1.
Name and Title of Presenter: Michael Wimberly
Co-Authors: Belay Beyene, Estifanos Bayabil, Mekonnen Bishaw, Alemayehu M. Lemma, Yi Liu, Christopher L. Merkord, Abere
Mihretie, Gabriel B. Senay, Worku Yalew, Geoffrey M. Henebry
Organization/Department: Geospatial Sciences Center of Excellence
Abstract Title: EPIDEMIA – An EcoHealth Informatics System for Integrated Forecasting of Malaria Epidemics
Early warning of the timing and locations of malaria epidemics can facilitate the targeting of resources for prevention and
emergency response. In response to this need, we are developing the Epidemic Prognosis Incorporating Disease and Environmental
Monitoring for Integrated Assessment (EPIDEMIA) computer system. The system incorporates software for capturing, processing,
and integrating environmental and epidemiological data from multiple sources; data assimilation techniques that continually update
models and forecasts; and a web-based interface that makes the resulting information available to public health decision makers.
This technology will enable forecasts based on lagged responses to environmental risk factors as well as information about recent
trends in malaria cases. Environmental driving variables will include a variety of remote-sensed hydrological indicators. EPIDEMIA
will be implemented and tested in the Amhara Region of Ethiopia in collaboration with local stakeholders. We conducted an initial
co-design workshop in July 2014 that included environmental scientists, software engineers, and participants from the NGO,
academic, and public health sectors in Ethiopia. A prototype of the EPIDEMIA web interface was presented and a requirements
analysis was conducted to characterize the main use cases for the public health community, identify the critical data requirements
for malaria risk modeling, and develop of a list of baseline features for the public health interface. Several critical system features
were identified, including a secure web-based interface for uploading and validating surveillance data; a flexible query system to
allow retrieval of environmental and epidemiological data summaries as tables, charts, and maps; and an alert system to provide
automatic warnings in response to environmental and epidemiological risk factors for malaria. Future system development will
involve a cycle of implementation, training, usability testing, and upgrading. This innovative translational bioinformatics approach
will allow us to assess the practical effectiveness of these tools as we continually improve the technologies.
2.
Name and Title of Presenter: Tao Lin, Postdoctoral Research Associate
Co-Authors: Tao Lin, Brandon Scott, Francisca Essel, Adam Hoppe, Suvobrata Chakravarty
Organization/Department: SDSU/ Department of Chemistry & Biochemistry
Abstract Title: The benchmark of FRET for PPI in living cells
In recent years, fluorescence resonance energy transfer (FRET) has become a powerful tool to study molecular interactions,
especially protein-protein interactions (PPI). Recombinant fluorescent proteins enable the study of such interaction in living cells.
Whilst the dynamics of live cells are known as the ultimate analysis, the limits of the strength of molecular interactions that can be
detected by live-cell FRET remain poorly understood as no appropriate indicator is available for this. To meet the demand on FRET
reporter molecules for live-cell, we introduce a new facile sensor analysis strategy. Using a test set of 11 pairs of small interacting
proteins for whom the respective affinities range between mM – nM, we determine protein concentration in living cells to compute
the interaction affinity using the intra-cellular FRET efficiency. Furthermore, we also compare affinity obtained from FRET with that
obtained from ITC. All of these results suggest that we establish the limits with live-cell microscopy. This study benchmarks
intracellular FRET and is a very useful reference for intracellular PPI methods (BiFC, IDPRIME etc).
3.
Name and Title of Presenter: Casey McKenzie1
Co-Authors: Branch Craige2, Tiffany Kroeger1, Todd Wyatt3, Joseph Sisson3, Jacqueline Pavlik3, George Witman2, and Lance Lee1
Organization/Department:
1
Sanford Research, Sioux Falls, SD, 2University of Massachusetts School of Medicine, Worcester, MA
3
University of Nebraska Medical Center, Omaha, NE
Abstract Title: Motile Ciliary Defects and Primary Ciliary Dyskinesia in Mice Lacking CFAP54
Primary ciliary dyskinesia (PCD) is a pediatric syndrome caused by dysfunction of motile cilia and flagella that typically results in
chronic rhinosinusitis, chronic otitis media, male infertility, and situs inversus, with female infertility and hydrocephalus also
observed in some patients and mouse models. PCD with a decrease in ciliary motility was previously observed in mice lacking ciliary
and flagellar associated protein 221 (CFAP221), also known as PCDP1, a ciliary protein that localizes to the central microtubule pair
apparatus of Chlamydomonas reinhardtii flagella and forms a complex that regulates motility in a calcium-dependent pathway.
Using a quantitative RT PCR approach, we show that the genes encoding the mouse homologs of the C. reinhardtii CFAP221 complex
members are expressed exclusively in motile ciliated tissues, suggesting that they have a conserved function in motile cilia. A genetrapped allele of one of these mouse genes, Cfap54, results in ciliary defects and phenotypes associated with PCD. Homozygous
mutant mice have hydrocephalus and an accumulation of mucus in the sinus cavity. Tracheal epithelial cilia have a reduced beat
frequency, and transmission electron microscopy reveals a defect in the structure of the C1d projection of the central microtubule
pair apparatus, suggesting that CFAP54 is required for C1d assembly. In addition, male mutants are infertile due to an absence of
mature sperm flagella, indicating that CFAP54 is also required for spermatogenesis. This study identifies an essential role for CFAP54
in proper assembly of mammalian cilia and flagella, and it establishes the gene-trapped allele as a new mouse model of PCD.
4.
Name and Title of Presenter: Bijaya Upadhyaya#, Graduate Research Assistant
Co-Authors: Dan Wang#, Yi Liu#, David Knudsen, and Moul Dey (Corresponding Author); # Equal Contributors
Organization/Department: South Dakota State University/Department of Health and Nutritional Sciences
Abstract Title: Dietary phenethyl isothiocyanate (PEITC) induces apoptosis and inhibits proliferation in human cervical cancer
stem-like cells
Scope: Cancer stem cells (CSC)- a rare and small subset of tumor cells that are responsible for tumor initiation and maintenance- are
often resistant to radiotherapy and chemotherapy, leading to cancer recurrence and metastasis. Phenethyl isothiocyanate (PEITC),
derived from cruciferous vegetables, is pro-apoptotic in various cancer cell lines including primary tumors but its effect on cancer
stem cells (CSC) remains unknown. TRAIL (tumor necrotic factor-related apoptosis-inducing ligand) is a cytokine that selectively kills
cancer cells but cancer cells are frequently resistant to TRAIL. In this study, we examined the effects of PEITC in attenuation of
human cervical CSC proliferation and tumorigenicity as well as its role in sensitizing TRAIL-induced apoptosis.
Results: PEITC attenuated proliferation of CD44high/+/CD24low/-, stem-like, sphere-forming subpopulations of HeLa cervical cancer
stem cells (hCSC) in a concentration- and time-dependent manner that was comparable to the effects of CSC-antagonist,
salinomycin. PEITC exposure-associated up-regulation of cPARP (cleaved poly ADP-ribose polymerase) levels and induction of DR4
and DR5 (death receptors 4 and 5) were confirmed by immunoblotting and flow cytometry analyses, respectively. Xenotransplantation in NOD/SCID mice revealed greater tumorigenicity for hCSC than HeLa cells, which was diminished along with serum
hVEGF-A (human-vascular endothelial growth factor A) levels in 10 µM PEITC-pretreated hCSC group. Further, H&E staining of lungs
sections showed lung metastasis only in hCSC injected group without PEITC-pretreatment.
Conclusions: Our results suggest anti-proliferative effects of PEITC in cervical cancer stem-like cells that may at least partially result
from sensitization of TRAIL-mediated apoptotic pathways through up-regulation of DR4 and DR5. PEITC may offer a novel approach
for improving the therapeutic outcomes in cancer patients.
5.
Name and Title of Presenter: Xijin Ge, Associate Professor
Co-Authors: Liming Lai, Wei Wang, Jason Hennessey, Yuguang Ban, Jianli Qi, Gaixin Jiang, Ye Kang, and Steven Xijin Ge
Organization/Department: Math/Stat., SDSU
Abstract Title:
Interpreting mouse genomics data with a comprehensive knowledgebase
Interpretation of genome-wide expression data in terms of biological pathways constitutes a constant challenge partly because of
the lack of pathway database. In this study, we collected 32,678 annotated gene sets for mouse from 41 annotation sources, such as
Gene Ontology, signaling and metabolic pathways, microRNA and transcriptional factor target genes, etc. In addition, we manually
compiled and curated 8,747 lists of differentially expressed genes from 2,518 gene expression studies. The comprehensive Gene Set
Knowledgebase (GSKB) can be queried as an information source on published expression signatures and also forms a foundation for
pathway analysis using various software such as gene set enrichment analysis (GSEA), enabling in-depth interpretation of mouse
genomics data both in terms of known pathways and the context of thousands of published expression signatures.
http://bioinformatics.sdstate.edu/gskb/
6.
Name and Title of Presenter: Li Li, Postdoc
Co-Authors Katie Picotte, Haotian Zhao
Organization/Department: Sanford Research/USD, Sioux Falls, SD
Abstract Title: Notch 1 signaling-induced choroid plexus tumor arises from epithelial progenitor and relies on Sonic Hedgehog
signaling for their growth
We used Rosa26-NICD1 strain which constitutively expresses the intracellular domain of Notch 1 (NICD1) from the Rosa26 locus
after Cre-mediated DNA recombination. Histological analysis revealed that CP from NICD1-expressing mutant mice contained an
abnormal growth in the 4th ventricle consistent with properties of choroid plexus tumor. Tumor cells exhibit enhanced proliferation
transiently after birth: tumor cell proliferation was highest at birth, then gradually decreased and completely stopped at 2 weeks
after birth. While CP tumor cells expressed early CP lineage markers such as Lmx1a and Otx2, they didn’t express Aquaporin 1
(AQP1), marker for differentiated CP epithelial cells, even after they exit the cell cycle, suggesting lack of terminal differentiation. We
further showed that CP tumor arises during development as ectopic Lmx1a+ cells in CP tissue and exhibit properties similar to those
of CP epithelium progenitors. However, unlike progenitor cells, tumor cells fail to exit the cell cycle and differentiate into mature
epithelial cells. We characterized changes in gene expression in tumor cells by quantitative RT-PCR. Surprisingly, we detected
increased levels of Shh, Gli1 and N-Myc, effectors of the Sonic Hedgehog (Shh) pathway, in proliferating tumor cells. CP tumor cells
cultured in serum-free conditions underwent rapid proliferation in the presence of Shh. Shh signaling is mediated through primary
cilia on cell surface. Ultra-structural studies revealed lack of multi-ciliation differentiation in tumors cells, whereas the expression of
Foxj1 and Midas, crucial regulators of cilia differentiation, was significantly downregulated.
We have developed a genetic model of CP tumor driven by Notch signaling activation. The proliferation of Notch 1-induced tumors is
supported by Shh pathway. Notch and Shh pathways collaborate to drive choroid plexus tumor formation, indicating Shh pathway as
a therapeutic target for Notch-driven CP tumors.
7.
Name and Title of Presenter: Siddharth S Kesharwani – Graduate Student Department of Pharmaceutical Sciences
Co-Authors: Prajwal P. Nandekar and Abhay T. Sangamwar
Organization/Department:
a
Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research,
Sector 67, S.A.S. Nagar, Punjab, India-160062 & bDepartment of Pharmaceutical Sciences, South Dakota State
University-Brookings-SD-USA-57007
Abstract Title: Simulation of Drug-metabolizing Cytochrome P450 1 Family of Enzymes: A Combined Approach employing
Proteomics, Molecular Docking, and Molecular Dynamics Simulation Analysis
Recent trends in new drug discovery (NDD) of anticancer drug has made the oncologists more aware of the fact that NDD must
target the developing mechanism of tumerogenesis to improve the therapeutic efficacy of antineoplastic drugs. Current research
highlights overexpression of CYP450s, particularly cytochrome P450 1A1 (CYP1A1), in tumor cells representing as a novel target for
anticancer therapy. However, CYP 1 family is identified posing problem in selectivity of anticancer molecular towards CYP1A1. Three
members have been identified in human CYP1 family: CYP1A1, CYP1A2, and CYP1B1. We investigated three isoforms of CYP1 family
(CYP1A1, CYP1A2, and CYP1B1) for their substrate specificity. The understanding of macromolecular features that govern substrate
specificity is required to understand the interplay between the protein function and dynamics. This can help in design of new
antitumor molecule specifically metabolized by CYP1A1 to mediate their antitumor activity. In the present study, we employed a
combination of computational methodologies such as molecular docking, molecular dynamics simulations, access channel analysis,
comparative protein structure analysis of the three isoforms (sequence alignment, root mean square deviation (RMSD) analysis, Bfactor analysis) to gain a better understanding of the macromolecular features involved in substrate specificity. We identified that
the differences in amino acid residues among the three isoforms of CYP1 family, may account for differential substrate specificity. Six
putative substrate recognition sequences (SRSs) are characterized along with the regions they form in the protein structure. Further
the RMSD and B-factor analysis provides the information about the identified residues having the maximum RMSD and B-factor
deviations. Lastly, we conclude that the substrate specificity of a particular substrate depends upon type of the active site residues,
the dynamic motions in the protein structure upon ligand binding, the physico-chemical characteristics of a particular ligand, the
channels utilized for access and egress.
8.
Name and Title of Presenter: Biyi Chen
Co-Authors: Dr. Kendra Kattelmann
Organization/Department: SDSU/ Department of Health and Nutritional Sciences
Abstract Title: Y.E.A.H Project: Using the Web to Increase Healthful Meal Behavior in Young Adults
Young adulthood, 18-24 years of age, is a transitional time when adverse changes in body weight often occur and being overweight
at this age is linked to obesity by mid-thirties. Approaches targeted to this life-stage are needed to prevent unhealthy weight gain.
Regular and healthful meals have been associated with obesity prevention. The objective is to report on the effectiveness of YEAH
(Yong adults Eating and Active for Health) Project (a theory-based, web-delivered weight maintenance intervention) to improve selfinstruction and self-regulation for healthful mealtime behavior.
9.
Name and Title of Presenter: Mr. Derek Timm
Co-Authors: Timm D, Castaneda J, Magee H, O'Toole R, Weimer J.
Organization/Department: Sanford Research/Children’s Health Research Center
Abstract Title: Autoantibody Identification in Batten Disease
Expression of autoantibodies is associated with a number of neurological diseases with many protein targets and epitopes.
Frequently, these autoantibodies target proteins essential to the function, development, and survival of the neuron. Here we
identify a new autoantibody associated with NCLs against CRMP2, a protein whose neuronal functions include axon/dendrite
differentiation, neurite outgrowth, and neuronal polarity. These antibodies are present in JNCL patient serum samples as well as the
serum of the Cln3Δ7/8 and Cln6nclf mouse models representing juvenile and variant late infantile NCL, respectively. The presence
of these autoantibodies in the Cln6nclf mouse model is the first indication of an autoimmune component in this form of NCL.
10.
Name and Title of Presenter: FAHD EISA
Co-Authors: KAUSHALKUMAR DAVE AND OMATHANU PERUMAL
Organization/Department: DEPT. OF PHARMACEUTICAL SCIENCES, SDSU.
Abstract Title: Transmammary Delivery of 4-Hydroxy Tamoxifen to the Breast
Breast cancer is the most common cause of cancer death among women, resulting in 458,000 deaths worldwide every year. Majority
of breast cancers are treated with selective estrogen receptor modulators (SERMs) which prevent the binding of estrogen to the
estrogen receptors in the breast. Recent studies have shown that 4-hydroxy tamoxifen (4HT), which is an active metabolite of the
parent drug tamoxifen, is up to 100-fold more potent than the parent drug against breast cancer. However, systemic administration
of SERMs is associated with severe adverse effects. Some of the most common adverse effects of SERM therapy include endometrial
cancer, blood clot and cardiovascular diseases. To this end, the goal of this study is to test the feasibility of localized delivery of 4HT
to the breast through the mammary papilla. The in-vitro penetration studies were conducted using porcine mammary papilla in a
vertical diffusion cell. Various vehicles were used to study 4HT penetration through the mammary papilla. The vehicles include
water, ethanol and propylene glycol and in combination at various proportions. The penetration studies were conducted using
tritium labeled 4HT and the drug concentration in the receptor medium and the breast tissue was analyzed by radiochemical
analysis. In-vitro permeation of 4HT through mammary papilla using different solvent systems showed that the water: ethanol
mixture (70: 30 v/v) gave the highest permeation of 4HT among all the solvent systems tested. The lowest permeation of 4-HT was
observed with propylene glycol. The results from this study demonstrate feasibility of localized delivery of 4HT to the breast through
the mammary papilla. Future studies will focus on testing the drug penetration through the human mammary papilla in-vitro and in
vivo bio-distribution in animals.
11.
Name and Title of Presenter: Pratik Katwal, Graduate Student, Microbiology
Co-Authors: Milton Thomas, Dr. Radhey Kaushik
Organization/Department: Biology and Microbiology
Abstract Title: Establishment and characterization of primary and immortalized bovine ileal epithelial cell lines from a young calf
Intestinal epithelial cells play an important role in mediating immune response to pathogens. No bovine intestinal epithelial cultures
from young calves are available. The major goal of this study is to establish pure primary cultures of bovine ileal epithelial cells
(BIECs) and then immortalize these cultures for developing continuous cell lines. Earlier we established bovine ileal cultures from a
young calf which had both intestinal myofibroblasts and epithelial cells. These primary cells were grown in culture media
supplemented with epidermal growth factors. We used limiting dilution method to obtain a clone of bovine ileal epithelial cells
(BIECs) which was further amplified and characterized using immunohistochemistry. The selected clone C4 was cytokeratin positive
and expressed low levels of vimentin, confirming the epithelial cell phenotype. Immortalization was done using simian virus 40 large
T antigen (SV40) containing plasmid. The presence of SV40 gene in immortalized BIECs was confirmed by PCR. Immunofluorescence
and immunohistochemistry assays also confirmed the expression of SV40 protein in these cells. Primary BIEC cultures were also
immortalized with human telomerase reverse transcriptase (hTERT) gene. The presence of hTERT gene was confirmed by PCR. Both
the immortalized cell lines had cytokeratin and vimentin expressions similar to parent cell phenotype. Establishment of primary and
immortalized BIECs will serve as a model system for studying the role of intestinal epithelial cells in mucosal immunity to enteric
pathogens.
12.
Name and Title of Presenter: Paola Vermeer, PhD
Co-Authors: Paul L. Colbert, Daniel W. Vermeer, Jennifer Schmidt, Laurie Gromer, John H. Lee, and W. Chad Spanos
Organization/Department: Sanford Research/Cancer Biology Research Center
Abstract Title: Characterizing Circulating Tumor Cells from Head and Neck Cancer Patients
Despite advances in treatment, the 5-year survival rate for head and neck cancer patients remains very poor (≅50%). Approximately
two thirds of head and neck squamous cell carcinoma (HNSCC) patients present with locally advanced disease and another 10-20%
develop distant metastases. Metastasis within the cervical lymph nodes is a predictor of poor outcome, decreasing survival
significantly. Tumor cells in the regional lymph nodes and/or at distant sites suggest their spread through the lymphatic and
circulatory systems. Circulating tumor cells (CTCs) have been isolated from HNSCC patient blood; their presence and number
correlate with poor prognosis. Thus, a molecular understanding of metastatic disease in HNSCC is required to improve patient
survival. The project objective is to molecularly characterize the mutations harbored by CTCs, a critical first step in identifying key
components in the metastatic process. We will compare this mutational profile to that of matched tumor, free-floating DNA
mutations and exosome-derived DNA mutations. These data will determine whether CTCs that reside within the primary tumor must
acquire additional mutations to gain the capacity to migrate away from the tumor, into the vasculature and survive at distant sites
(metastasize). Identifying the genes that are mutated in CTCs and that, therefore, might be critical for tumor emigration will provide
insights into the mechanism of metastasis.
13.
Name and Title of Presenter: Yan Lin, Assistant Professor
Co-Authors: Hilary Hungerford, Assistant Professor
Organization/Department: Department of Geography
Abstract Title: A Geographically Targeted Approach for Cancer Disparity Reduction
Minorities in the United States have a disproportionally high burden of female breast, cervical, and colorectal cancer. Because these
cancers are preventable, both their incidence and mortality rates can be dramatically reduced if effective prevention and
intervention programs are developed and implemented. Although significant progress has been made in the last few decades, the
three cancers remain the common cancers among people in the United States. The incidence and mortality rates for minorities such
as American Indians in South Dakota are higher than that of the non-Hispanic white or the overall U.S. population. Many of new
cases and deaths could be avoided if minorities in underserved communities take routine screening tests. A significant challenge to
reduce disparities is to develop education and intervention programs that will help increase cancer screening in minorities. This
study aims to develop a geographically targeted approach that can be used to develop personalized educational materials for
minorities in geographic areas where disparities exist. The study includes three research activities: (1) Develop a Geographic
Information System (GIS) for cancer disparity surveillance and analysis which will be used to identify geographic areas where
American Indians have higher rates than other groups in South Dakota; (2) Understand the barriers to health care services among
American Indians in South Dakota; and (3) Design an approach to develop geographically targeted and personalized educational and
intervention materials about cancer screening. While we will initially develop and test the approach in South Dakota, the overall
strategy can be easily extended and deployed in other states. The proposed approach will bring significant changes to the way we
identify minorities who need the most assistance and the way we develop the educational materials. We hope these changes will
result in significantly reduced cancer disparities over the next few decades.
14.
Name and Title of Presenter: Maggie Minett MS, ATC
Co-Authors: Lee Weidauer, Teresa Binkley, Bonny Specker
Organization/Department: Ethel Austin Martin Program
Abstract Title: Changes in Body Composition and Bone Density of Female Collegiate Soccer Players During a Competitive Season
BACKGROUND: The intensity of collegiate athletics may have a negative impact on the body due to minimal recovery time.
Objectives were to assess body composition and bone changes pre- to post-season in female collegiate soccer athletes (SC).
Hypotheses were that lean mass (LM) and hip bone mineral density (aBMD) would decrease in athletes and fat mass (FM) would
increase from pre- to post-season measures.
METHODS: Bone and body composition was assessed using DXA in 23 D-I women soccer players and 17 controls (<1hr/wk exercise)
pre- and post-season. Multiple regression was used to control for covariates.
RESULTS: Controls were older (20.4±0.4 vs. 19.5±0.2y, p=0.02), taller (168.3±1.1 vs. 164.7±1.3cm, p=0.05) and heavier (72.5±2.0kg
vs. 63.2±1.4kg, p<0.001) than SC. Baseline FM and body fat % were lower in SC (14.2±0.7kg; 21.7%) than controls (21.4±1.3kg;
28.8%: both p<0.001). Control subject femoral neck (FN) and hip BMC and aBMD increased, while SC did not. FN aBMD % change
from pre- to post-season was less in SC than controls (0.02±0.6% vs. 2.6±0.8% g/cm2, p=0.03) but FN area and BMC were not
different. Hip area, BMC and aBMD did not differ. There was no difference in LM or FM change. However, SC lost a significant
amount of lean mass from pre- to postseason (-0.9±0.2 kg; p<0.001), with non-starters (NST) having the greatest loss (-1.1±0.3 kg;
p<0.001) that was not different from starters (ST) or controls (both p>0.08). Percent change in FN aBMD was less in ST than controls
(-0.5±0.9 vs. 2.7±0.8% g/cm2; p=0.03) and NST (0.4±0.8% g/cm2; p=0.058).
DISCUSSION: FN aBMD percent change in SC was less than controls while controlling for baseline lean mass, fat mass, height,
change in LM and baseline bone measure. Percent change in FN area, BMC, hip area, BMC and aBMD as well as LM and FM was not
different between groups.
15.
Name and Title of Presenter: Kristin Olson
Co-Authors: Kendra K. Kattelmann1
Organization/Department:
South Dakota State University, Brookings, South Dakota
1
Abstract Title: Let Them Eat Beef: Effects of Beef Consumption on Markers of Metabolic Syndrome
Statement of Objective: The objective of this study is to determine the effects of a diet that contains a higher percentage of high
quality protein from lean red meat on risk factors of metabolic syndrome in humans.
Design, Setting, and Participants: This is a 3 month, randomized, control, intervention trial with a rolling enrollment. Assessments
will be conducted at baseline and post intervention. The Avera Heart Hospital and Watertown Brown Clinic registered dietitians will
partner with Health and Nutritional Sciences Department to recruit and provide the intervention to participants. Participants were
recruited through self-referral and clinic pamphlets.
Outcome Measures and Analysis: The following measures will be collected at baseline and post intervention: height, weight, fasting
serum lipoproteins (total cholesterol, LDL-cholesterol, HDL-cholesterol, Apo B, and triglycerides), C-reactive protein, fasting serum
glucose, Hemoglobin A1c, dietary intake. Participants were also queried for physical activity behavior, satisfaction with diet,
medication usage and quality of life.
Results: 34 participants have been recruited with results from outcome pending.
Conclusion and Implications: Conclusion and implications are pending.
16.
Name and Title of Presenter: Jessica D. Hanson
Co-Authors: Jamie L. Jensen, MS, Kelly Campbell, BA, Kaushal Raj Chaudhary, MS, and Susan E. Puumala, PhD
Organization/Department: Sanford Research/Center for Health Outcomes and Prevention Research
Abstract Title: Epidemiology of Substance-Exposed Pregnancies at One Great Lakes Hospital: The Case for Preconception and
Comorbidity Prevention Efforts
Objective: The purpose of this project was to determine the prevalence of substance-exposed pregnancies at a hospital in the Great
Lakes region of the U.S., highlighting pregnancy-related behaviors and evaluating the impact on birth outcomes. Method: Data were
collected via retrospective chart abstractions of patients who were seen for delivery at one Great Lakes region hospital during a one
year period who were given at least one of the International Classification of Diseases codes related to substance use. Results: A
total of n = 382 medical records were included in the analysis. The prevalence of substance-exposed pregnancies at this hospital
during a one-year period was 40.6%. The majority (75.7%) were tobacco users, and many were found to have multiple substance
exposures. In addition, 54.5% were found to have a mental health diagnosis in addition to substance use, and the gestational age of
the index pregnancy was significantly impacted by substances used during and prior to pregnancy. Conclusions: A large percentage
of women delivering a baby at this hospital were given ICD-9 codes related to some type of prenatal substance use. In addition to
high rates prenatal smoking and drug use, of note are the impact of these substances before the index pregnancy and also the large
issue of co-morbidity with mental health disorders. Data from this project can be used in prevention efforts, including promoting
preconceptional care for women at-risk for substance misuse and for those with mental health issues.
17.
Name and Title of Presenter: Yang Yang, Graduate student
Co-Authors: Xiangming Guan
Organization/Department: South Dakota State University/ Pharmaceutical Science
Abstract Title: Live cell thiol imaging and quantification with a novel benzofurazan sulfide triphenylphosphonium fluorogenic
compound
Thiols play a significant role in defense against reactive oxygen species, detoxification, signal transduction, apoptosis, and various
other cellular functions. A change in thiol level has been linked to the pathogenesis of a variety of disease states. Assessing thiol
levels in live cells through fluorescence microscopy provides a way of direct visualization of thiol-related biochemical processes.
Limited fluorescent agents are available to assess the level of thiols in live cells. We previously reported bis(7nitrobenzo[c][1,2,5]oxadiazol-4-yl)sulfane (BNOS) that effectively imaged and quantified total thiols through fluorescence
microscopy. In this poster, we would like to present a novel benzofurazan sulfide triphenylphosphonium fluorogenic compound that
can also effectively image and quantify thiols in live cells through fluorescence microscopy and be complementary to BNOS with
better sensitivity and water solubility. The synthesis, thiol specificity determination, fluorescence property characterization and total
thiol imaging in live cells through fluorescence microscopy will be presented.
18.
Name and Title of Presenter: ILIAN RADICHEV, PhD
Co-Authors: Lilia Maneva-Radicheva, Christina Amatya, Camille Parker, Jacob Ellefson, Clive Wasserfall, Mark Atkinson, Paul
Burn and Alexei Savinov
Organization/Department: Sanford Research, Sanford Project at the Children’s Health Research Center
Abstract Title: Proteolysis of VTCN1 (B7-H4) as a new biomarker for type 1 diabetes
T cell responses directed against insulin-secreting pancreatic β cells are the key events underlining type 1 diabetes (T1D). Therefore,
a crucial step in T1D development is the defective control of T cell activation. Recent studies implicated a B7-like negative costimulatory protein, VTCN1 (V-set domain-containing T cell activation inhibitor-1), as a molecule capable of inhibiting T cell
activation and, potentially, an important constituent in experimental models of T1D. Here, we unravel a general deficiency within
the VTCN1 pathway that is shared between diabetes-prone mice and a subset of T1D patients. Gradual loss of membrane-tethered
VTCN1 from antigen-presenting cells and pancreatic islets, combined with an increased release of soluble VTCN1 (sVTCN1) occurs in
parallel to natural T1D development, potentiating hyper-proliferation of diabetogenic T cells. Mechanistically, we demonstrate that
the loss of membrane-tethered VTCN1 is linked to proteolytic cleavage mediated by the metalloproteinase nardilysin (NRD1). The
cleaved sVTCN1 fragment was detected at high levels in the peripheral blood of 53% T1D patients compared to only 9% of the
healthy subjects. Elevated blood sVTCN1 levels appeared early in the disease progression and correlated with the aggressive pace of
disease, highlighting the potential use of sVTCN1 as a new T1D biomarker, and identifying NRD1 as a potential therapeutic target.
19.
Name and Title of Presenter: Randy Jackson, Joseph Dzisam
Co-Authors: Brendan L. Mitchell, Michael W. Stutelberg, Wenhui Zhou, Gary A. Rockwood, and Brian A. Logue
Organization/Department: SDSU Dept. of Chemistry and Biochemistry
Abstract Title: Diagnostic and Forensic Analysis of Cyanide Metabolites and Therapeutics
The analytical chemistry division of the Logue Research Group specializes in method development for the analysis of chemical
warfare agents, their metabolites, and therapeutic agents. A portable cyanide sensor based on reaction between cyanide,
naphthalene dialdehyde and taurine (yielding a β-isoindole fluorescent product) was developed in our lab. The sensor combines
simple sample preparation (active microdiffussion), reagent storage and delivery, and base capture and derivatization of HCN gas in
a single contained cyanide capture apparatus. For this technology, the linear range was 1-250 µM with a limit of detection of 0.5
µM, and there are no known interferrents. Most importantly, the sensor was 100% accurate in diagnosing cyanide poisoning for
acutely-exposed rabbits. Other projects include but are not limited to the analysis of phosphonates from hair and nails, possible
therapeutic agents for cyanide exposure, and environmental toxins.
20.
Name and Title of Presenter: Emily C. Huber, Graduate Assistant
Co-Authors: John M. Schuna, Jr., Becky Jensen, Jessica R. Meendering
Organization/Department: Department of Health and Nutritional Sciences
Abstract Title: Ability of a school-based nutrition intervention to affect physical activity: an insight into best practices for
transdisciplinary obesity interventions
Attributable to the amount of time children spend in a school environment, school-based interventions are an ideal and resourceful
method to address health behaviors. Due to the transdisciplinary nature of childhood obesity, many programs that historically
focused solely on nutrition are adding small physical activity (PA) components to their curriculum. PURPOSE: The purpose of this
study was to examine the ability of a school-based nutrition focused intervention with PA elements designed for fifth to sixth grade
students to increase PA and decrease sedentary time (ST) in child participants. METHODS: PA and ST were assessed via
accelerometry (ActiGraph GT3x+) in 395 fifth and sixth grade children for seven days pre and post intervention/control. Daily
minutes of ST, light physical activity (LPA), moderate physical activity (MPA), vigorous physical activity (VPA), and moderate-tovigorous physical activity (MVPA) were calculated for all subjects using age appropriate cut points. STATISTICAL ANALYSIS: Changes
in PA and ST were evaluated using mixed-model analysis of covariates (ANCOVA). Statistical significance was set at p≤ 0.05.
RESULTS: One hundred seven children (intervention N=43 [8 males, 35 females] and control N=64 [29 males, 35 females]) met
compliance requirements at both assessment periods. There were no significant differences between the intervention and control
groups for pre to post changes in ST (F=0.39, p=0.555), LPA (F=0.29, p=0.612), MPA (F=3.68, p=0.104), VPA (F=0.13, p=0.733), or
MVPA (F=1.11, p=0.333). CONCLUSIONS: The results of this study suggest no difference in PA and ST in nutrition intervention
participants compared to control. Transdisciplinary interventions should strive to give adequate focus to all incorporated
components in order to effectively alter physical activity and sedentary time behavior in participants.
21.
Name and Title of Presenter: Corey Selland, Graduate Assistant
Co-Authors: Emily Huber, Kristine Braastad, Mary Bowne, Jessica Meendering
Organization/Department: Health and Nutritional Sciences
Abstract Title: Influence of parenting style on body mass index, physical activity, and sedentary time
Purpose: To determine the influence of parenting style on body mass index (BMI) percentile and objectively measured physical
activity (PA) and sedentary time (ST) in 5th grade children.
Methods: Physical activity and ST were assessed via accelerometry in 152 fifth grade children for 7 days. Daily minutes of ST, light PA
(LPA), moderate PA (MPA), vigorous PA (VPA), and moderate-to-vigorous PA (MVPA) were calculated using age appropriate cut
points. Parenting style was assessed by the child participants’ responses to modified questions from the Parenting Style Inventory II.
Authoritative parenting style was compared against non-authoritative parenting styles (authoritarian, permissive, and uninvolved)
for statistical analysis. Multiple linear regression analyses were utilized to identify significant predictors of outcomes of interest
(BMI, ST, LPA, MPA, VPA, MVPA).
Results: Multiple linear regression models revealed authoritative parenting style did not predict ST, LPA, MPA, VPA, or MVPA;
however, BMI percentile and gender were found to be significant predictors of MPA, VPA, and MVPA (p < 0.01 for both predictors at
each intensity). BMI percentile was predicted to be lower in females with authoritative mothers (p < 0.01).
Conclusions: While authoritative and non-authoritative parenting style did not predict objectively measured PA or ST in 5th grade
children, authoritative parenting style did predict BMI percentile in female participants. Authoritative parenting style may provide
protection from overweight and obesity in adolescent girls and could be utilized as a parent education component in family-based
interventions aimed at reducing childhood obesity.
22.
Name and Title of Presenter: Christina Amatya
Co-Authors: Ilian Radichev, Jacob Ellefson, Matthew Charles, Mark Williams, and Alexei Y Savinov
Organization/Department: Sanford Research
Abstract Title: PDX1-FOXP3-TAT FUSION PROTEIN MODULATES AUTOIMMUNITY THROUGH TREG INDUCTION IN NOD MOUSE
MODEL OF T1D
Type 1 diabetes (T1D) is beta (β) cell specific autoimmune disease, characterized by massive β cells destruction and subsequent
insulin deprivation leading to hyperglycemia. Effective therapeutic strategies for T1D should combine agents abrogating islet-specific
autoimmunity and restoring endogenous insulin production. With this rationale, fusion protein (FP) combining key transcription
factors: FOXP3 and PDX1, was constructed. TAT protein transduction domain was added for the cellular delivery of these fusion
molecules. FOXP3 is a key factor for the differentiation and function of T regulatory (Treg) cells that mediate the maintenance of
peripheral tolerance. Accordingly, PDX1 is crucial for development and maintenance of β cells.
Treatment of naïve CD4+CD25- murine T cell cultures with FP resulted in emergence of increasing CD4+CD25+FOXP3+ T
subpopulation; and reduction of IL-2 and INF-γ on both mRNA and protein levels in concentration dependent manner. In hepatic
stem-like cells, FP treatment resulted in significantly higher the mRNA levels for PDX1 and its downstream targets. Our in vitro data
suggest that FP treatment is likely to facilitate induction of Treg phenotype in naïve T cells and initiate transdifferentiation of hepatic
stem-like cells towards hormone-producing pancreatic lineage.
Non-obese diabetic (NOD) mice develop spontaneous autoimmune insulin dependent diabetes and are a relevant model of T1D.
Daily FP treatment in highly diabetic female NODs resulted in significant increase of serum insulin and C-peptide levels. Interestingly,
there were increased percentages of FOXP3 positive cells within the CD4+CD25+ T cells in different lymphoid organs of FP treated
NODs. Also, elispot assay revealed higher frequencies of IL-10-producing cells and lower frequencies of INF-γ-secreting splenocytes.
Our in vivo data indicated that FP treatment is likely to stabilize FOXP3 expression in Treg population, and maintain
immunomodulatory functions. Thus, the rationale exists to investigate the observed Treg-inducing potential of FP to preserve β cells
in future islet transplantation studies.
23.
Name and Title of Presenter: Mohamed Teleb Ismail / Research Scholar- PhD student ( joint supervision PhD program)
Co-Authors: Ahmed M. Farghaly, Omaima M. AboulWafa, Ola H. Rizk and Hesham Fahmy 2
Organization/Department: College of Pharmacy- Department of Pharmaceutical Sciences
Abstract Title: Design & Synthesis of Novel Cardiovascular Agents
Cardiovascular diseases (CVDs) include heart diseases as cardiac arrhythmias, cerebrovascular diseases as stroke, and vascular
diseases as hypertension.
In 2002, The World Health Organization (WHO) reported that CVDs are the leading cause of mortality being responsible for one-third
of all global deaths. In 2011, WHO published the global atlas for CVDs prevention and control, confirming that CVDs remain the
biggest cause of deaths worldwide. Over 17 million people died from CVDs in 2008. The majority of heart attacks and strokes are
caused by one or more cardiovascular risk factors as hypertension, diabetes and hyperlipidemia. Significantly, hypertension is the
single most important contributing factor to CVDs.
In recognition of the burden posed by hypertension, the European Society of Hypertension (ESH) and the European Society of
Cardiology (ESC) published their ‘2013 Guidelines for Management of Arterial Hypertension’. Most recently, the Eighth Joint National
Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 8) completed the ‘2014 EvidenceBased Guidelines for Management of High Blood Pressure in Adults’. Accordingly, several classes of antihypertensive agents are
clinically used, including; diuretics, α-blockers, β-blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor
blockers (ARBs) and calcium channel blockers (CCBs). The 2013 ESH/ESC guidelines in common with the 2014 evidence-based
guidelines for hypertension management recommended CCBs as initial treatment. Based on their pharmacophore, CCBs are
classified into: arylalkylamines, benzothiazepines and 1,4-dihydropyridines (1,4-DHPs). The most valuable CCBs are 1,4-DHPs. Later,
interest has been focused on DHPs aza-analogs as dihydropyrimidines (DHPMs) which show very similar pharmacological profile to
classical DHPs CCBs. Several lead compounds have been developed; of these, SQ 32926 is superior in potency and duration of
activity to classical DHPs. Our main objective is to develop novel DHPMs as aza-analogs of the most recent 4th generation DHPs
CCBs.
NO2
O
O
O
O
N
O
O
N
H
N
O
N
H
Lercanidipine
"4th generation CCB"
24.
NO2
NO2
CONH2
O
SQ 32926
"Lead DHPM CCB in clinical trials"
N
O
N
H
R
O
Novel DHPMs
" Targeted DHPMs"
Name and Title of Presenter: Max Lebedev
Co-Authors: Alan Young
Organization/Department: Department of Veterinary and Biomedical Sciences
Abstract Title: Myeloid-Like γδ T Cell Subset and Its Role in Development of the Immune Response to Vaccine in Sheep
γδ T cells are a numerically significant subset of immune cells in ruminants, where they may comprise up to 70 % of all peripheral
blood mononuclear cells in young animals. These cells can be activated through pattern recognition receptors and are able to uptake
antigen, process, and present it to αβ T cells. We have demonstrated the presence of a CD11b+ subset of γδ T cells in normal sheep
peripheral blood, with a marked increase in the number of CD11b expressing γδ T cells 4 days after injection of vaccine adjuvant
Montanide ISA 25 VG, concomitant with an overall increase in γδ T cells. In vitro studies showed repeatable increases of CD11b,
CD14, CD86, CD40, and IFNγ expressing γδ T cells after 24 hours of incubation in the absence of mitogen. ConA activation increased
CD25, MHCI and MHCII expression in γδ T cells, but not myeloid proteins CD14 and CD11b and co-stimulatory molecules CD86 and
CD40. Moreover, after 24 hours of culturing only myeloid-like γδ T cells were producing IFNγ. These cells were also primed to
process and present the antigen. Culturing of γδ T cells with other PBMCs caused their transient proliferation response, however
their myeloid-like subset was not proliferating, suggesting that under certain circumstances these cells differentiate into the
terminal stage of effector cells. Considering the role of CD11b and CD14 in the activation of innate immunity, we speculate that this
subpopulation of sheep γδ T cells may function as innate antigen presenting and proinflammatory cells during immune responses. It
non-specifically contributes to innate immunity and resulting generation of the adaptive immune response to vaccines.
25.
Name and Title of Presenter: Emily Weber (Katie Picotte, M.S.)
Co-Authors: Li Li & Haotian Zhao
Organization/Department: Sanford/Children’s Health Research Center
Abstract Title: Metastatic medulloblastoma through the overexpression of Atoh1
Medulloblastoma (MB) is comprised of four main subgroups, one involving mutations of the sonic hedgehog (Shh) pathway.
Although metastasis is highly associated with subgroup 3, more aggressive cases within the Shh subgroup have shown metastasis of
tumor cells. There are several successful mouse models of MB involving this subgroup; however, there is lack of a strong model in
which the tumor is highly metastatic. We have developed a novel mouse model to overexpress the transcription factor Atoh1, a
protein which enhances Shh-dependent proliferation of granule neuron progenitors (GNPs) and has shown to promote MB
formation when overexpressed. For this mouse model (termed A1G), the transgenic construct involves an HA tagged Atoh1 cDNA
inserted into the Rosa26 locus; this is preceded by a CAG promoter and a loxP-flanked Neo-STOP cassette. An frt-flanked IRES-GFP
cassette is between the Atoh1-HA fragment and a polyadenylation signal. When bred to Math1-Cre, Atoh1 is overexpressed, but
development proceeds normally without alteration to the cerebellum. When Math1-Cre: A1G is also bred to the Ptch1LacZ/+
established mouse strain, 100% of the mice develop medulloblastoma. In addition, 100% of the mice develop leptomeningeal
dissemination into the brain and spinal cord. Characterization of this outcome was conducted through immunofluorescence and
immunohistochemistry of brain tissue and spinal cord. Additional work will involve determining levels of Atoh1 in A1G compared to
the Ptch1LacZ/+ tumor, in which metastasis does not occur. Functional analysis will also be conducted using cell culture of tumor
cells. This work will help to establish a transgenic mouse strain in which metastatic medulloblastoma can be studied.
26.
Name and Title of Presenter: Chris Comstock, RDN
Co-Authors: Marjorie Zastrow, MS, Kendra K. Kattelmann PhD, RDN, LDN
Organization/Department: Department of Health and Nutritional Sciences, South Dakota State University
Abstract Title: Mind Over Matter: Physical Activity in Rural Areas
Introduction: As a part of a five year, tri-state, Community Based Participatory Research Project (CBPR) titled “Ignite: Sparking Youth
to Create Healthy Communities,” this study sought to 1) assess environmental support of physical activity in rural areas and 2)
determine whether there is a correlation between the measured physical environment and the physical activity perceptions of the
study participants. We hypothesized that the perceptions of the study participants would correlate with the objective results
obtained from the built environment assessments.
Materials and Methods: Four rural low-income communities in South Dakota and Kansas (one intervention and one control
community within each state) were selected for the study. The physical environment within each community was assessed by
trained researchers using the Active Neighborhood Checklist (ANC) and the Physical Activity Resource Assessment (PARA). Youth
(6th to 8th grade) behavior and perceptions related to physical activity and the local environment were assessed using questions
sourced from previously validated tools (International Physical Activity Questionnaire (IPAQ), Adolescent Survey 1, and the Trial of
Activity for Adolescent Girls (TAAG)).
Preliminary Results: The ANC assessed key street level features such as land use, quality of the environment for a pedestrian, street
characteristics, transportation availability, and areas available for walking and bicycling. 19 locations were assessed within the South
Dakota control community, 10 locations were assessed within the South Dakota intervention community, 3 locations were assessed
within the Kansas control community, and 5 locations were assessed within the Kansas intervention community. Average scores for
these locations, respectively, were 19.4, 22.1, 23.0, and 16.6. Scores for the ANC range from 0 (least conducive to physical activity)
to 59 (most conducive to physical activity). The PARA provided information on the features, amenities, and incivilities within a
community. All scores were converted to a percentage of the total possible score (100). For features, scores ranged from 19.7 to
41.0; for amenities, scores ranged from 51.5 to 63.9; and for incivilities, scores ranged from 4.2 to 21.4. For features and amenities,
higher scores represent better environments for physical activity. For incivilities, lower scores were desirable. Data from the physical
activity questionnaire is still being analyzed.
Discussion and Conclusion: Discussion and conclusions will be completed once all data has been analyzed.
27.
Name and Title of Presenter: MD SAIFUL ISLAM,
Graduate Teaching Assistant
Co-Authors: Mohammed Alqahatani, Omathanu Perumal
Organization/Department: Pharmaceutical Sciences, College of Pharmacy, South Dakota State University
Abstract Title: “Zein based nanocarrier for oral drug administration”
Oral drug delivery is limited by several facotrs including poor solubility, poor permeability and stability of the drug in the gastrointestinal tract. To this end, the present study focuses on testing the feasibility of using food grade protein polymers to develop
nanocarriers for oral drug delivery. Three different zein based core-shell nanoparticles were developed including zein-casein (ZC),
zein-Lactoferrin (ZLF) and zein-PEG (Z-PEG). Fluorescent probes used to characterize the in-vitro and in-vivo transport of
nanoparticles. All the nanocarriers were less than 200 nm in diameter with uniform size distribution with varying surface charge. The
cell uptake studies in Caco-2 cells showed that the nanocarriers are taken up by endocytosis. Z-PEG showed higher cell uptake
among these three nanocarrier systems. The proteolytic stability of the nanocarriers was tested using simulated gastric and
intestinal fluid. In-vivo biodistribution was characterized using an in-vivo animal imaging system. The results showed that the
nanoparticles remained in the gastrointestinal tract for prolonged periods indicating its suitability of sustained drug delivery
applications. Overall, the results from this study indicate the suitability of the food grade protein based nanocarriers for drug
delivery applications.
28.
Name and Title of Presenter: Jacob Cain Ph.D.
Co-Authors: Spencer Duncan, Seung yon Koh, Helen Magee, Ryan O’Toole, Jill Weimer
Organization/Department: Children’s Health Research Center -- Sanford Research
Abstract Title: Molecular Switches: Guanine Exchange Factors in Cortical Development
The development of the nervous system is dependent upon precise control of neural stem cell proliferation, differentiation,
migration, and cell death. Regulation and balance of these processes are vital for normal development of the brain. The Rho family
of GTPases serve as regulators of these processes by acting as binary switches, activating or deactivating signaling pathways. RhoGTPases are molecular switches whose activity is positively regulated by a class of proteins known as Gaunine Exchange Factors
(GEFs), and negatively regulated by GTPases activating proteins (GAPs). Rho-GTPases acquire a ‘turned on’ state when they are
bound to a GTP molecule by a GEF. In this state, the proteins can bind and activate specific downstream effectors molecules, e.g.
kinases. The hydrolysis of bound GTP to GDP by a GAP ‘turns off’ the GTPase, which cannot activate downstream effectors.
We have identified a GEF, called SGEF, with expression in the developing cerebral cortex. In vitro SGEF induces the formation of Factin rich protrusions on the dorsal surface of fibroblasts and endothelial cells. SGEF specifically acts as a GEF to the Rho-GTPases
RhoG and cdc42. These Rho-GTPases have important roles in the developing cortex, cdc42 regulates fate determination of neural
progenitors, and disruption in this crucial signaling pathway disrupts apical-based polarity. RhoG regulates proliferation of neural
progenitors both in vitro and in vivo, although loss of RhoG causes nominal brain defects. By focusing on SGEF, whose expression is
restricted to a defined neurogenic niche in the cortex and whose deletion appears to have nominal consequences outside of the
central nervous system, we are able to use the developing cortex as a model to uncover clues about how GEFs function to regulate
Rho-GTPase signaling. This study provides a framework for how GEFs collectively function and defines the basic mechanisms of RhoGTPase regulation in the developing nervous system.
29.
Name and Title of Presenter: Shane Scholten1, Assistant Professor of Exercise and Sport Science
Co-Authors: Igor N. Sergeev2, Chad B. Birger3, Qingming Song2, Kirsten K. Townley4
Organization/Department:
1
Augustana College 2 South Dakota State University, 3 Sanford Research, 4 University of Sioux Falls
Abstract Title: Vitamin D Supplementation Has No Effect on Muscular Function in Vitamin D Sufficient Adults
Vitamin D supplementation has been associated with muscular function benefits in populations with insufficient vitamin D status
(circulating concentration of 25(OH)D <20 ng/mL). However, evidence supporting the ergogenic effect of vitamin D supplementation
on muscle function in healthy adults is lacking. We hypothesized that additional muscular function benefits can be achieved by
increasing vitamin D status. PURPOSE: To determine changes in muscular function with high vitamin D3 intake using multimodal
test: vertical jump (VJ), handgrip strength (HG), isokinetic knee flexion torque (IKF) at 60 deg/s, and isokinetic knee extension torque
(IKE) at 60 deg/s. METHODS: Forty healthy male subjects (age 31.3 ± 4.5 years, VO2max 55.7 ± 7.5 mL∙ kg-1∙min-1) were randomized
to either vitamin D (D; 4000 IU vitamin D3/d, which is the recommended upper level (UL) intake) or placebo (P) groups. Subjects
taking vitamin D supplements were excluded. Serum samples were analyzed for 25(OH)D after 8 weeks of supplementation using
chemiluminescent EIA (Diazyme 25-OH Vitamin D assay). A two-way ANOVA with interactions was used to compare differences
between variables. Data collection was performed in Sioux Falls, SD (latitude 43.5º N) between January and April of 2013. RESULTS:
Upon enrollment, 90% of the subjects were vitamin D sufficient (serum 25(OH)D ≥20 ng/mL). Eight-week supplementation
significantly improved 25(OH)D status in the D group (from 26.9 ± 4.4 to 48.0 ± 7.6 ng/mL, n=20, p<0.01) compared to no changes in
the P group (27.2 ± 3.4 vs. 30.1 ± 5.1 ng/mL, n=20). However, the increase in 25(OH)D concentration in the D group did not result in
significant increases in VJ (56.1 ± 5.3 cm vs. 57.7 ± 5.1 cm), HG (10.9 ± 0.8 kg vs. 11.1 ± 0.5 kg), IKF (103.9 ± 9.9 Nm vs. 108.2 ± 8.3
Nm), or IKE (202.8 ± 22.0 Nm vs. 208.0 ± 23.2 Nm). CONCLUSION: The results obtained demonstrated that vitamin D
supplementation at the recommended UL for 8 weeks significantly increased 25(OH)D serum concentration. However, this increase
was not accompanied by muscular function benefits, probably, because the participants had an adequate initial vitamin D status.
The findings also suggest that increasing vitamin D status in healthy adults does not improve muscular function. Supported by NIH
grant P20GM103443.
30.
Name and Title of Presenter: Brandon Scott
Co-Authors: Adam Hoppe
Organization/Department: SDSU Department of Chemistry and Biochemistry
Abstract Title: Optimizing the fluorescent protein trio for 3-Way FRET imaging of protein interactions in living cells
Fluorescence Resonance Energy Transfer (FRET) microscopy can image the interactions between fluorescently-tagged proteins inside
living cells. Powerful new methods have extended FRET microscopy to the imaging of three or more interacting proteins inside living
cells. Here, we compared existing fluorescent proteins to find the best trio for 3-Way FRET imaging. We focused on readily available
cyan, yellow, and red proteins that have high quantum yields, large extinction coefficients and good photostability. These criteria
indicate the following candidate proteins: CyPet/mTFP1/mTurqoise2(Tq2), mCitrine/YPet, and TagRFP/TagRFPt/mRuby2/mCherry.
By taking advantage of the high structural similarity across the fluorescent proteins, we generated structurally similar, but
photophysically distinct donor/acceptor and triple fluorophore fusion proteins and measured their FRET efficiencies inside living
cells. Surprisingly, their published photophysical parameters and calculated Förster distances did not predict the best combinations
of FPs. Using cycloheximide to inhibit protein synthesis, we found that the different maturation rates of the tested FPs had a strong
effect on the FRET efficiency and therefore the signal strength for measuring protein-protein interactions. This effect was most
pronounced when comparing rapidly maturing yellow and slowly maturing red FPs. We found that red FPs with inferior published
photophysical parameters gave superior FRET efficiencies because of their faster maturation rates. Based on combined metrics for
the FRET efficiency, fluorophore photophysics and fluorophore maturation we determined that Tq2, YPet and Cherry were the best
available FPs for live cell 3-Way FRET measurements. Additionally, these results define key principles for selecting fluorophores for
the design of FRET constructs.
31.
Name and Title of Presenter: Marianna Madeo
Co-Authors: M. Madeo, J. Edgar, F. Darios, T. N. Jepperson, J. Li, C. Blackstone, M. S. Robinson, J. Hirst, M. C. Kruer
Organization/Department: Sanford Research Center
Abstract Title: Mutations in adaptor protein AP-5 subunits lead to peripheral neuropathy, spastic paraplegia and parkinsonism
with aberrant endolysosomes
AP-5 is one of five adaptor protein complexes that play important roles in intracellular trafficking. We identified patients with
mutations in AP-5 subunits whose clinical phenotype ranged from isolated peripheral neuropathy to spastic paraplegia with
parkinsonism. Primary cultured fibroblasts from affected patients showed accumulation of enlarged endolysosomes. Patient cells
also displayed autofluorescence and accumulation of lysosomal storage material by electron microscopy. These findings indicate
that AP-5 mutations lead to diverse neurological phenotypes and further support links between endosomal-lysosomal dysfunction
and hereditary spastic paraplegia and parkinsonism
32.
Name and Title of Presenter: Elizabeth Droke, PhD, RDN, LN
Co-Authors:
Organization/Department: SDSU/HNS
Abstract Title: Chia Seeds: Potential to Influence Obesity and Inflammation – Proposed Study
Chia seeds have purported health benefits; however, little scientific evidence exists for these benefits. Obesity-induced
inflammation is associated with various conditions such as diabetes and cardiovascular disease. Proinflammatory mediators (e.g.,
tumor necrosis factor (TNF)- α, interleukin (IL)-6) may serve as the link between obesity, inflammation, and various diseases.
There is a critical need to determine how bioactive food components, such as omega-3 fatty acids, can attenuate the deleterious
effects associated with obesity-induced inflammation. Our central hypothesis is that consumption of chia seeds (25 g/d) for 12
weeks will improve inflammatory mediators and lipid profile to a greater extent in overweight and obese participants than in normal
weight participants. Objective #1: Identify the influence of chia seed consumption on the inflammatory mediator profile (IL-6, Creactive Protein (CRP), TNF-α, IL-10) in normal weight and overweight/obese humans. Objective #2: Identify the influence of chia
seed consumption on the adipokines, adiponectin and leptin, in normal weight and overweight/obese humans. Objective #3: Identify
the influence of chia seed consumption on glucose homeostasis in normal weight and overweight/obese humans. We expect that
consumption of foods containing chia-seeds will improve the inflammatory mediator profile in overweight/obese humans.
33.
Name and Title of Presenter: CHOWDHURY S ABDULLAH
Co-Authors: XIUQING WANG, ZHU-QIU JIN
Organization/Department: DEPARTMENT OF PHARMACEUTICAL SCIENCES, COLLEGE OF PHARMACY
Abstract Title: Genetic depletion of T cell S1P receptor 1 exhibits improved cardiac function and less fibrosis in streptozotocininduced type 1 diabetic mice
Background and Aims: T lymphocytes infiltration into myocardium has been observed in patients with diabetes. Sphingosine 1phosphate receptor 1 (S1P1) regulates mature T cells egress from lymphoid organ to blood and peripheral organs. The role of T
lymphocytes in diabetic hearts remained elusive. Methods and Results: Depletion of T cell S1P1 receptors was attained by breeding
of S1P1loxP/loxP mouse with Lck-driven Cre transgenic mouse. Offspring was genotyped by PCR and maintained in specific pathogen
free room. T-cell-specific S1P1 receptor knock-out mice carrying the Lck-Cre gene (TCS1P1KO) and littermate S1P1loxP/loxP mice
(WT) were divided into vehicle control and STZ groups. Type 1 diabetes was induced by five day injection (i.p.) of streptozotocin
(STZ) at a dose of 50 mg/kg. Control mice were injected buffer only. Body weight was monitored twice each week. Fasting blood
glucose level was measured at the beginning, 4, and 11 weeks. Mature CD4+ and CD8+ T cells in blood as well as regulatory T cells
(Tregs) and Th17 cells in spleen and blood were counted by flow cytometry. Masson’s Trichrome staining was conducted to assess
fibrosis. Cardiac contractile force was measured by Langendorff perfusion at the end of 11 week. TCS1P1KO mice had reduced CD4+
(1.15±0.30% vs 25.06±0.64% in WT, P<0.01, n=4-5) and CD8+ (2.09±0.42% vs 14.72±0.38% in WT, P<0.01, n=4-5) T cells in blood. In
WT STZ mice, Treg cells increased in blood (1.75±0.20% vs 0.39±0.18% in KO STZ mice) while in both vehicle control and STZ KO mice
proliferation of Th17 cells was detected in spleen. TCS1P1KO STZ mice show less fibrosis compared to WT STZ mice. Cardiac
contractile force is increased in TCS1P1KO STZ mice compared with WT STZ mice. Conclusion: Selective depletion of T cell S1P1
reduces mature T lymphocytes in circulation and exerts improved cardiac function and less fibrosis in diabetic hearts.
34.
Name and Title of Presenter: Ryan D. Geraets
Co-Authors: Jake N. Miller, David A. Pearce
Organization/Department: Children’s Health Research Center
Abstract Title: Stop the nonsense! Evaluating read-through compounds for the treatment of INCL.
A variety of genetic disorders are caused by nonsense mutations which result in premature termination codons (PTCs). Utilization of
read-through compounds (RTCs) causes the ribosome to recognize PTCs as non-termination codons, thus leading to normal
translation and full-length protein production. Currently, read-through compounds are being used in clinical trials for the treatment
of genetic disorders that stem from nonsense mutations. Based on genetic information, it is known that some cases of INCL result
from nonsense mutations. RTC-13, Amlexanox, Ataluren and other read-through compounds are being screened against patientderived, immortalized lymphoblasts and point-mutant mouse models in anticipation of identifying potential therapies for cases of
INCL that result from nonsense mutations.
35.
Name and Title of Presenter: Natalie Thiex
Co-Authors: Lu Huang, Jieqiong Lou, Hana Abdeljalil, Shalini Low-Name, Adam Hoppe
Organization/Department: Biology & Microbiology Department
Abstract Title: Clathrin facilitates macropinosome maturation and CSF-1 receptor degradation in bone marrow-derived
macrophages.
Macrophage colony-stimulating factor (CSF-1) supports the differentiation and growth of macrophages from myeloid precursors by
activating the CSF-1 receptor tyrosine kinase (CSF-1R). Recently, we have shown that upon ligand binding CSF-1R is rapidly
internalized by small-vesicle endocytosis and trafficked to macropinosomes that form in response to CSF-1. CSF-1 and the CSF-1R
that arrive on the limiting membrane of the macropinosome are subsequently delivered to the lumen of the macropinosome,
perhaps by the formation of multi-vesicular bodies. Here, we use immunofluorescence and live cell microscopy to demonstrate a
role for clathrin in the maturation of macropinosomes and the degradation of CSF-1R in primary macrophages. Using siRNA to
knockdown the clathrin heavy chain in bone marrow-derived macrophages resulted in a modest decrease in receptor endocytosis,
but a pronounced defect in macropinosome maturation and the delay of CSF-1R degradation. Furthermore, we observed that a
yellow fluorescent protein-clathrin light chain (YFP-CLTA) fusion assembled as a large ring surrounding CSF-1R-positive
macropinosomes prior to CSF-1R degradation. These data implicate clathrin in macropinosome maturation and cargo degradation in
macrophages potentially acting through the endosomal sorting complex required for transport (ESCRT).
36.
Name and Title of Presenter: Cristina Lammers MD, MPH
Co-Authors: Sh. Poigai PhD, MPH; T. Mertz (Nursing Undergraduate Student)
Organization/Department: SDSU - College of Nursing and Health Sciences
Abstract Title:
Understanding women’s preconception health care awareness and access in a Midwest rural state
Background and Objectives: Evidence shows that preconception woman’s health affects pregnancy and children health outcomes.
This study aimed to assess women’s awareness of preconception healthcare, what preconception services they received, and to
identify demographic and reproductive health factors associated with women’s knowledge and access to preconception health care.
Methods: A survey study was conducted in a convenient sample of women ages 18 to 45 attending Women Infant Children (WIC)
programs during six consequent months in 2011-12. Data from 1,426 surveys were analyzed and adjusted OR (95% [CI]) were
calculated to investigate associations between women’s awareness of preconception healthcare and services received by
demographics, and reproductive history.
Results: Sixty two percent were White, 29% were American Indian. More than two- thirds had health insurance, and 67% reported
previous unintended pregnancies. Most women (83%) saw a health provider the year before the survey, but one-half were either
unaware or did not receive preconception healthcare information, and 74.6% only received five or fewer of the preconception
services known to improve perinatal outcomes. Less than 18% were advised on folic acid supplementation, hepatitis B or rubella
immune status, or the risks of overweight and obesity, and substance use on pregnancy. Preconception healthcare awareness was
lower among women with previous unintended pregnancies (95%CI =1.45, 12.47), no health insurance (95%CI=1.05, 1.81), who were
single (95%CI=1.03, 1.60), used primarily Emergency Room care (95%CI=1.07, 2.08), and had lower education (95%CI=1.01, 1.61).
Conclusions: A gap was identified between preconception healthcare services recommended by the CDC, and women’s awareness
of preconception healthcare and the services they received. Variables associated with lower awareness and lack of preconception
services were identified. Findings support the need to investigate strategies to improve women awareness and to assure
preconception health care services reach reproductive-age women.
37.
Name and Title of Presenter: Regan Roat, MD/PhD Student
Co-Authors: A Ansarullah, Jenica Christopherson, Colette Free, Munir Hossain, Alex Rabinovitch, Zhiguang Guo
Organization/Department: The Sanford Project, Sanford Research/University of South Dakota
Abstract Title: Identifying a Panel of Plasma miRNAs as Potential Biomarkers for “Silent Diabetes” in NOD Mice
During the initial phases of Type 1 Diabetes (T1D), the immune system begins attacking the insulin-producing pancreatic β cells,
which ultimately leads to the substantial loss of β cell mass. However, there is currently no effective method for detecting early β
cell loss prior to the onset of hyperglycemia and other symptoms of diabetes. microRNA (miRNA) is small, non-coding RNA that
functions to post-transcriptionally regulate gene expression via translational inhibition or degradation of target mRNA. Previous
studies have shown that several miRNAs are up-regulated in islets during the progression of inflammation in prediabetic nonobese
diabetic (NOD) mice, a model of T1D. In this study, we investigated whether β cell-specific miRNAs can potentially serve as
biomarkers for detecting early β cell loss in NOD mice. We measured plasma miRNA levels in prediabetic (4, 8, and 12 weeks old),
silent diabetic (blood glucose 100-200mg/dL), new-onset diabetic (blood glucose 201-400mg/dL), and later diabetic (blood glucose
>400mg/dL for 3 weeks) NOD mice using a NanoString hybridization-based miRNA expression assay. H&E staining of pancreas
sections showed that the percentage of islets extensively disrupted and destroyed by leukocyte infiltration was significantly higher in
the silent diabetic mice than in the prediabetic mice (p < 0.05), indicating that a large proportion of β cells have already been
destroyed before diabetes is diagnosed. A panel of plasma miRNAs including miR-let-7c, miR-122, miR-1224, miR-148a, miR-1902,
miR-1951, miR-203, miR-21, miR-2137, and miR-709 was increased in the silent diabetic mice, further increased in the new-onset
diabetic mice, and subsequently decreased in the later diabetic mice (p < 0.05). This finding indicates that the increasing levels of
these miRNAs in the plasma may be correlated with β cell death and disease progression. Furthermore, real-time PCR data showed
that miR-1224 expression is significantly higher in isolated mouse pancreatic islets than in other tissues (p < 0.01), and in situ
hybridization results confirmed that this miRNA is strongly islet cell-specific. Together, our results suggest that miR-1224 and other
miRNAs in the plasma could potentially serve as biomarkers for detecting early β cell loss and for monitoring treatment outcomes in
patients with T1D.
38.
Name and Title of Presenter: Kristen Roles
Co-Authors: Bradley J Bowser
Organization/Department: Department of Health and Nutritional Sciences
Abstract Title: Differences in Running Mechanics Between Obese and non-Obese Children
INTRODUCTION: Recent research indicates that obese children have greater vertical loading and leg stiffness during running
compared to non-obese children. In adults, high vertical loading and leg stiffness are often accompanied by decreased joint flexion
of the lower extremities during running. Running kinematics have yet to be examined in obese children. We hypothesize that during
running, obese children will display less joint flexion at footstrike (FS) and vertical impact peak (VIP) than non-obese children.
PURPOSE: To determine the kinematic differences between obese and non-obese children during the early stance phase of running.
METHODS: Fourteen children classified as healthy, non-obese (Male=8, Female=6, age=9.86±1.56yr, height=1.44±0.10m,
mass=34.98±7.52kg, BMI=16.71±1.67) and five children classified as overweight/obese (Male=4, Female=1, age=10.4±1.14yr,
height=1.47±0.07m, mass=53.05±8.59kg, BMI=24.32±1.90) participated in this study. High speed motion capture recorded kinematic
data (200Hz) as participants ran (3.5±5% m/s) across a 15 m runway embedded with a ground reaction force platform (1000 Hz).
Independent sample t-tests and effects size were calculated to determine group differences. RESULTS: The obese group displayed
higher vertical impact peak (p=0.023), average vertical load rate (p=0.048), instantaneous vertical load rate (p=0.058), and leg
stiffness (p=0.002) and less hip flexion during VIP (p=0.015) and FS (p=0.031) and less knee flexion during VIP (p=0.013) compared to
the non-obese group. CONCLUSION: Similar to previous findings obese children displayed increased vertical loading and leg stiffness
during running. Furthermore, the obese children displayed decreased knee flexion and ankle dorsiflexion often found in individuals
who exhibit excessive vertical loading during running. The running mechanics exhibited by the obese group have been linked to
several overuse running injuries and have been suggested to increase joint loading. Excessive joint loading during childhood may
increase the risk of developing osteoarthritis later in life. Exercise prescription for obese children may need to start with lower
impact exercises prior to prescribing running.
39.
Name and Title of Presenter: Mrs. Padmapriya Swaminathan1
Co-Authors: Dr. Jose L. Gonzalez2, Dr. Donna Jacob3, Dr. Marinus Otte3
Organization/Department:
1
Dept. of Mathematics and Statistics, 2Dept. of Plant Sciences, SDSU, 3Dept. of Biological Sciences Wet
Ecosystems Research Group, NDSU
Abstract Title: Molecular responses of Spinach to Zinc oxide (ZnO) nanoparticles
Nanoparticles are increasingly used in industries such as in food packaging, water treatments, paints, electronics and sunscreens
eventually ending up in our waterways and hence crop plants. This poses a hazard in terms of food safety and necessitates studies to
determine the uptake and transport of, and plant responses to these nanoparticles. We used RNA-Seq to evaluate global gene
expression in spinach roots upon exposure to Zinc oxide (ZnO) nanoparticles. Spinach is a widely used fresh food crop consumed in
various forms (salads,soups) around the world. ZnO nanoparticle is widely used in sunscreens. cDNA libraries were constructed from
Spinach seedling roots exposed to ZnO nanoparticles as well as unexposed seedlings used as control.
High throughput sequencing yielded approximately 465 million sequence reads which were de novo assembled using CLC-Bio
Genomics workbench to obtain a large coverage transcriptome for Spinach. Contigs were functionally annotated through similarity
searches against Arabidopsis thaliana using BLASTX in CLC-Bio Genomics workbench and mapping of gene ontology (GO) terms to
the respective contigs. Gene expression levels for each contig were compared between non-nano ZnO vs. nano ZnO nanoparticle
treated root samples. Gene set enrichment analysis was done to identify functional categories enriched in nanoparticle treated
roots. Change in expression levels in different metabolic and signaling pathways were visualized using Mapman. Up-regulation of
genes associated with biotic stress responses, jasmonate synthesis, protein degradation, redox, sulphate assimilation, and cell wall
precursor synthesis suggested that ZnO nanoparticle exposure elicited responses similar to necrotrophic pathogen responses.
40.
Name and Title of Presenter: Diane Maher, PhD
Co-Authors: Amanda Schaefer1, Neeraj Chauhan2, Subhash C. Chauhan 2, Maria Bell3, and Diane Maher1
Organization/Department:
1
Cancer Biology Research Center, Sanford Research/USD, Sioux Falls, South Dakota, 2Department of
Pharmaceutical Sciences, Cancer Research Center, University of Tennessee Health Science Center, and 3Sanford Clinic Women’s
Health, Sioux Falls, SD
Abstract Title: Expression and localization of the Aryl Hydrocarbon Receptor in invasive cervical cancer
Despite cervical cancer screening and the introduction of promising Human Papillomavirus (HPV) vaccines, there are an estimated
275,000 deaths worldwide from cervical cancer, making it the third most frequently diagnosed cancer and the fourth leading cause
of cancer related deaths in women. Additional understanding regarding the molecular mechanisms driving cervical cancer
progression is needed to develop effective therapies for recurrent and advanced disease, which have a low 5 year survival rate of
16%. Historically, research on the Aryl Hydrocarbon Receptor (AhR) centered on its role in response to dioxins and carcinogenic
compounds as they relate to initiation of cancer. The canonical pattern of AhR activation centers on ligand induced translocation of
AhR to the nucleus where AhR acts as a transcription factor, regulating the expression of numerous genes. Recently, the
identification of endogenous ligands and recognition that AhR may affect progression of cancer, has opened up new directions for
AhR research. However, there is little information regarding the AhR pathway in cervical cancer. Our preliminary data shows that
cytoplasmic and nuclear levels of AhR protein significantly increase in invasive cervical cancer, compared to normal cervical
epithelium. Specifically, 33% of invasive cervical cancer tissues had high nuclear AhR staining (5 of 15). We are currently working to
understand the biological significance of AhR expression and localization in the progression of cervical cancer.
41.
Name and Title of Presenter: Amanda Schaefer
Co-Authors: Diane Maher
Organization/Department: Tumor Biology Core Facility, Cancer Biology Research Center, Sanford Research
Abstract Title: Tumor Biology Core Facility
42.
Name and Title of Presenter: Muzaffar Abbas (Graduate Student), Dr. Shafiqur Rahman (Mentor)
Co-Authors:
Organization/Department: Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University
Abstract Title: Role of alpha-7 nicotinic positive allosteric modulator on mechanical allodynia and TNF alpha following LPS-induced
neuroinflammatory pain in mice
Evidence indicates that inflammatory immune activation contributes to pathophysiology and maintenance of neuroinflammatory
pain involving central nervous system alpha7 nicotinic acetylcholine receptors (nAChRs). Here, we examined the effects of TQS, an
alpha7 nAChR positive allosteric modulator, on mechanical allodynia, hyperalgesia, tumor necrosis factor-α (TNFα) and
norepinephrine (NE) following lipopolysaccharide (LPS)-induced neuroinflammation in mice. Pretreatment of TQS (1 or 4 mg/kg, i.p.)
reduced LPS-induced increased mechanical allodynia in a dose-dependent manner. The effect TQS (4 mg/kg) was significantly
(p<0.05) different from control. Similarly, pretreatment of TQS (1 or 4 mg/kg) significantly (p<0.05) reduced LPS-induced increased
hyperalgesia in a dose-dependent manner. Furthermore, pretreatment of TQS (1 or 4 mg/kg) reduced LPS-induced increased TNFα
level in hippocampus. In addition, pretreatment of TQS (1 or 4 mg/kg.) reversed the LPS-induced reduction of NE level in
hippocampal tissue. Taken together, these results suggest that TQS decreases LPS-induced neuroinflammatory pain by modulating
hippocampal TNFα and NE levels. Therefore, alpha-7 nicotinic positive allosteric modulatory site could be a potential target for the
treatment of neuroinflammatory pain. (Supported by Fulbright Foundation USA).
43.
Name and Title of Presenter: Chase Merfeld
Co-Authors: Kendra K. Kattelmann1, Jessica R. Meendering1, Douglas R. Mathews2, Melissa D. Olfert3, Jade White3, Sarah E.Colby4,
Randa L. Meade4, Lisa Franzen-Castle5, Trina Aguirre6 , Adrienne A. White2
Organization/Department: Health and Nutritional Sciences
Abstract Title: iCook 4-H: Report of the correlation between quality of life measures and physical activity in 9-10 year old children
Statement of Objective: To examine the relationship between self-reported quality of life and accelerometer derived physical
activity (PA) in 9-10 year old children participating in iCook 4-H, a 5-state family centered, and childhood obesity prevention
program.
Design, Setting, and Participants: A cross-sectional study was conducted in 113 children who met accelerometer compliance
standards and completed the Pediatric Quality of life survey (Peds QL).
Outcome Measures and Analysis: All subjects wore an accelerometer (Actigraph GT3X+) for 7 days. Mean daily minutes of
accelerometer derived sedentary time (ST) and PA including light (LPA), moderate (MPA), vigorous (VPA) and moderate-to-vigorous
(MVPA) were evaluated during waking hours. Peds QL survey assessed physical, emotional, school, and social dimensions of quality
of life. Relationships between quality of life and mean daily minutes of PA were assessed via Spearman Correlation Coefficient.
Statistical significance was set at p ≤ 0.05.
Results: Accelerometer derived MPA (r=0.2, P=0.02), VPA (r=0.3, P=0.003), and MVPA (r= 0.3, P= 0.008) were positively correlated
with quality of life. There were no associations between ST or LPA and quality of life. Of the 4 subscales child physical functioning
was positively correlated with MPA (r=0.3, P=0.005), VPA (r=0.3, P=0.0006), and MVP (r=0.3, P=0.001); child school functioning with
MPA, (r=0.2, P=0.01), VPA (r=0.3, P=0.005), and MVPA (r=0.3, P=0.005). There were no associations between subscales emotional
and social functioning and PA.
Conclusion and Implications: Inclusion of quality of life dimensions into obesity prevention programs that increase physical activity
in 9-10 year olds warrants further exploration
44.
Name and Title of Presenter: Maria E. Moutsoglou, Graduate Research Assistant
Co-Authors: Gi-Ho Kim, John M. Robinson
Organization/Department: Chemistry and Biochemistry
Abstract Title: A FRET-based Assay for Monitoring Actions of Calcium Sensitizers on the Thin Filament
Cardiac troponin (cTn) is composed of troponins C, I, and T. cTnC is the Ca2+-dependent switch for cardiac muscle contraction. A
decrease in calcium activation, and a subsequent decrease in cardiac contractility, has been linked to cardiac diseases such as
familial hypertrophic cardiomyopathy. Calcium sensitizers targeting cTn are a promising pharmacological approach to stimulating
contractility through increased sensitization or stabilization of Ca2+-induced changes. We developed an in vitro assay to measure
the actions of Ca2+ sensitizers on cTn within reconstituted regulated actin (rAc) (cTn, tropomyosin, f-actin). The assay utilizes
fluorescence resonance energy transfer (FRET) to monitor structural changes of troponin as a function of pCa. A donor and acceptor
fluorophore were covalently attached to the mobile domain of cTnI and the N-lobe of cTnC, respectively. The fluorophore positions
were selected due to the large observed Ca2+-induced distance change (1.8 nm), allowing for an assay highly sensitive to pCa
fluctuations and Ca2+-sensitizing effects. Steady-state calcium titrations were performed to monitor fluctuations in Ca2+ affinity in
the presence of two Ca2+ sensitizers known to bind to cTnC: Levosimendan and bepridil. Both bepridil and Levosimendan increased
Ca2+ sensitivity. Bepridil appeared to prevent troponin from closing under Ca2+-saturating conditions, a structural effect that may
give insight into the mechanism of Ca2+ sensitization of cTn. The presence of myosin heads (S1) also increased the Ca2+ sensitivity of
the thin filament. This assay is a fast approach to monitor the effects of Ca2+ sensitizers on cTn within the thin filament.
45.
Name and Title of Presenter: Benjamin Forred
Co-Authors: Michelle Booze, Brianna Titus, Danielle Jensen, Ryan Wood, Darwin Daugaard, Miranda Floen, Peter Vitiello
Organization/Department: Sanford Children’s Health Research Center
Abstract Title: The Mitochondrial Thioredoxin System Detoxifies Reactive Oxygen Species and Prevents Cell Death during Hyperoxic
Injury
Mitochondria play a fundamental role by promoting cell death following accumulation of reactive oxygen and nitrogen species. High
concentrations of atmospheric oxygen (hyperoxia) used clinically to treat tissue hypoxia in premature newborns is known to elicit
oxidative stress and mitochondrial injury to pulmonary epithelial cells. The goal of these studies was to understand the link between
oxidative injury, activation of apoptotic signaling, and detoxification pathways in mitochondria during hyperoxic exposure. These
studies utilized human pulmonary adenocarcinoma H1299 and A549 cell lines that were cultured in 95% oxygen to study hyperoxic
injuries. Flow analysis of a redox-sensitive mitochondrial-specific fluorophore, mitoSOX, indicated increased levels of mitochondrial
superoxide anion. This correlated with pro-apoptotic molecular programming through phosphorylation of ASK1 and increased
protein levels of Bax and Bak. The mitochondrial thioredoxin system detoxifies reactive oxygen species by balancing dithiol/disulfide
status in targeted protein substrates. Increased transcript and protein of thioredoxin-2 (Trx2) and its corresponding reductase
(TrxR2) were detected following hyperoxic treatment. Upregulation of the mitochondrial thioredoxin system in response to
hyperoxia may be responsible for preventing deleterious changes in Trx2 redox potential. Mitochondrial thioredoxin activity was
modulated through pharmacological inhibition of TrxR2 with auranofin and genetically through siRNA knockdown of Trx2. Increased
accumulation of mitochondrial reactive oxygen species and cell death during hyperoxia occurred during impairment of
mitochondrial thioredoxin activity. Future studies will investigate correlations between the mitochondrial thioredoxin system and
apoptotic machinery. Taken together, these studies support that hyperoxic induction of mitochondrial reactive oxygen species may
have deleterious cellular effects which are detoxified by the mitochondrial thioredoxin system.
46.
Name and Title of Presenter: Ruanbao Zhou, Associate Professor
Co-Authors: Charles Halfmann, Liping Gu
Organization/Department: Biology and Microbiology
Abstract Title: Photosynthetic Production of a Cyclic Hydrocarbon by Engineered N2-Fixing Cyanobacteria
In cyanobacteria, the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway is an isoprenoid biosynthetic pathway that produces a
variety of important commodity chemicals. Limonene (C10H16) is a cyclic monoterpene synthesized from this pathway by citrus
fruits, and has many applications in pharmaceuticals, due to its anti-inflammatory and anti-carcinogenic properties, and in
cosmetics, industrial solvents, and biofuels. Global limonene production is far behind the arising demands. Currently, the majority of
limonene production is extracted primarily from the residue of harvested citrus fruits. However, this extraction method makes
production of this compound an energy intensive and costly process. Direct photosynthetic production of limonene through
cyanobacteria is particularly attractive, due to their high photosynthetic rates, ease of genetic modification, and simple growth
requirements.
This research focuses on a direct photons-to-product approach in limonene production by metabolically engineering a
cyanobacterium as cellular factory to over-produce and secrete valuable compounds using CO2, H2O, and sunlight. As a proof of
concept, we have engineered the filamentous, nitrogen-fixing cyanobacterium Anabaena sp. PCC 7120 to synthesize and secrete
limonene by transferring-in a plant limonene synthase gene. Our data revealed that limonene produced by the engineered
cyanobacterium was secreted across the cell membrane and volatilized into the headspace, allowing for easy separation of the
target compound from the culture biomass. Furthermore, a 3-fold increase in limonene production was achieved by creating a
synthetic operon coding three rate-limiting enzymes of MEP pathway to divert the carbon flux from the Calvin cycle into the
limonene synthesis. We envision that the platform of using N2-fixing cyanobacteria as a cellular factory, CO2 and N2 as sustainable
inputs can be applicable for the production of a wide range of pharmaceutical chemicals that benefit for human health.
47.
Name and Title of Presenter: Kennedy Mdaki
Co-Authors: Michelle Baack and Tricia Larsen
Organization/Department: Children’s Health
Abstract Title: Age-related Changes in Bioenergetic Profiles of Weaning (3 weeks old) and Young Adult (10 weeks old) Rat
Cardiomyocytes
Background: The heart must continuously recycle its ATP pool to maintain uninterrupted contractile function. Mitochondrial fatty
acid oxidation (FAO) is the most efficient source of energy but consumes oxygen; glycolysis provides less ATP per molecule but does
not require oxygen. Emerging evidence suggests that mitochondrial dysfunction plays a pivotal role in the pathophysiology of heart
disease.
Objective: To understand how fuel metabolism affects cardiac health throughout life, this study characterized normal bioenergetic
profiles of cardiomyocytes (CMs) at various developmental stages.
Methods: Using Seahorse real-time extracellular flux analyzer, mitochondrial and glycolytic stress tests were performed on isolated
rat primary CMs at newborn (NB1), weaning (3WK) and adult (10WK) time-points. Seeding density, drug concentrations (oligomycin,
FCCP, Antimycin A, Rotenone), and substrate conditions (glucose, pyruvate, and palmitate) were optimized at each time-point.
Results: NB1 CMs have a glycolytic preference and limited ability for fatty acid utilization compared to older CMs. Over the course of
development, CMs have a decreased glycolytic capacity. Fatty acid oxidation capacity increases from NB1 to adult time-points.
Conclusions: A substrate switch from glycolysis to fatty acid oxidation occurs during normal CM maturation. This switch is consistent
with a physiologic transition from the relatively hypoxic environment in utero to the highly efficient metabolism required by the
adult heart even during fasting.
In summary, this study defines normal cardiomyocyte bioenergetics from birth to adulthood and sets the groundwork to understand
metabolic reprogramming implicated in the developmental origins of adulthood cardiac disease.
48.
Name and Title of Presenter: Mohammed Alqahtani
Co-Authors: Dr. Omathanu Perumal
Organization/Department: Pharmaceutical Sciences
Abstract Title: Novel Core-Shell Protein Nanoparticles for Oral Drug Delivery
Due to IP reasons, please contact the author for the abstract.
49.
Name and Title of Presenter: Boris Shmagin, Adjunct Professor
Co-Authors:
Organization/Department: College of Agriculture and Biological Sciences
Abstract Title: Modeling the Nature (natural object/process): System Analysis to Obtaining the Knowledge and its Uncertainty
The main properties of a human mind in pattern recognition are the storage and reuse of information. Science as a social
phenomenon of human evolution allows one to formalize this process and create procedural culture, which includes media and tools
for records, storage, and the communication of information obtained during this process. Modes are used as tools to discover,
describe, and then represent patterns, and the modeling plays a key role in communicating every one of those steps. The poster
presents key topics in the ontology of modeling a natural object/process. To formalize the process of modeling patterns, one specific
system (specific for the field of knowledge), which might be depicted in most general view as Researcher – Object (Process) – Data –
Model – Results – User (Researcher), has to be considered as a structure in the interconnections of all components. To obtain and
then communicate the results of patterns recognition science uses specific coordinates in a variety of time and space scales.
Scientific knowledge is based on procedurally obtained information and has to be considered on an individual and professional
community level; those are also two kinds of knowledge without fully definite interactions; however, the conscious operation
(manipulation) of knowledge is available only with the community one. The first source of an uncertainty for modeling has to be
defined by system approach in a context of the human-object/process interaction. The media in use (scientific language) is the next
source of uncertainty (natural language combined with math logic; the first one is probabilistically structured by its origin and the
second is restricted by Gödel's incompleteness theorem). Communication in all uses brings its own sources of uncertainty. The
consideration of knowledge and uncertainty in application to the modeling of a natural object/process places the modeling in a
theoretical perspective, and creates the most general framework for initial and resulting stages of research, database development
and communication of results.
50.
Name and Title of Presenter: Maryam Salehi
Co-Authors: Alexei Y Savinov, Ilian Radichev, Jacob Ellefson
Organization/Department: Sanford Research/Children’s Department
Abstract Title: Investigating the Role of Vista Expressing Cells in the Context of Type 1 Diabetes
Type 1 Diabetes (T1D) is an early age chronic autoimmune disease for which a permanent cure is still not available. T1D is characterized
by the destruction of pancreatic beta cells by autoreactive T cells that escape deletion during negative selection in the thymus and are
released into the periphery. In the periphery, the immune system controls the immune responses toward different antigens by various
mechanisms including expression of stimulatory and inhibitory molecules. A major group of these molecules is the immunoglobulin
superfamily which includes B7 family ligands and receptors.
A new member of the B7 family, V-domain Ig Suppressor of T cell Activation (VISTA) is a novel inhibitory molecule which suppresses T
cell-mediated immune response. The regulatory function of VISTA molecule in an experimental autoimmune encephalomyelitis model
suggests a possible role of VISTA in T cell-mediated autoimmune diseases such as T1D.
Using immunofluorescent staining, we investigated the expression pattern of VISTA molecule in various cell types and tissues. We
found a difference in VISTA levels in the thymocytes of diabetic-prone vs. control mice. This finding was also confirmed by flow
cytometry analysis. Moreover, we identified a subset of high VISTA expressing endothelial cells in the secondary lymphoid tissues. To
investigate further this result we are applying Laser Capture Microdissection (LMD) technique which will allow us to dissect out VISTA
positive endothelial cells from lymphoid tissues and identify this subset of endothelial cells by qPCR.
51.
Name and Title of Presenter: Christopher Solis-Ocampo, Graduate Research Assistant
Co-Authors: Maria E. Moutsoglou, Gi-Ho Kim, and John M. Robinson
Organization/Department: Chemistry & Biochemistry
Abstract Title: Direct visualization of Cooperative Binding of Troponin-Tropomyosin to F-actin
In cardiac muscle, troponin (Tn) and tropomyosin (Tm) on f-actin (Ac) provide Ca2+-dependent regulation of force development by
myosin motors. Ca2+ activation is a highly cooperative process thought to be due to cooperative structural interactions among
Tn,Tn, and Ac. Previous measurements have quantified cooperative binding associations through indirect methods coupled with
modeling. We sought to characterize cooperative interactions within regulated actin (rAc) by directly observing individual actin
filaments. Tn,Tm, and Ac were labeled with AF 546,ATTO 655, and phalloidin AF488, respectively. rAc was reconstituted at different
concentrations under constant stoichiometry (1Tn:1Tm:1Ac7).The samples were diluted, immediately deposited on aminosilanized
glass coverslips, and imaged in an epifluorescence microscope. From the co- localization of the three dye colors, we observe that the
all-or-nothing binding of Tn-Tm to actin is not caused by cooperativity but by a actin filament size-dependence; Tn-Tm not bound to
actin are dissociated from each other. Filaments had varying lengths, and Tn-Tm bound preferentially longer filaments. Regulated
filaments were on average 4.75 times longer than unregulated filaments in presence and absence of Ca2+.The dissociation constant
for Tn-Tm is not affected under Mg2+- and Ca2+-saturated conditions. Our results suggest that surface-deposited rAc, combined
with single particle analysis and particle sorting, is a promising method for examining the structure of Tn as a member of rAc.
52.
Name and Title of Presenter: Kristin L. Bruns, Instructor, Clinical Mental Health Counseling Track Coordinator
Co-Authors:
Organization/Department: Counseling and Human Development
Abstract Title: Protective Factors as Predictors of Suicide Risk
The purpose of this study was to examine whether or not protective factors could predict levels of suicide risk among college
students. Additionally, this study aimed to examine if there were differences in protective factors between groups based on
demographic characteristics, such as: gender, race/ethnicity, sexual orientation, self-reported cumulative GPA, and undergraduate
versus graduate student status. A total of 555 college students (both undergraduate and graduate) completed an anonymous, online
survey. The survey included a variety of demographic information used to measure group differences and 3 inventories which
measured suicidal ideation and behavior, internal protective factors, external protective factors, emotional stability, parent support,
peer support, and significant other support. The analysis of the data resulted in significant findings for each primary research
question. For the first research question, peer support and emotional stability were shown to be statistically significant in predicting
a person’s level of suicide risk; higher levels of emotional stability and peer support predicted lower levels of suicide risk. Regarding
the second research question, group differences were found for: gender, sexual orientation, and GPA. For gender, females scored
significantly higher on scales measuring external protective factors, significant other support, peer support, internal protective
factors, and emotional stability. For sexual orientation, heterosexual participants reported higher levels of family support. For GPA,
significant differences were found on the subscale measuring emotional stability; participants who self-identified in the lowest
category of GPA also reported low levels of emotional stability. No significant differences were found between undergraduate and
graduate students, or race/ethnicity groupings.
53.
Name and Title of Presenter: Colette Free, Research Associate
Co-Authors: Ansarullah, Jenica Christopherson, Quanhai Chen, Regan Roat, Chengyang Liu, Ali Naji, Alex Rabinovitch, and
Zhiguang Guo
Organization/Department: Sanford Research/USD, The Sanford Project, Children Health Research Center
Abstract Title: GPR119 Activation Improves Human β-cell Function and Stimulates Human β-cell Replication and Neogenesis in
Humanized Mice
G protein-coupled receptor 119 (GPR119) is present in pancreatic insulin-producing β cells and enteroendocrine L cells. Activating
GPR119 can stimulate mouse β cell regeneration in vivo. In this study, we investigated whether PSN632408, a small molecular
GPR119 agonist, can stimulate human β cell regeneration in vivo in a humanized mouse model. Human islets isolated from young
pancreatic donors were transplanted under the left kidney capsule of immunodeficient NOD.scid mice with streptozotocin (STZ)induced diabetes. The mice were treated daily with PSN632408 (10 mg/kg) or vehicle by gavage and BrdU intraperitoneally. Human
islet graft function in the mice was evaluated by non-fasting glucose levels, oral glucose tolerance, and nephrectomy. Graft was
collected for immunostaining for insulin, glucagon and BrdU or Ki67 to evaluate α and β-cell replication. Insulin and CK19
immunostaining was performed to evaluate β-cell neogenesis. Four weeks after human islet transplantation, 70% of PSN632408treated mice achieved normoglycaemia compared to 23% of vehicle-treated mice (P<0.002). Oral glucose tolerance was significantly
improved in the PSN632408-treated mice. PSN632408-treated mice had an increase in blood glucose (168.0±6.7 mg/dL) that was
significantly less than in vehicle-treated mice (231.5±10.3 mg/dL) at 15 minutes post glucose challenge (P<0.002). Also, blood
glucose levels in PSN632408-treated-mice were significantly lower than in vehicle-treated mice at 30 and 60 minutes post glucose
load (P<0.001). PSN632408 treatment significantly increased both human α (P<0.02) and β-cell (P<0.001) areas in islet grafts and
stimulated α (P<0.001) and β-cell (P<0.001) replication. In addition, β-cell neogenesis was induced from pancreatic duct cells in the
islet grafts (P<0.001). Our studies found that activating GPR119 improves β-cell function and increases β-cell mass by stimulating βcell replication and neogenesis. Therefore, GPR119 agonists could qualify as therapeutic agents for patients with type 1diabetes.
54.
Name and Title of Presenter: Mr. Metab Alharbi
Co-Authors: Chandrasekher, Gudiseva, Chandradhar Dwivedi
Organization/Department Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings
Abstract Title: Suppression of Growth Factor Mediated Signaling and its Impact on Human Ocular Retinoblastoma Cell Survival.
Retinoblastoma (Rb) is the most common vision impairing malignancy affecting 1 in 18,000 children between ages 1-5. Rb tumor
develops due to mutation in the tumor suppressor gene Rb1 that controls the cell division through its product retinoblastoma
protein (pRb). Current research indicates that in addition to Rb1 gene mutation, other cellular factors may contribute to tumor
growth and treatment approaches that target such factors would provide more opportunities for the management of the disease.
Tyrosine kinase receptors (RTKs) play a critical role in the development of cancer in many tissues. This is because the downstream
signaling of these receptors play important part in triggering intracellular pathways involved in cell proliferation as well as survival
that cause tumor cell growth. The status of RTK activation effect on retinoblastoma tumor growth has not been thoroughly
investigated. In this study we have evaluated the response of Rb tumor cells to the ligands of different RTKs. Y79 human Rb tumor
cells were treated with insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), hepatocyte growth factor
(HGF), keratinocyte growth factor (KGF), fibroblast growth factor-2 (FGF-2), epidermal growth factor (EGF) and platelet-derived
growth factor (PDGF-AA or PDGF-Ab) for short (0-20 min) and long (0-24 hours) duration. Western immunoblotting was employed
for the analysis of different cellular responses. Significant increase in protein tyrosine phosphorylation an indication of stimulation of
RTK was observed within 10-15 minutes after treatment with IGF-1, VEGF and PDGF. Further, we found the activation of Erk and Akt
signaling in the presence of IGF-1, VEGF, PDGF, EGF and FGF between 5-15 min but not after 24 hours. Suppression of the receptor
tyrosine kinase activation caused a reduction in the levels of cell cycle proteins Cyclin A1, B1 and CDK4 and more than 50% decrease
in the viability of Rb cells within 24 hours. These results suggest that Rb1 gene mutation may not significantly override the influence
of RTK signaling in promoting Rb tumor growth and employment of RTK signaling targeting chemotherapeutic drugs in combination
with currently used DNA synthesis inhibitors such as topotecan, and vincristine may be worthy of consideration for clinical usage.
55.
Name and Title of Presenter: Francisca Essel (Mrs)
Co-Authors: Tao Lin, Suvobrata Chakravarty
Organization/Department: Department of Chemistry/Biochemistry
Abstract Title: Sequence Signature for Recognition of Histone H3 Arginine (R2), KDM5B-PHD1, a Case Study
We show that in the recognition of unmodified histone H3 by the first PHD finger of hKDM5B, the H3K4 specific demethylase, H3R2
and H3K4 respectively contribute maximally (hot spot) and negligibly towards the overall binding energy. This PHD finger is thus a
H3R2 reader; contrary to what generally would be expected to be a reader of the ‘product’ (H3K4) of the demethylating enzyme.
Methylation of H3K4, however, aborts peptide binding and this behavior is distinct from those of other known H3R2 readers. Unique
recognition features learned here will better guide in detailing the mechanism of action of KDM5B.
56.
Name and Title of Presenter: Padu Krishnan, Ph.D., Professor
Co-Authors: Jigyasha Mishra
Organization/Department: Health and Nutritional Sciences
Abstract Title: Novel Food Technology Techniques for the Production of Healthy Whole Wheat Products
Wheat bran is a byproduct of wheat milling and it represents a good source of fiber, minerals, vitamin B6, thiamine, folate and
vitamin E and some phytochemicals. The flavor and color of wheat bran can be improved using Supercritical Fluid Extraction (SFE)
and the improved bran can be incorporated back to all-purpose flour to get the same beneficial effect obtained from whole wheat
flour. There are many extraction techniques but SFE has gained wider attention due to its advantages of high solvent power, nontoxicity, and non-flammability. CO2 is probably the most widely used supercritical fluid. A liquid or a gas becomes supercritical if you
increase the temperature and the pressure above its critical point and for CO2 it occurs at temperature of 310C and pressure of 72
bar.
The reincorporation of bran into patent flour as part of whole grain food will improve nutrition and health as bran contains health
promoting bioactive constituents. However, taste and appearance of such products will be reduced.
This study attempts to evaluate CO2 treated bran from a SD white wheat variety development for the Asian and export market. Food
products such as Asian noodles and bread products have greater acceptance when they are not bitter.
57.
Name and Title of Presenter: Daein Kim, Ph.D.
Co-Authors: Dae In Kima, Birendra KCa, Wenhong Zhub, Khatereh Motamedchabokib, Valérie Doyec, Kyle J. Rouxa,d
Organization/Department: a: Children’s Health Research Center, Sanford Research; b: Sanford-Burnham Medical Research
Institute; c: cInstitut Jacques Monod, UMR 7592 CNRS, Université Paris Diderot; d: Department of Pediatrics, Sanford School of
Medicine, University of South Dakota
Abstract Title: Probing the Nuclear Pore Complex with BioID
Proximity-dependent biotinylation (BioID) is a method to identify protein associations that occur in living cells. Fusion of a
promiscuous biotin ligase to a bait protein for expression in live cells enables covalent biotin labeling, selective isolation, and
identification of proteins proximate to the bait. We have used BioID to study the human nuclear pore complex (NPC), one of the
largest macromolecular assemblies in eukaryotes. BioID was applied to constituents of the Nup107-160 complex and the Nup93
complex, two conserved NPC subcomplexes. A strikingly different set of NPC constituents was detected depending on the position of
the BioID-fusion proteins within the NPC. By applying BioID to multiple constituents located throughout the extremely stable
Nup107-160 subcomplex we have refined our understanding of this highly conserved subcomplex, in part by demonstrating a direct
interaction of Nup85 with Nup43. And by using the extremely stable Nup107-160 structure as a molecular ruler we have defined the
practical labeling radius of BioID, thus enabling a more rational use of the method and interpretation of results. These studies
further our understanding of human NPC organization and demonstrate that BioID is a valuable tool to explore the constituency and
organization of large protein assemblies in living cells.
58.
Name and Title of Presenter:
Co-Authors:
1
Brad Bowser, PhD
2
Cathleen Brown, PhD, ATC, 2Lesley White, PhD, 2Kathy Simpson, PhD
Organization/Department:
1
South Dakota State University/Health and Nutritional Science, 2University of Georgia/Kinesiology
Abstract Title: Loading Asymmetry During the Sit to Stand in People with Multiple Sclerosis
Mediolateral (ML) postural instability for people with multiple sclerosis (MS) is largely influenced by interlimb loading asymmetries.
During quiet standing people with MS are favoring their stronger limb by shifting their center of pressure towards the stronger leg
side while subsequently increasing the vertical ground reaction forces (GRF) to that leg. While ML postural stability and loading
asymmetries have been examined during quiet standing, no research has examined these two variables during a dynamic
movement. PURPOSE: To compare ML stability and loading asymmetry between MS and non-MS persons during a sit to stand (STS)
movement. METHODS: Participants were divided into three groups: an MS group with leg weakness, less than 1.4 BW on 1RM leg
press (MS-LW; n = 10; 49 ± 10 yr), an MS group with comparable strength to controls, greater than 1.4 BW on 1RM leg press (MS-CS;
n = 11; 40 ± 12 yr), and a non-MS control group (CON; n = 12; 43 ± 12 yr). GRFs were captured bilaterally during five STS trials.
ANOVAs followed by post-hoc testing (α = 0.05) were used to determine group differences for variables of interest. RESULTS:
ANOVAs revealed significant group differences for 1RM leg press, relative loading asymmetry (RLA), and ML stability (p<0.03). Posthoc comparisons indicate lower 1RM leg press and increased ML instability for MS-LW compared to both CON and MS-CS (p<0.03,
d>1.03). RLA was also higher in MS-LW compared to CON (p=0.036, d=1.12). CONCLUSION: During the STS persons with MS who
have leg weakness display greater ML instability that is likely due to greater vertical loading occurring on the dominant/stronger
limb. MS training protocols that emphasize both strength and symmetry training may be needed in order to improve ML stability
during dynamic movements such as the STS.
59.
Name and Title of Presenter: Mary E. Minton, PhD, RN, CNS; Associate Academic Dean for Graduate Nursing
Co-Authors: Amanda Mitchell, MA,; Elizabeth Nagelhout, BS; Jennifer Kerkvliet, MA, LPC ;_Nancy Fahrenwald, PhD, RN,
APHN-BC , FAAN_______
Organization/Department: SDSU College of Nursing
Abstract Title: An Assessment of Palliative and End of Life Care Services in South Dakota
Geographical disparities play a significant role in palliative and end of life care access. This study assessed availability of palliative
and end of life (hospice) care in South Dakota (SD). The Advance Care Planning (ACP) model guided this SD survey assessment of
healthcare facilities regarding: points of contact for palliative care, hospice services, and advance directives; healthcare providers
with specialized training in palliative and hospice care; and a facility‐based process for advance directives and advance care planning.
Of 668 healthcare eligible facilities, 455 facilities participated (response rate of 68%). Over one‐half of responding facilities had no
specific person as point of contact for palliative care, end of life services, and advance directives. Across facilities types, nursing
homes reported the highest percentage of available points of contact for each of the three services. Of participating facilities, 80%
reported no staff members who had completed training in palliative care, and 73% identified this same lack of training in end of life
care. Palliative care training was most commonly reported in hospice/home health facilities (45%). Despite a lack of a specific
contact point, nearly 75% of facilities reported having a process in place for advance directives and slightly over one‐half (53%)
reported having a process in place for advance care planning. The availability of a healthcare and allied healthcare workforce with
specialized training in palliative and end of life care is a clear need in SD. Engaging the three largest SD health systems as partners in
advance care planning discussions with the intent of establishing patient care model standards by 2015 is indicated. Input from
community groups in the advance care planning process to aid in the establishment of patient care expectations is needed as is
developing accessible end of life and palliative care training and education for rural and frontier healthcare providers.
60.
Name and Title of Presenter: Jordan N. Sheets, USD Graduate Student
Co-Authors: Marcin Iwanicki, Joyce Liu, Ronny Drapkin and Kristi A. Egland
Organization/Department: Sanford Research / Cancer Biology Research Center
Abstract Title: SUSD2 inhibits spheroids from breaching the mesothelium: A mechanism for increased longevity of patients with
SUSD2-expressing high-grade ovarian serous carcinoma
Epithelial ovarian cancer (EOC) remains the leading cause of death in gynecological malignancy. EOC cells exfoliate from the fallopian
tube or ovary, disseminate within the peritoneal cavity as free-floating single cells or spheroids and invade mesothelium-covered
organs. Thus, it is important to identify the factors that contribute to metastasis and invasion, including adhesion to the
mesothelium. Sushi Domain Containing 2 (SUSD2) encodes a type I transmembrane protein that localizes to the cell surface and
contains several functional domains inherent to adhesion molecules. To begin to define the role of SUSD2 in EOC, an
immunohistochemical analysis was performed on ovarian tissue samples from patients using an anti-SUSD2 antibody. Weak to no
staining was observed in normal epithelial cells. In contrast, various intensities of positive staining for SUSD2 were observed in
several subtypes of EOC, with increased intensity staining in high-grade serous ovarian carcinoma (HGSOC) samples. A HGSOC tissue
microarray containing samples from 128 patients was stained with an anti-SUSD2 antibody. A pathologist scored the intensity of
SUSD2 staining, and results indicated a significant separation for patients with weak SUSD2 staining, median survival 31.7 months,
versus patients with strong SUSD2 staining, median survival 49.1 months (p-value = 0.0083). This data suggests that low SUSD2 levels
in HGSOC tumors are associated with a poorer patient prognosis. Stable SUSD2 knock-down (KD) and non-targeting (NT) OVCAR3 cell
lines were generated. Boyden chamber and wound healing assays demonstrated that OVCAR3 SUSD2-KD cells migrated at
significantly higher rates than the OVCAR3-NT cells, suggesting that the presence of SUSD2 in OVCAR3 cells inhibits cell migration. In
addition, attenuation of SUSD2 levels in OVCAR3 cells significantly increased mesothelial clearance. Altogether, our findings indicate
that SUSD2 negatively impacts the ability of OVCAR3 cells to breach the mesothelium, which defines a mechanism for the increased
longevity of patients with SUSD2-expressing HGSOC.
61.
Name and Title of Presenter: SOMSHUVRA BHATTACHARYA
Co-Authors: CAMILLE BREULEUX, GUDISEVA CHANDRASEKHER
Organization/Department: PHARMACEUTICAL SCIENCES
Abstract Title: Cell regenerating potential of Cornea tissue derived Biomaterials (CDB)
Cornea serves as the protective window for the eye. It is accountable for refractive power of the eye and hence vision. The epithelial
cell layer on the corneal surface along with the stroma is responsible for this. In most clinical cases, recurrent epithelial erosions is a
problem. Any delay to treat these problems can lead to interference in the refractive function of the cornea. Current treatments
only aim to reduce pain and limit infections but not tissue repair or cell regeneration. Hence it is vital to develop an innovative
treatment approach for the cure of persistent epithelial damages by aiming to target tissue repair and cell regeneration.
Abnormality in the epithelial basement membrane structure is accountable for the loosening of multilayer epithelium and/or poor
adherence of the newly regenerated epithelial cells to this membrane. These are the major issues associated with the impaired
healing. Recent studies have shown that the corneal stroma generates signals which influence the growth of the epithelium. Stromal
protease activity generates modified collagen and laminin from the stromal matrix which forms the temporary basement membrane
and in turn helps to promote migration and adhesion of the regenerating epithelial cells. Thus, in order to develop a treatment to
cure these damages exploring the utility of stromal tissue materials for epithelial wound repair is important. In this study we have
isolated biomaterials from the stroma and evaluated their ability to promote regeneration of epithelial cells by investigating their
ability to activate cell regeneration signaling cascades intrinsic to the epithelium and also their capability to express cell cycle
proteins. The results from these studies promised translational potential of our approach and we prepared “Gel-Cell”s to further
establish our findings and confirm the possible corneal epithelial cell growth promoting potential of the materials isolated from its
stroma. This promises to open up new avenues to design approaches for the clinical management of recurrent corneal problems.
62.
Name and Title of Presenter: Robert Juenemann
Co-Authors: Sailendra N. Nichenametla1, Robert M. Juenemann1, Lee A. Weidauer2, Howard E. Wey3, Tianna M. Beare2, Bonny L.
Specker2 and Moul Dey1*
Organization/Department:
2
1
Department of Health and Nutritional Sciences, South Dakota State University, Brookings, SD, USA
Ethel Austin Martin Program in Human Nutrition, South Dakota State University, Brookings, SD, USA, 3 College of Nursing, South
Dakota State University, Brookings, SD, USA
Abstract Title: Prebiotic intervention improves dyslipidemia and body composition
A metabolic health crisis is eminent as cardiovascular diseases remain the leading cause of mortality in the United States. Effects of
resistant starch type-4 (RS4), a prebiotic fiber, in comprehensive management of metabolic syndrome (MetS) remain unknown. In a
double-blind, placebo-controlled, cluster crossover intervention (n=86, age≥18, 2 12-week interventions), individuals were classified
as having MetS (With-MetS) or not having MetS (No-MetS) following IDF criteria. This study examined the impact of a blinded
exchange of RS4-enriched flour (30% v/v) with regular/control flour (CF) diet on the comorbidities of MetS. RS4 consumption
compared with CF resulted in 7.2% (p=0.002) lower mean total cholesterol (TC), 5.5% (p=0.04) lower non-HDL, and a 12.8%
(p<0.001) lower HDL cholesterol in the With-MetS group. Individuals in the No-MetS group had a 2.6% (p=0.02) smaller waist
circumference and 1.5% (p=0.03) lower percent body fat following RS4 intervention compared to CF. A small but significant 1%
increase in fat-free mass also was observed in all participants combined (p=0.02). No significant effect of RS4 was observed for
glycemic variables and blood pressure. Our results show that RS4 consumption improved dyslipidemia and body composition.
Bacterial 16S rRNA V4 gene sequencing of the gut microbiome detected 5,949 unique operational taxonomic units in 80 samples
from 20 individuals with MetS. Functional and adaptable prebiotic food ingredients such as RS4 could be an effective strategy for
public metabolic and cardiovascular health promotion.
63.
Name and Title of Presenter: Jamie Jensen, MS
Co-Authors: Jessica D. Hanson, PhD
Organization/Department: Sanford Research/CHOPR
Abstract Title: Use of Technology to Collect Data on Risk Behaviors with College Women
Objective: To examine if electronic diaries produced more consistent output for self-reported alcohol consumption and birth control
utilization data in college-age women when compared to traditional paper diaries. Participants: A total of 100 undergraduate college
women from an Upper Midwest university were asked to track daily alcohol consumption and birth control use for one month. Data
collection spanned from August through September of 2013. Methods: Participants were randomly assigned to complete either the
electronic diary or the paper diary. Results: Nearly all electronic diaries were completed in full and were far more descriptive in the
open-ended questions as opposed to the returned paper diaries, which contained many blank and/or one-word responses.
Conclusion: Overall, the electronic diaries provided more thorough qualitative information than paper diaries, as well as more
completed data responses to questions on drinking alcohol, sexual activity, and use of birth control.
64.
Name and Title of Presenter: Lee Weidauer, Post-Doctoral Research Associate
Co-Authors: Teresa Binkley, Tianna Beare, Maggie Minett, Lacey McCormack, Bonny Specker
Organization/Department: Ethel Austin Martin Program in Human Nutrition
Abstract Title: Gender Differences in Risk Factors for Falls and Fractures in Rural & Non-Rural Populations Aged 20-66 Years
Falls and fractures are a major public health concern that have an economic impact of over 19 billion dollars each year. This study
aimed to determine if gender and population differences existed in the incidence rates for falls and fractures. Data from 1,256 (718
female, 538 male) participants of the South Dakota Rural Bone Health Prospective Cohort Study including (n=349), non-rural (n=335)
and Hutterite (n=572) individuals was used. Health histories, physical activity recall, anthropometric measurements, diet records,
and DXA measurements of body composition were obtained from participants every 18 months for 7.5 years. Falls and fractures
were self-reported and fractures were confirmed through medical record review. Fall rates were not different between males and
females aged <40 years (10.6/1000 p-y [95% CI: 8.3-12.8] and 9.9/100 p-y [8.1-11.7] respectively) or males and females >40 years
(16.1/100 p-y [13.6-18.6] and 12.7/100 p-y [11.0-14.5]); however, older males did fall at a significantly higher rate than younger
males (P=0.008). Incidence of fractures were not different between males and females <40 years old were 26.8 (15.3-38.2) and 8.9
(4.8-13.0) fractures/1000 p-y, respectively. In individuals >40 years males had a higher incidence of fractures than females (39.1
[26.8-51.3] vs. 20.9 [15.5-26.2]) fractures/1000 p-y (P=0.01). Rural non-Hutterite males (reference) had greater odds of falling
compared to rural males (OR=1.59, 95%CI=1.01-2.50). Among females, the non-rural population (reference) had a greater risk of
falling than rural populations (OR=0.67, 0.48-0.96). No population differences were observed for fracture incidence.
While no
gender differences exist for rates of falls and fractures in these groups, the population differences suggest that other risk factors
may be affecting risk. Future studies focusing on gender- and population-specific risk factors for falls and fractures is necessary to
develop prevention strategies tailored to specific individuals rather than populations as a whole.
65.
Name and Title of Presenter: Jane Christopher-Hennings DVM, MS
Co-Authors: A. Singrey, S. Lawson, F. Okda, X. Liu, T. Clement, J. Nelson, J. Christopher-Hennings and E.A. Nelson
Organization/Department: Veterinary & Biomedical Sciences Department
Abstract Title: Development and diagnostic application of monoclonal antibodies to porcine epidemic diarrhea virus (PEDV)
The mAbs and related reagents produced in this project should be of substantial value in the detection of PEDV antigen in a variety
of applications including: early verification of virus isolation attempts and in virus titrations; immunohistochemistry staining of fixed
tissues and fluorescent antibody staining of fresh tissues; development of field-based antigen capture assays such as lateral flow
devices; and ELISA applications (competitive ELISA and antigen capture). They are also a key component of the fluorescent focus
neutralization (FFN) assays for assessment of neutralizing antibodies produced following PEDV exposure. Evaluation of neutralizing
antibody responses may provide insight into protective immunity. This assay is currently being used as a tool in efforts to understand
duration of immunity and identify the most effective feedback and management strategies.
66.
Name and Title of Presenter: Mr. Satya Sadhu
Co-Authors: Ranjith Kumar Averineni, Teresa M Seefeldt, Jiashu Xie, Hemachand Tummala, Xiangming Guan
Organization/Department Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings
Abstract Title: Anti-metastatic effects of glutathione disulfide liposome
Cancer metastasis is associated with more than 90% of cancer mortality, hence considered the terminal stage for the patient.
Despite extensive research efforts, no effective anti-metastatic drugs are available. Glutathione disulfide (GSSG) is an endogenous
and cell membrane impermeable peptide. We have developed a cationic liposome formulation that effectively delivers GSSG into
cells leading to a 20 fold increase in intracellular GSSG. Through the use of B16F10 murine melanoma cells, we found that the GSSG
liposomes completely prevented key steps involved in cancer metastasis, namely cell detachment and migration. GSSG liposomes
also significantly inhibited cell invasion in vitro. Through a well-established murine melanoma metastasis model with C57BL6 mice
and B16F10 cells, it was shown that GSSG liposomes completely prevented pulmonary metastasis. The results reveal GSSG liposomes
could be very effective in the treatment of metastatic cancer.
67.
Name and Title of Presenter: Seung Yon Koh
Co-Authors: Jeremy Morgan, Helen Magee, Ryan Otoole, Titan Glasford, and Jill M. Weimer
Organization/Department: Children’s Health Research Center
Abstract Title: Role of CLN6 in Cortex Development: Neurite outgrowth and Vesicular trafficking
The neuronal ceroid lipofuscinoses (NCLs) are common fatal neurodegenerative diseases in childhood, clinically characterized by
seizures, vision impairment, motor dysfunction, and premature death. Mutations in CLN6 result in variant late infantile NCL
(vLINCL), with age of onset between 2 and 6 years with death occurring by the third decade of life, as well as type A adult onset
forms of NCL, or Kuf’s disease. CLN6 is an ER-membrane associated protein with unknown function that has been shown to complex
with CRMP2. CRMP2 is a cytosolic phosphoprotein which functions to specify axons/dendrites and regulate cargo transport through
an array of additional binding proteins. Disruption in CRMP2 signaling has been implicated in a host of neurological disorders,
including NCLs. CRMP-2 and CLN6 both interact with kinesin light chain 4 (KLC4). LKE which binds to CRMP2, stabilizes and promotes
neurite outgrowth and recovers the number of neurites in primary culture. vLINCL mouse primary cultures showed lower numbers
of ER vesicles in the processes. We hypothesize that this trimeric CLN6/CRMP-2/KLC4 (CCK) complex regulates proper trafficking
and/or delivery of vital cargo to the distal end of the growing axon and CLN6 serves as a “molecular tag” on ER-vesicles to specifically
segregate cargo to dendrites or axons. We are performing proteomic analysis to investigate the contents of CLN6 tagged ER vesicles,
as well as knocking down each component in this trimeric CCK complex to investigate their roles in vesicular trafficking.