abstract

Synthetic hydroxyapatite HAp bears poor mechanical properties that limit its
applicability in orthopedics. We study the possibility of overcoming such limitations by
incorporating functionalized single walled carbon nanotube fSWCNT and polymerized є-
caprolactam. Sonication method was used to disperse fSWCNT in the HAp. A simple hot
blending method was used to incorporate HAp/fSWCNT powder with melted polymerized
є-caprolactam. The fracture toughness of the composite material was tested in
compliance with ASTM D-5045 standard. A critical stress intensity factor K1C of the composite
material was found to be 3.55 MPa.m1/2, which is a value comparable to the one for cortical
bone.

Previous work demonstrates that PKG pathway modulation in Drosophila controls
tolerance to stress in adults and larvae. Through the use of genetics and pharmacology, PKG
inhibition leads to significant protection of function while activation causes increased sensitivity
and early coma onset. In this study we investigate the effect of PKG modulation on neurons and
glia during acute hyperthermia, and begin to determine the underlying physiological
contributions of both tissues.
Glia have been found to influence single neuron activity and global brain function. Neurons, the
most energy-demanding cells in our bodies, are most sensitive to stress. As humans, our neurons
function under stress until permanent failure, resulting in brain damage and even death. Insects
are much more tolerant to environmental stressors. Although stress-activated protective
pathways are highly conserved in both insects and humans, their outcome on neuronal function
and survival are very different.

Small conductance Ca2+ -activated K+ (SK) channels have physiological roles in
learning and memory, intrinsic excitability, synaptic transmission and plasticity, and addiction.
While SK2 and SK3 channels have been studied, the role of SK1 has not yet been determined
due to the prior lack of gene-specific antibodies and agonists. SK1 are robustly expressed in the
CA1 pyramidal neurons of the hippocampus and modulate their excitability by affecting
afterhyperpolarization. SK1 subunits are only sited in the plasma membrane when co-expressed
with SK2 or SK3. Co-expressed and co-assembled SK1, SK2, and SK3 subunits form functional
apamin-sensitive channels. SK1 are not apamin selective, suggesting the overriding hypothesis
that SK1 is a subunit of heteromeric SK channels that bind specific interacting proteins. We
examined the effect of a new SK1 selective activator, GW542573X, on hippocampal dependent
object memory in male C57BL/6J mice. The results showed that activating SK1 channels by
systemic injection of the SK1 agonist GW542573X before the sample session, led to impaired
object memory in mice 24 h later. Mice treated with GW542573X acquired the sample object
exploration criterion in a similar latency as the vehicle-treated mice.GW542573X treated mice
exhibited significantly less preference for exploring the novel object during the test session
compared to the vehicle-treated mice. These results suggest that the SK1 activator disrupted the
encoding of object memory without affecting the motivation to explore objects. This supports a
role for SK1 in the modulation of hippocampal synaptic plasticity and hippocampal-dependent
memory.

PTP69D is a receptor protein tyrosine phosphatase RPTP with two intracellular catalytic
domains Cat1 and Cat2, which has been shown to play a role in axon outgrowth and guidance of
embryonic motoneurons as well as targeting of photoreceptor neurons in the visual system of
Drosophila melanogaster. Here, we characterized the developmental role of PTP69D in the giant
fiber GF neurons; two interneurons in the central nervous system CNS that control the escape
response of the fly. In addition to guidance and targeting functions, our studies reveal an
additional role for PTP69D in synaptic terminal growth in the CNS. We found that inhibition of
phosphatase activity in catalytic domain Cat1 proximal to the transmembrane domain did not
affect axon guidance or targeting but resulted in stunted terminal growth of the GFs. Cell
autonomous rescue and knockdown experiments demonstrated a function for PTP69D in the
GFs, but not its postsynaptic target neurons. In addition, complementation studies and structurefunction
analyses revealed that for GF terminal growth Cat1 function of PTP69D requires the
Immunoglobulin and the Cat2 domain, but not the Fibronectin III and the Membrane Proximal
Region domains. In contrast, the Fibronectin III, but not the Immunoglobulin domains, were
previously shown to be essential for axon targeting of photoreceptor neurons. Thus, our studies
uncover a novel role for PTP69D in synaptic terminal growth in the CNS that is mechanistically
distinct from its function during earlier developmental process.

Disseminated metastasis accounts for a majority of breast cancer deaths. Recently,
elevated serum levels of a glycoprotein known as chitinase-3 like-protein-1 CHI3L1 has been
correlated with poor prognosis in both breast cancer and asthmatic patients. We have combined
mouse models of breast cancer and pulmonary inflammation to determine if CHI3L1 associated
pulmonary inflammation accelerates metastasis. We found that allergic pulmonary inflammation
significantly enhances primary tumor growth in 4T1, 4T07 and 67NR mammary tumors by 10-
fold, while decreasing survival. 4T1 tumor bearers with allergic pulmonary inflammation
showed a 100-fold increase in metastatic tumor formation. We also assessed CHI3L1 levels and
myeloid cells in the lungs of wild type and CHI3L1 knockout mice with allergic pulmonary
inflammation and 4T1 mammary tumors. CHI3L1 levels were higher in the lungs of mammary
tumor bearers with allergic pulmonary inflammation and correlated with increased metastasis.
Wild type mammary tumor bearers with allergic inflammation had higher numbers of myeloid
cells in the lungs in comparison to CHI3L1 knockout tumor bearers with allergic pulmonary
inflammation. CHI3L1 knockout mice tumor bearers had significantly fewer myeloid cells in the
lungs, decreased tumor growth and metastasis, along with increased survival. We propose that
increased CHI3L1 in the lungs attracts myeloid cells that promote tumor growth and breast
cancer metastasis.

Matrix metalloproteinases MMPs are one of the major families of proteinases that play
key roles in maintaining an appropriately assembled extracellular matrix ECM. MMPs are
essential to many biological processes, such as wound healing, embryo implantation, bone
remodeling, and organogenesis. Their biological antagonists, the tissue inhibitors of
metalloproteinases TIMPs, regulate the enzymatic activities of MMPs. Uncontrolled ECM
degradation occurs when the delicate balance between TIMPs and MMPs is disrupted, resulting
in many diseases such as rheumatoid and osteoarthritis, cancer cell metastasis, and heart disease.
There are currently no effective treatments for osteoarthritis OA except for joint replacement
surgery. Therefore, gaining the knowledge about the structures and molecular mechanisms of
these key enzymes in order to uncover new ways to specifically inhibit these proteinases are an
opportunity for the development of therapeutics and treatments to prevent the joint destruction
seen in OA.
Our goal is to understand the biophysical interaction of catalytic domain of MMP-1 with NTIMP-
3 using isothermal calorimetry ITC. The ITC determines if binding between the proteins is
entropy or enthalpy driven and heat capacity will indicate the hydrophobic or hydrophilic
contributions of the interaction. The information from the ITC results in combination with the
known structures of N-TIMP-3/cd_MMP-1 will provide a more complete picture of the
interaction. This is in particular of relevance with respect clinical application by engineering
TIMPs for targeted inhibition of particular MMPs to treat diseases such as: cancer and arthritis.

We recently reported that male C57BL/6J mice navigate in spatial tasks, such as the
Morris water maze MWM, by swimming in a particular direction to a location relative to poolbased
cues, rather than to an absolute location defined by room-based cues. Neural mechanisms
supporting this bias in rodents for relative responding rather than absolute responding in spatial
tasks are not yet understood. Anterior thalamic neurons discharge according to the current
directional heading of the animal. The contribution of head direction HD cell activity to
navigation has been difficult to elucidate. Selective inactivation of anterior thalamic nuclei ATN
by microinfusion of muscimol or fluorophore-conjugated muscimol caused a near complete shift
in preference from relative to absolute responding. Interestingly, inactivation of the dorsal CA1
region of the hippocampus did not affect relative responding. A land based version of the MWM
has been developed to permit the recording of anterior thalamic HD cells during spatial search
behavior. These experiments have been conducted to further examine the contribution of the HD
cell activity to relative responding during spatial navigation.

Urban and residential land uses in the Indian River Lagoon IRL watershed contribute
sewage and fertilizers to stormwater runoff, resulting in increased nitrogen N and phosphorous P
loadings that can fuel harmful algal blooms. The goal of this project is to quantify dissolved
concentrations of ammonium, nitrate and soluble reactive P in storm water from agricultural,
natural, and urban land uses adjacent to seven of the canals and tributaries within the IRL
watershed. Preliminary results based on water samples taken at the beginning, middle and end of
storm events at 10 sample points suggest initial spikes of soluble reactive P, nitrate and ammonia
in storm water runoff. These results represent the first attempt to characterize nutrient
concentrations of stormwater among various tributaries and land uses on the IRL.

The ability to exhibit altruistic behaviors is considered as one feature that distinguishes
humans from other species Haviland et al. 2004. A recent surge of studies regarding children’s
altruistic behavior has emerged. Benenson et al. 2007 used a Dictator Game to test 4-, 6-, and 9-
year old’s altruistic behavior towards a classmate and found that even the youngest children
behaved altruistically some of the time. Moore 2009 tested differences in children’s altruistic
behavior using group membership and found that giving depended on group membership. These
findings may have been skewed by the presence of the researcher Fehr, Bernhard, &
Rockenbach, 2008. This study seeks to replicate the findings of Moore 2009 while using a
modified Dictator’s Game and an anonymous design in order to measure 3, 4, 5, and 6-year-old
children’s altruistic giving without the influence of a researcher. We found that a significant
percentage of children did not donate any stickers to any recipient, suggesting that young
children are not as altruistic as they are portrayed. We also found that, amongst those that did
donate, in-group received more than out-group members, but not as much as a genetic relative.

Ischemic stroke is one of the leading causes of human death worldwide. It occurs due to
high susceptibility of neurons to anoxia and reoxygenation. Unlike mammals, invertebrate
Drosophila melanogaster withstands low oxygen levels without showing pathology. In the
present study, Drosophila Schneider (S2) cells were employed to investigate the role of the
cGMP-dependent Protein Kinase (PKG) signaling pathway in Drosophila anoxia-tolerance in
vitro. This was accomplished by subjecting cells to chemical anoxia and oxidative stress
concurrently with treatments by pharmacological agents affecting specific targets of the PKG
pathway and assessing cytotoxicity. In this study, activation of the PKG pathway protected S2
cells from the aforementioned stresses. The results of this study may lead to a better
understanding of fruit fly’s innate anoxia-tolerance strategies. Consequently, this knowledge may
be used to identify potential therapeutic targets to prevent detrimental neurological effects of an
ischemic stroke in humans.