PC

R.
Pingry
Community
Research

Fall 2021
Showcasing the next generation of
scientific researchers.
Contents.
Novel Research
A Structural Basis for the Catalytic Activity and Unique Functions of Dnase1
Family Endonucleases 7-19

Interleukin-33 Expression is Upregulated in Colon Stem Cells After

Irradiation 19

Examining Star Formation in the Evolution of Elliptical Galaxies 20-22

The Post-Transcriptional Role of Igf2bp3 and its Interactions with NF-кB in

Cancer 23-26

The Role of Narrative-based Advocacy in Advancing the Talanoa on

Climate 26-37

Understanding Protein Interactions with BACE1 38-40

2
Reporter Articles
23.46 Cents: Exploring the Development of 12 TET Through History and
Understanding the Cosmic Flaw at the Center of All Tuning Systems 41-44

Crime in the Era of COVID-19 45

Maggot Debridement Therapy 46-47

The Incredible Mozart Effect 47

The Perseverance Rover’s Scientific Instruments 48-50

Possible Dinosaur DNA Discovered in Remarkably Preserved Hypacrosaurus

stebingeri Cartilage 51-54

Temozolomide in the Treatment of Gliomas 54-55

Oncolytic Viruses in Cancer Treatment 56-57

Transcriptomic Analysis of COVID-19 Patients 58-60

Trisomy Formation Within Cancers 61

Treatment of Metastatic Cancer with Statins 62

3
Editor’s Note.
Welcome to the Fall 2021 issue of the Pingry Community Research (PCR)
Journal. We are delighted to showcase Pingry’s top scientific talent, both in
terms of research skills and knowledge of scientific concepts and
discoveries.

The PCR journal provides students the opportunity to publish novel

research. Through a written medium, students demonstrate their in-depth
understanding of complex, collegiate-level scientific topics, and their
applications in research at Pingry.

The fall edition of PCR highlights work in two categories: reporter articles,
which are written by students on a scientific topic of their choosing, and
novel research articles, which communicate the findings of novel research
conducted by Pingry students outside of school in a myriad of fields.

Through the PCR journal, we hope to spark intellectual curiosity and

promote scientific inquiry amongst the next generation of Pingry
researchers.

Read, learn, and inquire. Dive into the wonders of Pingry Research through
this issue of PCR: Pingry’s foremost journal of scientific research.

Kristin Osika (VI), Editor-in-Chief
Caitlin Schwarz (VI), Head Copy Editor
Christine Guo (VI), Head Layout Editor

4
Editorial Staff.
Editor-in-Chief: Head Layout Editor:
Kristin Osika (VI) Christine Guo (VI)

Head Copy Editor: Layout Editors:

Caitlin Schwarz (VI) Sarah Gu (IV)
Leon Zhou (IV)
Copy Editors: Sriya Tallapragada (III)
Brian Li (VI)
Aanya Patel (VI) Art Editors:
Ashleigh Provoost (VI) Allen Wu (VI)
Max Watzky (V) Connor Chen (VI)
Mirika Jambudi (V) Lleyton Lance (VI)
Hansen Zhang (IV) Kelly Cao (IV)
Ali Santana (IV) Ava Khan (III)
Annabelle Shilling (IV)
Sophia Odunsi (IV) Faculty Advisor:
Sarina Lalin (IV) Mr. Maxwell
Gabrielle Marques (IV)

5
Novel Research.
A Structural Basis for the
Catalytic Activity and Unique
Functions of Dnase1 Family
Endonucleases
by Kristin Osika (VI), Jon McCord2, Dr. Peter Keyel1

Department of Biology, Texas Tech University, Lubbock, TX

1

2
Health Sciences Center, Texas Tech University, Lubbock, TX

Abstract
DNA degradation is a key post-apoptotic process which is facilitated by the Dnase1 family of
endonucleases. By cleaving DNA, these enzymes mitigate the aggregation of highly inflam-
matory chromatin microparticles; thus, they play a critical role in prevention of multiple hu-
man autoimmune diseases, such as lupus erythematosus and parakeratosis, which result from
DNA accumulation. While Dnase1 has been extensively investigated, structural questions re-
main surrounding the other Dnase1 family enzymes, Dnase1L1, Dnase1L2, and Dnase1L3. All
of these endonucleases degrade DNA, but each is distinctly localized to specific parts of the
human body, and each exhibits unique structural characteristics; these structural features
have not been thoroughly examined in silico to date, but they could provide unique insight
into the enzymatic activity of Dnase1 family members and their crucial role in human health.

We computationally predicted structures for Dnase1L1, Dnase1L2, and animal homologs of

Dnase1L3; to attain high accuracy, we utilized a three-track neural network approach, com-
parative modelling against Dnase1 and the newly-crystallized human Dnase1L3, and Roset-
ta-based energy minimization. Based on these models, here we uniquely illustrate the struc-
tural basis for Dnase1L2 catalysis and highlight the stabilizing impact of Dnase1L2’s distinct
proline rich domain. We also elucidate the structural implications of catalytic residue dis-
crepancies between human Dnase1L3 animal models, which provide renewed support for al-
ternative catalytic mechanisms across Dnase1 family members. Finally, we identify contact
residues facilitating Dnase1L1-EtpE binding, a process which mediates Ehrlichia chaffeensis
endocytosis, and thus pathogenic entry as a whole; our molecular Dynamics (MD) simulations
isolated Dnase1L1-EtpE binding and Dnase1L1 activity to within 45Å of the cell membrane.
Our findings reveal distinct structural mechanisms underlying the unique functions of

7
multiple Dnase1 family endonucleases, and in
the future, our work could provide the basis for
future endonuclease-based therapeutics and in-
terventions beneficial to human health as a whole.
Introduction
DNA degradation precludes the aggregation
of highly inflammatory nucleic acids after cell
death. The Dnase1 family comprises four dis-
tinct endonucleases, Dnase1, Dnase1L1, Dna-
se1L2, and Dnase1L3, which all degrade DNA.
Each Dnase1 family member requires divalent
cations Mg2+ and Ca2+, is inhibited by Zn2+,
and cleaves DNA into 3’-OH 5’-P oligonucle-
osomal fragments (1). Furthermore, Dnase1
family members share common structural
characteristics, such as a N terminal signal se-
quence and two histidines which are vital for
catalytic activity (2); however, in vitro and in
vivo studies have also identified unique func-
tions, domains, and characteristics specific to
each Dnase1 endonuclease. Their respective
absences are responsible for the onset or pro-
gression of inflammatory human autoimmune

Figure 1: Dnase1L1 and Dnase1L2 homology models illustrate folding and distinct protein-specific domains
a. PyMOD model of Dnase1L1 b. PyMOD model of Dnase1L2 c. Robetta model of Dnase1L1 d. Robetta
model of Dnase1L2

8
Figure 2: Comparison of Dnase1L2 and Dnase1L2 ΔPRD structures
Dnase1L2 is in pink. Dnase1L2 ΔPRD is in teal.
diseases specific to locations within the human
body. Dnase1 is highly expressed in the diges-
tive tract and blood (3) while Dnase1L3 can be
found in myeloid cells in the blood, liver, and
spleen (4) (5) (6); both are linked to Systemic
Lupus Erythematosus (SLE) (3). Dnase1L1 is
found in skeletal and cardiac muscle (3) and
has been tentatively associated with Pompe’s
disease (7) and muscular health (8), while
Dnase1L2 is largely present in keratinocytes (9)
and is associated with parakeratosis (10). Struc-
tural insight into the Dnase1 family has been
limited. Of the Dnase1 family, only Dnase1 has
publicly available crystallized structures. Dna-
se1L3 was recently crystallized by the Sutton
lab at Texas Tech University Health Sciences
Center; their structures are awaiting publica-
tion. In contrast, the structures of Dnase1L1 and
Dnase1L2 have not been solved, leaving ques-
tions about the structural basis of their cata-
lytic activity and unique functions unanswered.
Dnase1L2 is distinguished by both its proline
9
rich domain (PRD) and optimal catalytic activ-
ity at an acidic pH. While the PRD has been
observed to have no effect on catalytic activi-
ty (11), the function and stability of the PRD,
along with the potentially correlated struc-
tural basis for Dnase1L2’s low pH optimum,
have not been identified. Since Dnase1L2 is
active at an acidic pH rather than a neutral
pH, it also may employ an alternative catalyt-
ic mechanism. There have been two proposed
mechanisms for Dnase1 family endonuclease
catalytic activity which may apply: one suggests
that two histidines play a role in acid-base ca-
talysis, while the other implicates D168 as the
catalytic base in Dnase1 (12). Previous muta-
genesis indicates that both histidines and D168
are catalytically required; however, D168 could
also be a divalent cation coordinating residue.
Similarly, the catalytic mechanism may be dif-
ferent for atypical Dnase1L3 variants expressed
by other organisms. To compare Dnase1L3 cat-
alytic sites across species, we first generated a
Table 1: Energy Scores of Dnase1L2 and Dnase1L2 ΔPRD. All scores are rounded to three decimal places.
Relaxed energy scores are the average of 30 trials.
multiple sequence alignment (MSA), intending
to predict the catalytic residues of six specific
animal homologs which displayed distinct se-
quence variation from human Dnase1L3 (Fig-
ure 4). The MSA showed that all DNA binding
contacts and cation contacts in Dnase1L3 were
conserved by sequence location across species,
but residues at the same sequential position
of human Dnase1L3 catalytic histidines varied
dramatically. Of particular interest are the owl
monkey and box turtle variants, which are each
missing nearly the same stretch of residues,
which includes the first catalytic histidine, a
residue present in all other homologs (Figure
4). Homology modeling based on the recent
Dnase1L3 crystal structure could provide in-
sight into the catalytic potential of these homo-
logs. Understanding each variant’s catalytic po-
tential could elucidate the molecular evolution
of Dnase1L3 and the Dnase1 family in general.
Unlike other Dnases, Dnase1L1 has a glycosyl-
phosphatidylinositol (GPI) anchor on its C-ter-
minus which permits membrane binding (13).
In macrophages, Dnase1L1 uniquely facilitates
the endocytosis of Ehrlichia chaffeensis, a tick-
borne rickettsial pathogen. It binds to EtpE,
an Erlichia receptor protein, potentially via a
“zipper mechanism” (14); however, the struc-
tural basis for this protein-protein interaction,
and thus for pathogenic endocytosis of Ehrli-
chia as a whole, has yet to be identified. (15).
Using computational analysis, including ho-
mology modeling, molecular dynamics, and
Rosetta-based protein energy minimization,
our study investigates the unique structural
10
features of the Dnase1 family. It concurrently
details these features’ proposed implications
on Dnase1 enzyme catalytic activity and pro-
tein-specific functions. We hypothesized that
the Dnase1L2 PRD located off of its core nu-
clease domain would prove energetically (and
thus structurally) unfavorable, but we found
that this domain actually enhances molecu-
lar stability. Though we proposed that catalyt-
ic site differences between Dnase1 and Dna-
se1L2 would account for Dnase1L2’s acidic
pH, key catalytic and DNA binding residues
are nearly identical among the two. Similarly,
we comparatively investigated catalytic sites of
Dnase1L3 animal homologs. We illustrate the
active site conformation of key catalytic resi-
dues in these variants, and specifically note the
surprising folding pattern and catalytic resi-
dues of the box turtle variant. We additionally
confirmed our hypothesis that Dnase1L1 would
function within near-membrane proximity, as
it was simulated to remain within 45 Å of the
plasma membrane. Finally, binding contacts
between Dnase1L1 and Ehrlichia protein EtpE
were identified. Overall, our results illustrate dis-
tinct Dnase1 family structural features in silico
and their functional implications, and they may
have significant applications in human health.
Results
Homology modeling predicts structures for
Dnase1L1 and Dnase1L2
Recent advances in computational technolo-
gy permit the prediction of unsolved protein
structures using homology modeling. Here, two
preeminent approaches, PyMOD and Robetta,
were used to generate putative structures for
Table 2: Residues near the DNA binding site in Dnase1 and Dnase1L2. Text colors are based on the residue
colors in Figure 3.
Dnase1L1 and Dnase1L2 (Figure 1). Though Ro-
betta uses RoseTTA fold, a fairly comprehen-
sive, three-track neural network approach (16),
PyMOD-based (17) models had the advantage
of additionally including Dnase1L3 structures
recently crystallized by the Sutton Lab, which
are not yet available online. PyMOD modeling
based on the Dnase1 and Dnase1L3 structures
generated a more compactly folded structure
for Dnase1L1, whose C-terminus adhered tight-
ly to the rest of the structure (Figure 1a), and
Dnase1L2, whose proline rich domain (PRD)
also folded closer to the protein (Figure 1b).
In contrast, the Robetta models depict an ex-
tended C-terminus loop in Dnase1L1 (Figure
1c) and a protruding PRD in Dnase1L2 (Figure
1d). These homology models serve as the ba-
sis for our further structural experimentation.
Dnase1L2 proline rich domain enhances pro-
tein stability
In order to compare the structural stability of
native Dnase1L2 with Dnase1L2 lacking its Pro-
line rich domain (Dnase1L2 ΔPRD), we used
PyMOD homology modeling to determine a
structure for Dnase1L2 ΔPRD, having cleaved
the proline rich domain (PRD) from G140 to
A160 (Figure 2). Both Dnase1L2 and Dnase1L2
ΔPRD were scored using the Rosetta all-atom
energy function and relaxed to identify the most
11
energetically favored conformation (18). Except-
ing the removal of the PRD, Dnase1L2 ΔPRD
remains otherwise unchanged in comparison
to Dnase1L2, as evidenced by the seamless
overlay of the respective beta sheets (Figure 2).
Surprisingly, Dnase1L2 demonstrated a lower
energy score than Dnase1L2 ΔPRD, and despite
its large, protruding PRD loop, this lower score
indicates it is the more structurally stable of the
two enzymes (Table 1). Dnase1L2’s enhanced sta-
bility could explain its generally high expression,
specifically in keratinocytes (9), since the PRD
does not affect Dnase1L2 catalytic activity (11).
The structural basis for Dnase1L2 catalytic
activity and intermolecular contact
The structural basis for Dnase1 DNA bind-
ing and catalysis has been illustrated (19),
but it could benefit from further inves-
tigation. Aligning DNA bound Dnase1
(PDB ID: 1dnk) with the homology model of
Dnase1L2 (Figure 3) illustrated that all cata-
lytic residues, critical DNA contacts, and cat-
ion contacts were positionally conserved in
the structure of Dnase1L2 (Table 2) (20) (21).
Though we anticipated structural differenc-
es between the Dnase1 and Dnase1L2 catalyt-
ic sites, they appear to be nearly identical, so
it is unlikely that Dnase1L2’s DNA binding
domain or catalytic mechanism is respon-
sible for its optimal activity at an acidic pH.
Atypical Dnase1L3 animal homologs display
varied catalytic residues
To extend our understanding from primary to
tertiary structure, we homology modeled and
relaxed (18) each of the six atypical Dnase1L3
animal homologs, using the newly-crystallized
Dnase1L3 structures from the Sutton Lab as
our basis. In general, human Dnase1L3 and an-
imal homolog structures aligned closely, while
the Rosetta structural relax function further en-
hanced energetic favorability (Table 3). Aligning
with the sequence prediction, the owl monkey
variant was missing one beta sheet and alpha
helix, corresponding to A144-N182 in human
Dnase1L3 (Figure 5a). Of note, the absence of
this region did not significantly alter the rest of
the folded variant, or the residues located at its
catalytic site, because though the owl monkey
homolog is missing one histidine, its remain-
ing catalytic residues and critical DNA con-
tacts remain structurally conserved (Figure 6).
In contrast, though the box turtle Dnase1L3
sequence resembled that of the owl monkey,
its 3D structure exhibited a surprising sec-
ondary structure pattern and catalytic residue
positioning. The box turtle variant’s missing
region, which sequentially includes residues
from D126 to W159 in human Dnase1L3 (Fig-
ure 4), does not structurally result in a missing
helix or sheet. Instead, the box turtle residues
corresponding to K160 onwards still fold in an
astonishingly similar pattern to Dnase1L3, de-
spite having a sequence shifted by 33 residues;
its relaxed energy score and R.M.S.D are weak-
er than most of the other variants (Table 3).
Furthermore, the catalytic histidines struc-
turally align to M150 and L267 respectively.
M150 and L267 are both uncharged and hy
drophobic side chains and therefore cannot
give or receive a proton in acid base catalysis.
All variants excepting the box turtle displayed
catalytic residues consistent with our sequence
prediction; these may still be catalytically ac-
tive (Figure 6). For example, in the chimp ho-
molog, the first catalytic histidine is conserved,
and the residue in place of the second catalyt-
ic histidine, serine, could still hydrogen bond
to other catalytic residues, and participate in
catalysis (Figure 6b). The Chinese alligator
variant also possesses the first catalytic his-
tidine, but in contrast, its second histidine is
substituted for a valine; though the valine is
unlikely to be involved in catalysis, depend-
ing on the exact biochemical catalytic mecha-
nism in Dnase1s, the variant could still remain
active (12). Of particular interest is the fact
that all variants possess glutamate and aspar-
tate cation contacts; each one also possesses
an aspartate catalytic site residue, and all but

As a result, although all box turtle catalytic

residues downstream of this shift sequential-
ly align to human Dnase1L3 (Figure 4), they Figure 3: Dnase1L2- DNA Binding. Dnase1 is in
do not structurally align. Therefore, similar- lime green. Dnase1L2 is in pale blue. Cation contacts
ity appears to be isolated to a primary struc- are in purple. Critical DNA binding contacts are in
tural level, as the hypothesized catalytic res- red. Catalytic residues are in blue. Dnase1 residues
are darker in color than those of Dnase1L2.
idues are not located near the catalytic site
and therefore cannot participate in catalysis.
12
Figure 4: Multiple sequence alignment of seven different species isoforms of Dnase1L3 Residues are highlight-
ed based on their structural position. Cation contacts are in purple. Critical DNA binding contacts are in red.
Catalytic residues are in blue.

13
the box turtle possess a glutamate catalytic
residue.Whether these structural facets support
the single divalent carboxylic acid mechanism
or the principal importance of divalent cation
coordination in the active site is not yet clear, but
our results indicate the relative importance of
these site residues, given their high conservation.
Dnase1L1 membrane binding dictates the
range of its catalytic activity and facilitates
Ehrlichia chaffeensis pathogenic entry
Dnase1L1 binds to the cell membrane via a
Glycosylphosphatidylinositol (GPI) anchor. To
identify the impact of membrane localization
on the range of Dnase1L1 catalytic activity, we
conducted a NAMD-based CHARMM36 force
field molecular dynamics simulation in explicit
solvent in the presence of the physiologically
relevant membrane, with Dnase1L1 attached
to a GPI anchor embedded in the membrane.
Dnase1L1’s simulated location was consistently
within around 45 Å of the membrane, indicat-
ing its catalytic activity is isolated within that re-
gion as well (Figure 7) (Supplementary Video 1).
In order to predict the structure of EtpE,
which has been shown to bind to Dnase1L3
but has not been widely investigated, we ran
a BLAST search to identify sequence homo-
logs. We discovered that a cAMP-dependent
protein kinase (PDB ID: 4HPT) exhibited the
highest sequence similarity. We then homol-
ogy modeled EtpE against 4HPT and relaxed
its structure. We found that polar contacts be-
tween Dnase1L1 and EtpE included hydrogen
bonds between Val97 and Gly369 and Tyr452
and Thr66, and therefore we predict that these
residues are critical to the EtpE-Dnase1L1
binding interface (Figure 8). Identification of
the key binding residues is critical to targeted
disruption of EtpE-Dnase1L1 affinity, which
could prove critical to therapeutic intervention.
Discussion
Here we demonstrate in silico the structur-
al characteristics of Dnase1 family nucleases
which contribute to their crucial catalytic ac-
tivity and specialized cellular functions. We
employed homology modeling as the basis for
our investigation, generating novel structures
for Dnase1L1, Dnase1L2, and six animal homo-
logs of Dnase1L3. We found that the Dnase1L2
proline rich domain stabilized the molecu-
lar structure. We also identified the structural
mechanism for Dnase1L2 catalytic activity, and
its similarity to Dnase1. We further investigated

Figure 5: Comparison of Animal Homologs to Human Dnase1L3. The specific human Dnase1L3 region miss-
ing from the owl monkey (T122-W159) and box turtle (D126-W159) homolog sequences is highlighted in red.
a. Owl monkey Dnase1L3 (grey) and human Dnase1L3 (black). The owl monkey Dnase1L3 magenta loop
consists of four residues to either side of the missing region, for illustrative purposes. b. Box turtle Dnase1L3
(brown) and human Dnase1L3 (black).
14
Table 3: Dnase1L3 Animal Homolog R.M.S.D. and Energy Scores. Energy scores are rounded to three deci-
mal places.
catalysis by modeling Dnase1L3 animal homo-
logs, in which we observed the structural im-
plications of catalytic residue discrepancies be-
tween human Dnase1L3 animal models. Most
prominently, the Box turtle variant was missing
a stretch of residues which included its first
catalytic histidine, and this variant’s tertiary
structure folded differently than our primary
structure-based prediction. Finally, we propose
contact residues between Dnase1L1 and EtpE
that mediate Ehrlichia chaffeensis endocytosis.
Proteins with PRDs are known to be difficult to
crystallize; often, the PRD must be cleaved to
successfully execute the crystallization process.
Homology modeling demonstrated the positive
impact of the PRD on energetic favorability
and therefore structural stability, indicating it
likely exists for a specific function. Though the
PRD does not impact on the catalytic activity of
Dnase1L2, its purpose has yet to be identified
(11). We hypothesize the PRD may be an SH3
binding domain (22) and hope to investigate
this possibility as a course for further study.
Our Dnase1L3 animal homolog homology
models also had the unique advantage of uti-
lizing crystallized human Dnase1L3 structures
as their basis. These structures reveal unique
folding patterns which were not recognizable
15
simply by sequence analysis, and which could
have broader significance in understanding
Dnase1 family molecular evolution. Notably,
the box turtle Dnase1L3 was of particular in-
terest due to its unique folding mechanism,
which resulted in distinctive catalytic residues
unlike those of any other variant. These results
raise new questions as to Dnase function and
folding. The varied residues substituted for the
second catalytic histidine in many of the ho-
mologs, coinciding with the conservation of as-
partate and glutamate cation binding residues,
and conservation of separate aspartate and glu-
tamate catalytic residues, could support an al-
ternative biochemical basis for Dnase catalyt-
ic mechanism as well. Here we also illustrated
that the residues likely involved in Dnase1L2
DNA binding and catalysis are nearly identi-
cal to those in Dnase1. Understanding specific
structural facets driving DNA-degrading ac-
tivity can open new doors for therapeutics or
have alternative applications in human health.
Our simulation of membrane-bound Dnase1L1
activity demonstrated the membrane proximi-
ty which is likely necessary for DNA degrada-
tion. This specific membrane localization is a
distinguishing feature to Dnase1L1, though
further studies are needed for confirma-
tion. Furthermore, homology modeling EtpE
and docking it to Dnase1L1 uniquely illustrat-
ed key residues involved in the interaction.
Because Dnase1L1-EtpE interaction is abso-
lutely critical for the pathogenic endocyto-
sis of Ehrlichia chaffeensis, the residues we
illustrated could serve as therapeutic targets
to prevent the human disease Ehrlichiosis.
One shortcoming of homology modeling is
its failure to perfectly account for unique do-
mains. For example, many of the animal homo-
logs, most obviously the owl monkey variant,
possess lengthy domains (often at the N- and
C-terminus) which are not conserved in human
Dnase1L3; though none interfere with catalytic
activity, these may not be modeled in exactly the
correct position. Due to this shortcoming and
the generally putative nature of in silico research,
further in vitro studies are necessary to validate
and expand upon our notable structure-based

Figure 6: Active sites of Dnase1L3 animal homologs

Human Dnase1L3 catalytic residues are in blue. Animal homolog residues are in cyan. The human Dna-
se1L3 backbone is black. Each specified animal homolog has a colored backbone.
16

Figure 7: Dnase1L1 is bound to the cell membrane
via a GPI anchor
Full-atom molecular dynamics in explicit solvent
modeled on a phospholipid membrane with lipid
components: 74 cholesterol, 72 POPE, and 67 PSM in
the upper leaflet and 73 cholesterol, 75 POPE, and
67 PSM in the lower leaflet. The MD setup was per-
formed with CHARMM-GUI, and ran with NAMD
in the CHARMM36m force-field. The centroid of
the Dnase1L1 core domain is roughly 45 Å from the
surface of the cell membrane. For the full simulation,
please view Supplementary Video 1.
results. In the future, further understanding the
structural facets of Dnase1 family proteins will
create new pathways for preventing, treating,
and mitigating human autoimmune diseases.
Materials and Methods
Homology Modeling Dnase1, Dnase1L2, and Dna-
se1L2 ΔPRD:
Homology models for uncrystallized pro-
teins were generated using PyMOD, a PyMOL
plugin (17), unless otherwise specified. Dna-
se1L1 and Dnase1L2 structures were based
on four crystallized Dnase1 structures (PDB
IDs: 4awn, 3dni, 1dnk, 1atn, 2a40) and four
crystallized Dnase1L3 chains (unpublished).
SALIGN was used to generate the sequence
alignment, while MODELLER was used to
predict the target’s 3D structure. Cleavage of
the PRD in Dnase1L2 was conducted and vi-
17
sualized in PyMOL; homology modeling of
DNase1L2 ΔPRD was based on the same afore-
mentioned Dnase1 and Dnase1L3 structures.
Dnase1L3 Animal Homologs Sequence and Struc-
ture Assessment:
We used Clustal Omega to generate the mul-
tiple sequence alignment of DNase1L3 animal
homologs (23). Structures were generated using
PyMOD homology modeling and were based on
four crystallized Dnase1L3 chains (unpublished).
Within PyMOD, SALIGN was used to generate
the sequence alignment, while MODELLER
was used to predict the target 3D structures.
Rosetta structural relax:
Before testing each of our homology mod-
eling-based hypotheses, we employed Ro-
setta’s FastRelax and all-atom energy
function in order to achieve, assess, and
compare energetically favorable conforma-
tions of each of our homology models (18).
Dnase1L1 GPI anchor attachment and membrane
simulation:
We used CHARMM-GUI membrane build-
er to attach a GPI anchor at the C-terminus
to our homology model of Dnase1L1. The GPI
anchor was embedded in the membrane us-
ing the orientation of proteins in membrane
prediction and the Molecular Dynamics in-
put files were generated for NAMD. The sim-
ulation was run for 100 ns on the High Per-
formance Computing Center (HPCC) at TTU.
Dnase1L1 EtpE binding:
A BLASTp search (24) identified sequence
homologs for EtpE. We noted the highest se-
quence identity match with a crystallized struc-
ture, which was a cAMP-dependent protein
kinase (PDB ID: 4HPT). We used PyMOD to
homology model EtpE against 4HPT. SALIGN
was used to generate the sequence alignment,
while MODELLER was used to predict the tar-
get’s 3D structure. We modeled EtpE docking
to Dnase1L1 on ZDock (25) The ZDock output
was relaxed with Rosetta (see Rosetta struc-
tural relax) to account for any residue clashes.

Figure 8: EtpE-Dnase1L1 binding
EtpE is shown in marine blue. Dnase1L1 is shown in
cyan. Critical binding contacts are highlighted in red.
Supplementary Video 1:
Membrane-bound Dnase1L1 activity
https://drive.google.com/file/d/1qcnMBTd-
JGrHZbqBH36b2NVx0AOkNscDQ/view?us-
p=sharing
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 Interleukin-33 Expression is
Upregulated in Colon Stem
Cells After Irradiation
by Mirika Jambudi (V), Ya-Yuan Fu PhD1
1
Memorial Sloan Kettering Cancer Center, New York, NY
Abstract
Interleukin-33 (IL-33), a pleiotropic cytokine,
plays critical roles in intestinal immunity, con-
tributing to tissue homeostasis and responses
to infection and inflammation. Extracellular
IL-33 can be sequestered by its decoy receptor,
soluble ST2 (sST2). While sST2 has been iden-
tified as a predictive biomarker of intestinal
injury, including graft-versus-host disease and
inflammatory bowel disease, the role of IL-33 in
intestinal stem cell (ISC) compartment remains
unclear. In the colon, the ISC compartment
consists of colonic stem cells necessary for ep-
Muscle layer of colon tissue, stained with
DiD and DAPI
19
ithelial regeneration upon damage and niche
cells providing growth factors to the stem cells.
Given the inability of traditional two-dimen-
sional (2-D) imaging to precisely evaluate the
IL-33-producing cell localization and its rela-
tionship to the ISC compartment, we sought to
develop an approach using three-dimensional
(3-D) microscopy of intact colonic tissue from
IL33-GFP reporter mice following total body
irradiation (TBI) to analyze the specific loca-
tions of IL-33-producing cells within colon af-
ter damage. Using this approach, we found that
IL33-GFP+ cells were predominantly locat-
ed at the submucosal layer while others were
located at the crypt base during homeostasis.
IL33-GFP+ epithelial cell number significantly
increased in the colonic crypt base after TBI.
To phenotype IL33-GFP+ epithelial cells in the
colonic stem cell compartment at crypt base,
Lgr5-GFP ISC reporter mice were used to es-
tablish an approach for evaluating the colonic
stem cells and niche cells. Using Lgr5-GFP mice
with whole-mount immunofluorescence stain-
ing, cKit immunostaining labeled Lgr5-GFP-
colonic niche cells and Smoc2 immunostaining
labeled Lgr5-GFP+ colonic stem cells in the
stem cell compartment. Assessment of IL33-
GFP+ epithelial cells in the stem cell compart-
ment with immunostaining of cKit and Smoc2
demonstrated upregulation of IL-33 expression
in Smoc2+ colonic stem cells after radiation in-
jury. These findings suggest that IL-33 plays a
role in colonic stem cells after intestinal damage.
 Examining Star Formation in
the Evolution of Elliptical
Galaxies
by Max Watzky (V), Milenka Men (V), Inimai Subramanian1, Juliana Karp1
1
Astronomy Camp, University of Arizona, Tucson, AZ

Abstract
The predominant theory of galaxy evolution holds that elliptical galaxies are formed when
two or more spiral galaxies merge with one another. We hypothesized that if elliptical galax-
ies do indeed form in this way, they would exhibit a low star formation rate (SFR) compared
to other types of galaxies, as they had exhausted their reserves of star-forming gas in vio-
lent collisions. In order to test this hypothesis, we used a hydrogen-alpha (H-alpha) filter,
which isolates light from the ionized hydrogen found in stellar nurseries, to image star-form-
ing regions in multiple galaxies at different stages in the galaxy merger process. Although
we are still in the process of drawing quantitative measurements from the data, we spec-
ulate that star formation in the sample elliptical galaxy is less pronounced than in the sam-
ple spiral and merging galaxies, indicating that it may have been formed in a galaxy merger.

Introduction
According to Hubble’s Galaxy Classification System, there are four major types of galaxies: spiral,
barred spiral, elliptical, and irregular. Spiral and barred spiral galaxies like the Milky Way were
formed by collapsed clouds of gas that clumped together into larger hierarchical structures. Many
spiral galaxies exist in structures known as galaxy clusters, which consist of several galaxies gravi-
tationally bound to one another. Within such clusters, spiral galaxies frequently collide and merge
with one another. As galaxy mergers take place, high-density regions of interstellar gas collide,
creating an environment of enhanced star formation. In these violent events, the merging gal-
axies burn through their reserves of star-forming gas, meaning that the resulting galaxies would
then exhibit relatively little active star formation. Elliptical galaxies, which have well-established

Figure 1: M106 in all visible light Figure 2: M106 in H-alpha

20
 Figure 3: Stephan’s Quintet in all visible light
low SFRs, match this description, leading some
to believe that they are formed in galaxy merg-
ers. Alternative hypotheses attribute ellipticals’
low SFR to ram pressure stripping and thermal
evaporation, processes by which spiral galaxies
in galaxy clusters and groups lose star-forming
gas through interactions with the surrounding
medium. The merger theory of elliptical evo-
lution is supported by the fact that relatively
few ellipticals are spotted billions of light years
away, indicating that they had not yet had time
to form via collision in the early universe. In
an effort to confirm or refute this theory, we
decided to compare the SFRs of spiral and
merging galaxies to that of ellipticals, a proven
technique which has been used by several prior
studies to investigate elliptical evolution. Our
comparison was performed by imaging samples
of the different types of galaxies using a filter
that isolates light in the H-alpha wavelength.
Hydrogen-alpha is a spectral line emitted when
electrons in hydrogen atoms fall from the third
energy level to the second. This energy level
jump is indicative of hydrogen ionization, which
sometimes occurs when hydrogen is exposed to
newly-formed stars. Thus, by imaging the gal-
axies with a H-alpha filter, we were able to de-
tect star formation. Using this kind of filter, we
took data from the spiral galaxy M106, a group
of merging galaxies in Stephan’s Quintet, and
the elliptical galaxy NGC 5813. In order to take
baseline measurements of the galaxies’ lumi-
nosity, we also imaged M106, Stephan’s Quin-
21
Figure 4: Stephan’s Quintet in H-alpha
tet, and NGC 5813 with filters that allowed all
light from the visible spectrum to pass through.
Results
In the full visible spectrum image of the spi-
ral galaxy M106, a central nucleus, an inner disc
containing two prominent spiral arms, and two
faint outer arms are visible (Fig. 1). By compari-
son, only the central nucleus and two inner spi-
ral arms are discernible in the H-alpha image
(Fig. 2). In both the H-alpha image and the full
visible spectrum image of Stephan’s Quintet
(Fig. 3, 4), two galaxies with spiral arms, NGC
7318a and NGC 7318b, can be seen undergoing
collision at the center. However, the spiral arms
of another galaxy above and to the left of the
colliding pair, NGC 7319, are only clearly vis-
ible in the full spectrum image. A fourth gal-
axy, NGC 7320, is visible below NGC 7319, but
this galaxy is actually hundreds of millions of
light-years away from the others, and not in-
volved in the merger. In the full visible spec-
trum image of the elliptical galaxy NGC 5813,
a bright core surrounded by a faint yellow disc
can be seen (Fig 5.), but these features are con-
siderably dimmer in the H-alpha image (Fig 6.).
Discussion
​​Due to the use of various telescopes and in-
struments in this project, our images are of
differing quality, meaning that reliably inter-
preting the data has been difficult, and the ef-
fort to produce quantitative measurements of
star formation is still ongoing. Nonetheless, a
few aspects of the results stand out to us. Only
some of the features detected in the full visible
spectrum image of the spiral galaxy M106 are
defined in the H-alpha data (Fig. 1, 2), indicat-
ing that star formation is localized to certain
regions of the galaxy. By contrast, the features
of the colliding galaxies in Stephan’s Quintet,
NGC 7318a and NGC 7318b, are well defined
in both images (Fig. 3, 4), suggesting a higher
SFR in the merging pair than in M106. The
fuzzy disc and central core of the elliptical gal-
axy NGC 5813 are much dimmer in the H-alpha
image than in the full visible spectrum image,
which we speculate reflects a low SFR com-
pared to the spiral and merging galaxies (Fig.
5,6). If correct, this observation indicates that
NGC 5813 may be the result of a galaxy merg-
er. However, because NGC 5813 is located in a
small galaxy group, ram pressure stripping or
thermal evaporation may have played a role in
its low SFR, although the extent of these in-
fluences is unclear. All things considered, our
results’ qualitative nature, the plausibility of
alternative explanations for the data, and the
small scope of our project make it difficult to
draw a meaningful conclusion. We hope that
future quantitative analysis of our data and the
conduction of broader surveys will offer greater
insight into the evolution of elliptical galaxies.
Figure 5: NGC 5813 in all visible light
22
Methods
In order to produce the hydrogen-alpha images
of M106, Stephan’s Quintet, and NGC 5813, we
took between 10 and 20 two-minute exposures of
each target using the 24” Mt. Lemmon SkyCen-
ter telescope, a 16 megapixel CCD camera, and a
narrowband H-alpha filter. The images of each
galaxy were then stacked together in the Maxim
DL astronomy image processing software. We
also took images of NGC 5813 and M106 using
the 32” Schulman telescope, a 16.78 megapixel
CCD, and red, green, and blue filters, which we
stacked together to create full color images of
the galaxies, which contain light from the entire
visible spectrum. The same effect was achieved
for Stephan’s Quintet by taking an image us-
ing a clear filter, which also allows light from
the entire visible spectrum to pass through.
Acknowledgements
Thank you to the University of Arizona’s Mt.
Lemmon SkyCenter Observatory for access to
the telescopes, as well as Don McCarthy and all
camp counselors at the University of Arizona Ad-
vanced Astronomy Camp 2021 for their guidance.
Figure 6: NGC 5813 in H-alpha
 The Post-Transcriptional Role
of Igf2bp3 and its Interactions
with NF-кB in Cancer
by Anuska Agarwal ‘21

Insulin-like growth factor 2 mRNA binding protein 3 (Igf2bp3) is part of a family of RNA-binding pro-
teins that mediate post-transcriptional gene regulation. Insulin-like growth factor 2 mRNA binding
proteins (Igf2bps) form stable complexes with target mRNA strands, effectively shielding them from
microRNA (miRNA) degradation. They can bind a wide range of mRNAs and therefore have effects
on various cellular pathways. Igf2bp3 expression in normal adult tissues is rare. Conversely, its ex-
pression in cancerous tissues is implicated in cell proliferation, adhesion, invasion, and migration (1).

I researched Igf2bp3 in the context of investigating genes of interest from RNA-sequencing (RNA-seq)
data from mouse models with a RelA Thr505 mutation. RelA is an NF-кB subunit and transcription
factor that can promote tumor formation. RelA Thr505 phosphorylation is linked to pro-apoptotic
effects in response to replication stress; a RelA T505A mutation prevents Thr505 phosphorylation
and therefore promotes tumor cell viability and proliferation. RNA-seq data of the RelA T505A
cells revealed a log2(FC) increase of 3.5 for Igf2bp3 mRNA, and this was the focus of my research.

High Igf2bp3 expression has also been correlated with lower median survival rates
in patients with multiple tumor types. Figure 1 displays Kaplan-Meier plots of pa-
tients with high and low Igf2bp3 expression in renal clear cell carcinoma, renal pap-
illary cell carcinoma, lung adenocarcinoma, and pancreatic ductal adenocarcinoma.

Igf2bp3 expression has been identified in an estimated 80% of tumor types, and its over-
expression is frequently associated with aggressive tumors and a higher risk of death (3). Ex-
pression varies by tumor type, but it is consistently detected in a majority of cases of lung
cancer, germ cell cancer, colon cancer, pancreatic cancer, gastric cancer, liver cancer, and kid-
ney cancer (3,4,5). In contrast, expression is rarely detected in gastrointestinal stromal can-
cer, leiomyoma, and bladder cancer (3,6). The cause of these variations in Igf2bp3 expression
among tumor types is unclear. However, in cancers where it is commonly expressed, overex-
pression has been suggested as a biomarker for advanced grade tumors. Figure 1 demonstrates
how high expression correlates with lower chances of survival in four sample tumor types.

Igf2bp3 binds RNA via four K homology (KH) domains, conserved sequences that are essen-
tial for target strand recognition (9). Mutations in Igf2bp3 KH domains are uncommon, but
generally inhibit its ability to bind mRNA. Somatic mutations are present in less than 1% of
cancer patients (10). Amplification is present in less than 2% of all cancer patients but oc-
curs at a much higher rate in some cancer types (10). Copy number variation (CNV) gain oc-
curs in over 30% of the tumors in autonomic ganglia tissues and pancreatic tissues (8).

23
Igf2bp3’s ability to promote the translation of a
range of target transcripts means that it can af-
fect a range of cellular pathways. Its role in pro-
moting cell proliferation and migration varies
by tumor type. For example, its regulation of the
oncogene Myc has been noted in mixed lineage
leukemia, B-acute lymphoblastic leukemia, and
pancreatic cancer (1,9). It has also been shown
to promote the translation of several other com-
mon oncogenes, including Ras and Igf1r, and cell
cycle factors such as cyclin D1 and cyclin D2 (1).
In the interest of further investigating the up-
regulation of Igf2bp3 in RelA T505A cells, I
researched the relationship between Igf2bp3
and NF-кB. Igf2bp3 has been implicated in a
regulatory role of RelA expression in glioblas-
toma, thereby promoting glioma cell migration
(11). In renal clear cell carcinoma, Igf2bp3 has
been shown to directly interact with the mRNA
of all NF-кB subunits and promote their trans-
lation. Its overexpression also promotes NF-кB
activity through increased phosphorylation of
IкBa, an inhibitor of p50 and RelA (12). In ad-
dition, Igf2bp3 has been identified as a tran-

Figure 1: Kaplan-Meier plots of high and low expression of IGF2BP3 in various tumor types: a) renal clear
cell carcinoma, 1% false discovery rate (FDR); b) renal papillary cell carcinoma, 1% FDR; c) lung adenocar-
cinoma, 5% FDR; d) pancreatic ductal adenocarcinoma, 1% FDR (2).
24
scriptional target of RelA, providing evidence
of a positive feedback loop between the two
proteins (1,11). Expression of Igf2bp3 has been
suggested as a marker for a greater risk of me-
tastasis and lower survival rate in both glio-
ma and renal clear cell carcinoma (13,14). One
study suggests that Igf2bp3 expression in renal
cell carcinoma correlates with a 42% increase
in risk of death and nearly a five times great-
er risk of developing tumor metastases (15).
These interactions between Igf2bp3 and NF-
кB are a possible explanation for the significant
overexpression of Igf2bp3 in the RelA T505A
cells that I initially observed. The upregulation
of RelA may contribute to increased expression
of Igf2bp3, thus promoting the translation of
oncogenic transcripts and cell proliferation.
Interactions between Igf2bp3 and NF-кB have
been noted in multiple cancers where Igf2bp3
serves as a prognostic for advanced grade tu-
mors, metastases, and lower survival rates. Fur-
ther research is required to elucidate the nature
of these interactions, their contribution to tumor
formation and metastases, and whether simi-
lar interactions exist within other tumor types.
Works Cited
1. Mancarella, C., & Scotlandi, K. (2020). IGF2BP3 From
Physiology to Cancer: Novel Discoveries, Unsolved Issues,
and Future Perspectives. Frontiers in cell and developmen-
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2. Nagy A, Lánczky A, Menyhárt O, Győrffy B. Validation
of miRNA prognostic power in hepatocellular carcinoma
using expression data of independent datasets, Scientific
Reports, 2018;8:9227
3. Burdelski, C., Jakani-Karimi, N., Jacobsen, F., Möller-
Koop, C., Minner, S., Simon, R., Sauter, G., Steurer, S.,
Clauditz, T. S., & Wilczak, W. (2018). IMP3 overexpression
occurs in various important cancer types and is linked to
aggressive tumor features: A tissue microarray study on
8,877 human cancers and normal tissues. Oncology re-
ports, 39(1), 3–12. https://doi.org/10.3892/or.2017.6072
4. Tang, H., Wei, Q., Ge, J., Jian, W., Liu, J., Zhong, L., Fu,
B., & Zhao, T. (2013). IMP3 as a supplemental diagnostic
marker for Hodgkin lymphoma. Human pathology, 44(10),
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5. Pryor, J. G., Simon, R. A., Bourne, P. A., Spaulding, B.
O., Scott, G. A., & Xu, H. (2009). Merkel cell carcinoma
expresses K homology domain-containing protein overex-
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crine carcinomas. Human pathology, 40(2), 238–243. https://
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doi.org/10.1016/j.humpath.2008.07.009
6. Yamamoto, H., Arakaki, K., Morimatsu, K., Zaitsu, Y., Fu-
jita, A., Kohashi, K., Hirahashi, M., Motoshita, J., Oshiro,
Y., & Oda, Y. (2014). Insulin-like growth factor II messenger
RNA-binding protein 3 expression in gastrointestinal mes-
enchymal tumors. Human pathology, 45(3), 481–487. https://
doi.org/10.1016/j.humpath.2013.10.010
7. Xu, W., Sheng, Y., Guo, Y., Huang, Z., Huang, Y., Wen, D.,
Liu, C. Y., Cui, L., Yang, Y., & Du, P. (2019). Increased IG-
F2BP3 expression promotes the aggressive phenotypes of
colorectal cancer cells in vitro and vivo. Journal of cellu-
lar physiology, 234(10), 18466–18479. https://doi.org/10.1002/
jcp.28483
8. Tate, J. G., Bamford, S., Jubb, H. C., Sondka, Z., Beare,
D. M., Bindal, N., Boutselakis, H., Cole, C. G., Creatore, C.,
Dawson, E., Fish, P., Harsha, B., Hathaway, C., Jupe, S. C.,
Kok, C. Y., Noble, K., Ponting, L., Ramshaw, C. C., Rye, C.
E., Speedy, H. E., … Forbes, S. A. (2019). COSMIC: The
Catalogue Of Somatic Mutations In Cancer. Nucleic acids
research, 47(D1), D941–D947. https://doi.org/10.1093/nar/
gky1015
9. Wächter, K., Köhn, M., Stöhr, N., & Hüttelmaier, S. (2013).
Subcellular localization and RNP formation of IGF2BPs
(IGF2 mRNA-binding proteins) is modulated by distinct
RNA-binding domains. Biological chemistry, 394(8), 1077–
1090. https://doi.org/10.1515/hsz-2013-0111
10. Gao, J., Aksoy, B. A., Dogrusoz, U., Dresdner, G., Gross,
B., Sumer, S. O., Sun, Y., Jacobsen, A., Sinha, R., Larsson,
E., Cerami, E., Sander, C., & Schultz, N. (2013). Integrative
analysis of complex cancer genomics and clinical profiles
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ri, S., Das, S., Hegde, A. S., Arivazhagan, A., Santosh, V., &
Somasundaram, K. (2017). IGF2 mRNA binding protein 3
(IMP3) promotes glioma cell migration by enhancing the
translation of RELA/p65. Oncotarget, 8(25), 40469–40485.
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hanced IMP3 Expression Activates NF-кB Pathway and
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 The Role of Narrative-based
Advocacy in Advancing the
Talanoa on Climate
by Natalie DeVito (VI)

“Talanoa is a traditional word used in Fiji and across the Pacific to reflect a process of inclusive,
participatory and transparent dialogue.”

Key Question: What factors currently prevent unified action against climate change and its
impacts? What is the power of community advocacy based in narrative to surmount humani-
ty’s patchwork of differences and lead us to a response to the threat of climate change?

Climate change is the most pressing existential threat facing humanity in the 21st century. It is of-
ten seen as an interminably advancing physical process, but a community’s experience of climate
change cannot be encompassed solely by corporeal changes. It is in fact intimately entangled
with the belief systems and religions they follow (1), with the gradually accrued cultural contexts
and perceptions that surround them (2), and with the resources and privileges available to them,
which determine their relative share in the “unequal ‘distribution of pain’” wrought by climate
change (2). The first part of this research will examine the disparate patchwork of differences
which so fragment the response of our species to climate change. Myths and religious narratives
ascribe meaning and morality to climate events, leaving room for individuals to deny or ignore
the reality of anthropogenic climate change. Issues of inequity and access ensure a further frag-
mentation of experience of climate change and undermine a sense of solidarity among different
peoples. Social contexts such as history, political messaging, and models of understanding and
action shape our perceptions and attitudes, and limit the range of options our communities are
likely to pursue. Within this context, scientists, advocates, politicians and religious leaders have
all struggled to find a cohesive, universally accessible plan to halt climate change. The second
part of this research will propose that advocacy steeped in emotional expression and personal
narrative can reframe the above factors which complicate a response to the indisputable threat
that climate change poses. It can leverage the far reach of religion to help communities adapt,
and raise questions about the allocation and even the definition of resources our communi-
ties need to combat climate change. Community climate advocacy can synthesize diverse cultur-
al perspectives and advance concrete action. Community advocacy based in narrative can sur-
mount humanity’s patchwork of differences and create a response to the threat of climate change.

Religions and myths augment the realities of rising sea levels and intense episodic weather with
diverse meanings, ranging from moral judgment to proof of our dominion over the earth. For us
to understand how these diverse belief systems determine how cultures across the world respond
differently to the threat of climate change, we must realize that “the idea of climate exists as much
in the human mind and in the matrices of cultural practices” as in the physical world, accord-

26
ing to scholars of comparative religion Willis
Jenkins, Evan Berry, and Luke Beck Kreider (1).
Storytelling, myth, and religion grew out of our
desire for etiological explanations for things we
did not understand, and today religious institu-
tions construct a meaning of climate change, no
less than they have constructed a meaning of
death. Religious agents use the values of a par-
ticular religious tradition to determine the rela-
tionship between ourselves and our conditions,
and therefore the extent of our responsibility for
climate change (1). This prismed interpreting of
climate change by different religions not only
refracts one real issue into a conflict of ideas,
it entrenches this conflict in moral prerogative.
By examining the individual religions that have
dominated and shaped the histories of differ-
ent world cultures, we discover deeply frag-
mented perspectives on climate change. For ex-
ample, Christianity is “the dominant religion of
the North Atlantic societies that developed fos-
sil-fuel industrialism” (1). In light of America’s
enormous singlehanded contribution to global
CO2 emissions and our long entanglement with
Christianity, ascribing moral sense to climate
change is threatening. Under a Christian treat-
ment, responsibility for the sin of condemning
whole communities, species and ecosystems to
extinction will come to rest on our shoulders.
This religious entanglement can help to con-
textualize the reticence of some to acknowl-
edge and address climate change, and the con-
tention of the issue in the United States overall.
Meanwhile, in Polynesia, where atoll commu-
nities like Kiribati are projected to be mostly
underwater by the end of the century (3), a res-
ervoir of flood myths shape public perception
(4). Myths recorded from Tahiti, Raiatea and the
South Island of New Zealand share common
elements of punishing gods; virtuous, indi-
vidualized survivors; and new covenants with
the creator. The resulting message that disas-
ter operates according to moral order, and that
virtuous behavior can avert such disaster, runs
counter to the reality that no one on Kiriba-
ti will be left unscathed by a sea level rise of
27
1.1 to 2 meters by the end of the century. One
traditional retelling of the Tahitian flood myth
concludes that even after a cataclysmic flood,
“[l]ook, Tahiti is still existing, lush and luxuriant
(transl)” (4). In the South Island myth, a king’s
covenant with the creator god takes the form
of a kahukura or rainbow (4). The belief of in-
evitable renewal of land and life again clashes
with scientists’ findings that unless or even if
we slash our carbon output immediately, the ef-
fects of climate change will be irreversible. This
comforting mythic backdrop, however, shapes
how Pacific Islanders experience the threat
of climate change. A recent survey on Kiriba-
ti found that 20% of responders cited faith in
God as their reason for being unconcerned
about climate change: “the Creator made Kiri-
bati and no one can change that so nothing
can drown our islands. It was God’s promise
that there won’t be big floods,’’ (5). Religious
faith is therefore a potent vessel for avoidant
behavior. The belief that God is greater than
the real threat of climate change, undermines
the urgent need for behavioral change (5).
The I-Kiribati are not the only ones for whom
religion is a means of denial. In the United
States, some Evangelical Christians under-
mine the reality of anthropogenic climate
change by refuting “the notion that planetary
systems are vulnerable to human action” (1).
They believe in God’s gift of a world imper-
vious to the destruction that science proves
we have wrought around us. With real conse-
quences, faith and dogma influence wheth-
er we accept, ignore, or deny climate change.
Even attempts at interreligious unity on cli-
mate have their own flaws. Most major reli-
gions agree on a shared stewardship role over
the Earth, entrusted to people by God (1).
Representatives of Indigenous belief systems
point out, however, that if the wrong message
of stewardship is amplified, it can entrench
anthropocentric arrogance and the commod-
ification of the Earth (1). A seemingly incon-
trovertible claim of responsibility is exposed
as a disastrous assertion of ownership, which
legitimizes exploitation. Another common and
controversial theme in religious treatments of
climate change is the apocalyptic. Biblical lit-
eralist Christians believe that the world will
end with the apocalypse detailed in the Bible
(1). This valence presents Evangelicals with a
narrative of preordained cataclysm which se-
verely undermines the perceived self-effica-
cy of their actions, and even frees them not to
act. At the interplay of climate reality and its
religious significance is the potential for deni-
alism, anthropocentrism, false hope, and the
fragmentation of climate intentions and goals.
Financial barriers to adaptation or relocation,
initial effects as disparately felt as they are ex-
treme, and the lack of preparedness of insti-
tutions responsible for the vulnerable further
fragment humanity’s experience and attitude
towards climate solutions. For Native Alas-
kans struggling to relocate away from eroding
coastlines, institutional constraints make the
process of relocation prohibitively expensive
(6). Kiribati islanders also cite cost as the main
factor preventing them from transitioning
to more sustainable water resource routines
(5). Poverty is therefore a factor in fragment-
ing our preparation for climate change which
spans the global North and South. The best
strategies for the preservation of at-risk ways
of life, relocation and anticipatory adaptation,
are contingent upon wealth, a resource largely
withheld from the most at-risk communities.
Experience of the effects of climate change
also hinges on the relative privilege of commu-
nities. Through the long association between
race, wealth, imperialism, and patterns of set-
tlement, indigenous and poor communities
have emerged overrepresented in the “10% of
the world’s population . . . 10 m or less above
current sea level” (6). A sea level rise of upwards
of a meter by the end of the century seems un-
avoidable, and the “land facing inundation is
racialized land—land that has been appropriat-
ed, settled, cultivated, and distributed through
a long history of deeply racialized projects” (7).
Marginalized peoples all over the world have
28
been effectively condemned to weather the
most immediate impacts of climate change
on the front lines of sea level rise, while those
in wealthy nations like the United States will
largely not be affected until long after I-Kiri-
bati and Alaskan Natives have been displaced.
The disproportionate impact of immediate cli-
mate change falls on communities whose adap-
tive capacity and whose role in solutions is
lower due to larger inequities. Many I-Kiribati
community members recognize the futility of
asking Kiribati, where annual CO2 emissions
per capita in 2016 were 0.463 metric tons in
comparison to the United States’ 15.564 (8), to
decrease its own carbon footprint: “What can
we do about sea level rise? . . . . Australia and
USA don’t even want to sign up to Kyoto. It’s
all lip service but no action, this is capitalism”
(5). They have minimal influence in world pol-
itics, and over the warming temperature and
rising sea level that will determine their future.
Rather than advocating doubly hard for I-Kiri-
bati interests, the United States and other big
emitters seem to marginalize them all too often.
Meanwhile, Alaska Native communities that
once shifted around to follow the bowhead
whale and other staple prey, have become set-
tled during the 20th century. Their resulting
vulnerability and dependence on government
solutions enmires the prospect of relocation,
which would once have been simple and nat-
ural for them, in bureaucracy and frustration
(6). Both the set of resources available to them
as they adapt, and their ability to effectively
leverage those resources (5), relies on inchoate
extensions of support from institutions such as
FEMA and the Alaskan and federal government.
Institutions, meanwhile, are stunningly un-
prepared to act as dynamically and collabora-
tively as the threat of climate change demands.
Around the world, traditional humanitarian
responses to crises are medical relief and ref-
ugee aid, along with long term provisions for
the return of infrastructure and economic ac-
tivity to an affected site. Both of these are futile
against a chronic geophysical process such as
climate change; relocation may be the only vi-
able option (6). The current post-disaster legal
framework, however, cannot handle that real-
ity. FEMA’s Stafford Act does not cover grad-
ual biophysical properties like erosion and
sea level rise, and even in those cases where
FEMA attempts to intervene, financial re-
sources are channeled into futile avenues (6).
This absence of necessary bureaucratic struc-
ture, “of clear guidelines and criteria . . . [cause]
distrust and frustration with state and federal
government authorities” (6). As shown, a com-
munity’s historical privilege, access to wealth,
and place in institutional power structures
contribute to determining its individual experi-
ence of climate change, and whether it receives
the external support necessitated by this his-
torical inequity can negatively impact its expe-
rience of solidarity and unity with other cul-
tures and institutions battling climate change.
As well as by religion and inequity, communi-
ties’ response to climate change are steeped
in the cultural context of recent history, polit-
ical messaging, communal values and models
for understanding and action. How a society
responds to natural disasters is not static; it
has evolved over centuries of experience and
change. For example, Americans’ view of na-
ture as a resistant frontier is a fundamental
product of our historical context: our fervent
pursuit of manifest destiny and the Wild West
(2). Around the world, as for Americans, com-
munal values forged throughout history shape
and often limit responses to climate change.
For example, Alaskan Natives struggling to find
a site for relocation must consider cultural
criteria (6). The I-Kiribati, on the other hand,
cite cultural affinity for their homeland in
their strong reluctance to leave Kiribati at all:
“I don’t want to leave my land and go to a big
country” (5). When culture ascribes such value
to tradition and permanence, it undermines
a community’s ability to adjust to changes in
behavior and location, even for their survival.
Political and societal messaging also impact a
community’s response to climate change. In
29
Kiribati, the government has done well to com-
municate the severe and dramatic impacts of
climate change, such as sea level rise. Messaging
on the changes in behavior needed at the indi-
vidual level in order to anticipate these impacts
and weather them with resilience, is far less
comprehensive. As a result, “existing climate
change discourses in Kiribati place responsibil-
ity on the government . . . reasserting their pater-
nalistic role” (5). Incomplete political messaging
has downplayed the I-Kiribati responsibility
to adapt, and left the community inadequate-
ly prepared for the threat of climate change.
Shared paradigms for action and understand-
ing are perhaps the most decisive determi-
nant of individual and communal response to
climate change. Through climate adaptation
specialist Natasha Kuruppu’s detailed study
of adaptive behavior in Kiribati, it has become
clear that individuals’ “belief in their own abil-
ities to manage water stress play a crucial role
in driving intentions to adapt” (5). Belief that
one cannot determine one’s own experience
leads to fatalism, denialism and avoidant be-
havior in the face of threat. Increased feelings
of self-efficacy, however, promote the intention
to adapt and form new behaviors (5). Whether
or not one perceives oneself to have a mean-
ingful impact on one’s own experience of the
threat of climate change determines how one
will act. However, in Kiribati, Kuruppu found
that there is limited understanding of what
specific behavioral changes can help fami-
lies prepare for climate change. Under this
model of action, without self-efficacy feelings,
the potential for adaptive behavior is limited.
Individuals’ responses to climate change are
limited not only by their existing models of ac-
tion, but by models of understanding. Among
those surveyed, Kuruppu found that “a ma-
jority (75%) had no idea of the causal drivers
behind changes to local climatic patterns” (5).
Many I-Kiribati seemed to need to see it to
believe it: “They said in the paper that global
warming is caused by a blanket covering the
atmosphere but because I can’t see the blan-
ket, it makes it hard for me to fully understand
and believe in global warming” (5). In fact, most
I-Kiribati respondents did not even identi-
fy “anthropogenic climate change” as a factor
in changing climate patterns, instead blaming
factors that were local and easier to concep-
tualize, such as their neighbors’ farming prac-
tices. A majority were aware of climate change
and its consequences, but understanding of its
causes and possible solutions, and its impact
on water resources, was weak (5). As shown,
inadequate models of knowing and under-
standing can leave a community feeling uncer-
tain and limit its ability to respond to climate
change with informed and confident action.
Social and cultural factors such as religion, in-
equity, and cultural context add a dizzying di-
mension to the search for a cogent response to
climate change. Advocacy based in emotion, ex-
pression and personal narrative can engage that
same social and cultural complexity to probe
for a solution. Historian Uwe Lübken argues
that the accelerating effects of climate change
“demand a unique mode of historical under-
standing appropriate to their dramatic pace”
(1). Similarly, the growing multitude of subjec-
tive factors which makes agreeing and acting in
unity on climate so difficult, requires a unique
cultural and personal solution to unify them.
Our understanding and response to natural
disasters already hinges on subjective emotion
and social behavior: “The social dimension of
natural disasters is evident . . . in the waves of
solidarity and readiness to help that regularly
accompany them” (1). Just as solidarity and sup-
port are our natural response to natural disas-
ters, an outpouring of expression and narrative
will be our way to overcome conflict due to be-
liefs, resources and contexts, and advance the
discussion on climate. We can “integrate ecolog-
ical integrity and societal well-being”, reaching
people and reaching a consensus while aiming
to protect the climate from further change (6).
The art of storytelling and the potency of per-
sonal narrative can reconcile communities to
rapid change and reach those unsure how to
30
proceed. In Kiribati, women are shrugging off
the paradigm of ‘extreme victimization by cli-
mate change’, choosing instead to “use their
experiences and their voices to tell stories with
the aim of creating change on social and po-
litical levels” (9). When women in Kiribati em-
ploy storytelling as a tool for advocacy, they af-
firm the truth of the narrative paradigm; every
human uses narratives to connect with others
and comprehend the world. By communicating
its reality in a universally accessible medium,
storytelling can share the moral impetus and
urgency of climate change with others. The re-
ciprocal exchange of stories is often key. One
female I-Kiribati advocate recounts how “in-
stead of telling them, this is climate change,
we went out there and said: ‘Did you notice
any changes … in your island?’” (9). By shar-
ing narratives and accepting personal stories in
return, these women cultivate connections of
reciprocity and trust, and transmit knowledge
and comfort to those unsure how to proceed.
Another female advocate shares, “I tell per-
sonal stories, and those are powerful stories,’ .
. . . I don’t like telling the story that Kiribati
is hopeless . . . . I also want to tell people that
we can do something” (9). To these advocates,
storytelling, especially when based in emotion
and experience, can transmit hopeful versions
of the future, leaving listeners with the sense of
self-efficacy which has been discussed as essen-
tial for individual behavioral change, especially
when cultural paradigms for action fall short.
For the Iñupiat of Alaska, storytelling is of value
to whole communities as well. Since worsening
erosion mandated the relocation of Point Hope
Iñupiat to “New Town”, a settlement two miles
from their ancestral coastal village, storytelling
has been “a way of maintaining a connection
to a disappearing place” (10). In a culture for
whom sense of home and place are vital to life,
the ability to maintain an identity based no lon-
ger in the physical place but in the continu-
ally renewing stories of it, is self-preservation.
Storytelling is a critical form of cultural adap-
tation in the face of existential change, a way
for the Iñupiat to turn their surroundings “into
humanized and inhabited places” (10). Thus,
with narrative, they can establish a hardy sense
of place in an unfamiliar home. Familiar sto-
ries of “the drowning home unified the people
into one place . . . . the symbolic relationship
between the villagers and the environment re-
mains close to the heart of the telling” although
the environment itself has changed (10). In Pa-
cific Island communities, advocates are using
“the story of our journey to . . . shape a narrative
that paints us not as victims of the climate cri-
sis but as the leaders, the healers . . . we are” (11).
Storytelling can communicate truth and forge
trust, project a positive future, shape physical
places and even redefine the roles of the mar-
ginalized in the fight against climate change.
In advocacy, communities use narrative to re-
act to and typify the urgency and uncertainty
of the climate change realities they face. Cli-
mate change-related sea level rise threatens
indigenous cultural identities by erasing whole
landscapes. With that destruction, “what’s go-
ing on is [the] destruction of the oldest contin-
uously known people and place. You’re looking
at them right now” (10). In this urgent context,
when every incremental rise in sea level sub-
merges not only artifacts and areas but the
tangible proof of a people’s history, the criti-
cal role of storytelling is to declare a commu-
nity’s continued existence. For Pacific Island-
ers, this narrative power can manifest itself in
a simple statement: “We are not drowning” (11).
Through narrative, they respond to the threat
of oblivion with a firm refusal to fade away.
As well as cultures’ fight for survival, storytell-
ing reveals unprecedented changes playing out
as communities respond to the encroaching
threat of climate change. Stories told since the
Point Hope Iñupiat’s relocation to New Town
highlight the evolving relationship between
themselves and their spiritual surroundings.
Burdened by extreme existential anxiety, the
generation that made the move to New Town
told stories of restless spirits. As the Iñupiat ad-
just to New Town and mourn cultural losses, the
evolution of their stories mirrors the uncertain-
ty of their environment: “as the Arctic environ-
31
ment becomes more unpredictable, so do the
distribution and behavior of its spirit beings” (10).
Today, the evolution of the Iñupiat people’s
adaptive storytelling has entered a new stage. As
revealed in emerging folk stories, Alaskan Na-
tive communities are, for the first time, “making
conscious and unconscious alliances with spirit
beings in order to remain rooted in their land”
(10). This is a new and necessary bond, absent
from previous tales. A spiritual context once re-
garded as mischievous and alien, perhaps un-
friendly, has become a reservoir of comfort and
familiarity to help Alaskan Native communi-
ties contend with the external stress of climate
change. Able to adapt and provide new comfort
in the face of extreme change, storytelling main-
tains a “viable place of cultural survival” for the
Iñupiat and others when climate change threat-
ens not only the physical places they know but
the cultural traditions better adapted to those
vanishing environments (10). Storytelling allows
communities to respond to urgency with de-
termination, and adapt dynamically to change.
Storytelling and other narrative modes of advo-
cacy are notable for the way they use emotion
and empathy to advance action. In Kiribati, ad-
vocates believe that emotions, chiefly communi-
cated through folk songs, can mitigate feelings
of helplessness and induce change (12). I-Kiri-
bati songs are emotionally evocative, frequently
pairing emotional appeals with calls to action.
On a related note, “the land, in the cultural log-
ic of the I-Kiribati, is . . . an indissoluble, ideal
unity” with its people, and thus the vernacular
terms for “land” and “people” are the same (12).
Love of both land and people are key to the
narrative advocacy of the I-Kiribati. These links
between emotions and actions, between people
and their homeland, are evident in the way ad-
vocates have repurposed the song “Koburake!”.
Its lyrics describe a frigate bird searching for
its drowned home, an extended metaphor
for the uncertain future of the I-Kiribati. The
song, as advocates employ it, first elicits empa-
thy for the I-Kiribati people, then presses the
world to translate that emotional concern into
meaningful action by doing all it can to pro-
tect their homeland. A common refrain found
in I-Kiribati narratives around climate change
is nanoanga, a word which means “giving heart/
feelings/thoughts”, or empathy (12). For them,
empathy is foundational to action. I-Kiribati
advocates display emotional vulnerability in
music and narrative, then “call on other nations
to show empathy too” by taking action (12). The
title of the song, koburake!, means “rise up!”,
a phrase which doubles as an encouragement
for the I-Kiribati and a mandate to the rest of
the world. For Kiribati and its people must be
“lifted up” in part by others. They ask for em-
pathy and action from the world-- and external
audiences do feel compassion and motivation
to act in response to songs like “Koburake!”.
I-Kiribati performers touring the United States
in 2011 reported a “reaction in audiences . . .
. “the audience really feel the song” . . . . even
moved to tears.” What the I-Kiribati conclude
from experiences like these is that external au-
diences do, in fact, develop empathy and will
come to the aid of the land of Kiribati” (12).
Lastly, advocacy based on the emotions and
narratives of a community is anti-hegemonic.
It demands that work towards a climate solu-
tion be driven equally by all stakeholders in
the future of our climate. In Kiribati, external
and internal discourses on climate change have
mounted up, each canvassing projected con-
sequences. The Kiribati Adaptation Program
(KAP), launched in 2003, aims to encourage
people to adapt accordingly (12). The most ba-
sic discourse, however, remains this: rising sea
level is dramatic and inevitable. The I-Kiribati
perceive a “hegemonic status, demanding con-
sensus” between the KAP idea of cautious ad-
aptation, and the change climate change will
wreak (12). Ultimately, many feel powerless. In
Kiribati culture, messages of the future and of
coming danger are perceived to have unique
power, and the I-Kiribati feel their power be-
ing stripped by the discourses inundating
them (12). These competing discourses of adap-
tation and destruction, both, to the I-Kiribati,
pervaded with power, are “generally denying
32
agency to local actors. Accordingly, they com-
bine their critique [of external discourses]. .
. with a plea for more attention to be paid to
what the people of the Pacific region actually
think, say and do” (12). Their advocacy is an an-
ti-hegemonic response not only to the threat
of climate change but to the idea of exter-
nal powers determining the I-Kiribati future.
Ironically, musical composition was once a
carefully guarded knowledge on Kiribati, re-
served for expert, ritual composers who were
endowed with the power to project the future
through their music (12). Now folk songs, the
opposite of guarded institutional power-knowl-
edge, are being recast as commentary on cli-
mate change (12). “Koburake!” has paradoxically
been endowed with the future-projecting sig-
nificance once reserved for elite compositions.
Thus, folk music, the very medium of I-Kiribati
advocacy, combats hegemony and champions
inclusion. Through musical expression of this
sort, the I-Kiribati can “engage with globally
circulating discourses of climate change and
sea level rise” on their own terms (12). They
both express acceptance of scientific projec-
tions of existential change, and affirm a deter-
mination to act against hegemonic knowledge
structures. Community narrative and advo-
cacy such as that of the I-Kiribati demands
and allows for the involvement of all voices.
Community advocacy imbued with emotion
and personal experience reframes religion as a
tool for communities to leverage as they adapt,
not as an obstacle to unity and change. In front-
line communities, evidence such as the role of
adaptive storytelling in Alaska and the link be-
tween land and people in Kiribati demonstrates
that behaviors exhibited by resilient communi-
ties in the face of climate change are rooted in
spiritual, if not religious, connections to place.
In the above cases, spiritual value placed on a
homeland necessitates the adaptive storytell-
ing or aggressive advocacy which have served
to keep both places “alive” (in vibrant and dy-
namic stories if not physically, in the case of the
Point Hope Iñupiat). Community-level adaptive
behaviors such as advocacy and storytelling are
therefore both linked to and fed by spiritual
prerogative. Formal statements of such spiritu-
al prerogative ask for behavioral change on a
global scale instead, but also carry the narrative
and emotional weight that makes community
advocacy so potent. Pope Francis demands “an
inward change, within the human spirit . . . to
hear “both the cry of the earth and the cry of the
poor” (1). If spiritual prerogatives both formal
and informal are after all linked with narrative
and emotion, those elements can strengthen re-
ligion into a tool to aid communities in adapting.
Indigenous faith-based responses to climate
change are another instance where religion
does not serve to fragment, but rather strength-
ens a response to climate change in which el-
ements of narrative and emotion are present.
Because colonial and imperial systems are the
embedded causes of climate change and also
of indigenous suffering, “indigenous climate
statements tend to show less interest in pre-
senting themselves in alliance with statements
of other religious bodies” (1). For indigenous cli-
mate advocates, who find themselves and their
communities uniquely imperiled by changes
such as rising sea level, the question of reli-
gious responsibility for climate change is inte-
grated with that of their political and cultural
survival (1). So they argue not always for unity
but for fairness, for indebtedness and amends.
These arguments are emotionally driven, influ-
enced by the personal and spiritual narratives
of indigenous people, and uniquely potent.
Although religious communities may be in con-
flict over the moral sense of climate change, the
most successful religious climate advocates are
those who use personal narrative and emotion
in their attempts to integrate religious morality
with climate change. Confessional thought and
literature aims to make climate change matter
within the morality of a particular religious
community. For Jews, it may be a matter of pur-
suing justice, aiding the vulnerable, and repay-
ing a debt incurred to earth (1). Muslims may see
anthropogenic climate change as disrespectful
33
to Allah’s revelation of creation, and work to
remedy the insult (1). Those Evangelicals who
accept that anthropogenic climate change is
possible, may see it as God’s ruthless judgment
of our extractive society, and what we deserve
for believing in a fantasy of “secular salvation”
through mastery of nature (1). What these ap-
proaches share is an attempt to present respon-
sibility for climate change in a way that can be
easily incorporated into religious individuals’
personal narratives. Constructive thought and
literature, which attempts to make secular mor-
al sense of climate change by drawing from
religious elements, but need not be limited to
believers, is similarly effective because it pres-
ents moral ideas that appeal to and are incor-
porated into individuals’ personal narratives.
Again, it is an interplay of religious reasoning
and personal narrative which can advance cli-
mate action in individuals and communities.
Returning to the religious theme of stewardship
discussed earlier, we can examine spiritual tra-
ditions where personal narratives reinforce the
stewardship role. In these traditions, the idea
of stewardship is far more nuanced. The indig-
enous sense of stewardship and generational
responsibility for the planet is not the same
as that of Judeo-Christians, who passively re-
ceived the stewardship role from God. Instead,
indigenous communities perceive themselves
as in relationships of reciprocity and inter-
dependence with their natural environment.
Furthermore, they reaffirm this commitment
through personal narratives, empirical stories
of reciprocal and respectful interactions with
the world around them. Therefore, personal
narratives, not arbitrary prerogatives from God,
are the basis of humanity’s role as careful and
respectful steward of the earth. The crude idea
of God-endowed stewardship which threatens
to “reinscribe colonialist ideologies into global
environmental politics, . . . objectify, commod-
ify, and put a monetary value on the sacred”
lacks the narrative component which sup-
ports indigenous traditions of stewardship (1).
Personal narrative can even direct a less fatal-
istic interpretation of the theme of the apoca-
lyptic in climate change. Inasmuch as climate
change is an apocalypse for the anthropocene
era, individuals can choose to craft a story of
virtue and choice. They can construe the cli-
mate change apocalypse not as the inevitable
end of time, rather as a time of revelation, de-
cisive action and responsibility, when “God be-
gins the final overthrow of extractive empires,
perhaps by drawing all Earth into violent judg-
ment on a corrupt civilization”, and real change
away from exploitative capitalism is possible (1).
The cultural experience of climate change pres-
ents a significant enough threat to humanity as
to be almost religious in nature. The destructive
reality of anthropogenic ecological destruction
“seems to represent at once the apotheosis of
humanity and its eclipse” (1). That we can wreak
such major change both advances us almost to
the status of gods, and exposes our sinful and
destructive nature. To choose to ascribe one of
these two possible meanings to climate change,
then, is a form of adaptive storytelling to one-
self. “To establish the moral value of Earth’s
living systems, then, it is … doing a kind of re-
ligious work” but also a work inseparable from
subjective emotion and personal narrative (1).
Ultimately, religion has fragmented humanity’s
experience of climate change and introduced
a complicating moral dimension. At its best,
however, when religious thought on climate
change engages with personal narratives and
subjective emotions, it can be a valuable tool.
Narrative advocacy has the potential to
combat inequity by reallocating and redefin-
ing resources which determine communities’
response to climate change. In coastal Alaska,
where neither the Alaskan nor federal govern-
ment have institutions in place to allocate funds
for Native villages to relocate, communities have
turned to creative means to raise funds (6). In
one village, “efforts to raise additional relocation
funds from a climate-change lawsuit against
oil, coal, and gas companies” ultimately proved
unsuccessful (6), but the attempt is an exam-
ple of narrative advocacy, which is interested in
34
emotional issues of justice and fairness, identi-
fying an opportunity for resource advancement
Community advocacy around the world urges
us to view cultural assets we may not have con-
sidered before as meaningful resources in the
fight against climate change. For example, indig-
enous weather prediction strategies, which rely
largely on holistic observation, are proving to
be more useful as rapid climate change makes
years of carefully recorded climate data obso-
lete in predicting future patterns. While these
and other such “diverse knowledge systems of
the third world are claimed as heritage that be-
longs to all humanity, the knowledge about how
to apply this diversity is often exclusive to the
domain of the people who have developed it”
(13). This knowledge, often portrayed as back-
wards and superstitious, is a resource. Once
realizing this, we must “integrate the collective
wisdom” of humanity, both formal and infor-
mal, in the fight against climate change (13).
The specific sphere of influence of women in
least developed nations, while evidence of ineq-
uity in and of itself, also proves to be a resource.
In Kiribati, women hold critical knowledge of
daily water routines, and how to integrate adap-
tive behaviors into these routines to carefully
steward water resources. As well as their knowl-
edge, though, women’s membership in cohesive
community networks such as church and shared
chores gives them a means of sharing such crit-
ical information (9). Women’s knowledge, and
access into community networks, is another
resource in the fight against climate change.
Lastly, community advocacy is the kind of ad-
vocacy which is strengthened, not stymied,
by diverse cultural perspectives. It asks for an
inclusive and participatory approach to cli-
mate work, with “a shift in paradigm from “top
down” strategy to a “bottom up” one in order
to value the ideas of those who often go un-
heard (13). This approach leaves room for dif-
ferent models of action and understanding.
The Alaskan planning group most successful
in relocating a Native Alaskan village so far is
“unique in Alaska in its multidisciplinary and
multijurisdictional structure . . . . all voluntarily
collaborate to facilitate Newtok’s relocation” (6).
Interaction between different disciplines and
models of thought, then, is a strength of such
groups. Under the systems for which this sort
of climate advocacy calls, diverse perspectives
can exist in tandem, thrive on shared knowl-
edge, and adjust for each other’s weaknesses. In
Kiribati, one community advocate shares, “we
are advocating because we feel there is a need
for the international community to hear our
voices in Kiribati … our work in Kiribati is real-
ly on adaptation, our work internationally is on
advocacy for mitigation” (9). Formed out of the
emotions, goals and narratives of individuals,
such advocacy is uniquely attuned to perceive
subtle differences in the way audiences will
respond to its work. This type of advocacy can
dynamically lace together the different goals
necessitated by the different perspectives exist-
ing across its areas of work, such as promotion
of adaptation strategies internally, and demand
for reduced emissions globally, into one com-
prehensive plan for action and advocacy. Where
cultural preparation and context falls short of
advancing action, community advocacy savvy
enough of these contexts can move the needle.
The human patchwork of myths and religions,
differing access to resources, and cultural con-
texts seems at first to prevent a unified response
to climate change. Community advocacy and
emotional personal narratives can transmit
knowledge and sense of place, typify uncer-
tainty and reveal change, reach others through
emotion, and counter hegemonic structures
of knowledge and power. We can also begin
to address our fragmented perceptions and
attitudes toward climate change by search-
ing for a solution in the intersection of reli-
gion, inequity, and cultural contexts with the
power of narrative and community advocacy.
To humanity, climate change presents “‘a ques-
tion of ultimacy,’ in the sense that it is a site
of conflicting interpretations about what it
means to be human” (1). Above, multiple pos-
35
sible meanings for humanity and our role in
anthropogenic climate change have been pro-
posed. There are indigenous narratives, sup-
ported by storytelling and contemporary in-
digenous advocacy, of an interdependence
and indebtedness to the earth gone awry. This
framing waits only for our commitment to alter
the course and carefully steward the earth once
again. Unfortunately, there are also the Evan-
gelical interpretations of climate change as an
impossibility in the perfect and unchanging
world gifted to us by God, or as a pre-ordained
apocalypse. There are I-Kiribati villagers who
trust that God will protect their island from
the coming flood, and others who struggle to
believe that their planet is being smothered by
a blanket of gas which they can neither touch
nor see. There are Americans, whose obses-
sion with the frontier and the subjugation of
nature frames anthropogenic climate change
as just another barrier broken, another test
of the limit of human power over the natural
world. For them, how far is too far? What evi-
dence of their irreversible, willful destruction,
if any, will be enough to advance meaningful
policy or behavioral change? Whichever of
these interpretations emerges dominant, it will
shape our policy and action during the criti-
cal window we have to attempt to mitigate cli-
mate change. It is crucial that we understand
the different factors at play in fracturing and
especially unifying humanity’s response to an-
thropogenic climate change, if we hope to find
that unity, first in consensus on some small
shared goal, and eventually, in a way forward
that unites humanity against climate change.
Appendix A
Matagi Mālohi
By Fenton Lutunatabua
You are matagi mālohi. Strong winds. A symbol
of our movement blurring identities, validating
purpose and strengthening stewardship over
this vanua we are called to protect.
You are stained bark cloth for skin, saltwater
chants dancing with the moon and reimagined
dreams pacing with the tides.

You are matagi mālohi. Strong winds from sa-
cred places and revered spaces.
A spiral kaleidoscope of broken coral and
memory called to collect, curate and reconcile.
You are matagi mālohi. Strong winds rising up
and villaging children.
Brown bodies moulding brown minds. Mov-
ing between healer and warrior, you are future
ancestors carving visions of liberation we can’t
even imagine.
You are matagi mālohi. Strong winds seeking
frontline truths in this transcendent talanoa of
knowledges.
Masculine culture, feminine consciousness,
woven together, lose’d together- wai….donu….
You are matagi mālohi. Strong winds from the
four pillars of our fale.
The same ancestors that are calling you to be-
lief will also call you to unbelief, so your faith
can take a new form. So you can return to the
source and be reminded of the commonality of
our plurality.
You are matagi mālohi. Strong winds listening,
nourishing, transforming.
We are stewards of gifts from our old people.
Noqu wasawasa, era sa vura, era sa vura, era sa
vura (my ocean, they have emerged)
Appendix B
https://www.youtube.com/watch?v=xOcML-
WVNIms
Works Cited
1. Jenkins, Willis, et al. “Religion and Climate Change.”
Annual Review of Environment and Resources, vol. 43,
2018, pp. 85-108. Annual Reviews, https://doi.org/10.1146/an-
nurev-environ-102017-025855. Accessed 26 July 2021.
2. Lübken, Uwe, and Christof Mauch. “Natural Disasters in
Transatlantic Perspective: River Floods in German and U.S.
36
History.” Bulletin of the German Historical Institute, no.
35, fall 2004, pp. 99-111, www.ghi-dc.org/fileadmin/publica-
tions/Bulletin/bu35.pdf. Accessed 26 July 2021.
3. Ray, Caleb. “Rejecting Reality: Kiribati’s Shifting Climate
Change Policies.”
4. Bucková, Martina. “Deluge in Polynesian Mythology.”
Asian and African Studies, vol. 13, no. 2, 2004, pp. 191-97,
www.sav.sk/journals/uploads/040214187_Buckova.pdf. Ac-
cessed 26 July 2021.
5. Kuruppu, Natasha, and Diana Liverman. “Mental Prepa-
ration for Climate Adaptation: The Role of Cognition and
Culture in Enhancing Adaptive Capacity of Water Manage-
ment in Kiribati.” Global Environmental Change, https://
doi.org/10.1.1.457.8121. Accessed 26 July 2021.
6. Bronen, Robin, and F. Stuart Chapin. “Adaptive Gov-
ernance and Institutional Strategies for Climate-induced
Community Relocations in Alaska.” Proceedings of the
National Academy of Sciences of the United States of
America, vol. 110, no. 23, June 2013, pp. 9320-25, https://doi.
org/10.1073/pnas.1210508110. Accessed 26 July 2021.
7. Hardy, R. Dean, et al. “Racial Coastal Formation: The Envi-
ronmental Injustice of Colorblind Adaptation Planning for
Sea-level Rise.” Geoforum, vol. 87, Dec. 2017, pp. 62-72. Sci-
enceDirect, https://doi.org/10.1016/j.geoforum.2017.10.005.
Accessed 27 July 2021.
8. European Commission. Joint Research Centre., et al.
Fossil CO2 and GHG Emissions of All World Countries.
Luxembourg, European Union, 2017. Core, https://doi.
org/10.2760/709792. Accessed 27 July 2021.
9. Haughton, Pippa. Women’s Climate Change Advocacy
in Kiribati: Vulnerability, Agency and Storytelling. 2020.
Malmö U, MA thesis. Malmö University Electronic Publish-
ing, Malmö University, ls00012.mah.se/handle/2043/32621.
Accessed 26 July 2021.
10. Sakakibara, Chie. “’Our Home Is Drowning’: Iñupiat
Storytelling and Climate Change in Point Hope, Alaska.”
Geographical Review, vol. 98, no. 4, Oct. 2008, pp. 456-75.
JSTOR, www.jstor.org/stable/40377348. Accessed 26 July
2021.
11. Woodward, Forest, et al. “Matagi Mālohi : Strong Winds.”
Facebook, 20 Sept. 2020, www.facebook.com/350Pacific/vid-
eos/matagi-m%C4%81lohi-strong-winds/621328961898500/.
Accessed 26 July 2021.
12. Hermann, Elfriede, and Wolfgang Kempf. “2 ‘Prophe-
cy from the Past’: Climate Change Discourse, Song Cul-
ture and Emotions in Kiribati.” Pacific Climate Cultures:
Living Climate Change in Oceania, by Tony Crook and
Peter Rudiak-Gould, Warsaw, De Gruyter, 2018, pp. 21-33.
De Gruyter, https://doi.org/10.2478/9783110591415-003. Ac-
cessed 26 July 2021.
13. Pareek, Aparna, and P. C. Trivedi. “Cultural Values and
Indigenous Knowledge of Climate Change and Disaster
Prediction in Rajasthan, India.” Indian Journal of Tradi-
tional Knowledge, vol. 10, no. 1, Jan. 2011, pp. 183-89. Nis-
cair Online Periodicals Repository, nopr.niscair.res.in/han-
dle/123456789/11079. Accessed 26 July 2021.
The University of Texas at Austin, 31 Dec. 2019, sites.utex-
as.edu/climatesecurity/2019/12/31/kiribati-policy-shift/. Ac-
cessed 27 July 2021.
 Understanding Protein
Interactions with BACE1
by Sriya Tallapragada (IV), Dr. Marc Tambini1
Rutgers Brain Health Institute, Piscataway, NJ
1

Abstract
Alzheimer’s disease is the most common neurodegenerative disease in the world, affecting more
than five million Americans and amounting to $148 billion in healthcare expenses in the US alone.
Mounting research has shown that amyloid plaques composed of β-amyloid peptides are a factor in
Alzheimer’s.The enzyme BACE1 is an initiating enzyme in β-amyloid peptide formation, making it a
prime target for Alzheimer’s treatments. BACE1 works by cutting the peptide bonds of the Amyloid
Precursor Protein (APP), the longer protein from which β-amyloid is made, at a specific cleavage site.

β-Amyloid peptide formation requires two proteolytic cleavages (the hydrolysis of two peptide
bonds in a protein): the first is through β-secretase in APP, and the other is by β-secretase within
the hydrophobic lipid bilayer. BACE1 is the principle β-secretase responsible for the first pro-
teolytic cleavage. Since BACE1 is important in additional bodily functions, it is challenging for
scientists to find an inhibitor that does not inadvertently interrupt other essential processes.

BACE1 is usually found in the Endoplasmic Reticulum (ER) or Golgi Apparatus, which trims
proteins involved in neuronal functions. Structurally, the enzyme has two portions: the cata-
lytic domain (at the start of the protein, its N-terminus) that cleaves proteins, and the por-
tion on the end of the protein embedded in the membrane (the C-terminus), which controls
direction and regulates enzymatic activity (N-terminus refers to the amine end of the ami-
no acid while C-terminus refers to the carboxyl end). BACE1’s long tail holds the enzyme on
a membranous surface, so it does not float freely throughout the cell. A GPI anchor, a post-
translational lipid attachment, targets the enzyme and holds it to lipid raft domains. It also
has a deep active site cleft to hold onto proteins and a pair of aspartate amino acids that cut
certain protein chains, which are vital to typical cell function. Neuregulin– a protein that
helps control the formation of myelin sheaths around nerve axons, and voltage-gated so-
dium channels, which are necessary for transmitting nerve signals– is cut by the GPI anchor.
While BACE1 is essential to protein maturation, it is involved in disease processes. BACE1 cuts
APPn, breaking the protein chain and releasing a small amount of amyloid peptide. While normal
amounts of peptides are crucial for normal function, if BACE1 is hyperactive, this peptide can tan-
gle into amyloid fibers and potentially impact nerve transmission, leading to Alzheimer’s disease.

Results
Figure 1 shows the names of the compound bonded with the BACE1, the amino acid se-
quence of the compound, the number of polar contacts, and the distance between po-
lar contacts. Analyzing the interactions between these compounds and BACE1 interac-
tions helps to understand Alzheimer’s disease pathology and potential drug targets by
learning how certain inhibitors binding to BACE1 can affect the way it cuts the amyloid fibers.

37
Figure 1: Images of compounds and active site of BACE1. Compounds are in purple, residues within five ang-
stroms of the compound are in green, and water molecules are in red
Figure 2 shows BACE1 protein-protein interac-
tions to better understand its basic biology and
contribution to Alzheimer’s Disease pathology.
The figure focused on examining these inter-
actions in terms of hydrogen bonds formed
and measured the number of polar contacts
formed and the distance between them. The
compounds 3, 8b, 7, and 6b have a high num-
ber of polar bonds formed. Compounds 3,
4-piperidine, and 6b have a short distance
between polar contact, meaning the bond
formed would be stronger. Understanding the
strength of hydrogen bonds can show how well
the compounds work in attaching to BACE1.
PDB number 2OHN seems to have the
strongest bond formed in relation to the
hydrogen bonds of all analyzed PDB.
38
Conclusion
Based on what could be found from the re-
sults, PDB number 2OHN forms a stronger
hydrogen bond than the other examples. The
strength of the inhibitor affects the way BACE1
is able to release certain amounts of amyloid
fibers; in the case of PDB 2OHN, the leaving
portion of BACE1 will not be able to cut APPn
at all, and will not be able to release amyloid
fiber. Thus, while studying these interactions
between BACE1 and other inhibitors is helpful
in learning more about Alzeihmer’s Disease pa-
thology, relying on the inhibitors is not a viable
solution in stopping the amyloid fibers being
tangled up. After all, a healthy amount of pep-
tide being released from BACE1 cuts is vital for
some particularly important neural function.
 Works Cited
1. Hemming ML, Elias JE, Gygi SP, Selkoe DJ (2009) Iden-
tification of β-Secretase (BACE1)
Substrates Using Quantitative Proteomics. PLOS ONE
4(12): e8477.
2. Cole, S L, and R Vassar. “The Basic Biology of BACE1: A
Key Therapeutic Target for
Alzheimer’s Disease.” Current genomics vol. 8,8 (2007):
509-30.doi:10.2174/138920207783769512
3. “Picking through the Rubble, Field Tries to Salvage
BACE Inhibitors.” ALZFORUM, 20 Dec. 2019, https://
www.alzforum.org/news/conference-coverage/picking-
through-rubble-field-tries-salvage-bace-inhibitors.

Figure 2: Chart with information about bonds formed with each compound. In this project, the x-ray crystal
structure of BACE complexed with different compounds is modeled.

39
Solar system by Kelly Cao (IV)
Astronaut by Ava Khan (III)
Reporter Articles.
23.46 Cents:
Exploring the Development of 12- TET
Through History and Understanding the Cos-
mic Flaw at the Center of all Tuning Systems
by Ryan Arrazcaeta (VI)

Most people are familiar with the basics of music tal frequency (often referred to simply as the
theory from years of immersion in popular cul- fundamental) is what the ear perceives as the
ture at the very least, if not from formal educa- pitch of the note. However, due to the different
tion in it. The solfege method is taught in grade modes of a string’s vibration occurring at once,
school, and most know the basics of major and other higher frequencies – known as overtones–
minor scales. These are often taken as objective occur at integer multiples of the fundamental.
fact: the notes are organized this way because These follow a simple harmonic series, mean-
that is simply the way things are. Very rarely is ing that a given fundamental of frequency n
the mathematical foundation behind tonality has overtones at 2n, 3n, 4n, and so on (Figure 1).
ever explained. The truth is, despite music as an This multiplicative structure for overtones re-
art being a subjective experience, its mechanics
are based in the fundamental truths of physics.
The math informing music has been studied
extensively by many cultures across the world
and across all of human history. Thus, by ex-
ploring some of the mathematics and how they
influenced the way music was made and orga-
nized over time, one can arrive at a better un-
derstanding of this concept of music as a whole.

Whenever an object vibrates, it creates changes

in air pressure, which are interpreted by the ear
as sound. The frequency at which the pressure
changes determines the pitch, which is the low-
ness or highness of the sound. In the case of
a vibrating string, its lowest frequency can be
modeled with the equation f=12LTµ, where L is
length, T is tension, and µ is linear density (i.e.
mass per unit length). This lowest or fundamen-
Figure 1: The above diagram shows the vibrations of several
common overtones. These different modes of vibration occur
during the superimposition of multiple waves, which causes
parts to either cancel (nodes) or reinforce (antinodes). This
follows Fourier’s theorem stating that any waveform can be
synthesized by combining sine and cosine functions of appropri-
ate amplitude and frequency.

41

Figure 2: List of frequency ratios for justly tuned
intervals. These ratios are derived from the harmonic
series of overtones.
veals the nature of frequency versus pitch: the
interval between two pitches, such as a perfect
fifth, is not the difference between the frequen-
cies, rather it is their ratio. In the case of a fifth,
it’s ratio is 3:2 (Figure 2). In a musical context,
imagine an A4, which has a frequency of 440 Hz.
The frequency of an A5 (an octave above A4) is
880 Hz, which yields a ratio of 2:1 between an A4
and A5: the frequency ratio of a perfect octave.
One of the earliest instrumentations of this
math was by the Pythagoreans, the cult follow-
ing of Pythagoras of Samos, who believed that
frequency ratios based on smaller integers (oc-
taves, perfect fifths, perfect fourths) sounded
the most consonant or “in-tune.” Greek mu-
sic at the time used 7 tones, which were often
strung onto a lyre (which had fixed strings).
These were set at the intervals calculated by
the Pythagoreans to be the most consonant
with each other. The intervals closely resem-
bled a modern major scale in what would now
be referred to as a single “key”. While, at first,
it seems difficult to grasp that one “key” cre-
ated diverse enough sound to compose an en-
tire musical tradition, the Greeks had a clever
way of filling in the emotional range: modes.
By changing the tonic center of a given piece
without retuning the instrument, Greek mu-
sic could have seven distinct emotional “feels”,
rather than only one. This concept of modal-
ity remains in western music to this day. The
most familiar example of modality is the idea
42
Figure 3: List of the most commonly used modes in
western music.
that a key is Major (Ionian mode) or Minor(Ae-
olian mode) (Figure 3), although Pythagorean
modality was distinct from its modern counter-
part and has unfortunately been lost to time.
Looking at the math, an observant read-
er might begin to notice a glaring issue with
the Pythagorean tuning system, and poten-
tially with math as a whole. Mathematicians
and musicians alike have grappled with this
problem for the past 3 millennia. This is the
“cosmic flaw” of the harmonic series and
it throws a massive wrench in the plans of
anyone hoping to devise a musical system.
In order to fully understand the problem, let’s
conduct a thought experiment: imagine a grand
piano. It has 88 keys spanning from A0 to C8.
It is known that multiplying a frequency by 32
will yield a pitch a perfect fifth above its funda-
mental (because a perfect fifth has frequency
ratio of 32:1), so by starting on a C1 and multi-
plying by 32, one should end on a G1. By repeat-
ing this process 11 more times, one eventually
reaches the C8. A musician would recognize
this series as simply going around the cycle
of fifths. This is just a geometric progression
with a frequency of C1 (33 Hz) as the principal
value. Plugging these values into the equation
fC8=33*(3/2)12yields a product of 4281.63 Hz for a
C8. One can check this work by using octaves
instead of fifths. As it takes 7 octaves to get from
C1 to C8, and knowing that an octave is a ratio
of 2:1, the equation fC8=33*27 should also yield
4281.629 Hz, but the math states otherwise. The
second equation yields a slightly flatter 4224.00
Hz. To the untrained ear, this difference of
23.46 cents, not even a quarter of a semitone,
is barely perceptible. But the deviation has im-
mense implications on all aspects of music the-
ory. This gap, known as the Pythagorean com-
ma, means that when tuning an instrument
with fixed strings, such as a harp or piano, it
is impossible for all frequencies to be in tune
with each other because their frequencies do
not physically add up correctly (Figure 4). Fur-
thermore, it is only possible to tune an instru-
ment “correctly” for a single key, and playing
out of that key will be incredibly dissonant.
Figure 4: A visual representation of the Pythagorean
comma.
In 1636, a French mathematician named Marin
Mersenne published his seminal work Harmo-
nie Universelle in Paris, the largest documen-
tation of music theory at the time, that held
hundreds of pages of information on stylistic
practices, acoustics, as well as mathematics.
The equation for the fundamental frequen-
cy of a vibrating string discussed in the intro-
duction to this report, f=(1/2L)*√(T/µ), was first
recorded by Mersenne, who also proposed a
potential solution to the Pythagorean comma:
meantone temperament. In contrast to the Py-
thagorean tuning method which emphasized
tuning based on the perfect fifth, meantone
43
tuning was a set of tuning systems that tried to
rectify the Pythagorean comma by narrowing
the ratio of a fifth. For example, the ¼ comma
meantone system tempered fifths out of tune
by about ¼th of the Pythagorean comma. This
improved major and minor thirds, as well as
octaves, but the system still had the same ma-
jor flaw of Pythagorean tuning: modulation.
While modulation was not quite as impossi-
ble as in the Pythagorean system, it was still
rarely viable. All hope was not lost, however,
as the next century would see an innovation
in music the world had never seen before.
The year is 1722. The pirate Bartholomew Rob-
erts has been killed in battle, Benjamin Frank-
lin has just written the Silence Dogood letters,
and Johan Sebastian Bach has published the
Well-Tempered Clavier, a collection of pieces
for solo keyboard written in each of the 24 major
and minor keys. Perhaps the most important leg-
acy of the WTC was in the tuning instructions.
Bach intended his pieces to be played in equal
temperament, a tuning system that claimed to
solve the Pythagorean comma dilemma. Al-
though it had early advocates, such as Andreas
Werckmeister in the late 1680s, at that point very
few people seriously considered such a sys-
tem.
But how exactly would the proposed system
work? In order for equal temperament to work,
it would need 12 equally spaced tones within
an octave. Since frequencies are multiplicative,
proponents of equal temperament used 2f=f*x12,
where f was any given fundamental and x was
the common ratio, to find the number to base
frequency ratios. Evidently, solving the equa-
tion made it clear that using 122 as the basis
for equally tempered ratios would work (Figure
5). While equal temperament “fixed” tuning, it
presented its own unique set of challenges. As
theorized by the Greeks, the psychoacoustic
phenomenon of consonance occurs when the
overtones of two notes line up. By adjusting the
values of intervals ever so slightly, equal tem-
perament made all of the intervals that much
less consonant. Equal temperament did not get
rid of the Pythagorean comma, rather it spread
the Pythagorean comma across the octave. How Music Really Works.
Today, 12 tone equal temperament (12-TET) is
the most widely used and taught musical sys-
tem on the planet. Its presence has influenced
centuries of musical composition. Ultimately,
the choice of a musical system comes down to
an artist’s personal creative vision. With their
knowledge of temperaments and musical the-
ory, concert pianists will often request special
tunings for their pianos before a performance,
as tuning for specific keys will often result in a
better sound. For better or for worse, 12-TET’s
elegant solution to one of nature’s cruelest
jokes stands to represent humanity’s ingenuity
and intelligence even in the face of cosmic odds.
Works Cited
1. 1/4-comma meantone / quarter-comma meantone. (n.d.).
Tonalsoft. http://www.tonalsoft.com/enc/number/
1-4cmt.aspx
2. Beat frequency formula. (n.d.). Toppr. https://www.toppr.
com/guides/physics-formulas/
beat-frequency-formula/
3. Bradley, C. A. (n.d.). Polyphony in medieval paris: The art
of composing with plainchant [Google Books].
Figure 5: Table showing differences in frequency ratio between equal-tempered and just-tuned intervals.
44
4. Chapter 4: How scales and intervals REALLY work. (n.d.).
https://howmusicreallyworks.com/Pages_Chapter_4/4_2.
html
5. Duffin, R. W. (2008). How equal temperament ruined har-
mony: (and why you should care). W.W. Norton.
6. Equation for sound created from a string. (n.d.). Ron
Kurtus’ School for Champions.
https://www.school-for-champions.com/science/sound_
from_string_equation.htm#.YGMoFK9KiMp
7. Marin mersenne. (n.d.). Encyclopaedia Britannica On-
line. https://www.britannica.com/biography/
Marin-Mersenne
8. Russell, D. A., Ph.D. (n.d.). The vibration of a fixed-fixed
string. Acoustics and Vibration
Animations. https://www.acs.psu.edu/drussell/Dem-
os/string/Fixed.html#:~:text=When%20a%20fixed%2D-
fixed%20string,of%20the%20initial%20string%20displace-
ment.
9. Vibrations of a string. (n.d.). The Fact Factor. https://the-
factfactor.com/facts/pure_science/
physics/vibrations-of-string-harmonics-over-
tones/8410/#:~:text=Concept%20of%20Overtones%3A,-
multiples%20of%20the%20fundamental%20frequency.
10. Winternitz, Emanuel. The Musical Quarterly, vol. 44, no.
4, 1958, pp. 534–540. JSTOR,
www.jstor.org/stable/740715. Accessed 30 Mar. 2021.
 Crime in the Era of COVID-19
by Parth Patel (III)

At the onset of the COVID-19 pandemic, con-
cerns about a spike in urban crime rate began to
circulate. Potentially, the fear of illness could
slow down urban crime or the redirec-
tion of the police’s time to enforcing quar-
antines and curfews could unleash chaos.
In June of 2021, Following the initial surge of
Covid-19 cases worldwide, Manuel P. Eisner
of The University of Cambridge conducted a
global analysis of the effect of COVID-19 stay-
at-home restrictions on urban crime rates.
Eisner analyzed police records in 27 cities– in-
cluding, San Francisco, Lima, and London–
focusing on the trends for 6 types of crime.
Eisner saw a thirty-seven percent reduction of
reported cases of assault, theft, burglary, rob-
bery, vehicle theft, and homicide in the cities.
Conversly, COVID’s impact on homicide and
intentional first-degree murder fell by only four-
teen percent, which was the smallest decrease
out of the types of crime observed. A substantial
number of domestic homicides is thought to
account for the discrepancy in the crime rates.
Accounts of burglary (entering a building with
the intent to steal) declined by twenty-eight
percent; however, it is worth noting that some
of the cities in the sample do not distinguish
between commercial and residential burglary.
When studying the data from the cities that
have differentiated the two subsets of burglary,
they found that because of the increased pres-
ence in homes, residential burglary rates went
down significantly. On the contrary, due to the
lack of supervision in commercial buildings,
there was a smaller decrease in cases of com-
mercial burglary. Reported cases of theft also
fell, as they saw a monumental decline of 47%
compared to pre-pandemic levels, which is
most likely attributed to less social interaction,
therefore less opportunity to steal. As a whole,
urban crime rates decreased across all six cat-
egories, in spite of less police supervision.
Eisner’s study suggests that preliminary fears
of a state of global anarchy due to the Pandmeic
are not necessarily warranted. People panicked
and worried that if the police fell ill, a reign
of lawlessness would increase crime rates. Oth-
ers believed that fear of falling ill would dis-
suade large amounts of criminal activity, citing
lower crime rates in the winter. With Eisner’s
data on decreased crime rates, the question
becomes: Why were so many people wrong
about this outcome? Why did people expect
the worst? Just how can our newfound under-
standing of crime impact the field of criminal
psychology or even the fields beyond that?
Works Cited
1. Nivette, A.E., Zahnow, R., Aguilar, R. et al. A global anal-
ysis of the impact of COVID-19
stay-at-home restrictions on crime. Nat Hum Behav 5,
868–877 (2021). https://doi.org/10.1038/s41562-021-01139-z
2. Abrams, David S. “Crime Rates Dropped in 2020—Just
as They Did in 1918.” Wired, 14 Jan.
2021, www.wired.com/story/crime-rates-
dropped-in-2020-just-as-they-did-in-1918/.
Gavel by Connor Chen (VI)

45
 Maggot Debridement Therapy
by Sarina Lalin (IV)
While most people shudder at the thought of
writhing fly larvae, the act of intentionally put-
ting maggots into the human body has led to
notable medical advances since some of the
world’s earliest civilizations. In maggot debride-
ment therapy (MDT), disinfected maggots are
introduced into an open wound with the pur-
pose of eliminating necrotic tissue. Once the
maggots are placed onto the wound, they re-
lease an enzyme in their excretion that lique-
fies dead tissue. The maggots then feed on this,
leaving behind only healthy, living tissue. As
antimicrobial resistance becomes increasingly
prevalent, maggot debridement therapy proves
to be a promising solution for those suffering
from non-healing wounds and diabetic ulcers.
The use of maggots as wound treatment can be
traced back centuries to the Aboriginals of Aus-
tralia and the Mayan tribes in Central America,
who regularly used larvae to clean wounds. In
1557, French surgeon Ambroise Paré found that
his patients with maggot-infested wounds tended
to heal faster and better than those who lacked the
larvae. This observation was made several times in
the future by surgeons like Baron Dominique-Jean
Larrey, who went one step further, discovering
that maggots removed dead tissue by feeding on it.
During the American Civil War, John Forney
Zacharias purposely exposed maggots to fester-
ing wounds after noticing that soldiers with un-
kempt and maggot-born wounds were more like-
ly to survive. Over the next few decades, interest
in maggots and their ability to treat wounds and
ulcers heightened, reaching its peak in the 1930s
after a study on maggots’ role in removing dead
tissue was released by Johns Hopkins University.
This, as scientists call, “golden age of maggots”
quickly subsided due to the commercialization of
penicillin. Towards the end of the 1980s, maggot
therapy gained popularity once again after numer-
46
Maggots by Allen Wu (VI)
ous studies revealed that maggots were a cost-ef-
fective alternative to traditional debridement
methods. Robert Sherman’s studies, for example,
showed that dead tissue was completely removed
from 80% of maggot-treated wounds, compared
to 48% of surgically debrided wounds. By 2002,
maggot debridement therapy was being used by
over 2,000 medical facilities, and in 2004, mag-
gots were approved as an official medical device.
From antiquity to the present day, maggots have
proven to be a safe and effective method for
debriding ostensibly non-healing wounds. Al-
though the stigma surrounding maggots pre-
vents the treatment from reaching its full poten-
tial, maggot debridement therapy is an accessible
and affordable technology for chronic wounds.
Works Cited
1. Whitaker IS, Twine C, Whitaker MJ, Welck M, Brown CS,
Shandall A. (2007, June) “Larval therapy from antiquity to
the present day: mechanisms of action, clinical applica-
tions and future potential” Postgraduate Medical Journal.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2600045/
2. Chan D. (2015, January 17).”Maggot debridement therapy
in chronic wound care”
Hong Kong Medical Journal. Retrieved from https://www.
hkmj.org/abstracts/v13n5/382.htm
3. Gaydos J. (2016, March 30). “History of wound care:
Maggots: An extraordinary natural phenomenon” Today’s
Wound Clinic. https://
www.todayswoundclinic.com/articles/histo-
ry-wound-care-maggots-extraordinary-natural-phenome-
non
4. Mole B. (2012, December 10). “Maggot Medicine” The
Scientist Magazine. https://www.the-scientist.com/the-nut-
shell/maggot-medicine-40066
5. Ngan V. (2005) “Maggot Debridement Therapy” Derm-
Net NZ. https://dermnetnz.org/topics/maggot-debride-
ment-therapy/
6. Medical Maggots™ (maggot therapy, maggot debride-
ment therapy, MDT, biotherapy, biosurgery, biodebride-
ment, larval therapy). (n.d.). Monarch Labs.http://www.
monarchlabs.com/mdt

The Incredible Mozart Effect

by Krish Patel (III)

In 1993, Frances Rauscher started playing mu- The theory presented in the article touches
sic composed by Mozart to help patients with upon the critical emotional response that is
epilepsy. Epilepsy is a neurological disorder able to decrease the IED rate. One truly shock-
that causes abnormal brain activity that leads toing revelation was that duration of the auditory
seizures. It impacts one percent of the general stimulus actually would determine the reduc-
population and yet a cure remains elusive. Prior tion of the IEDs. Some directions this study
studies have demonstrated that about one-third can go in are ponder questions like “Are Mozart
of epilectic patients experience intracranial in-K448 and Mozart K545 really the only two songs
terictal epileptiform discharges (IEDs), brief that elicit the emotional response that com-
neural discharges that increase the frequency bats the IEDs?”, or “Would a playlist of songs
of seizures in people with refractory epilepsy. that utilize the sixteenth notes be an effective
treatment of the future, and would the vari-
Eleven researchers from Geisel School of ety of songs have an impact on the IED rate?”.
Medicine at Dartmouth University have shown
that Mozart K448 can decrease the frequen- In summation, the experiment demonstrates
cy of seizures in refractory eplieptic patients. how Mozart K448 can reduce IED rates in refrac-
84% of people with refractory epilepsy have tory epilectic patients which decreases the fre-
a significant reduction of IED upon listening quency of seizures. Mozart K448 has been help-
to the sonata. In the study, the subjects were ing patients with refractory epilepsy since 1993,
split into two groups (Group 15, and Group 90) but its service to these patients can only increase
and participated in two different treatments as we learn more about epilepsy and the Mozart
that each lasted twenty-five minutes. Using Effect. And maybe, this could be the founda-
electrodes, the scientists tracked the IED dis- tion of a long awaited cure for the one percent.
charges. Group 15 listened to the song for fif-
teen seconds before taking a fifteen second Works Cited
break. Group 90 listened to the song for two 1. Quon, R.J., Casey, M.A., Camp, E.J. et al. Musical compo-
minutes, and answered true or false questions nents important for the Mozart K448 effect in epilepsy. Sci
for the last 30 seconds, before taking a one Rep 11, 16490 (2021).
minute break. The subjects were then played a
sound and were asked if it was the same sound
as earlier. The researchers found that during
the control breaks, there was no significant
fluctuation in IEDs. They also found that the
IED reduction was dependent on the duration
of the auditory stimulus, as the GEE models
used by the researchers detailed how Group
90s IED rate decreased more than Group 15s.
47
 The Perseverance Rover’s
Scientific Instruments
by Evan Xie (IV)
On February 18th, 2021, NASA’s Perseverance
Rover successfully landed on Mars in the Jeze-
ro Crater. Following the Sojourner, Spirit, Op-
portunity, and Curiosity rovers, NASA’s previous
Mars missions, Perseverance is tasked with four
key missions: determine if life previously existed
on Mars, identify the characteristics of past Mar-
tian climates, characterize the geology on Mars,
and prepare for future human-led missions. With
such difficult and important objectives to com-
plete on a foreign planet, it should come as no
surprise that this rover features some of human-
ity’s most advanced and revolutionary technol-
ogy. Spending a great amount of time and $2.2
billion designing, prototyping, and building the
rover, the scientists at NASA’s Jet Propulsion
Lab (JPL) were able to pack an astounding sev-
en scientific instruments, alongside a rock sam-
pling system, a tiny helicopter, and more, within
Perseverance’s 2260 pound, 10ft x 9ft x 7ft frame
(Figure 1). Each scientific instrument combines
different technologies to perform their respec-
tive experiments on Mars, which will hopefully
broaden our understanding of the Red Planet.
First, Mastcam-Z is Perseverance’s intricate cam-
era system that will capture pictures of the Mar-
Figure 1: Image of the Perseverance Rover from the
front
48
Rocket by Ava Khan (III)
tian surface and atmosphere while also helping
scientists select rocks to core and study. Mas-
tcam-Z is an upgrade from Curiosity’s camera
system in almost every aspect: each individual
camera can shoot 20-megapixel colored images,
rather than 1-megapixel black and white imag-
es, contains powerful zoom capabilities to study
smaller objects, and has a wider field of view pro-
viding Mastcam-Z with a full 360-degree perspec-
tive. With these features, Perseverance can photo-
graph and record different terrain features, rocks,
soil, and Martian phenomena (dust storms, cloud
motions, etc), providing scientists with invaluable
visuals to further their understanding of Mars.
Next, the Mars Environmental Dynamics Ana-
lyzer (MEDA) is a group of sensors responsible
for measuring different aspects of the Martian
environment —namely wind speed, temperature,
humidity, dust particle size, and radiation lev-
els. This data will be crucial for future manned
missions, as weather predictions will protect as-
tronauts in the dangerous Martian environment
and weather. For example, intense dust storms
can reduce the amount of sunlight reaching solar
panels, decreasing energy production and caus-
ing equipment shut-downs, just as the Spirit and
Opportunity rovers did. Being warned before-
hand would allow astronauts to conserve some
 emits a fluorescent X-ray. This can then be ana-
lyzed to determine the object’s elemental com-
position since each element produces its own
unique fluorescent X-ray. With this technology,
PIXL will be able to identify 26 different ele-
ments, including sodium, sulfur, and iron, al-
lowing it to potentially identify signs of past life.

The fifth instrument is the Radar Imager for

Mars’ Subsurface Experiment (RIMFAX), a
ground-penetrating radar (GPR) that can detect
and map underground rock layers, water, and
Figure 2: JPL scientists installing MOXIE (car bat- ice on Mars. All GPRs work in a similar fashion,
tery sized) in the rover sending a series of tiny electrical pulses into the
ground and then recording the strength and re-
energy and protect their equipment. Additional- turn time of the reflected signal. After numerous
ly, measurements of radiation levels would allow pulses are released in a given area, the collected
scientists to better understand signs of past life. data can be input into special software that pro-
As stronger solar energetic particles (SEPs) and duces depth slices, or horizontal cross-sections,
galactic cosmic rays (GCRs), two sources of radia- at specific depths underground. In the case of
tion in space, are capable of penetrating the Mar- RIMFAX, the emitted electrical pulses vary from
tian soil, any signs of life near the Martian surface 150 MHz to 1.2 GHz, enabling a wide variety of
could have been destroyed by gamma rays. If this scans; higher-frequency pulses can detect small-
is the case, scientists would have to collect sam- er targets but cannot penetrate as deep while
ples from deeper in the Martian surface to deter- the opposite is true for lower frequency puls-
mine if the planet ever housed living organisms. es. In the end, RIMFAX is capable of scanning
up to and potentially even past depths of 10m.
Possibly the most intriguing instrument of the
seven, the Mars Oxygen In-Situ Resource Utili-
zation Experiment (MOXIE) is a device theoret-
ically capable of generating oxygen from Mars’s
95% carbon dioxide concentrated atmosphere
(Figure 2). Using one-third of the rover’s power,
MOXIE will use heat and electricity to split car-
bon dioxide (CO2) molecules into carbon mon-
oxide (CO) and oxygen (O) molecules. Despite
this device’s high energy consumption, it is only
capable of producing 6 to 10 grams of oxygen per
hour, which is not sufficient to support even a
single human. Thus, this technology is currently
only in a testing phase and much larger versions
of MOXIE will be used for any manned missions.

The Planetary Instrument for X-ray Lithochem-

istry (PIXL) uses a high-resolution camera and
an X-ray fluorescence spectrometer to identify
the small-scale composition of Martian materi-
als. When PIXL shines a narrow, focused X-ray
Perseverance Rover’s SuperCam by Allen Wu (VI)
beam onto a tiny spot of rock or soil, the object

49
The next instrument is quite similar to PIXL, in
terms of both technology and purpose. SHER-
LOC, short for the Scanning Habitable Envi-
ronments with Raman and Luminescence for
Organics and Chemicals device, consists of a
Raman and fluorescence spectrometer and a
laser. Similar to fluorescence spectroscopy, Ra-
man spectroscopy identifies an object’s chemical
structure using a laser. Specifically, the laser light
reflecting from that object is analyzed by a spec-
trometer — only the approximate 0.0000001% of
light with different wavelengths to the original
laser provides data — which is able to identify
different bonds (C-C, C=C, N-O, etc) and groups
of bonds (benzene rings, lattice modes, etc). Thus,
SHERLOC can determine an object’s elemen-
tal composition and chemical structure, and
this data can be used to detect minerals, organic
materials, and potential biosignatures on Mars.
Lastly, the SuperCam is a collection of instru-
ments capable of identifying rock textures, atomic
and molecular compositions, and chemical struc-
tures of different rocks and soils. Carrying tech-
nology from the Curiosity Rover’s ChemCam, the
SuperCam can zap objects up to 20 feet away with
a laser and analyze the resulting vapor to deter-
mine that object’s elemental composition. Fur-
thermore, it can perform Raman spectroscopy to
determine chemical structures, Time-Resolved
Fluorescence spectroscopy (TRF) to identify in-
termolecular interactions and Visible and Infra-
red reflectance spectroscopy (VISIR) to classify
the mineralogy of different soils and regoliths.
Overall, these various instruments that consti-
50
tute the SuperCam enable the rover to study
the molecular structure of different samples as
well as search for organic materials, all from afar.
With all the data already sent back by Persever-
ance, it appears that the rover and its scientific
instruments are functioning as planned. Now, it
is the rover’s responsibility to explore Mars and
complete its tasks as we patiently wait and watch.
Undoubtedly, this mission will be vital for future
Mars exploration, from increasing our under-
standing of the foreign Red Planet to preparing
for future manned missions. Hopefully, Perse-
verance will be a major success that we can look
back on in gratitude during future Mars missions.
Works Cited
1. Bell, J., Rodriguez-Manfredi, J. R., Hecht, M., Allwood,
A., Hamran, S.-E., Luther Beegle, & Wiens, R. (n.d.). In-
struments. NASA. Retrieved March 16, 2021, from https://
mars.nasa.gov/mars2020/spacecraft/instruments/
2. Gifford, S. E. (2014, February 18). Calculated Risks:
How Radiation Rules Manned Mars Exploration. Space.
Retrieved March 16, 2021, from https://www.space.
com/24731-mars-radiation-curiosity-rover.html
3. Mars 2020 Mission Contributions to NASA’s Mars Ex-
ploration Program Science Goal. (n.d.). NASA. Retrieved
March 16, 2021, from https://mars.nasa.gov/mars2020/
mission/science/goals/#:~:text=The%20Perseverance%20
rover%20is%20designed,in%20which%20it%20was%20
formed
4. Redd, N. T., & Wall, M. (2021, March 2). Perseverance
rover: NASA’s Mars car to seek signs of ancient life. Space.
Retrieved March 16, 2021, from https://www.space.com/per-
severance-rover-mars-2020-mission
5. Wood, C. (2021, March 1). With MOXIE, Perseverance
will try to make oxygen on Mars. Popular Science. Re-
trieved March 16, 2021, from https://www.popsci.com/story/
science/moxie-instrument-on-perseverance-mars/#:~:tex-
t=Instead%2C%20MOXIE%20takes%20in%20all
Diagram of the rover’s scientific
instruments
 Possible Dinosaur DNA Discov-
ered in Remarkably Preserved
Hypacrosaurus stebingeri Cartilage
by Adrian Kurylko (V)

A nesting ground filled with disarticulated bones of Hypacrosaurus stebingeri, a herbivorous

duck-billed dinosaur, was discovered in Montana during the 1980s. Further studies on sever-
al limb and skull elements of the discovery were recently performed, and a piece of calcified
cartilage located within a supraoccipital, a region in the back of the skull, differentiated itself
from the rest. Fossils typically form when an organism dies and after the fleshy parts of their
body decompose; the bones are buried in sediment where they harden into fossils. Molecular
changes to bones begin immediately after death, making the bones more thermodynamically
stable. Collagen, the main structural protein found in the extracellular matrix, is degraded - flu-
ids can then move through the much more porous bones, causing them to crystallize. However,
calcified cartilage contains an extracellular matrix that is much less porous than bone, limiting
the entry of water or microbes that would cause biodeterioration. As a result, the cartilage may
have been preserved at the molecular level. Ground sections of the supraoccipital presented
chondrocytes, or cells associated with bone growth, that consisted of darker spots that resemble a
nucleus (Figure 1).The calcified cartilage of the Hypacrosaurus stebingeri was compared with calcified
cartilage of a young emu to highlight differences between dinosaur and extant, or living, cartilage.

Figure 1: Calcified cartilage of Hypacrosaurus stebingeri compared with calcified cartilage of a young emu. A) A
Hypacrosaurus supraoccipital, or a bone located in the skull. B-D) Ground section of calcified cartilage containing
hypertrophic chondrocytes lacunae. In figure 1C, the cells shown by the green arrow appear to be empty while the cells
shown by the pink arrow present dark, condensed material consistent with a nucleus. Figure 2D shows material with
characteristics consistent with chromosomes in metaphase. E) A young emu skull. F-G) Ground section of emu calcified
cartilage exhibiting cells similar to those seen in the Hypacrosaurus cartilage.
51
The extracellular matrix of extant cartilage and bone can be differentiated using Alcian
Blue, or a stain that reacts heavily with acidic material such as acid mucins and glycosami-
noglycans. These molecules are found in cartilage but not in bone. Both dinosaur and emu
cartilage were compared to demineralized bone of their respective organisms and results
support the notion that there are chemical differences between calcified cartilage and bone (Figure 2).

Figure 2: (A, B, E, F) Unstained bone and cartilage of the Hypacrosaurus and emu. (C, D, G, H) Although
shown with less intensity, the Hypacrosaurus cartilage shares similar characteristics with emu cartilage, as
the Alcian blue stain highlights the acidic material naturally found within cartilage. Both Hypacrosaurus
and emu bone presented a lighter stain.

As previously mentioned, collagen is a protein found in the extracellular matrix of chon-

drocytes, or cells located in calcified cartilage. Assays using collagen II, or the most abun-
dant protein epitope in extant cartilage, were performed on Hypacrosaurus and emu carti-
lage in an attempt to generate an immune response (Figure 3). The antiserum containing
collagen II consisted of chicken protein in order to enhance immunoreactivity due to the
limited phylogenetic distance between dinosaurs and chickens. The results prove that col-
lagen II was preserved within the calcified cartilage, as it is not produced by microbes.

In order to test for DNA, the researchers isolated Hypacrosaurus chondrocytes. When photo-
graphed, they appeared to be transparent. Similar results were observed with emu chondrocytes.
The cells were tested with propidium iodide, a stain that inserts itself between every four or
five base pairs in DNA and is shown in red under fluorescent light. A limited stain was shown,
and in order to confirm these results the cells were also stained with DAPI (which requires
at least three successive A-T base pairs as a binding site). This trial produced similar results.

The findings of the various experiments performed on the calcified cartilage of the Hypacrosau-
rus stebingeri prove exquisite preservation at both the histological and molecular levels, with the
remnants of chondrocytes and nuclear material consistent with DNA. The discovery of DNA in a
fossil suggests that there could be an abundance of the genetic material of a variety of prehistoric
animals (such as mammoths or other dinosaurs) throughout the natural world. However, many
questions regarding the legitimacy of these findings arise: Could the DNA found belong to bacte-
ria that reside within the bone during fossilization? Are there other molecular aspects of fossiliza-
tion that account for such a rare discovery? Wouldn’t we have discovered more examples of a phe-
nomenon like this by now? There are still many unknowns, but for now the prospect of obtaining
genetic sequences of animals long extinct will become a focus of scientists for years to come.
52
Figure 3: (A, B, E, F) The green fluorescence shows antibody-antigen complexes in the extracellular matrix
of the calcified cartilage. Immunoreactivity was shown to be more intense in the calcified cartilage of the emu,
representing superior functionality. However, antibody activity was decreased after being exposed to collage-
nase II (C, D, G, H) in both the Hypacrosaurus and emu cartilage, proving that reactivity with collagen II is
specific to a protein found in cartilage of both animals. (I, J, K, L) A lab added as a control. Collagen I is not
expressed in primary extant cartilage and no binding was observed in either animal.

Figure 4: Hypacrosaurus chondrocytes isolated as individual cells (A), and as cell doublets (B). Both
Hypacrosaurus and emu cells displayed positive reactions to PI, a stain that intercalates DNA and highlights
it (C,F). DAPI (a different type of stain) produced similar results to PI, with the staining in the emu cells
being significantly more intense (D,G).

53
 Works Cited
1. Keenan, S. (2021). The Timing and Scales of Fossilization.
Fossilization - an overview | ScienceDirect Topics. Re-
trieved October 8, 2021, from https://www.sciencedirect.
com/topics/earth-and-planetary-sciences/fossilization.
2. Bailleul, A., Zheng, W., Horner, J., Hall, B., Holliday, C.,
& Schweitzer, M. (2020, January 12). Evidence of proteins,
chromosomes, and chemical markers of DNA in exceptional-
ly preserved dinosaur cartilage. National Science Review.
Retrieved October 3, 2021, from https://academic.oup.com/
nsr/article/7/4/815/5762999.
3. Black, R. (2020, April 17). Possible dinosaur DNA has been
found. Scientific American. Retrieved October 3, 2021,
from https://www.scientificamerican.com/article/possible-
dinosaur-dna-has-been-found/.

Dinosaur by Allen Wu (VI)

Temozolomide in the
Treatment of Gliomas
by Mirika Jambudi (V)

Accounting for more than 78% of brain can-
cers (AANS) and almost 15,000 casualties a year
(AANS), gliomas are among the most common
forms of brain cancer. Characterized as in-
tra-axial tumors (because they interfere with
brain tissue), glioma develops in glial cells, in-
cluding astrocytes, ependymal cells, and oli-
godendrocytes. Traditionally, these glial cells
support and surround nerve cells in the brain
(2). The specific glioma cell type involved in the
tumor determines the tumor’s genetic char-
acteristics and can help predict various treat-
ments’ efficacy (3). A variety of factors are con-
sidered when determining treatment, which
may include a combination of chemotherapy,
radiation, or surgery. Treatment also depends
on the tumor’s grade, ranging from “low grade”
or “high grade.” This grade is determined by
the tumor’s aggressiveness and growth rate ac-
cording to a predetermined scale. Developing
alternative and targeted therapies has posed a
challenge to scientists because glioma tumor
cells are protected by the blood-brain barrier
54
(BBB), which has highly selective permeability.
A typical therapy used for many forms of can-
cer is alkylating agents. They are used in cancer
therapies because they have the ability to pre-
vent a cell from replicating by inflicting damage
to the cell’s DNA (3). Alkylating agents are also
able to permeate the BBB, making it an optimal
choice. Temozolomide is a typical alkylating
agent used for treating glioblastoma multiforme,
a type of glioma originating in the astrocytes.
Glioblastoma multiforme is the most aggres-
sive form of brain cancer and is characterized
by its high invasiveness and mortality rates.
Temozolomide is typically used in conjunc-
tion with radiotherapy and then as a mono-
therapy. It has been a standard chemotherapy
drug used to treat gliomas since 2000. Being
an alkylating agent, its mechanism of action
is its ability to add methyl groups to DNA af-
ter conversion into MTIC. Methyl groups are
most commonly added on the N-7 or O-6 po-
sitions on guanine residues (4). Alkylation of

Temozolomide chemical composition
the DNA results in damage, which subsequent-
ly triggers these malignant cells’ apoptosis (4).
However, some tumor cells can be resistant to
Temozolomide’s effect, especially if they con-
tain the MGMT gene (4). MGMT allows the
cancerous cells to repair the DNA damage, pre-
venting apoptosis and allowing the damaged
cells’ uncontrolled proliferation to continue (4).
Temozolomide is orally administered and ab-
sorbed in the small intestine (3). Due to its
small size, it can effectively penetrate the
blood-brain barrier. As a prodrug, a change
in pH triggers Temozolomide to undergo
a conformational change via hydrolysis (5).
It turns into the cytotoxic MTIC (3-meth-
yl-triazine-1-y1-imidazole-4-carboxamide),
which has a growth inhibitory function (5).
Works Cited
1. American Association of Neurological Surgeons. (2016).
Glioblastoma multiforme. Retrieved March 26, 2021, from
https://www.aans.org/en/Patients/Neurosurgical-Condi-
tions-and-Treatments/Glioblastoma-Multiforme#:~:tex-
t=Glioblastoma%20multiforme%20(GBM)%20(also,as%20
a%20grade%20IV%20astrocytoma.
2. Johns Hopkins University. (2017). Gliomas. Retrieved
March 26, 2021, from https://www.hopkinsmedicine.org/
health/conditions-and-diseases/gliomas
3. Cancer Association. (2018). How chemotherapy
drugs work. Retrieved March 26, 2021, from https://
www.cancer.org/treatment/treatments-and-side-effects/
treatment-types/chemotherapy/how-chemothera-
py-drugs-work.html#:~:text=Alkylating%20agents%20
keep%20the%20cell,%2C%20multiple%20myeloma%2C%20
and%20sarcoma.
4. Zhang J;Stevens MF;Bradshaw. (2012, January). Temo-
zolomide: Mechanisms of action, repair and resistance.
Retrieved March 26, 2021, from https://pubmed.ncbi.nlm.
nih.gov/22122467/
5. Wesolowski, J., Rajdev, P., Mukherji, S. (2010, Septem-
ber 01). Temozolomide (Temodar). Retrieved March 26,
2021, from http://www.ajnr.org/content/31/8/1383#:~:-
text=The%20proposed%20mechanism%20of%20ac-
tion,small%20size%20(194%20Da).

Oncologists and brain cancer researchers have

seen that administering the drug with radi-
ation therapy has increased the time before
disease progression. A significant drawback of
this drug is its very high costs, but this can be
offset by the fact that most of Temozolomide’s
expenses are covered by governmental health
care programs such as Medicaid. Researchers
are now looking to investigate where pairing
Temozolomide with another pharmacologic
agent would increase its cytotoxicity and effica-
cy. Additionally, after extensive research on cre-
ating therapies that can permeate the blood-
The blood-brain barrier by Kelly Cao (IV)
brain barrier, alkylating agents have paved the
way for new therapy technologies such as na-
no-particle mediated brain drug delivery (1).
55
 Oncolytic Viruses in Cancer
Treatment
by Annabelle Shilling (IV)

Vaccines have been used to prevent cancer-caus-

ing infections such as HPV, but their applica-
tions within cancer research extend further
than that. While virtually every vaccine in histo-
ry has been wielded to prevent the acquisition
of some infectious disease, oncolytic virothera-
py is a novel branch of oncology pertaining to
vaccines used not to prevent an infectious dis-
ease, but designed to cure a noninfectious one.

An oncolytic virus is one that seeks and de-

stroys exclusively tumor cells. It typically does
so by lysing such cells, but this direct cytore-
duction is not the only effect of these virus-
es. A helpful byproduct of the infection is
the stimulation of the immune system with-
in the tumor microenvironment. While the
viruses go about lysing tumor cells, the tu-
mor antigens released induce both an in- Oncolytic virus particle by Lleyton Lance (VI)
nate and an adaptive immune response (ex.
increasing tumor T-Cell counts), the latter of
cle arrest after becoming infected with it. With
which functions as a lasting immunotherapy.
adenoviruses, quiescent cells can be pushed
into S phase by E1A proteins after they bind to
Oncolytic viruses can be lab-made or naturally
retinoblastoma proteins within the cell. These
occuring; the former of which ensures the viruses
Rb proteins are used to regulate the transition
must depend on tumor cells for replication and
from G1 to S phase through interactions with
its establishment of tumor-specific alterations
E2F transcription factors, and the Rb binding
for lysis. The Onyx-015 Adenovirus was one of
to E1A subsequently causes the release of E2F.
the first oncolytic viruses used in clinical trials,
E1A, undesirably, causes p14ARF to be released
and in spite of its benefit proving slightly un-
as well, a protein that inhibits Mdm2 (Murine
derwhelming, the trials did confirm two things:
double minute 2) from degrading p53. The tran-
oncolytic viruses are safe to be administered
scription factor p53 is used to initiate cell cycle
to humans and they hold the potential to work
arrest or apoptosis as a consequence of signals
in conjunction with systemic radiotherapy and
revealing damage to DNA—it can also do this
chemotherapy as a combined cancer treatment.
due to cellular stress. However, if p53 accumu-
lates due to the lack of degradation, the cell cy-
Onyx-015 is selective, not in the sense that
cle arrest or apoptosis that can occur is detri-
it will not infect healthy cells, but that only
mental to the viral life cycle—if the cell dies or
healthy cells will undergo apoptosis or cell cy-
ceases growth before the viral cycle is complete,
56
it will reduce the amount of viral offspring
produced. Adenoviruses contain E1B genes to
combat this threat to their reproduction, one
of which, known as E1B55K, codes a product
that binds to p53 and renders it nonfunctional.
Cancerous cells are those with damaged DNA
that continue to replicate and exist. Thus, the
lack of functional p53 is universal to almost all
known cancers—the damaged DNA and result-
ing protein does not signal p53 to initiate apop-
tosis or restrict cellular growth. Onyx-015 was
genetically engineered (827 bp deletion and a
point mutation--causing an early stop codon-
-in E1B), preventing the proper expression of
E1B55K’s product. Thus, in infected healthy
cells, the adenovirus cannot restrict the buildup
of p53. The resulting apoptosis or restricted cel-
lular growth interferes with the viral life cycle
and thus prevents the infection from spreading
among healthy tissues. However, as tumor cells
do not possess functional p53, the lack of func-
tional E1B55K does not make a difference in
the viral life cycle. The virus can go about repli-
cating itself and ultimately lyse the cell without
any risk of apoptosis or restricted cell growth
occurring. Thus, Onyx-015 is selective in its abil-
ity to replicate in and lyse tumor cells without
posing a threat to surrounding, healthy tissues.
As of now, only one therapy using an onco-
lytic virus has been FDA-approved for cancer
treatment: Talimogene laherparepvec, which
is used to treat melanoma using a genetically
modified herpesvirus. It bolstered the theory
that oncolytic viruses can systematically target
cancer manifested when tumors not directly
injected with the treatment began to shrink.
While none are approved by the FDA, many
other viruses are being examined for oncolytic
potential–even a genetically modified form of
the poliovirus is now in trial for targeting brain
tumors. Another treatment in development
uses reoviruses capable of crossing the brain-
blood barrier to target brain tumors as well.
57
While these treatments do seem very prom-
ising, there are limitations to the capabilities
of oncolytic viruses. They are susceptible
to neutralization, hypoxic environments,
high IFPs (interstitial fluid pressures), being
wiped out by the immune system, move-
ment-inhibiting stromal barriers, and trans-
duction errors. That being said, oncolytic
viruses remain a possibility for cancer treat-
ment, combined or solitary.
Works Cited
1. Harbour, J. W., & Dean, D. C. (2000). Rb function in
cell-cycle regulation and apoptosis. Nature Cell Biology,
2(4), E65-E67. https://doi.org/10.1038/35008695
2. Munhoz, R. R., & Postow, M. A. (2016). Recent advances
in understanding antitumor immunity. F1000Research, 5,
2545. https://doi.org/10.12688/f1000research.9356.1
3. Oncolytic virus therapy: Using tumor-targeting viruses to
treat cancer. (2018, February 9). National Cancer Institute.
Retrieved October 7, 2021, from https://www.cancer.gov/
news-events/cancer-currents-blog/2018/oncolytic-virus-
es-to-treat-cancer
Woller, N., Gürlevik, E., Ureche, C.-I., Schumacher,
A., & Kühnel, F. (2014). Oncolytic viruses as anticancer
vaccines. Frontiers in Oncology, 4. https://doi.org/10.3389/
fonc.2014.00188
4. Zhao, Y., Yu, H., & Hu, W. (2014). The regulation of
mdm2 oncogene and its impact on human cancers. Acta
Biochimica Et Biophysica Sinica, 46(3), 180-189. https://doi.
org/10.1093/abbs/gmt147
5. Lawler SE, Speranza MC, Cho CF, Chiocca EA. On-
colytic Viruses in Cancer Treatment: A Review. JAMA
Oncol. 2017 Jun 1;3(6):841-849. doi: 10.1001/jamaon-
col.2016.2064. PMID: 27441411.
6. Hemminki, O., dos Santos, J.M. & Hemminki, A.
Oncolytic viruses for cancer immunotherapy. J Hematol
Oncol 13, 84 (2020). https://doi.org/10.1186/s13045-020-
00922-1
 Transcriptomic Analysis of
COVID-19 Patients
by Maya Khan (V)

This past summer, I participated in a virtual Transcriptomic Analysis + COVID-19 course run by
Milrd, an educational organization in New York City, supported by the Mason Lab at Cornell Medical
Center. I was new to transcriptomic analysis, the study of RNA transcripts, but the course gave me a
strong foundation and incredible mentors. Through this program, I learned how to analyze a broad
collection of data and use specific programs to compare reference genomes. This course would be
perfect for anyone interested in computational biology and large-scale sequencing surveillance.

The class focused on a two-step analysis of COVID-19 transcriptomic data. While the ge-
nome is a larger collection of all nucleic or mitochondrial DNA, the initial product of ge-
nome expression is the collection of mRNA copied from the genes during transcription. The
transcriptome measures this complete set of RNA transcripts in the intermediary stage be-
tween genes and proteins. For the analysis, cDNA is synthesized from the single-strand-
ed RNA. Using a series of programs to clean and organize the raw sequencing data, we
transformed it into an understandable format. Then, using the Integrated Genomics View-
er (IGV), we generated visualizations of the genomic data and identified point mutations.
Over the past decade, more reliable sequencing methods to track and map genes have been

Figure 1: Graphic showing the transcriptome’s variability due to alternative splicing.

58
Figure 2: The IGV program was used to compare the cleaned COVID-19 patient sample and the reference
genomes.

developed. In response to the COVID-19 pandemic—caused by Severe Acute Respirato-

ry Syndrome Coronavirus 2 (SARS-CoV-2)—many countries have invested in genome se-
quencing (a process used in molecular biology to study genomes and the resulting proteins).
However, transcriptomic analysis can further explain the complexity of gene expression.
The nucleotide sequence found in RNA reflects the code in DNA. By analyzing the tran-
scriptome, researchers also investigate the COVID-infected cell gene expression and ac-
tivity. Because of alternative splicing, each gene may produce more than one type of mRNA.
Changes in normal gene activity may signal disease and may help guide vaccine development.

To perform our analysis, we cleaned and organized the data in stages using the Terminal found
in most computers. In the first stage, we turned our sets of raw DNA reads into a _strain pro-
file_ of SARS-CoV-2 patient isolate that delineates nucleotide and amino-acid level muta-
tions in the sample. This process had two major steps: quality control and mutation analysis.

During the second stage, we removed human DNA from our samples using a program
called Bowtie2 and a human reference genome. Most SARS-CoV-2 patient samples con-
tain human RNA that gets converted to cDNA, but we were not interested in analyzing
it. To focus on the important COVID genomic data, we had to get rid of the host cell RNA.

We then aligned our data with the indexed SARS-CoV-2 Reference Genome to find muta-
tions. This alignment format gave coordinates indicating where mapped segments had mis-
59
matches between the reference sequence nucleotides and our COVID-19 patient sample.

The discovered mismatches between the reference genome and our sam-
ple could be due to two factors: (1) a genuine biological mutation in the sam-
ple or (2) an error as a result of the sample preparation and sequencing process.

After we had aligned reads in our sample and (hopefully) called a list of high-quality vari-
ants, we visualized the results and listed the nucleotide position and associated amino acid
mutations. These counted mutations allow genomic epidemiologists to track how a particu-
lar virus travels around the globe. We used a genome browser called the Integrated Genomics
Viewer (IGV), which is authored and distributed by the Broad Institute of Harvard and MIT.

Performing sequencing on viral and host cell genomes is important for many reasons. On average,

Figure 3: Final results, on mutations in the patient sample, displayed by a table.

the SARS-CoV-2 genome accumulates about two changes per month. Sequencing SARS-CoV-2
genomes and identifying subtle shifts help researchers follow how the virus spreads. Most of
the mutations don’t affect how the virus functions, but a few may change the virion’s transmis-
sibility or severity. Sequencing is an important tool, especially during this pandemic because
it allows lineages and virulent genetic shifts to be tracked around the globe. For example, they
have found that the Coronavirus outbreak in New York City stemmed primarily from Europe,
while the SARS-CoV-2 genomes sequenced in Washington State indicate a Wuhan origin. Us-
ing the data and mutations, scientists can group global outbreaks and build phylogeny “fami-
ly” trees for viruses. These trees are constantly being updated on GISAID and nextstrain.org.

All in all, this was a great class to take to get an inside look on the tools being used to track and se-
quence SARS-Cov-2. Taking part in this program is a great way to explore current research being
done in computational biology.After applying, I chose from a variety of classes and different sessions.
The experience was virtual, extremely flexible, and allowed me to pursue my interests in science.

60
Trisomy Formation Within Cancers
by Annabelle Shilling (IV)
Trisomies are the most common cancerous
chromosomal abnormalities. As a result, many
researchers have attempted to identify how
they form. Many consider a dysfunctional
spindle assembly checkpoint (SAC) to be the
cause of such errors, implying that the improp-
er separation of sister chromatids during mi-
tosis causes the gain of an extra chromosome
in some cells; however, researchers studying
the childhood kidney cancer nephroblastoma
have discovered evidence suggesting otherwise.
Tripolar mitosis is often a distinguishing fea-
ture of cancerous tissue. Because bipolar
mitosis is the default for many healthy cells,
tripolar mitosis, a mitotic division creating
three daughter cells instead of two, is a dan-
gerous abnormality (Figure 1). Bipolar mitosis
requires two centrosomes to be active, but any
quantity greater than two can result in unde-
sired spindle poles. These spindle poles guide
the chromosomes to different parts of the cell
for replication (anaphase), but when there are
three of them active rather than two, the chro-
mosomes are pulled in three different direc-
tions. Thus, the cell is preparing to split the
chromosomal content into three daughter cells.
Figure 1: Tripolar mitosis
Nephroblastoma models used by research-
ers at Lund University demonstrated that it is
possible for trisomies to form even when the
SAC is functional. This formation is possible
when triple mitosis begins to occur but fails
during cytokinesis, resulting in the produc-
tion of two cells but with a mismatch in chro-
61
mosome counts. Multipolar divisions are 16 to
128 times more likely to result in chromosom-
al aberrations than bipolar segregation errors,
and of the 18 initial cells involved in the study
that exhibited tripolar mitosis, only two did
not fail during cytokinesis. Researchers later
found, using a different set of cells, that 80%
of tripolar replications fail during cytokinesis,
in contrast to a mere 5% of bipolar replications.
These failures in cytokinesis often lead to tri-
somies in the subsequent binucleated daugh-
ter cells. Contrary to popular belief, mutations
present in genes involved in the mitotic check-
point are uncommon in human cancers, thus
further debunking the SAC theory. That being
said, it is not yet certain how epigenetic com-
ponents affect this process, so the lack of mu-
tations cannot be taken as complete evidence.
The mechanisms through which cancer is in-
duced are very complex, and there is no standard
to be applied to cancer as a whole. Tripolar mito-
sis has not been proven to cause all trisomies in
cancers, and the research discussed above sim-
ply discredits the common assumption that the
SAC is solely responsible for those trisomies.
Works Cited
Gisselsson, D., Jin, Y., Lindgren, D., Persson, J., Gissels-
son, L., Hanks, S., Sehic, D., Mengelbier, L. H., Ora, I.,
Rahman, N., Mertens, F., Mitelman, F., & Mandahl, N.
(2010). Generation of trisomies in cancer cells by multi-
polar mitosis and incomplete cytokinesis. Proceedings of
the National Academy of Sciences, 107(47), 20489-20493.
https://doi.org/10.1073/pnas.1006829107
Kalatova, B., Jesenska, R., Hlinka, D., & Dudas, M. (2015).
Tripolar mitosis in human cells and embryos: Occur-
rence, pathophysiology and medical implications. Acta
Histochemica, 117(1), 111-125. https://doi.org/10.1016/j.
acthis.2014.11.009
Ottolini, C. S., Kitchen, J., Xanthopoulou, L., Gordon,
T., Summers, M. C., & Handyside, A. H. (2017). Tripolar
mitosis and partitioning of the genome arrests human
preimplantation development in vitro. Scientific Reports,
7(1). https://doi.org/10.1038/s41598-017-09693-1
Treatment of Metastatic Cancer
with Statins
by Grace Stowe (IV)
In an effort to eradicate cancer, scientists are
researching a variety of treatments and possible
cures. One such treatment involves a drug pre-
viously only used to treat high cholesterol: sta-
tin, an inhibitor of HMG-CoA reductase in the
mevalonate pathway. When statins inhibit the
HMG-CoA reductase, they inhibit the down-
stream effects of the signaling cascade in the me-
valonate pathway: increased membrane integ-
rity, increased protein synthesis, increased cell
cycle progression, and increased cell signaling,
which all promotes cell proliferation. The in-
hibition promotes cell apoptosis (programmed
cell death), which reduces the risk of meta-
static cancer and uncontrolled tumor growth.
While there is no definitive association between
statins and the risk of developing cancer, there
is promising evidence that statins are efficient
at slowing the progression of metastatic pros-
tate cancer. For example, in Coogan’s 2002 study
on the association between statin use and inci-
dents of prostate cancer the odds ratio (statis-
tic that quantifies the association between two
events, a value greater than one indicated that
there is a correlation between the two parame-
ters)of statin users with prostate cancer was 1.2,
but in advanced cases, it was 0.9, meaning that
there is a correlation between statin use and
a decrease in the progression of non-metastat-
ic prostate cancer, suggesting that the usage of
statins reduces progression of metastatic pros-
tate cancer. A similar result is seen in Platz’s
2006 report, which demonstrates that as the
cancer progressed, the odds ratio decreased.
Platz’s report indicates that the later the stage
of prostate cancer, the more effective statins are
at decreasing the progression of the disease.
62
While these promising statistics are seen in
the treatment of metastatic prostate cancer,
they are not seen in the treatment of breast,
colorectal, lung, or reproductive organ can-
cer, which all had an odds ratio of less than
one when tested (no correlation between the
risk of cancer and statin usage). As the use of
statins for metastatic prostate cancer is new,
there is limited data to support the efficacy of
this treatment in the long term. In spite of the
lack of data for usage over a longer period of
time, statins are potentially a promising treat-
ment for metastatic and fatal prostate cancer.
Works Cited
1. Boudreau, D. M., Yu, O., & Johnson, J. (2010, April 9).
Statin Use and Cancer, Risk: A Comprehensive Review.
Retrievedfrom: https://www.ncbi.nlm.nih.gov/pmc/articles/
PMC2910322/#R36
2. Coogan, P. F., Rosenberg, L., Palmer, J. R., Strom, B. L.,
Zauber, A. G., & Shapiro, S. (2002, May). Statin use and the
risk of breast and prostate cancer. Retrieved from: https://
pubmed.ncbi.nlm.nih.gov/11964926/.
3. Kochhar, R., Khurana, V., Bejjanki, H., Caldito, G., &
Fort, C. (2005, June 1).
4. Statins to reduce breast cancer risk: A case control
study in U.S.
female veterans. Journal of Clinical Oncology. Retrieved
from: scopubs.org/doi/abs/10.1200/jco.2005.23.16_sup-
pl.514.
5. Platz, E. A., Leitzmann, M. F., Visvanathan, K., Rimm, E.
B., Stampfer, M. J., Willett, W. C., & Giovannucci, E. (2006,
December 20). Statin drugs and risk of advanced prostate
cancer.
6. Retrieved from: https://pubmed.ncbi.nlm.nih.
gov/17179483/.
7. Singh, H., Mahmud, S., Turner, D., Xue, L., Demers,
A., & Berstein, C. (2009, December). Long-Term Use of
Statins and Risk of Colorectal Cancer: A population-Based
Study.
Retrieved from: https://insights.ovid.com/pubmed?p-
mid=19809413.
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