />
tetracycline-class antibiotic.<br />
While doxycycline and minocycline kill<br />
all types of bacteria—meaning they are<br />
broad-spectrum antibiotics—sarecycline has<br />
narrow-spectrum activity against only certain<br />
Gram-positive bacteria, including C. acnes.<br />
Christopher Bunick, associate professor<br />
of dermatology at the Yale School of<br />
Medicine, noticed the importance of this<br />
novel antibiotic and decided to look into<br />
its molecular mechanism. “Because of our<br />
expertise in protein synthesis, ribosome<br />
structure, and dermatology, we couldn’t<br />
resist taking on this project,” said Ivan<br />
Lomakin, an associate research scientist in<br />
the Bunick lab. Lomakin, Bunick, and their<br />
collaborators analyzed how sarecycline<br />
interacts with the C. acnes ribosome using<br />
cryogenic electron microscopy (cryo-EM),<br />
and published the results in Nucleic Acids<br />
Research. They discovered that sarecycline<br />
binds to the C. acnes ribosome at two<br />
different sites, which had not been observed<br />
in structures with other tetracyclines or<br />
model bacteria. They also discovered two<br />
novel ribosomal proteins and demonstrated<br />
their antimicrobial properties independent<br />
of the ribosomal complex. This study<br />
ultimately confirmed that sarecycline may<br />
be a more effective treatment option for C.<br />
acnes infections.<br />
Why Bind To Ribosomes?<br />
Since protein synthesis is an<br />
indispensable part of life, many antibiotics<br />
inhibit the activity of bacterial ribosomes,<br />
and sarecycline is no exception. As a<br />
complex—an assembly of multiple subunits<br />
that carry out a function together—the<br />
ribosome is made of ribosomal RNA<br />
(rRNA) associated with certain ribosomal<br />
proteins. Translation, the process it<br />
catalyzes, involves messenger RNAs<br />
(mRNAs) and transfer RNAs (tRNAs). The<br />
mRNA contains information ‘copied’ from<br />
the DNA that the ribosome must ‘read and<br />
translate.’ The tRNA contains nucleotides<br />
that recognize specific, three-base long<br />
mRNA sequences and the amino acid that<br />
corresponds to this sequence. The ribosome<br />
consists of large and small subunits, which<br />
are responsible for different steps of the<br />
process. The small subunit binds to the<br />
mRNA strand and identifies the correct<br />
tRNA molecule for every three bases within<br />
the decoding center. The large subunit then<br />
catalyzes the addition of the new amino<br />
acid to the growing polypeptide<br />
(protein) chain, which exits<br />
the ribosome through a<br />
structure called the nascent<br />
peptide exit tunnel (NPET).<br />
This process is how cells<br />
make proteins.<br />
Structural biologists have<br />
characterized the binding<br />
mechanisms of many antibiotics<br />
with ribosomes of model<br />
bacteria like E. coli and Thermus<br />
thermophilus. For first- and<br />
second-generation tetracyclines,<br />
all existent structures suggest that<br />
they bind to the decoding center<br />
of the small ribosomal subunit,<br />
inhibiting mRNA-tRNA interactions<br />
and slowing protein synthesis. The<br />
interaction patterns that Lomakin and<br />
colleagues characterized with cryo-EM<br />
agree with models of other tetracyclines.<br />
They show that the stacking of three<br />
hydrophobic layers stabilizes the binding of<br />
sarecycline in the decoding center of the C.<br />
acnes ribosome and inhibits tRNA arrival.<br />
Besides the canonical binding site,<br />
researchers were surprised to discover that<br />
sarecycline has a second binding site (SBS)<br />
on the C. acnes large ribosomal subunit,<br />
in the NPET. Here, sarecycline blocks<br />
the NPET and is thought to suppress the<br />
growth of the peptide chain. This binding<br />
site is specific to the C. acnes ribosome,<br />
as X-ray crystallography of sarecycline in<br />
complex with the Thermus thermophilus<br />
ribosome—also performed by the Bunick<br />
Lab—showed only the canonical binding<br />
site. Based on indirect experiments,<br />
researchers speculated that sarecycline<br />
could probably bind to both sites with<br />
similar affinities, and the sarecycline<br />
molecule in the SBS may assist with<br />
function in the canonical binding site.<br />
The paper compared this binding<br />
interaction with an antibiotic from<br />
another structural family, tetracenomycin<br />
X, which was recently shown to bind to<br />
the E. coli ribosome at a similar site. The<br />
team postulated that certain uridine bases<br />
were important in this interaction, and<br />
mutations from uridine to another base,<br />
cytosine, would confer resistance. However,<br />
Lomakin is not too worried about bacteria<br />
gaining sarecycline resistance, compared<br />
to other tetracyclines. “For sarecycline,<br />
we have an additional site on the large<br />
ribosomal subunit, encoded<br />
by a different gene than<br />
the small ribosomal<br />
subunit. The probability<br />
of simultaneously getting<br />
mutations on both of them<br />
is the multiplication<br />
of getting mutations<br />
on each, so it is very<br />
low,” Lomakin said.<br />
www.yalescientific.org<br />
May 2023 Yale Scientific Magazine 17
FOCUS<br />
Dermatology<br />
Potential Antimicrobial Properties<br />
Using cryo-EM, the researchers<br />
managed to capture the first highresolution<br />
structure of the C. acnes<br />
ribosome. They also examined the<br />
ribosomal proteins attached to the<br />
ribosomal RNA and explored how the C.<br />
acnes ribosome’s catalytic mechanisms<br />
could differ from other known bacterial<br />
models. This knowledge would help<br />
inform the future design of antibiotics<br />
against C. acnes.<br />
But of particular interest to the team<br />
were the bacterial small ribosomal subunit<br />
protein 22 (bS22) and the bacterial large<br />
ribosomal subunit protein 37 (bL37).<br />
These proteins are normally part of the<br />
ribosome and help synthesize proteins,<br />
but independent of the complex, they have<br />
displayed antimicrobial properties. C.<br />
acnes exists in normal skin, so researchers<br />
wonder if it helps defend the skin against<br />
other pathogenic bacteria. “From a<br />
dermatology perspective, we know C. acnes<br />
lives in our follicles and pilosebaceous units<br />
as a commensal organism—only certain<br />
strains of it are pathogenic for acne. We<br />
are trying to probe whether or not C. acnes<br />
has a natural defense mechanism against<br />
Staphylococcus aureus, which is a major<br />
pathogenic skin organism,” Bunick said.<br />
They discovered that the bS22 could inhibit<br />
the growth of E. coli and S. aureus while the<br />
bL37 only affected S. aureus but not E. coli.<br />
The next step down the antimicrobial<br />
properties path was to understand whether<br />
these proteins were present independent<br />
of the ribosome. Usually, ribosomal<br />
proteins form a complex with ribosomal<br />
RNAs to catalyze protein synthesis, but<br />
additional functions outside of ribosomes<br />
are possible. Bunick proposes that C. acnes<br />
may either secrete these peptides directly<br />
or release them when they die and lose<br />
their membranes.<br />
Sarecycline: The Better Acne-Biotic?<br />
Sarecycline was introduced in 2018 as a<br />
drug with higher specificity and fewer side<br />
effects than minocycline and doxycycline.<br />
However, primarily due to pricing issues,<br />
it only has about six percent of the<br />
prescription market for oral tetracycline<br />
in dermatology. To Bunick, sarecycline<br />
deserves more recognition. “At least to my<br />
knowledge, it is the only FDA-approved<br />
PHOTOGRAPHY BY EMILY POAG<br />
Dr. Christopher Bunick (left) and Dr. Ivan Lomakin (right) discussing a model of the ribosome.<br />
drug that targets two active centers of the<br />
ribosomes currently,” he said.<br />
The human gastrointestinal tract<br />
contains many beneficial Gram-negative<br />
bacteria. Since sarecycline is more specific<br />
to certain Gram-positive bacteria and<br />
spares Gram-negative bacteria, it causes<br />
fewer side effects in the gastrointestinal tract<br />
while effectively targeting Gram-positive<br />
C. acnes. Doxycycline is photosensitive,<br />
so certain users may experience rashes,<br />
itching, or severe sunburn, while<br />
sarecycline is not. Sarecycline is also<br />
less hydrophobic, meaning a decreased<br />
possibility of diffusing through the bloodbrain<br />
barrier and causing dizziness, vertigo,<br />
or tubular disturbance.<br />
The Bunick lab partners with Almirall, the<br />
pharmaceutical company that licenses and<br />
ABOUT THE AUTHOR<br />
sells sarecycline in the United States. “Our<br />
laboratory [work] has been predominantly<br />
keratins, intermediate filaments, and the<br />
skin barrier for over a decade. But [learning<br />
about sarecycline] presented a unique<br />
opportunity as an entryway into a new area<br />
of research understanding the molecular<br />
mechanisms of dermatology drugs.<br />
Sometimes the science leads you to where<br />
you need to be,” Bunick said. He does<br />
not rule out the possibility of developing<br />
a fourth-generation tetracycline. This<br />
paper was the first to publish a C. acnes<br />
ribosomal structure. Given the new<br />
information about multiple active sites, it is<br />
possible to further optimize the structure<br />
of the antibiotic to achieve more precise<br />
treatment of the infection behind your<br />
bumps and whiteheads. ■<br />
CRYSTAL LIU<br />
CRYSTAL LIU is a sophomore at Pierson College majoring in molecular, cellular and developmental<br />
biology. Besides writing for <strong>YSM</strong>, she is involved in the Irish Lab, Chinese Undergraduate Students<br />
at Yale, and Club Jump Rope. You can also find her trying out new restaurants and boba, playing<br />
IM volleyball, and listening to a lot of Mandopop and Cantopop songs.<br />
THE AUTHOR WOULD LIKE TO THANK Christopher Bunick and Ivan Lomakin for for their time<br />
and enthusiasm about their research.<br />
FURTHER READING:<br />
Lomakin, I. B., Devarkar, S. C., Patel, S., Grada, A., & Bunick, C. G. (2023). Sarecycline inhibits<br />
protein translation in Cutibacterium acnes 70S ribosome using a two-site mechanism. Nucleic<br />
Acids Research. https://doi.org/10.1093/nar/gkad103<br />
Batool, Z., Lomakin, I. B., Polikanov, Y. S., & Bunick, C. G. (2020). Sarecycline interferes with tRNA<br />
accommodation and tethers mRNA to the 70s ribosome. Proceedings of the National Academy of<br />
Sciences, 117(34), 20530–20537. https://doi.org/10.1073/pnas.2008671117<br />
Grada, A., Del Rosso, J. Q., Moore, A. Y., Stein Gold, L., Harper, J., Damiani, G., Shaw, K., Obagi, S.,<br />
Salem, R. J., Tanaka, S. K., & Bunick, C. G. (2022). Reduced blood-brain barrier penetration of acne<br />
vulgaris antibiotic sarecycline compared to minocycline corresponds with lower lipophilicity.<br />
Frontiers in Medicine, 9. https://doi.org/10.3389/fmed.2022.1033980<br />
18 Yale Scientific Magazine May 2023 www.yalescientific.org
Ecology<br />
FOCUS<br />
ANIMALS<br />
AGAINST<br />
RISING<br />
TIDES<br />
BY ABIGAIL JOLTEUS<br />
ART BY LUNA AGUILAR<br />
How mussels flex to keep<br />
coastal ecosystems afloat<br />
Due to climate change, sea levels could rise twelve inches<br />
in the next three decades, equivalent to the measured<br />
rise seen over the last century. This rise stresses<br />
vegetated coastal ecosystems, which include mangroves, salt<br />
marshes, and seagrasses. Coastal ecosystems provide habitats<br />
for a wide variety of wildlife and protect both humans and<br />
animals from storms. They also stabilize the shoreline, filter<br />
nutrients, and store carbon dioxide from the atmosphere in<br />
the ground. “Coastal ecosystems are very near and dear to my<br />
heart,” said Sinéad Crotty, associate director of science at the<br />
Yale Carbon Containment Lab, said.<br />
In a recent paper published in Nature Communications,<br />
Crotty examined the direct and indirect effects of one<br />
unassuming invertebrae—mussels—on the persistence of<br />
vegetated coastal ecosystems.<br />
Even small changes in sea levels can substantially alter these<br />
ecosystems through coastal flooding, resulting in higher<br />
storm surges—the rise of seawater during a storm—and an<br />
influx of saltwater into freshwater habitats. Rising sea levels<br />
www.yalescientific.org<br />
have prompted the increase in resources directed to vertical<br />
and horizontal accretion, a natural process that results in a<br />
change in the elevation of salt marshes. Accretion can indicate<br />
how well a salt marsh is persisting in spite of changes in sea<br />
level, and, according to Crotty, refers to how the marsh moves<br />
upwards to compensate for sea level rise. It can increase<br />
vertically or horizontally, in the landward direction of the<br />
boundary of the marsh.<br />
Studying accretion is particularly important because it helps<br />
prevent a phenomenon known as drowning, in which the<br />
vegetated area of a salt marsh is converted into an open water<br />
area. This originally looks like a small pond that eventually<br />
grows larger. As the salt marshes drown, the vital services<br />
that they provide, including habitation, storm buffering, and<br />
carbon storage, also disappear, destabilizing the wildlife around<br />
it.“We care deeply about accretion because for marshes to not<br />
drown, we need the rate of accretion to be greater than the rate<br />
of sea level rise,” said Hallie Fischman, a Ph.D. student at the<br />
University of Florida and an author of the paper.<br />
May 2023 Yale Scientific Magazine 19
FOCUS<br />
Ecology<br />
Historically, studies on accretion<br />
focused on environmental factors, such<br />
as tidal range and sediment supply. The<br />
tidal range consists of the difference<br />
between the highest and lowest point<br />
of the tide, and sediment supply refers<br />
to the availability and transport of<br />
sediment. However, organisms can also<br />
shape their environment, which includes<br />
modifying accretion processes. This<br />
concept is known as faunal engineering.<br />
It refers to animals that provide habitats,<br />
nutrients, or some other alterations that<br />
allow other organisms, as Crotty put it,<br />
to ‘persist and thrive.’<br />
Mussels: The Underdogs Of Coastal<br />
Ecosystems<br />
One of the most abundant faunal<br />
engineers present in salt marshes in<br />
the United States are Atlantic ribbed<br />
mussels. Mussels can be easy to miss in<br />
these vast ecosystems. Yet even though<br />
these organisms are tiny, their functions<br />
are vital—they can, either directly or<br />
indirectly, alter plant growth and improve<br />
water quality by removing organic<br />
matter and unwanted particles. These<br />
particles and organic matter are filtered<br />
by mussels, processed, and subsequently<br />
excreted. Therefore, mussels help with<br />
sediment deposition, the excretion of<br />
Atlantic ribbed mussels.<br />
It was a crazy idea that we could feed mussels<br />
orange chalk, they would poop it out, and<br />
we could follow it across the marsh.<br />
digested organic material. Mussels are<br />
also an important food source for many<br />
terrestrial and aquatic organisms.<br />
Researchers at the Yale Carbon<br />
Containment Lab and the University of<br />
Florida were interested in quantifying<br />
the effects of the Atlantic ribbed mussel<br />
on accretion in southeastern US salt<br />
marshes. They performed three field<br />
experiments to fulfill this objective.<br />
The first field experiment was to<br />
investigate whether the sediments<br />
deposited by mussels could supply<br />
marshes beyond the areas where the<br />
mussels were gathered. Where exactly<br />
was the sediment spreading? To answer<br />
this question, the researchers tagged<br />
biodeposits that were already on the<br />
mound. Then, the fluorescent chalk<br />
was mixed with already deposited<br />
biodeposits, and the researchers came<br />
PHOTOGRAPH COURTESY OF FLICKR<br />
back to trace the movement at night.<br />
“It was a crazy idea that we could feed<br />
mussels orange chalk, they would poop<br />
it out, and we could follow it across the<br />
marsh,” Fischman said.<br />
The researchers returned at night and<br />
used black light detection to trace the<br />
distribution of the fluorescently-tagged<br />
biodeposits. Blacklight, or ultraviolet<br />
(UV) light, is a tool commonly used to<br />
detect fluorescently-tagged materials.<br />
The maximum distance that fluorescent<br />
biodeposits traveled was measured in<br />
every direction.<br />
Interestingly, the team discovered<br />
that the biodeposits were quickly<br />
redistributed beyond the areas where<br />
mussels were present. To confirm<br />
these results, the researchers collected<br />
approximately ten mussels from each<br />
of their six mounds, brought them to<br />
the University of Georgia’s laboratory,<br />
and fed them a mixture of seawater and<br />
chalk, which resulted in the excretion of<br />
fluorescently-tagged biodeposits. After<br />
the previous fluorescent material was<br />
washed away, the researchers planted the<br />
mussels in the respective mounds and<br />
performed the study again, subsequently<br />
confirming their previous findings.<br />
One limitation of this experiment that<br />
the researchers hope will be addressed<br />
in future studies is that the dye in the<br />
biodeposits fluoresced for only the first<br />
twenty-four hours, so the study was<br />
performed on a limited time scale.<br />
In the second field experiment, the<br />
researchers wanted to investigate the effects<br />
of cordgrass, also known as marsh grass,<br />
and mussels on sediment deposition at<br />
different marsh elevations. Seven different<br />
scenarios were tested in two zones in the<br />
state of Georgia for a month: the creekhead,<br />
where a narrow inlet called a tidal creek<br />
20 Yale Scientific Magazine May 2023 www.yalescientific.org
Ecology<br />
FOCUS<br />
to sediment deposition and vertical<br />
accretion in salt marshes.<br />
New Ideas For Mitigating Sea Level Rise<br />
A salt marsh in Georgia.<br />
enters onto the marsh, and the marsh<br />
platform, the main flat surface of the mark<br />
that extends landward.<br />
Cordgrass was found to have no<br />
significant effect on sediment deposition<br />
in both zones, which further highlights<br />
the importance of mussels. As for mussels,<br />
after performing statistical analysis,<br />
the researchers discovered a positive<br />
correlation between the number of mussels<br />
and increased sediment deposition. The<br />
implications of this study are limited by the<br />
size of the areas that were observed.<br />
In the third field experiment, to assess<br />
the potential effects of mussels on marsh<br />
accretion at the level of a creekshed, a<br />
smaller version of a watershed, researchers<br />
manipulated the presence and population<br />
size of mussels. Approximately two hundred<br />
thousand mussels were manually moved<br />
from one creekhead to another. A control<br />
creekhead side in the same marsh was also<br />
established. With the help of a tool called<br />
the Digital Elevation Model (DEM), the<br />
researchers were able to assess the elevation<br />
of the creekheads after three years. DEM<br />
was created using drone imagery, which<br />
was then filtered and edited to remove<br />
vegetation to focus on the sediment. The<br />
team discovered that the creek from which<br />
the mussels were removed decreased in<br />
elevation, but the creek to which mussels<br />
were added increased in elevation. Mussels<br />
were putting in the work.<br />
To further explore and validate the<br />
conclusions from their field experiments,<br />
the researchers used the Delft-3D-<br />
BIVALVES model, a digital tool to<br />
IMAGE COURTESY OF FLICKR<br />
create simulations, generating different<br />
scenarios that mimicked salt marshes in<br />
the region. This model determined that<br />
the highest sediment accretion was found<br />
on mussel aggregations using simulations<br />
based on the assumption that mussels<br />
filter the water column—which refers to<br />
the space between the surface and floor of<br />
a body of water. Mussels expel the filtered<br />
content and their feces on mounds, which<br />
facilitates a build-up of sediments that<br />
increases the elevation of the salt marsh.<br />
“While the manual labor and<br />
methodology development were at times<br />
challenging, I think ultimately this has<br />
been one of the most collaborative and<br />
gratifying scientific efforts that I have<br />
been a part of,” Crotty said. Each of<br />
these field experiments in addition to<br />
the simulation models contributed to<br />
the overall claim that mussels increase<br />
salt marsh accretion. The results suggest<br />
that mussels contribute significantly<br />
ABOUT THE AUTHOR<br />
“The coolest takeaway of this study<br />
is that mussels increase salt marsh<br />
accretion, which means that mussels<br />
are important in helping marshes keep<br />
up with sea level rise,” Fischman said.<br />
Other researchers can use the insights<br />
provided by this study to direct their<br />
research projects on animals similar to<br />
mussels. Mussels may not, however, be<br />
the only animals that are contributing to<br />
the health of their ecosystems.<br />
Due to climate change, small animals<br />
are adapting their roles to their<br />
changing environment. Understanding<br />
the behavior of these animals can help<br />
guide future research on other types<br />
of terrestrial and marine ecosystems.<br />
“Relatively small animals are increasing<br />
in their relative importance and the roles<br />
that they play in response to the changes<br />
that climate change is implementing,”<br />
Crotty said.<br />
As for next steps, Fischman is interested<br />
in the effect of mussels on nitrogen<br />
cycling, which is a cycle of various<br />
processes in which nitrogen moves<br />
through living and non-living things in<br />
the environment.<br />
As climate change continues to worsen,<br />
an additional rise in sea levels is inevitable.<br />
Among its dangers are more frequent and<br />
intense floods, higher storm surges, and loss<br />
and alteration of coastal habitats. Future<br />
studies, including those on overlooked<br />
parts of an ecosystem, can hopefully help<br />
mitigate its harmful effects. ■<br />
ABIGAIL JOLTEUS<br />
ABIGAIL JOLTEUS is a sophomore in Berkeley College studying Ecology and Evolutionary Biology.<br />
In addition to managing the website for <strong>YSM</strong>, she conducts research in the Konnikova Lab.<br />
THE AUTHOR WOULD LIKE TO THANK Sinéad Crotty and Hallie Fischman for their time and<br />
enthusiasm about their research.<br />
FURTHER READING:<br />
Jones, Clive G., et al. “Organisms as Ecosystem Engineers.” Ecosystem Management, 1994, pp. 130–<br />
47, https://doi.org/10.1007/978-1-4612-4018-1_14.<br />
FitzGerald, D. M. & Hughes, Z. Marsh Processes and Their Response to Climate Change and Sea-<br />
Level Rise. Annu. Rev. Earth Planet. Sci. 47, 481–517 (2019).<br />
www.yalescientific.org<br />
May 2023 Yale Scientific Magazine 21
FOCUS<br />
Public Health<br />
FATAL ATTRACTION<br />
Using fly pheromones against disease<br />
A natural tsetse fly odorant could<br />
help prevent African sleeping sickness<br />
BY CINDY MEI<br />
ART BY COURT JOHNSON<br />
From evoking long-forgotten memories through nostalgic scents to detecting<br />
imminent danger through noxious odors, smells hold undeniable power.<br />
Our sense of smell has served as a prime mechanism for survival since the<br />
beginning of time. Much of the work in the lab of John Carlson, a Yale professor<br />
of Molecular, Cellular, and Developmental Biology, is dedicated to studying the<br />
intricate mechanisms of Drosophila (fruit fly) olfaction: how do these insects detect<br />
and behave in the presence of volatile pheromones? An example of chemosensation,<br />
these pungent odorants—chemical compounds that have a smell—produced by<br />
organisms facilitate sexual attraction and mating by affecting behavior. The lab is<br />
interested in studying chemosensation as a method to control populations of insects<br />
that spread disease—such as the tsetse flies, insects that are responsible for spreading<br />
African trypanosomes, the causative agents of African sleeping sickness in Sub-<br />
Saharan regions.<br />
22 Yale Scientific Magazine May 2023 www.yalescientific.org
Public Health<br />
FOCUS<br />
In a paper published in Science earlier<br />
this year, a team of researchers conducted<br />
a study to find natural odorants that<br />
may control the behavior of tsetse flies.<br />
Led by Shimaa Ebrahim, a postdoctoral<br />
researcher in the Carlson lab, the project<br />
was conducted in collaboration with Hany<br />
Dweck, an associate scientist in the Carlson<br />
lab, and Brian Weiss, a senior research<br />
scientist at the Yale School of Public Health.<br />
“I fell in love with the [tsetse fly],” Ebrahim,<br />
who studies the courtship behavior of<br />
Drosophila, said. Weiss echoed Ebrahim’s<br />
fascination, pointing out behaviors unique<br />
to the tsetse flies, such as the live birth and<br />
nurturing of their young, in contrast to the<br />
majority of insects, which lay eggs.<br />
Importantly, tsetse flies feed exclusively<br />
on vertebrate blood, leading to the<br />
transmission of Trypanosoma brucei<br />
(trypanosomes), a classification of<br />
protozoan parasites that cause African<br />
sleeping sickness and nagana in humans<br />
and domesticated animals, respectively.<br />
These diseases have devastating effects:<br />
nagana is responsible for an average loss of<br />
4.5 billion dollars in resources every year<br />
in Africa. If left untreated, African sleeping<br />
sickness has a one hundred percent<br />
mortality rate. Unfortunately, access to<br />
treatment is not available everywhere.<br />
“Most of the drugs used to treat sleeping<br />
sickness are arsenic-based and horribly<br />
toxic. Very recently, there’s been some<br />
newly-developed medications, and they're<br />
much less toxic—but they’re much more<br />
expensive,” said Weiss, who studies tsetse<br />
flies and their associated microorganisms.<br />
To find alternative solutions, the<br />
researchers turned their attention to<br />
preventative measures. According to Weiss,<br />
the best solution to reduce fly populations is<br />
to use traps, as they are cheap and effective.<br />
However, not much is understood about<br />
the chemical signaling of tsetse flies, which<br />
may be key to luring the flies to traps. “If<br />
you want to control any insect that could<br />
cause disease or damage to any crop, you<br />
have to study their behavior to find the way<br />
to control this insect,” Ebrahim said.<br />
The Role Of Smell In Mating<br />
The researchers utilized the tsetse fly<br />
species Glossina morsitans. While Glossina<br />
fuscipes is the most abundant species in<br />
Kenya, they are difficult to rear in the<br />
insectary, according to Weiss. To examine<br />
possible odorants in sexual attraction, the<br />
researchers first studied tsetse fly mating<br />
behaviors. When paired together, G.<br />
morsitans males initiate mating with G.<br />
morsitans virgin females within seconds,<br />
and copulation continues on average for<br />
an hour. However, this reaction was not<br />
observed when G. morsitans males were<br />
paired with mated females, suggesting<br />
that there may be a difference in chemical<br />
signaling that results in the male’s<br />
behavioral responses.<br />
To determine whether differences<br />
in mating are driven by olfaction,<br />
pheromone extracts were obtained from<br />
the exoskeleton, also called the cuticle<br />
(the layer that covers the extracellular<br />
surface of the fly), of male and female<br />
flies that were soaked and gently shaken<br />
in hexane for ten minutes. Dummy tsetse<br />
flies made out of yarn were sprayed with<br />
these extracts and placed in a container<br />
with male G. morsitans, and a measure<br />
of attraction was determined by the<br />
percentage of males that initiated mating<br />
and stayed attached to the decoy flies for<br />
more than five minutes. However, the<br />
males were not attracted at all, suggesting<br />
that any odorants associated with mating<br />
are stored beyond the cuticles.<br />
After soaking another set of tsetse flies<br />
in hexane for twenty-four hours, it was<br />
observed that males were attracted sixty<br />
percent of the time to dummies sprayed<br />
with extracts from virgin females and<br />
twenty-seven percent of the time with<br />
extracts from mated females, with no<br />
response observed with male extracts.<br />
This observation indicates that there may<br />
be a difference in the composition of the<br />
extracts that made male flies more attracted<br />
to virgin than mated female G. morsitans.<br />
The longer soaking time may also explain<br />
why these compounds were not detected as<br />
potential pheromones in earlier research.<br />
The Discovery Of A Key Pheromone<br />
To determine if differences in compound<br />
composition were responsible for mating<br />
behaviors, the researchers obtained the<br />
chemical profile of the extractions via gas<br />
chromatography-mass spectrometry (GC-<br />
MS), which separates and detects different<br />
compounds. GC-MS identified three fatty<br />
acids and three fatty acid methyl esters that<br />
were not present in the ten-minute hexane<br />
immersion, which suggests the pheromones<br />
stored in internal glands may play a part in<br />
facilitating attraction.<br />
To test this hypothesis, the researchers<br />
repeated the previous experiment by<br />
spraying the dummy flies with each of<br />
these six compounds. They found that the<br />
male flies were strongly attracted to certain<br />
compounds that are present in higher<br />
levels in virgin females, such as methyl<br />
palmitoleate (MPO)—which attracted G.<br />
morsitans males eighty-seven percent of<br />
the time even when diluted—methyl oleate<br />
(MO), and methyl palmitate (MP). The<br />
www.yalescientific.org<br />
May 2023 Yale Scientific Magazine 23
FOCUS<br />
Public Health<br />
male fly stayed attached to the dummy for<br />
a prolonged period of time, suggesting that<br />
these compounds also act as arrestants—<br />
halting all motion—to prevent premature<br />
interruption of mating. Clearly, smell<br />
seemed to play a powerful role in mating!<br />
Next, the researchers sought to investigate<br />
cellular mechanisms that may facilitate<br />
the observed behavioral responses.<br />
Removing G. morsitans males’ antennae<br />
eliminated their attraction response,<br />
suggesting that the observed behavioral<br />
responses in mating are facilitated by scent.<br />
Furthermore, research has suggested that<br />
volatile odors are detected via the trichoid<br />
sensilla, a sensory organ located in the<br />
antenna of the fly.<br />
In a method called single-sensillum<br />
electrophysiology, the researchers<br />
obtained recordings of trichoid sensilla<br />
response to odors detected in the air<br />
by antenna. Initially, only MPO elicited<br />
excitatory responses from both sexes, but<br />
particularly from males. After reducing<br />
the distance from which the odor was<br />
delivered, activation in neurons was seen<br />
with MP, MO, and MPO, correlating<br />
with the behavioral results observed<br />
in earlier experiments. However, there<br />
was little to no response in olfactory<br />
neurons to these six compounds in G.<br />
fuscipes, another tsetse species that is<br />
the prominent vector of trypanosomes<br />
in east Africa. This finding suggested<br />
that these pheromones are specific to G.<br />
morsitans mating mechanisms. Indeed,<br />
it was found that G. morsitans males<br />
made no attempt to mate with untreated<br />
G. fuscipes females; however, when G.<br />
fuscipes females were sprayed with MPO,<br />
the males began to engage, suggesting<br />
that MPO may act as an<br />
aphrodisiac, a stimulant<br />
for sexual desire, for G.<br />
morsitans males.<br />
Could Infection Change<br />
Mating?<br />
The last study<br />
examined if these<br />
findings held for<br />
tsetse flies infected<br />
with trypanosomes,<br />
which is the<br />
ultimate target for<br />
traps to prevent<br />
the spread of African sleeping sickness.<br />
There were no changes in single-sensillum<br />
electrophysiology, meaning there was no<br />
change in neuronal response. However,<br />
there were significant behavioral changes<br />
observed in mating.<br />
When paired together, uninfected<br />
virgin female G. morsitans mated with<br />
infected and uninfected males at the same<br />
frequency. However, uninfected virgin<br />
male G. morsitans mated with uninfected<br />
females one hundred percent of the<br />
time over infected females, suggesting<br />
that there may be a compound that<br />
lowers the sexual receptivity of infected<br />
females and acts as a repellent against<br />
G. morsitans males. The group hopes to<br />
further study twenty-one compounds<br />
that were identified in GC-MS as specific<br />
to infected flies. “I'm interested to study<br />
if this compound is produced as a defense<br />
against the parasites,” Ebrahim said.“We<br />
don't know if those compounds were<br />
produced by the tsetse fly in response<br />
to an infection, or maybe they were<br />
produced by the parasites themselves,”<br />
Weiss said.<br />
Harnessing The Power Of Pheromones<br />
The results of the study suggest that<br />
MPO acts specifically as an attractant,<br />
aphrodisiac, and arrestant on G. morsitans<br />
males to activate circuits that mediate<br />
olfactory attraction, sexual desire, and the<br />
halting of movement, respectively. The<br />
usage of MPO in traps holds great promise<br />
from both an environmental and economic<br />
perspective. “Compounds from the fly itself<br />
[…] will be less toxic if we want to use it in<br />
the field compared to other compounds like<br />
DEET,” Ebrahim explained. These natural<br />
ABOUT THE AUTHOR<br />
compounds are also much less expensive<br />
than DEET, which makes implementation<br />
of tsetse fly control more realistic in<br />
developing countries.<br />
In the future, the researchers hope to test<br />
MPO in Kenya with collaborators, who are<br />
currently using tsetse fly host odors such<br />
as cow urine as attractants. “If we combine<br />
MPO with natural host odors, it might<br />
increase the efficiency of control for a trap,”<br />
Ebrahim said. “A more specific odor might<br />
attract more flies and reduce the number<br />
of cases of infection by trypanosomes.”<br />
However, there are challenges<br />
validating field work with lab work, since<br />
the flies in the experiment are different<br />
from those found in a typical African<br />
savanna. In addition, in the real world,<br />
there are many fluctuating and uncertain<br />
factors, according to Ebrahim. Despite<br />
these challenges, the group remains<br />
undeterred, and their passion stays<br />
vibrant. “You will have to be optimistic<br />
and creative for the biggest experiments<br />
you design,” Ebrahim said. ■<br />
CINDY MEI<br />
CINDY MEI is a sophomore in Grace Hopper studying neuroscience. In addition to writing for <strong>YSM</strong>,<br />
she serves as communications chair on Yale Math Competitions and volunteers with Yale DEMOS<br />
and Yale New Haven Hospital. She also conducts epilepsy and Tourette’s syndrome research at the<br />
Yale School of Medicine.<br />
THE AUTHOR WOULD LIKE TO THANK Shimaa Ebrahim, Brian Weiss, and John Carlson for their<br />
time and enthusiasm in answering questions and providing interactive insight about their research.<br />
FURTHER READING:<br />
Ebrahim, S.A.M., Dweck, H.K.M., Weiss, B.L., & Carlson, J.R. (2023). A volatile sex attractant of tsetse<br />
flies. Science, 379 (6633), doi: 10.1126/science.ade1877<br />
24 Yale Scientific Magazine May 2023 www.yalescientific.org
Environmental Engineering<br />
FEATURE<br />
SEEDING<br />
ROBOTS<br />
WOODEN CORKSCREW<br />
ROBOTS PLANT SEEDS<br />
BY MADELEINE POPOFSKY<br />
Look, up in the sky! It’s a bird! It’s a plane! It’s… hundreds of<br />
autonomous self-burying seed carriers? These small wooden<br />
contraptions are built with a unique design that lets them bury<br />
a seed into the ground after dropping from a great height. While<br />
unlikely to drop into your backyard, this new invention spearheaded<br />
by Lining Yao of Carnegie Mellon University and Teng Zhang of<br />
Syracuse University could change the face of reforestation via air. The<br />
design for these carriers is inspired by Erodium seeds and their natural<br />
dispersal mechanisms, and they are made using natural materials such<br />
as wood. The carriers provide a nature-based solution to our manmade<br />
problems regarding habitat loss, forest shrinkage, and even<br />
agricultural complications.<br />
Aerial seeding—scattering seeds by plane, drone, or helicopter—<br />
is an invaluable technique when it comes to wildland restoration,<br />
reforestation, and agriculture, especially for large swaths of hard-toaccess<br />
land. However, the scattered seeds often fail to penetrate the<br />
ground. This dramatically decreases their chances of germination, as<br />
they can get eaten by wildlife or swept away by harsh weather conditions.<br />
The device is closely modeled on the seeds of Erodium, a flowering<br />
plant that has seeds with a special design: a coiled body and single<br />
twisting tail that allows them to bury into the soil. “It’s very hard to<br />
reproduce the performance and also the biodegradable nature of the<br />
Erodium seeds,” Zhang said.<br />
After many rounds of testing, the final design has a twist: three<br />
tails instead of one. “These three points provide a stable contact<br />
between the structure and<br />
the soil,” Zhang said.<br />
Imagine a propeller<br />
with three blades<br />
circling each other<br />
on top—these are the<br />
three tails. In the center,<br />
where the three tails meet,<br />
a coil extends downward<br />
in a straight line—this is the coil<br />
body. At the end of the coil body lies the seed<br />
tip, where the seed is stored. In addition to the<br />
three tails, the other main innovation is the coil,<br />
which provides the mechanical force to allow the<br />
carriers to drill into the ground. The researchers<br />
treated the wood used to make the coil body<br />
with multiple rounds of chemical<br />
treatment and mechanical<br />
deformation in order to<br />
create its twisting shape.<br />
ART BY KARA TAO<br />
www.yalescientific.org<br />
The carrier is rain-driven—another concept borrowed from<br />
Erodium seeds, which change shape depending on humidity. The<br />
wood cells in the coil swell during rainfall, with those on the inside<br />
swelling more than those on the outside, causing the coil to unwind<br />
and the seed to be drilled into the ground. As the coil dries, the<br />
cells on the inside shrink more than<br />
those on the outside, promoting<br />
another coiling mechanism in<br />
the opposite direction that<br />
further embeds the seed.<br />
The main challenges<br />
faced by the researchers<br />
included field tests that<br />
could be done best only in<br />
the spring, resulting in months of<br />
wait time until conditions were suitable,<br />
in addition to day-of weather concerns.<br />
Furthermore, the researchers created a simulation<br />
to test the device’s performance which proved difficult,<br />
considering friction and the many connections between<br />
the tails and coil body.<br />
The carriers have a few issues: they can be negatively<br />
affected by extreme weather conditions, the tip-coil connection<br />
can sometimes break, and the tails can tangle during release. The<br />
team aims to fix these issues as well as test other types of materials.<br />
The tested carriers were made of white oak, but other woods or<br />
materials could potentially be used with the design. A larger material<br />
library will enhance the feasibility of production in different regions.<br />
Additionally, the researchers are exploring other dimensions for the<br />
seed carriers that could improve their performance.<br />
Currently, the carriers are lovingly crafted by hand—which is<br />
not a production method that can continue long-term. The team<br />
is now focusing on producing on an industrial scale. “The cost [of<br />
production] is really about the time and the effort. The material<br />
cost is relatively cheap,” Zhang said.<br />
Yao, Zhang, and their team are currently seeking partners and<br />
stakeholders to expand their impact. “Responsive and functional<br />
structures that are powered by renewable energy could play a<br />
critical role in natural contexts, for ecological purposes such as<br />
restorations and environmental monitoring,” Yao said.<br />
When faced with a problem, sometimes the best inspiration is to<br />
look to nature. That has certainly proved to be the case with these<br />
self-drilling seed carriers. And in ten years’ time, maybe the future<br />
of our world’s forests will be saved by a swarm of plucky, threetailed<br />
robots falling from the sky. ■<br />
May 2023<br />
Yale Scientific Magazine<br />
25
FEATURE<br />
Anatomy<br />
YOUR UNIQUE FINGERPRINT<br />
GENETIC AND NON-GENETIC DETERMINANTS OF<br />
FINGERPRINT PATTERN FORMATION<br />
BY ELISA HOWARD<br />
ART BY BREANNA BROWNSON<br />
Look at your hands. Look closely at the patterns drawn on<br />
the tips of your fingers. The fingerprint is present from<br />
birth, unchanging over the human lifespan, and unique<br />
to each and every individual. Even identical twins with the<br />
same genes exhibit distinct fingerprints. So, how does your<br />
fingerprint develop? And what factors contribute to the unique<br />
patterns that you see?<br />
Fingerprints exhibit three main pattern types: arches, loops,<br />
and whorls. Fingerprint ridges begin to form in the twelfth<br />
week of gestation, the period between conception and birth,<br />
and the organization of the fingerprint pattern is defined by<br />
week fourteen. However, little is known about the biological<br />
mechanisms underlying fingerprint variation. In a recent paper<br />
published in Cell, researchers at the University of Edinburgh<br />
and the Shanghai Institute of Nutrition and Health provide<br />
insight into the genetic foundations of fingerprint development.<br />
“We are interested in individual molecules and genes and how<br />
they work together to create structure and form,” said Denis<br />
Headon, a senior research fellow at the University of Edinburgh<br />
and an author of the study.<br />
Leading the project, Shanghai Institute researchers in the<br />
Laboratory of Dermatogenomics performed genome-wide<br />
association studies (GWAS) linking fingerprint pattern type<br />
with genetics. A GWAS is a research approach that correlates<br />
variation in observable traits with variation in the DNA. The<br />
Shanghai researchers conducted GWAS of several thousand Han<br />
Chinese individuals characterized for the three main fingerprint<br />
patterns. This GWAS method identified forty-three locations of<br />
genes associated with developing arches, loops, or whorls.<br />
The researchers then studied the functions of fingerprintassociated<br />
genes and the timing of their activity in development.<br />
“Interestingly, locations in the genome that correlate with<br />
fingerprint type are populated by genes involved in limb<br />
formation, rarely skin development,” Headon said. That is, genes<br />
involved in embryonic limb formation appear as the predominant<br />
factors determining heritable variation in fingerprint patterns.<br />
The researchers also found that many of the fingerprint-associated<br />
genes identified through GWAS are not even active in the skin<br />
when the fingerprint forms. Rather, the genes function early in<br />
development to set up the proportions and shapes of the fingertips.<br />
As development progresses, the genes switch off. These findings can<br />
be understood in the context of correlative work from the twentieth<br />
century, which argues that the shape of the finger strongly influences<br />
fingerprint<br />
patterns. Thus,<br />
it appears<br />
that limb<br />
development<br />
genes dictate the<br />
presence or absence<br />
of arches, loops, or<br />
whorls through their involvement in<br />
finger shape.<br />
However, the GWAS results<br />
only explain part of the variation<br />
in fingerprints across the human<br />
population because fingerprint type<br />
is not entirely heritable. For instance,<br />
identical twins have different fingerprints,<br />
and the fingerprints of the left and right hand are<br />
not mirror images. “The same genome running through the process<br />
of making a fingerprint at different times, for different fingers,<br />
for different individuals will come up with a slightly different<br />
outcome,” Headon said. Therefore, rather than simply focusing<br />
on genes, it is important to consider development as a process.<br />
“The genes inform, but then there is a process of development that<br />
interprets and gives an outcome in the anatomy,” Headon said.<br />
How can this study help explain the distinct fingerprints of<br />
identical twins? If one identical twin has all arches, then the<br />
other twin is more likely to have all arches than a random,<br />
unrelated member of the population. In other words, there is<br />
at least some genetic influence. “But genetic variation will go<br />
through a developmental process that has a certain amount<br />
of randomness to it,” Headon said. Simply knowing the list<br />
of genes active in a particular tissue provides an incomplete<br />
understanding of how that tissue develops. “You need to<br />
abstract a step from that and say, ‘what is the process through<br />
which these genes operate together to produce a particular<br />
outcome?’” Headon said.<br />
Look at your hands again. How might your fingerprints<br />
have formed? ■<br />
26<br />
Yale Scientific Magazine<br />
May 2023<br />
www.yalescientific.org
FEATURE<br />
Materials Engineering<br />
Astrophysics<br />
FEATURE<br />
THE<br />
IMPOSSIBLE<br />
ART BY YUROU LIU<br />
STAR<br />
A NEWBORN STAR LIVING ON<br />
THE CUSP OF A BLACK HOLE<br />
BY ELIZABETH WATSON<br />
Most of the stars we see in the night sky are billions of<br />
years old, their light only just now reaching us from<br />
light-years away. But what lies beyond what we can see?<br />
The reach of the universe extends far beyond the stars that we’re<br />
able to observe with the naked eye.<br />
A team led by Florian Peißker, a postdoctoral researcher at the<br />
University of Cologne’s Institute of Astrophysics in Germany,<br />
recently discovered a newborn star named X3 whose existence<br />
defies all odds. Dubbed “the impossible star,” X3 is located over<br />
twenty-five thousand light-years away and is currently undergoing<br />
early stages of stellar formation in the vicinity of Sagittarius A*, the<br />
supermassive black hole at the heart of our galaxy. Star formation<br />
so close to a black hole was thought to be theoretically impossible,<br />
but X3 persists all the same.<br />
“I enjoy thinking about the opportunity to witness processes<br />
nobody else has seen before,” Peißker said. The paper, published in<br />
The Astrophysical Journal, is the product of two and a half years of<br />
work and explores how X3 was able to form in spite of Sagittarius A*.<br />
Star formation typically requires two conditions: relatively low<br />
temperatures and high gas density, neither of which holds true for<br />
the environments created by black holes. The area that Sagittarius A*<br />
occupies, known as the Galactic Center, is extremely hot and volatile.<br />
“This source should not exist in the first place because of the<br />
harsh environment of the supermassive black hole Sagittarius<br />
A*,” Peißker said. “The fact that we observe such a young object<br />
so close to Sgr A* implies that this is not the only [such object].<br />
It furthermore shows that star formation can occur, although the<br />
classical criteria are not fulfilled.”<br />
Previous research in the field identified clumps of silicon<br />
monoxide (SiO) gas near Sagittarius A* that may have been dense<br />
enough to permit high-mass star formation. A study in 2014<br />
suggested that these clumps originated from the Circumnuclear<br />
Disk (CND), a ring of molecular gas that surrounds Sagittarius A*.<br />
It was proposed that some SiO clumps found within the CND either<br />
had high enough velocity gradients or had experienced a sufficient<br />
decrease in angular momentum to spiral closer to Sagittarius A*<br />
www.yalescientific.org<br />
than would be otherwise possible. This process, called molecular<br />
cloud inspiraling, was thought to be part of what could foster<br />
stellar formation so close to a black hole.<br />
The team behind Peißker’s study sought to build upon this work.<br />
They compiled data on X3 spanning three decades from four<br />
different telescopes, including the Very Large Telescope in Chile, to<br />
better map out the X3 system and its surroundings. The team divided<br />
the X3 system into three components—designating the young stellar<br />
object as X3a and two neighboring thermal blobs as X3b and X3c—<br />
and collected data about nearby stars and gas clusters. The analysis<br />
helped the team confirm the star’s proximity to Sagittarius A* and<br />
better understand its origins by examining its characteristics.<br />
In addition to the accretion of the SiO gas clumps discussed in<br />
previous research, the team believes that rotating regions of dust<br />
and gas in the Galactic Center, called stellar disks, may also have<br />
been key to X3’s formation. The thickness of these disks would have<br />
been sufficient to lower the temperature within the region for star<br />
formation to be feasible, while simultaneously protecting the area<br />
from the black hole’s radiation.<br />
As they rotate, these stellar disks become dense enough to create<br />
massive gas clusters conducive to high-mass stellar formation. The<br />
team believes that one of these clusters, IRS 13, was instrumental<br />
to the formation of the X3 system. Based on the team’s data points,<br />
the timeline for this formation theory aligns with our current<br />
understanding of this region’s stellar history.<br />
Peißker was excited upon confirming X3’s proximity to Sagittarius<br />
A*, but joked that the process of discovery was far more prolonged<br />
than an ordinary surprise reaction. “For six months, I ran day-in and<br />
day-out simulations to fit the data points,” Peißker said. “Back then,<br />
my daughter demanded milk almost every three hours each night.<br />
So I woke up, gave baby milk to my daughter, and started simulations<br />
with the new parameters. I did this around the clock.”<br />
Peißker hopes to build upon this work in the future to learn<br />
more about how the mechanisms of stellar formation respond to<br />
unconventional situations, which could lay the groundwork for a<br />
richer understanding of star evolution and our universe at large. ■<br />
May 2023 Yale Scientific Magazine 27
FEATURE<br />
Bioelectronics<br />
CYBORG ZEBR AFISH<br />
BY NATHAN MU<br />
USING THE BODY TO GROW FLEXIBLE ELECTRODES<br />
The human body is a machine. At a<br />
fundamental level, it depends on<br />
electrical currents within cells and<br />
electrical signals between cells to function.<br />
So, in a sense, the body produces its own<br />
electricity. But what happens if this power<br />
gets unplugged? This is the problem that<br />
researchers have faced in trying to cure<br />
diseases such as Parkinson’s, Alzheimer’s,<br />
epilepsy, and depression. In the brain—<br />
where electrical signaling is paramount—<br />
any small "unplugging" can throw off the<br />
system of electrical currents and quickly<br />
lead to improper function. Without a way<br />
to fix an improper pattern of electrical<br />
signaling, that part of the brain will slowly<br />
lose its charge and fizzle out, leading to the<br />
visible symptoms of these diseases.<br />
A team led by organic bioelectronics<br />
researchers Xenofon Strakosas and<br />
Hanne Biesmans of Linköping University<br />
in Sweden may be on track to develop<br />
a viable solution to this problem. They<br />
have targeted this issue of restoring<br />
dysfunctional electrical pathways by<br />
harnessing the body’s chemistry to form<br />
an electrode, or electrical conductor<br />
that helps produce a current, within the<br />
IMAGE COURTESY OF UC SAN DIEGO<br />
Researchers have developed brain sensor implants<br />
that can detect electrical signals.<br />
brain. “The really cool thing about this<br />
electrode is that it is a soft polymer that<br />
forms in situ, or within the brain, unlike<br />
metal electrodes that are harsh and rigid,<br />
and require open skull surgery,” Biesmans<br />
said. Any implant in the human body<br />
that does not belong there runs the risk<br />
of causing inflammation and inducing an<br />
immune response that will try to fight the<br />
implant. Current standards for inducing<br />
artificial electrical currents in the brain,<br />
such as gold electrodes, are not optimal.<br />
Biesmans’ team’s primary goal was to<br />
develop a "softer" alternative that could be<br />
formed within the body.<br />
Their approach was to create a gel<br />
mixture that, once injected into the brain,<br />
could self-assemble into a polymer that was<br />
able to restore electrical activity. There’s a<br />
popular saying that "the answer you seek is<br />
within you," and that’s the advice that the<br />
researchers followed. Previous researchers<br />
at Stanford had used an outside solution—<br />
genetic modification—to produce soft<br />
electrodes. However, this pathway comes<br />
with its own problems when it comes to<br />
human application due to ethical concerns<br />
over modifying human DNA. “With our<br />
simple injectable gel, there’s no need for<br />
genetic modification. And in the long<br />
term, maybe there is also no more need for<br />
open skull surgeries,” Biesmans said.<br />
This gel cocktail concoction is composed<br />
of monomers, or building blocks, as well<br />
as enzymes that will be used to make the<br />
polymer electrode. The powerful part of<br />
this research is that it takes advantage of<br />
the enzymatic breakdown of two types<br />
of biological sugars found in the body to<br />
assemble these monomers into a polymer<br />
electrode. First, glucose or lactate—<br />
two types of sugars in the body—are<br />
converted into hydrogen peroxide by<br />
common enzymes known as oxidases.<br />
Next, hydrogen<br />
peroxide is used<br />
by horseradish<br />
peroxidase (HRP),<br />
a naturally<br />
occurring enzyme,<br />
to start the<br />
p o l y m e r i z a t i o n<br />
process. And that’s<br />
it—a simple, twostep<br />
process links<br />
together the monomer<br />
components from the<br />
injected gel to form a soft<br />
electrode directly in the body.<br />
But even the coolest products still<br />
need to be tested for quality, and that’s why<br />
Biesmans and her team came up with a set<br />
of seven criteria ranging from fluidity to<br />
biocompatibility and stability to assess the<br />
electrodes. The first test they ran assessed<br />
the effectiveness of their injected electrode<br />
gel on 0.6 percent agarose gels, which is a<br />
well-known model for simulating brain<br />
chemistry and conditions. “In the early<br />
stages of research, if you don’t know<br />
much, you don’t want to go straight to<br />
zebrafish or animal models because you<br />
don’t know what works yet,” Biesmans<br />
said. In this initial stage of testing, the<br />
researchers went through at least fifty to<br />
sixty different injectable electrode gels to<br />
find a few that were promising enough to<br />
continue working with. “Some gels were<br />
too thick and did not even make it into the<br />
agarose gels,” Biesmans said.<br />
The team then moved on to<br />
demonstrating the conductivity,<br />
28 Yale Scientific Magazine May 2023 www.yalescientific.org
Bioelectronics<br />
FEATURE<br />
stability, and biocompatibility of the<br />
gel and the formed electrode. It would<br />
have been ideal to test these long-term<br />
effects with zebrafish, but this was not<br />
possible. “Our ethical permits did not<br />
allow us to keep the zebrafish alive for<br />
more than three days, so we had to find<br />
a different way,” Biesmans said. Instead,<br />
the researchers used electrode arrays to<br />
test for electrical currents maintained by<br />
the electrode polymer. They also exposed<br />
the polymers to harsh sound energy and<br />
live cell conditions to ensure that the<br />
polymer would not degrade. Both tests<br />
showed excellent results and confirmed<br />
the stability of the gel.<br />
These tests showed that the gel performs<br />
well, but is it safe to use? This was the<br />
team’s next question and perhaps the<br />
trickiest because of the potency of glucose<br />
oxidase enzymes. These enzymes can<br />
quickly produce lots of hydrogen<br />
peroxide, which can kill cells at<br />
very high concentrations. “We<br />
had to find an optimal balance<br />
between lactate oxidase and<br />
HRP enzymes so that we could<br />
get rid of the hydrogen peroxide<br />
as fast as it was being produced,”<br />
Biesmans said. Finally, the team<br />
had a breakthrough and found<br />
that a twenty-seven to one ratio of<br />
HRP to lactate oxidase worked best. “We<br />
were finally able to tune the amount of<br />
hydrogen peroxide so that we are not<br />
creating more problems than we<br />
are fixing,” Biesmans said.<br />
The final hurdle for Biesmans<br />
and her team was to test<br />
their gel in two live models:<br />
zebrafish and medicinal<br />
leeches. In zebrafish, the<br />
gel was introduced in the<br />
tailfin first, followed by<br />
the brain and heart.<br />
The gel turns deep<br />
blue when successfully<br />
polymerized, and the team<br />
saw this beautiful color in all<br />
three locations. Their hard work<br />
had finally resulted in a working<br />
electrode, without noticeable<br />
side effects on the zebrafish.<br />
www.yalescientific.org<br />
One of Biesmans’ favorite experiments<br />
was soaking zebrafish hearts in the gel<br />
cocktail. “I really like that the polymer<br />
formed around the arteries, where<br />
you find glucose and lactate. It’s not<br />
covering the entire heart. That was a nice<br />
demonstration of the specificity of this<br />
gel,” she said.<br />
Leeches were another nice proof<br />
of concept for demonstrating the<br />
effectiveness of this polymer electrode<br />
since they are easy to visualize. “Leeches<br />
have one central nerve, and if you stimulate<br />
the nerve, it will contract immediately. So,<br />
you get instant visual proof of whether<br />
your stimulation worked,” Biesmans said.<br />
A key finding from the leech model was<br />
that the polymer electrodes produced a<br />
gentler, tissue-friendly current as opposed<br />
to the stronger, harsher current produced<br />
by gold electrodes.<br />
Even with the success of this initial<br />
experiment, there is still much work to<br />
be done. Biesmans and her research team<br />
plan to further optimize the current gel,<br />
test new versions of gels with different<br />
monomer building blocks, and introduce<br />
their current gel in mice models.<br />
Biesmans is also working on trying to<br />
induce a similar gel-based polymerization<br />
in single cells, as opposed to tissues.<br />
“Overall, we are working<br />
on building up this<br />
toolbox of<br />
monomers and<br />
techniques for so many<br />
different applications,” Biesmans said.<br />
These applications include treating<br />
various diseases requiring electrical<br />
stimulation by forming polymer<br />
electrodes at many different sites with<br />
disparate properties.<br />
This is just the beginning of exploring<br />
electrical patterns in the brain. While<br />
this team focused on restoring electrical<br />
activity, there are also projects such as<br />
Elon Musk’s Neuralink program that seek<br />
to use machines to interpret the meaning<br />
of the brain’s electrical signals. Perhaps<br />
this research will lead us towards a future<br />
of not just cyborg zebrafish, but cyborg<br />
humans that fully utilize the brainmachine<br />
interface. This makes organic<br />
bioelectronics a highly interdisciplinary<br />
field, and for Biesmans, this has been one<br />
of her favorite aspects of the work. “It’s<br />
interesting and fun to work with all these<br />
collaborators from different disciplines<br />
together. So, let’s see where it brings me,”<br />
Biesmans said. ■<br />
ART BY<br />
COURTNEY JOHNSON<br />
May 2023 Yale Scientific Magazine 29
FEATURE<br />
Palaeogenomics<br />
BY MATTHEW BLAIR<br />
ART BY MALIA KUO<br />
VACATIONING IN SPAIN<br />
HOW ANCIENT HUMANS ESCAPED THE ICE AGE<br />
Genetic testing platforms like<br />
23andMe and Ancestry.com<br />
have been in the spotlight for<br />
many years now. These testing programs<br />
have grown immensely popular, with<br />
some people finding long-lost relatives<br />
or discovering that a historical figure is<br />
somewhere in their family tree.<br />
But for those living over forty thousand<br />
years ago, unfortunately, no such genetic<br />
testing was available. Those early humans<br />
lived without ever knowing their full<br />
genetic history. Some early humans<br />
perhaps wholly missed the opportunity to<br />
gloat that they were related—somewhere<br />
in their bloodline—to the first Homo<br />
sapiens to discover fire.<br />
Now, however, He Yu of Peking<br />
University in Beijing, China and her<br />
team of researchers have constructed a<br />
genetic narrative for these early humans.<br />
Their study is the most comprehensive<br />
examination of certain hunter-gatherer<br />
groups living in Europe around the Ice<br />
Age. It reveals important information<br />
about the mixing between different<br />
groups and their migratory patterns.<br />
This study shines a light on the genetic<br />
differences and similarities of different<br />
hunter-gatherer groups and focuses<br />
especially on how these groups survived<br />
the Last Glacial Maximum (LGM), which<br />
was the most intense period during the<br />
last Ice Age.<br />
The group’s study examined where<br />
hunter-gatherer groups migrated in<br />
order to evade the massive glaciers and<br />
blisteringly cold temperatures moving<br />
across the globe during the LGM, which<br />
lasted from twenty-five thousand to<br />
nineteen thousand years ago. The LGM is<br />
particularly interesting to study because<br />
researchers believe it created a large<br />
migration of hunter-gatherer groups.<br />
Prior studies have found that the LGM<br />
pushed hunter-gatherer groups to move<br />
into southern latitudes, specifically the<br />
Iberian peninsula and southern France,<br />
with some studies also suggesting that<br />
hunter-gatherers could have moved into<br />
the Italian peninsula, the Balkans, and<br />
the southeastern European Plain.<br />
It is impossible to determine where<br />
groups may have moved during the<br />
LGM without having a snapshot of their<br />
locations and genetic makeups before and<br />
after this period. As such, the study spans<br />
from thirty-five thousand to five thousand<br />
years ago, covering before, during, and<br />
after the LGM. “This paper focuses on<br />
where people traveled to find refuge and,<br />
after the LGM, expanded again to form<br />
the later population structure,” Yu said.<br />
Using mostly bones, teeth, and other<br />
materials that could contain genetic<br />
information, Yu and her research team<br />
created new genomic information for<br />
hunter-gatherer groups that are now<br />
extinct. It is easy to send in your saliva<br />
sample to a genetic testing company site,<br />
but researchers had to meticulously comb<br />
through paleogenomic data to construct<br />
a very large and complex family tree. In<br />
this paper, 356 ancient hunter-gatherer<br />
genomes were analyzed, 116 of which were<br />
newly reported by researchers across the<br />
globe in fourteen countries throughout<br />
western and central Eurasia.<br />
Once the researchers confirmed that<br />
these samples contained genetically viable<br />
information, they began the process of<br />
genetic testing. The first, most crucial,<br />
step in this process is to extract the<br />
DNA and sequence the genome. Often,<br />
however, sequencing the genome is the<br />
simplest part. “When we get the data, we<br />
have a lot to do with it. We first examine<br />
their genetic differentiation, trying to<br />
see what samples look more similar and<br />
which are more dissimilar. Specifically,<br />
we focus on the alleles and other genetic<br />
information that could be shared between<br />
some individuals and not others,” Yu<br />
said. Alleles are the genetic information<br />
that could potentially be shared between<br />
individuals—the genetic information that<br />
could contribute to physical traits like<br />
blue eyes or brown hair. This process of<br />
analyzing these alleles and other genetic<br />
information involves a great deal of<br />
high-level statistical analysis and other<br />
methods of biological comparison.<br />
This data analysis allows researchers<br />
to test specific hypotheses about the<br />
movement and mixing of hunter-gatherer<br />
groups. There are many different ideas<br />
about where a group could have gone<br />
and which other hunter-gatherers they<br />
30 Yale Scientific Magazine May 2023 www.yalescientific.org
Palaeogenomics<br />
FEATURE<br />
might have<br />
e n c o u n t e r e d<br />
along the way, but<br />
this method of data<br />
collection and analysis can<br />
quantitatively prove or disprove<br />
these conclusions.<br />
The researchers also considered a<br />
multitude of other factors, including<br />
the radiocarbon dates of the materials,<br />
so that they can pinpoint the age<br />
of the samples and discover other<br />
archaeological information. Simply,<br />
radiocarbon dating is the process by<br />
which researchers analyze the amount<br />
of radioactive carbon-14 left in a sample<br />
in order to measure its age. Further,<br />
cultural information about specific<br />
hunter-gather groups, such as knowledge<br />
about their mortuary practices or the<br />
types of weaponry they commonly used,<br />
allowed the researchers to make<br />
increasingly sound conclusions about the<br />
movements of certain hunter-gatherer<br />
groups and their possible relations to<br />
other groups.<br />
With this research, Yu and her team of<br />
researchers have established a genomic<br />
study of remarkable depth and breadth.<br />
By drawing on multitudes of biological<br />
and historical information, they created<br />
a firmly-rooted “family tree” for huntergatherer<br />
groups.<br />
When working with a data set that is so<br />
ancient, many challenges can arise. The<br />
majority of the time, the samples used<br />
usually come from bones or teeth. These<br />
physical samples last through the ages<br />
which makes them strong candidates<br />
for DNA extraction. In especially old<br />
samples, however, the DNA degenerates<br />
and is poorly preserved. “The samples<br />
that are reported, of course, are not the<br />
only samples that we have processed.<br />
There were various samples that did not<br />
produce enough DNA and some which<br />
had none at all, failing during the DNA<br />
extraction process,” Yu said.<br />
Even when a sample does<br />
produce enough DNA, that data<br />
must be observed with a critical eye. As<br />
these samples have often been studied by<br />
multiple parties and transported across<br />
the globe, the risk for contamination is<br />
high. “For many samples, we also had a<br />
hard time trying to detect and confirm if<br />
they are contaminated or not. Further, if<br />
samples were found to be contaminated,<br />
we then had to go through the process<br />
of separating the DNA of that specimen<br />
from its contaminants so that we could<br />
get real information,” Yu said.<br />
This study showed that huntergatherer<br />
groups flocked to western and<br />
southwestern Europe to escape the Ice<br />
Age. “It was always assumed that the<br />
Iberian Peninsula was a refuge during<br />
the Ice Age, but this is the first time we<br />
genetically confirmed that there is really a<br />
human population—with the same genetic<br />
ancestry found earlier in other regions of<br />
Europe—living in that area,” Yu said. This<br />
is a powerful confirmation that paints a<br />
clearer picture of the survival, migration,<br />
and mixing of hunter-gatherer groups.<br />
But researchers still have questions,<br />
especially about the importance of another<br />
region as a refuge during the Ice Age: the<br />
Italian Peninsula. In this region, there<br />
were massive genomic changes before<br />
and after the Ice Age, so researchers<br />
cannot make a succinct conclusion on<br />
whether or not it was a refuge based<br />
on DNA evidence alone. These<br />
regions saw a huge genomic<br />
turnover, with distinct genetic populations<br />
before and after the LGM. “Genetic<br />
information could help us to answer or<br />
confirm some points, but it alone cannot<br />
confirm them all. It is important in these<br />
sorts of studies to combine information<br />
from different sources and evidence from<br />
different disciplines,” Yu said.<br />
History itself is expansive, and trying to<br />
capture the movement of many different<br />
groups over tens of thousands of years is an<br />
exceedingly difficult task, but researchers<br />
like Yu and her team are embarking on this<br />
journey through time to reveal important<br />
information about how our earliest<br />
ancestors survived and how all of us are<br />
here today. As we move forward and learn<br />
more about our personal genomic histories<br />
through popular testing platforms, we can<br />
appreciate the work they are doing to<br />
capture the genomic ancestry of<br />
humans across the world. ■<br />
www.yalescientific.org<br />
May 2023 Yale Scientific Magazine 31
FEATURE<br />
Immunology<br />
PLANT-ANIMAL<br />
HYBRIDS<br />
PROTECTING PLANTS<br />
WITH ANIMAL ANTIBODIES<br />
BY SAMANTHA LIU<br />
ART BY KARA TAO<br />
Plant-animal hybrids are here, and<br />
they are exactly what they sound<br />
like. In the Sainsbury Laboratory<br />
in Norwich, UK, wild tobacco plants have<br />
been engineered to produce "pikobodies,"<br />
synthetic proteins that can recognize and<br />
attack pathogens expressing fluorescent<br />
proteins. These pikobodies are made<br />
by taking rice-derived receptors and<br />
swapping in antibody<br />
f r a g m e n t s<br />
originating<br />
from<br />
camelid mammals, specifically llamas and<br />
alpacas. In a proof-of-concept study—<br />
carried out by postdoctoral scientist Jiorgos<br />
Kourelis of the group headed by Sophien<br />
Kamoun—the team discovered that these<br />
pikobody-producing tobacco plants could<br />
successfully stave off viral invaders.<br />
This discovery arrives at a crucial<br />
moment: in the past year alone, wars,<br />
climate change, and trade routes in flux<br />
have ferried pathogens around the<br />
globe in dangerously unprecedented<br />
ways. Meanwhile, as a wheat<br />
blast devastates crop yields<br />
in Africa and Asia,<br />
and scientists<br />
sound<br />
alarm<br />
bells to food security worldwide, protection<br />
against plant diseases is more important<br />
than ever.<br />
While current mechanisms of disease<br />
resistance in agriculture are mostly<br />
chemical (think pesticides, fungicides,<br />
and a host of other -ides), with pikobodies,<br />
genetic treatments may replace our reliance<br />
on chemical treatments. “We can generate<br />
made-to-order resistance genes against<br />
virtually any pathogen,” Kourelis said.<br />
The idea is certainly an imaginative if<br />
not unbelievable one, almost like science<br />
fiction. But it didn’t originate out of the blue.<br />
Scientists have long been interested in the<br />
integrated domain (ID) of plant receptors,<br />
which is responsible for recognizing<br />
pathogen effectors and triggering an<br />
immune response. In one key study by<br />
French scientist Stella Cesari, engineering<br />
the ID of Pik-1—a receptor that normally<br />
attacks fungal invaders—could allow<br />
tobacco plants to gain specificity and bind<br />
new sequences. Ever since then, Kamoun<br />
has wondered if he could engineer Pik-1 to<br />
recognize other pathogens.<br />
The second piece of the puzzle—<br />
introducing the animal antibody—came<br />
four years ago, with Kourelis’ arrival at<br />
the lab. During a lab meeting, Kourelis<br />
proposed “A General Solution for Plant<br />
Pathology”—a title which, of course, caught<br />
the attention of everyone in the room.<br />
As Kourelis noted, one problem with<br />
plant immune defenses is that they lack<br />
mobile or specialized cells for attacking<br />
32 Yale Scientific Magazine May 2023 www.yalescientific.org
Immunology<br />
FEATURE<br />
viruses, unlike animals. Plants instead<br />
rely on nucleotide-binding, leucine-rich<br />
receptors (NLRs), which can recognize<br />
diverse pathogen components and<br />
activate the immune response. But NLRs<br />
are limited in what they can recognize—<br />
and their scope is hard-coded by DNA,<br />
which cannot evolve as fast as rapidlychanging<br />
viruses.<br />
In contrast, mammals can create and<br />
proliferate specific antibodies for virtually<br />
any virus they are exposed to. Not only do<br />
these antibodies target, mobilize, and kill<br />
viral particles, but the animal also retains<br />
them well after the infection, in case of<br />
future threats—the same principle which<br />
guides vaccines. “Basically, you could<br />
potentially build a disease resistance gene<br />
against any plant pathogen by exploiting<br />
the adaptive immune system of animals,”<br />
Kamoun said.<br />
Enter the llamas. Kourelis suggested<br />
taking camelid mammal nanobodies—<br />
the fragment of antibodies which actually<br />
binds to the pathogen—and fusing them<br />
to Pik-1. In this way, plants’ integrated<br />
domains could serve as a scaffold to trigger<br />
the immune response, while mammalian<br />
antibodies could let them recognize a host<br />
of other pathogens.<br />
To turn their concept into practice,<br />
Kourelis still needed a framework for<br />
where and how to engineer the receptors.<br />
His answer was bolstered by an earlier<br />
project by colleague and Ph.D. student<br />
Aleksandra-Ola Bialas, who investigated<br />
how the Pik-1 receptor arose fifty million<br />
years ago. Critically, by looking at the<br />
evolutionary origins of Pik-1, Bialas’s<br />
work helped delimit the boundaries of the<br />
domain that Kourelis was so interested in.<br />
“So fifty million years ago, nature<br />
actually did this engineering and<br />
integrated the domain into this [Pik-<br />
1] receptor,” Kamoun said. “And if you<br />
understand how nature has done it, you<br />
could repeat it in the lab.<br />
Even with Bialas’s contribution, the<br />
process to pare down potential candidates<br />
was arduous. It required iterations of<br />
revisiting basic science, tweaking existing<br />
combinations, and, at some point, sheer<br />
brute force, Kourelis recalled. “Sometimes<br />
we were like, ‘Let's drop in as many<br />
nanobodies as we can and see if some of<br />
them work,’” Kourelis said. “‘And then, if a<br />
Transgenic tobacco plants serve as the model organism for pikobody testing.<br />
few work, even if they don't work great, let's<br />
understand what's going on there.’”<br />
Eventually, he engineered eleven<br />
pikobody candidates to recognize<br />
fluorescent proteins. They were vetted<br />
for autoimmune responses and cell death<br />
responses until only four pikobodies<br />
remained. After introducing a live Potato<br />
virus X, which was engineered to express<br />
fluorescent proteins, two pikobodies were<br />
found to halt viral spread substantially.<br />
And if used together, these two pikobodies<br />
proved to be even more effective.<br />
Now, Kourelis and Kamoun are looking<br />
toward future applications for pikobodies.<br />
They are both enamored with the potential<br />
of “designer” domains, with each plant<br />
tailored with pikobodies against diseases<br />
that might threaten it. They even speculated<br />
that, with advanced artificial intelligence,<br />
computers may someday design the<br />
binding domains, circumventing the need<br />
for antibodies altogether.<br />
For Kourelis, one of the challenges lies<br />
in accounting for—and staying ahead<br />
of—pathogen evolution. As he looks to<br />
apply his model and develop a toolkit of<br />
new receptors, he hopes to identify target<br />
sequences that will be long-lasting. If they<br />
can pick target sequences that are unlikely<br />
to change, then the pathogen is less likely<br />
to evolve to resist that receptor. “Then<br />
IMAGE COURTESY OF PIXABAY<br />
again, I like to say, ‘Never bet against the<br />
pathogen,’” Kamoun said.<br />
In the book-lined office from which<br />
Kamoun and Kourelis take this Zoom<br />
interview, it is not difficult to envision<br />
them collaborating in a laboratory.<br />
Kourelis fields a question. Kamoun<br />
modifies Kourelis’s answer, then raises<br />
another point, which reminds Kourelis of<br />
another idea. Even as they talk to me, their<br />
conversation with each other never ceases.<br />
Their dialogue—revising, rephrasing,<br />
circling—reflects the cycles it took Kourelis<br />
to get to his top-performing pikobodies.<br />
But this is their process and, perhaps,<br />
the reason they are successful. Kourelis<br />
emphasized multiple times that they<br />
regard themselves as scientists first, and<br />
engineers second. No matter what sciencefiction<br />
universe plant-animal hybrids and<br />
pikobodies seem to resemble, for Kourelis<br />
and Kamoun, these ideas are firmly rooted<br />
in listening to what already exists—to<br />
plants, to other scientists, to each other—<br />
before they create something new.<br />
“There’s a more fundamental<br />
understanding in seeing how, in nature,<br />
these proteins have evolved, how these<br />
domain integrations have happened,”<br />
Kourelis said. “You have to understand<br />
before you can take the next step. You have<br />
to understand nature by making it.” ■<br />
www.yalescientific.org<br />
May 2023 Yale Scientific Magazine 33
UNDERGRADUATE PROFILE<br />
CHARNICE HOEGNIFIOH<br />
YC ’24<br />
BY EMILY SHANG<br />
A<br />
double major in Classical Civilizations and Molecular<br />
Biophysics and Biochemistry, Charnice Hoegnifioh (BF ’24)<br />
is studying the science behind ancient makeup and skincare<br />
artifacts. Hoegnifioh was recently awarded the Edward A. Bouchet<br />
Fellowship and the $35,000 Beinecke Scholarship, which will support<br />
her academic research and post-graduate studies in the medical<br />
humanities, respectively.<br />
Hoegnifioh fell in love with biochemistry in<br />
high school. She especially enjoyed conducting<br />
experiments involving spectroscopy, the study of<br />
the emission and absorption of electromagnetic<br />
radiation by matter. After participating in<br />
the MIT Introduction to Technology,<br />
Engineering, and Science program<br />
in high school, she realized that she<br />
wanted to devote her undergraduate<br />
studies to biophysics. At the same<br />
time, she loved Latin, and her<br />
passion for Classics was cemented<br />
by a school trip to Greece. Ultimately,<br />
she found that “following her passion”<br />
at Yale meant loading up on five credits<br />
of Classical Civilization courses in her first<br />
year, while also researching ultrafast protein<br />
folding in the Davis Lab. She decided to pursue<br />
a double major and focus her time on honing her<br />
skills in these two areas.<br />
One of Hoegnifioh’s most recent classes applied spectroscopy and<br />
isotopic dating—the analysis of materials based on the decay rates of<br />
unstable elemental isotopes—to examine seals from the ancient Near<br />
East. Traditionally, these seals, which were ubiquitous in Mesopotamia<br />
and used for administrative and decorative purposes, were dated based<br />
on their iconography since their styles could be traced back in time.<br />
Hoegnifioh explained that studying the seals’ isotopic proportions can<br />
allow researchers to determine their geographical origins. “By looking<br />
at isotopic ratios of materials, you can differentiate whether a material<br />
or mineral came from Scandinavia or the Middle East,” Hoegnifioh said.<br />
As an Edward A. Bouchet Fellow, Hoegnifioh will study abroad in<br />
Germany, Greece, Italy, the United Kingdom, and France this summer<br />
and visit archaeological sites to research ancient cosmetic artifacts and<br />
their effects on healing. One artifact she’s particularly excited to see is an<br />
ointment tin from ancient Rome, excavated by the Museum of London<br />
twenty years ago, that still shows the preserved<br />
fingerprints of the original owner. Beyond<br />
the Museum of London,<br />
Hoegnifioh will go to the<br />
archeological museum in<br />
Frankfurt to view<br />
their exhibition<br />
of paint pots. “[Cosmetics] were posited as healing outward feminine<br />
flaws but also inward flaws in women. So I’ll be going to some healing<br />
sanctuaries and learning more about healing authority and what<br />
ingredients were thought [to have] curative properties,” Hoegnifioh said.<br />
Her work will culminate in her senior thesis, tentatively titled<br />
“Remedies for Roman Beauty: Curative Cosmetics during the<br />
Roman Empire.” Hoegnifioh’s interest in cosmetics<br />
began during her summer internship at Harvard,<br />
where she conducted a research project on the<br />
painful and poisonous aspects of beauty as<br />
a first-year student. Through her research,<br />
she learned that one of the most popular<br />
misconceptions about beauty routines<br />
in the classical world is that the ancient<br />
Romans unknowingly used lead<br />
within the cosmetic pigment. “It<br />
turns out that the Romans were<br />
actually aware that white lead<br />
was extremely toxic, as there was<br />
a treatise written that lead shouldn’t<br />
be used in pipes or buildings because it<br />
will lead to poisoning. But women were<br />
still being hurt, so I wanted to investigate<br />
why these societal standards were coming<br />
before women’s health,” Hoegnifioh said.<br />
Hoegnifioh cites multiple major influences in<br />
PHOTOGRAPHY BY HANNAH HAN<br />
her journey throughout Yale, the first being her<br />
Latin professor from her first year, Irene Peirano Garrison, who<br />
left Yale to teach at Harvard but remained her close confidant and<br />
advisor. Peirano Garrison advised Hoegnifioh to pursue a Ph.D.<br />
in the humanities and guided her through an ongoing graduate<br />
project on makeup in antiquity. “Her impact on my life is<br />
beyond words. I would not be where I am without her and<br />
her motivational presence in my life,” Hoegnifioh said.<br />
She also cites Jessica Lamont, an assistant professor of<br />
Classics, and Milette Gaifman, the Andrew Downey<br />
Orrick Professor of Classics and History of Art, as<br />
other advisors who have guided her through her<br />
undergraduate studies.<br />
When asked what advice she would give to<br />
underclassmen, Hoegnifioh emphasized that double<br />
majoring in two disparate fields is achievable given<br />
proper preparation, and she hopes that no one is<br />
deterred because of the prerequisite courses. “Planning<br />
is key, but don’t hold yourself to super strict standards<br />
because things change. So allow yourself that flexibility,”<br />
Hoegnifioh said. “Remember that imposter<br />
syndrome is real, but you are talented, and if<br />
you’re at Yale, you definitely deserve to be here.” ■<br />
34 Yale Scientific Magazine May 2023<br />
www.yalescientific.org
ALUMNI PROFILE<br />
AMYMARIE BARTHOLOMEW<br />
YC ’13<br />
BY WILLIAM ARCHACKI<br />
This June, graduates from Yale’s Class of 2013 will flock back to<br />
campus for their ten-year reunion. For Amymarie Bartholomew<br />
(YC ’13), the trip will be as simple as a walk down Science<br />
Hill from her new lab at Kline Chemistry Laboratory. Appointed an<br />
assistant professor in January of this year, Bartholomew now works<br />
in the chemistry department alongside many of the faculty members<br />
she had as teachers and mentors during her time as an undergraduate.<br />
Back and better than ever, Bartholomew is a doctorate-wielding<br />
chemist whose work focuses on synthesizing stimuli-responsive<br />
inorganic materials. The graduate-level course she teaches, “Molecular<br />
Materials,” reflects the aims of her research: to produce materials that<br />
change their physical, magnetic, and electrical properties in response<br />
to interactions at the molecular level. For instance, the absorption of<br />
light might change the way bonds form, or an increase in temperature<br />
might alter the way electrons behave in a magnetic field.<br />
Bartholomew thinks of her work as a search for new ways to apply<br />
these tiny molecular changes to the creation of useful materials.<br />
“I’ve always had a lot of ideas for things to synthesize and things to<br />
try, and I think in chemistry—as well as in<br />
other fields—it’s really about just trying<br />
things,” Bartholomew said. “Being<br />
able to see which of my ideas hold<br />
promise and which of them are able<br />
to move forward—I think that’s<br />
really exciting.”<br />
One project the lab group is<br />
working on seeks to use the<br />
molecule azobenzene to<br />
produce electricity from<br />
sunlight. For a long time,<br />
scientists have known<br />
that azobenzene can switch<br />
between two shapes:<br />
one that bends back<br />
on itself and one that is<br />
long and straight. When<br />
high-energy ultraviolet<br />
light strikes azobenzene<br />
crystals, they tend to<br />
flex and deform as their<br />
many constituent atoms<br />
switch between the two shapes. Bartholomew’s<br />
research is taking this behavior of azobenzene to<br />
new heights. By creating larger molecules that contain<br />
multiple azobenzene components bonded at special angles,<br />
Bartholomew and her collaborators have produced a<br />
material that rotates around a central axis when<br />
exposed to visible light. Under a microscope,<br />
crystals of this material appear to continuously<br />
www.yalescientific.org<br />
PHOTOGRAPHY BY HANNAH HAN<br />
roll like long axles, performing the kind of mechanical work that<br />
can generate electricity. Bartholomew hopes that this single-step<br />
conversion from solar energy to mechanical work will provide a<br />
starting point for more efficient solar power.<br />
Bartholomew also focuses on the kinds of stimuli-responsive<br />
changes that could pave the way for new nanoscale electronics.<br />
Like the azobenzene complexes, most of Bartholomew’s materials<br />
are crystalline in structure. Not only does the ordered pattern of<br />
crystals make for useful physical properties, but it also provides<br />
chemists with an insight into how and why stimuli responses occur.<br />
“If you ever need to find me, I’m probably trying out crystals on the<br />
diffractometer in the crystal lab,” Bartholomew said. “I love being<br />
able to make something, crystallize it, and then use those crystals<br />
to determine the three-dimensional structure of what I’ve made.”<br />
The research that Bartholomew has carried out in her first months<br />
as a professor has largely taken place thanks to generous colleagues<br />
who have lent their research spaces to her. After all, it takes time<br />
to acquire all the equipment necessary to run a cutting-edge<br />
chemistry lab. Bartholomew’s own space is just a short<br />
walk from the lab of chemistry professor Nilay<br />
Hazari, where Bartholomew conducted research<br />
as an undergraduate. Bartholomew explained<br />
that Hazari acts as a model for her now that<br />
she has the responsibility of mentoring.<br />
Bartholomew also credited Professor<br />
Kurt Zilm, the instructor of<br />
her undergraduate physical<br />
chemistry class, for showing<br />
her how to teach chemistry.<br />
“I think pedagogically I<br />
definitely took a lot from<br />
that class—hopefully.<br />
You’ll have to ask the<br />
graduate students in my<br />
class now if that’s the case,<br />
but that’s the aim anyway,”<br />
Bartholomew said.<br />
Now with the classroom<br />
and the lab under her control,<br />
Bartholomew is putting her own<br />
creativity to the test. Fortunately,<br />
Bartholomew has an endless stream of fresh<br />
ideas in her niche of synthetic chemistry. “I<br />
sit at home and think of new things we should<br />
try to make, and I have to sketch them out at<br />
like ten p.m. and send myself a weird email<br />
with two sentences of an idea,” Bartholomew<br />
said. To handle the strange world of molecular<br />
materials, there may be no better approach. ■<br />
May 2023 Yale Scientific Magazine 35
MEASURE FOR MEASURE<br />
BY HENRY CHEN<br />
IMAGE COURTESY OF MEASURE FOR MEASURE<br />
SCIENCE<br />
How would you rank the following: Friends, The Office, and Modern<br />
IN<br />
Family? How do you—and other people—differentiate between your<br />
favorite shows, books, and podcasts? Is there a universally defined<br />
scale? What are some factors we use to compare? These are all questions that<br />
“Measure for Measure” seeks to explore.<br />
Run by the organization Ministry of Ideas and co-hosted by Liya Rechtman<br />
and Andrew Middleton, “Measure for Measure” is a limited podcast series<br />
that investigates a different form of measurement in our daily lives. The<br />
nine episodes, which range from nine to twenty-five minutes in length, are<br />
perfect to squeeze in during a walk between classes. The podcast covers topics<br />
spanning the Scoville spice scale, used to measure the pungency of chili<br />
peppers, to star “heartbeats,” which are pulses that cause a star to expand and<br />
contract, leading to variations in brightness. Most importantly, each episode<br />
tries to answer the overarching question: why has measurement been crucial<br />
throughout human history?<br />
For example, in episode two, Rechtman talks about how the Talmud, a central<br />
Judaic text, contains a number of references to measurements, like how much<br />
matzah to eat during Passover, that were based on the size of other foods, like<br />
olives. Because olive sizes have varied over the centuries, many Jewish people<br />
today have tried to update the medieval measurement to determine how much<br />
matzah to eat. The story of the olive is one of unity across time—how even<br />
though Jewish people are separated from their ancestors by thousands of years,<br />
they can still celebrate in the same way, following similar cultural guidelines.<br />
Importantly, each episode presents a narrative about using measurement as a<br />
way for us to (re)connect with the rest of the world—both past and present.<br />
As I made my way through the series, it became clear where each of the cohosts’<br />
passions came into the episodes. Rechtman is a Jewish climate activist,<br />
while Middleton is a cartographer and ocean enthusiast. As a result, each episode<br />
was a science lesson infused with niche, thoroughly interesting historical and<br />
cultural facts—an engaging format that sparks questions about the intersection<br />
between the humanities and science. For instance, in episode three, we learn about<br />
the Mohs scale for categorizing the hardness of rocks and how it was created by<br />
the Habsburg Empire to distinguish itself from competing empires and increase<br />
national unity. These stories reinforce the idea that measurement isn’t restricted<br />
to the International System of Units we use in chemistry class. Instead, it extends<br />
far beyond, into almost every facet of human life.<br />
At the end of the nine episodes, I still haven’t found a definitive scale to rank<br />
podcasts, but I have learned the importance of tools for measurement in our lives<br />
and how they turn a continuous reality with infinite possibilities into discrete<br />
categories—and maybe that’s the point. For its combination of historical facts,<br />
scientific trivia, and broad cultural trends, I’m placing “Measure for Measure”<br />
in the category of “highly recommended.” ■<br />
T<br />
36 Yale Scientific Magazine May 2023 www.yalescientific.org
THE DARKNESS MANIFESTO<br />
You’ve probably flown over a city at night and noticed the bright glow of<br />
lights staring back at you through the airplane window. As intriguing<br />
and surreal as it feels to see such a sight, these lights are disrupting<br />
the behavioral patterns and circadian rhythms of many organisms across<br />
the globe, from insects and bats to bioluminescent creatures and humans. In<br />
his newly released book, The Darkness Manifesto, Johan Eklöf describes the<br />
myriad consequences related to light pollution and urges readers to defend<br />
the darkness.<br />
The majority of nature’s activities, such as mating and pollination, occur<br />
at night because eighty percent of all organisms are nocturnal. Humans are<br />
diurnal organisms (active during the day) and, as a result, have resorted<br />
to artificial light to extend our activities into the night. Eklöf echoes the<br />
claims that we have entered a new era: the Anthropocene, in which humans<br />
have had a critical impact on the Earth’s ecosystems. In particular, he argues<br />
that man-made sources of light are disrupting Earth’s natural rhythms by<br />
generating light pollution.<br />
Eklöf devotes several chapters to describing the ways in which light<br />
pollution has thrown off the reproductive cycles of organisms across the<br />
planet. For instance, he claims that the pollination rate of some plants like<br />
apple trees has slowed down because moths, which serve as pollinators, get<br />
easily confused by artificial sources of illumination. For animals like our<br />
beloved friend Nemo, the consequences of light pollution are as severe as eggs<br />
failing to hatch since clownfish larvae rely on the darkness to signal when it<br />
is time to break free from their sacs. Without complete darkness at night, the<br />
behavioral patterns of organisms are becoming increasingly out of tune, and<br />
as a result, the ecosystems they inhabit are being destroyed.<br />
But it isn’t just plants and animals that are affected. We humans are facing<br />
serious consequences as well. Because humans aren’t nocturnal, we rely on<br />
our natural sleep cycles to rest. But true rest is difficult to achieve when we are<br />
using our phones too late into the night. Blue light from our phones tricks our<br />
brains into thinking it is still daytime, so we produce insufficient levels of our<br />
natural sleep hormone, melatonin, making it difficult to fall asleep. Similarly,<br />
Eklöf states that people who work night shifts are at a higher risk of hormonal<br />
cancers such as breast and prostate cancer. We can prevent a multitude of<br />
THE<br />
SPOTLIGHT<br />
serious health conditions by restoring our natural circadian rhythms and<br />
avoiding light at night.<br />
In his manifesto at the end of the novel, Eklöf calls upon readers to cherish<br />
and learn more about the darkness due to its importance in our behavioral<br />
patterns. Some countries, like France, are already moving towards decreased use<br />
of artificial light at night, and Eklöf hopes that more countries will follow suit.<br />
“The darkness is not the world of humans. We’re only visitors,” Eklöf reminds<br />
readers. It’s not too late to change our habits and start protecting the darkness. ■<br />
BY FAITH PENA<br />
IMAGE COURTESY OF WALLPAPER FLARE<br />
www.yalescientific.org<br />
May 2023 Yale Scientific Magazine 37
COUNTERPOINT<br />
QUANTUM<br />
BY MATTHEW DOBRE<br />
CRYPTOGRAPHY<br />
Encrypting data in holograms composed of corkscrews of light<br />
In 1933, Nobel Prize-winning chemist Sir William<br />
Bragg said, “Light brings us the news of the<br />
Universe.” Though it would take decades before<br />
scientists better understood the properties of light,<br />
researchers today are devising ways to utilize this<br />
resource to store information by uniting information<br />
theory and quantum mechanics, a subfield of physics<br />
that governs the behavior of photons, or light particles.<br />
Among the general public, anything that includes the<br />
word “quantum” elicits a degree of awe. Even Einstein<br />
was troubled by one of the theoretical implications of<br />
quantum mechanics, which he called “spooky action<br />
at a distance.” Today, Einstein’s boogeyman is called<br />
entanglement. When two particles are entangled, their<br />
quantum states, which may include properties like<br />
geometric orientation, angular momentum, and energy,<br />
are inextricably linked. A change in the state of one<br />
particle will immediately affect its twin. For example,<br />
consider a pair of entangled mittens: one is given to a<br />
lab assistant named Bob, and the other to his partner,<br />
Alice. No attempt is made to observe either mitten. Bob<br />
is then sent to a neighboring solar system. Up to this<br />
point, nobody in the universe knows the handedness of<br />
either Alice’s or Bob’s mittens. In fact, by the postulates<br />
of quantum mechanics, their handedness will be<br />
indeterminate until they are observed. If this experiment<br />
was repeated many times, it would reveal that when<br />
Alice observes her mitten, she will have a right-handed<br />
mitten half the time, and a left-handed mitten the other<br />
half. Eerily, Bob’s mitten will instantaneously acquire<br />
the opposite handedness, even though he’s two million<br />
light years away from Alice.<br />
These same principles of entanglement have been<br />
used to send data over thin air. In 2015, a research<br />
team in Vienna transmitted information by changing<br />
the relative angular momentum, or “twistiness,” of<br />
entangled pairs of photons. In quantum mechanics,<br />
angular momentum can only take on certain values<br />
called discrete quantities, separated by a constant ‘step<br />
size’. These entangled particles stored information by<br />
acting analogously to computer bits, which can only<br />
have a value of zero or one. In the experiment, each twist<br />
served as an alternative channel of communication,<br />
enabling ultra-high-speed data transmission.<br />
A group of physicists from the Beijing Institute of<br />
Technology (BIT) recently expanded on this research<br />
to create an unprecedented storage system. Instead of<br />
transmitting information via distinct light channels,<br />
they stored several unique data sets at a time by creating<br />
holograms made of entangled photon pairs. Though<br />
holograms seem to be a quintessential element of<br />
science fiction, they already have applications in<br />
everyday life. Used as a security feature in credit<br />
cards, passports, and banknotes, holograms are stacks<br />
of slightly misaligned images that are difficult for a<br />
computer to read. The physicists generated holograms<br />
made of twisted, entangled photon pairs by using<br />
β-barium borate crystals to manipulate the relative<br />
angular momentum between the particles, creating<br />
corkscrew patterns of light that resemble rotini pasta.<br />
To prove their setup worked, the researchers encoded<br />
words in the holograms and used twisted light to<br />
reconstruct the data by measuring the coincidence<br />
between the particles’ angular momentums.<br />
By increasing the number and diversity of twists<br />
in a single hologram, the system securely encrypted<br />
information since the odds of guessing the degree and<br />
direction of the twisted light’s path became very low. For<br />
instance, seven distinct twists, which is a relatively small<br />
system, led to millions of potential combinations.<br />
Many quantum technologies are sensitive to noise.<br />
However, the researchers asserted that entanglement<br />
can diminish the effect of classical noise sources, which<br />
include mechanical vibrations and thermal fluctuations.<br />
Thus, the decrypted output was of a higher quality<br />
compared to other similar systems.<br />
This technology, however, is still in its infancy.<br />
Utilizing six forms of entangled light, the group was<br />
able to decode an image of the acronym “BIT” by<br />
measuring the orbital angular momentum states of the<br />
particles over the course of twenty minutes, which is far<br />
from practical. Fortunately, the group is optimistic that<br />
these difficulties can be overcome with improvements<br />
in quantum technology. Though holographic data<br />
storage is still in a nascent stage, today’s scientists<br />
are utilizing techniques that the founders of modern<br />
physics laid the groundwork for—but may not have<br />
even understood. ■<br />
38 Yale Scientific Magazine May 2023 www.yalescientific.org
Wrought into a cycle,<br />
carbon schleps from one stop<br />
to the next.<br />
Perhaps I recall it<br />
swept along the atmosphere, or<br />
gathered by the ground.<br />
But in this primordial painting,<br />
lumbering green bacteria<br />
nose for warmth in the ocean,<br />
their cellular frames tousling the tides.<br />
Eventually, they dissolve<br />
like salt, and carbon stretches<br />
down to retire under the sand. And in<br />
this dizzying deepsea, the muddy<br />
seafloor, slumbering beneath<br />
carbon’s gray lines like a shutter<br />
over the dark, unsheathes<br />
the largest passage.<br />
Slate-streaked rocks from the byway<br />
pull open their pores. Quietly,<br />
I watch as carbon rolls out<br />
toward the surface.<br />
PERI<br />
A CARBON SEA SCENE<br />
POEM AND ART BY<br />
SOPHIA ZHAO<br />
Artist’s Statement<br />
I wanted to convey research’s brilliant<br />
ability to shift preconceived notions<br />
through my poem, “A Carbon Sea Scene,”<br />
which offers a window into the findings<br />
of Lidya Tarhan, Jiyuan Wang, and their<br />
colleagues recently published in Nature.<br />
Inspired by their stepwise discovery of an<br />
abiotic deep-sea carbon sink, I aimed to<br />
depict my own gradual understanding of<br />
their research by crafting a metaphoric<br />
“painting” representative of their study.<br />
To draw out the beauty of the authors’<br />
breakthrough, I relied on a poetic<br />
structure that “streche[d] down” the<br />
page—much like how the carbon cycle<br />
transcends depth—to emphasize the rich<br />
information that the deepest waters hold.<br />
Phrases such as “tousling the tides” and<br />
“seafloor, slumbering” maintain a steady<br />
rhythm that crescendos with “pull open<br />
their pores”—the most pivotal moment<br />
of this poem, and ultimately, the research<br />
of Tarhan, Wang, and their colleagues<br />
(Tracking Carbon’s Underwater Dive, pg.<br />
12-13). ■<br />
METER<br />
www.yalescientific.org<br />
May 2023 Yale Scientific Magazine 39
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YSEA's 2023 Awardees for<br />
Outstanding Academic Achievement<br />
Aliza Fisher<br />
BS Mechanical Engineering<br />
Charlie Loitman<br />
BS Mechanical Engineering<br />
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BS Engineering Sciences - Mechanical<br />
Class of 2023<br />
Katerina Kargioti<br />
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BS Applied Physics<br />
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Cooper Newsom<br />
BS Applied Physics<br />
Yu Jun Shen<br />
BS Electrical Engineering (ABET)<br />
Tamar Geller<br />
BS Electrical Engineering and Computer Science<br />
Ahtena Stenor (F22)<br />
Engineering Sciences - Chemical<br />
Sam Karp<br />
Engineering Sciences - Chemical<br />
Laiba Akhtar<br />
Engineering Sciences - Chemical<br />
Emily Quisenberry<br />
Chemical Engineering<br />
Hoang Le<br />
Chemical Engineering<br />
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Chemical Engineering<br />
Thomas Blum<br />
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Sophie Naud<br />
BS/MS Biomedical Engineering<br />
Grayson Wagner<br />
BS Biomedical Engineering & Mechanical Engineering<br />
Tanya Jomaa<br />
BS Engineering Sciences – Electrical<br />
Michal Gerasimiuk<br />
Computer Science<br />
Lachlan Keller<br />
Computer Science & English<br />
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Computer Science & Economics<br />
Aidan Evan<br />
Computer Science & Philosophy