INQUIRY

New York University • College of Arts and Science
sequence on crystal formation and resolution. X-ray diffraction
data from beam line NSLS-X25 revealed that the
crystal resolution was somewhat better for the 2-nt sticky
end having an TG:CA (4.2 Å) base pair than AA:TT (4.75
Å), GA:CT(4.9 Å) and CC:GG (6.0 Å). Moreover, the 1-nt
sticky end (C:G) yielded a diffraction pattern whose resolution
(3.5 Å) compared favorably with all the three 2-nt
sticky end systems (Ohayon, Chandrasekaran et al., 2013).
For motifs with 3-nt sticky ends, the sequence GAG:CTC
produced small crystals while larger crystals were obtained
with the sequences TAG:ATC (4.20 Å) and TAT:ATA (6.0
Å). Triangles having a 2-nt CC:II sticky-end diffracted to
4.7 Å while triangles having 4-nt sticky with sequence
GCTC:CGAG diffracted to 5.2 Å at APS-ID19. The results
indicate that the lengths and sequences of the sticky ends
define the interactions between motifs and also have an
impact on the resulting resolution. Redesigned assemblies
are expected to form 3-D crystals with better resolution that
can aid in the scaffolding of biological macromolecules
for crystallographic structure determination.
The Effect of Chronic Unpredictable Stress on eIF4E
Transgenic Mice, a Mouse Model of Autism Spectrum
Disorder
Zonia Ali, Neural Science
Sponsor: Professor Eric Klann, Neural Science
Autism spectrum disorders (ASDs) are a highly prevalent
group of neurodevelopment disorders with a complex
and unclear etiology. Interestingly, individuals with ASD
are more susceptible to stress, although the reasons are
unclear. Stress is a natural biological response to perceived
threats; chronic stress, however, upsets this response by
unbalancing the hypothalamic-pituitary-adrenal (HPA)
axis. Chronic stress can result in learning and memory
deficits and reduced activity of the mammalian target
of rapamycin complex 1 (mTORC1) signaling pathway,
which regulates cap-dependent translation. Crucially,
long-term memory requires protein synthesis. This study
explored the effect of chronic stress on mTORC1 signaling,
learning and memory and autistic-like behaviors in 4E
transgenic (4E Tg) mice a rodent model of ASD. A chronic
unpredictable stress (CUS) protocol was used to demonstrate
that chronic stress decreases the phosphorylation of
mTORC1 proteins in the hippocampus and prefrontal cortex
of wildtype mice. This study then investigated whether
CUS affects ASD-like behaviors and/or learning and
memory in 4E Tg mice. In stressed 4E Tg mice, the results
showed a significant increase in freezing during cued fear
conditioning but no change in ASD-like behaviors. This
may indicate a relationship between chronic stress and fear
memory in 4E Tg mice. This research may ultimately lead
to a better understanding of the biological and behavioral
effects of chronic stress in ASD and potential targets for
stress alleviation.
Combination of Interleukin-15 and Fractionated
Radiotherapy for Cancer Treatment
Joseph Aryankalayil, Psychology
Sponsor: Professor Sandra Demaria, Pathology, NYU
School of Medicine
The common gamma-chain cytokine interleukin-15
(IL-15) promotes the proliferation of activated T cells, has
low toxicity and lacks regulatory T cell stimulation, all of
which makes it an attractive candidate for immunotherapy.
This study tested the hypothesis that IL-15 administration
strengthens the pro-immunogenic effect of hypofractionated
RT and contributes to inducing anti-tumor responses
in the TSA breast cancer model. Tumor inoculated mice
were randomly assigned to one of 4 treatment groups
(N=4-5/group): control, RT, IL-15 or RT+IL-15. RT
was delivered in 8 Gy fractions over 3 consecutive days,
starting on day 13 post-tumor inoculation. IL-15 (2μg/
mouse) was administered daily for 10 days starting on day
12. Tumor regression was seen when RT was combined
with IL-15. This suggests that IL-15 can potentiate T cell
responses elicited by RT. Combination therapy consistently
showed a marked increase in CD8+ T cells expressing the
activation marker CD137 while the increase was modest
with each monotherapy. In addition, this study showed a
significant increase in the ratio of effector CD4+ T-cells
from combination therapy. Overall, these results support
the hypothesis that IL-15 is a valuable partner for combination
treatments with local RT.
Cryptic Genetic Variation Revealed via Perturbation
of Intersex in 16 DGRP Lines
Christopher Aseervatham, Biology
Sponsor: Professor Mark Siegal, Biology
Cryptic genetic variation (CGV) characterizes genetic
variation among individuals of a natural population that
has no evident phenotypic effect until the individuals
are perturbed environmentally or genetically. This study
explores this concept with a genetic perturbation involving
the knockout of the intersex (ix) gene in 16 randomly
chosen Drosophila Genetic Reference Panel lines. ix is
expressed in both sexes and is involved in the development
of female specific characteristics in Drosophila
melanogaster. Initially the ix knockout was tagged with
GFP for ease of identification in future crosses. Knockout
males were selected and crossed with the 16 DGRP lines
that were randomly picked to introduce the mutation into
the DGRP background. The next cross was a sibling cross
between the male and female progeny, who are heterozygous
for GFP tagged ix knockout and the corresponding
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