Posted by: kelsijo97 | March 27, 2012

March 2012

Armour, C., Elhai, J. D., Richardson, D., Ractliffe, Kendra, Wang, L., and Elklit, A. “Assessing a Five Factor Model of Ptsd: Is Dysphoric Arousal a Unique Ptsd Construct Showing Differential Relationships with Anxiety and Depression?” Journal of Anxiety Disorders 26, no. 2 (2012): 368-76.

Posttraumatic stress disorder’s (PTSD) latent structure has been widely debated. To date, two four-factor models (Numbing and Dysphoria) have received the majority of factor analytic support. Recently, Elhai et al. (2011) proposed and supported a revised (five-factor) Dysphoric Arousal model. Data were gathered from two separate samples; War veterans and Primary Care medical patients. The three models were compared and the resultant factors of the Dysphoric Arousal model were validated against external constructs of depression and anxiety. The Dysphoric Arousal model provided significantly better fit than the Numbing and Dysphoria models across both samples. When differentiating between factors, the current results support the idea that Dysphoric Arousal can be differentiated from Anxious Arousal but not from Emotional Numbing when correlated with depression. In conclusion, the Dysphoria model may be a more parsimonious representation of PTSD’s latent structure in these trauma populations despite superior fit of the Dysphoric Arousal model. (C) 2011 Elsevier Ltd. All rights reserved.

Psychology Department.


Berg, Patti, Becker, Tiffany, Martian, Andrew, Primrose, Kimberly D., and Wingen, Julie. “Motor Control Outcomes Following Nintendo Wii Use by a Child with Down Syndrome.” Pediatric Physical Therapy 24, no. 1 (2012): 78-84.

Purpose: The purpose of this work was to examine motor outcomes following an 8-week intervention period of family-supported Nintendo Wii use by a child with a diagnosis of Down syndrome (DS). Summary of Key Points: A 12-year-old child with a diagnosis of DS and with limited Wii exposure was asked to play Wii games in the home 4 times each week for 20 minutes each session for 8 weeks. Family members were encouraged to participate. The participant chose what games to play and selected 4 different games. Repeatedly practicing the skills involved in these games resulted in improvements in the child’s postural stability, limits of stability, and Bruininks-Oseretsky Test of Motor Proficiency, 2nd edition balance, upper-limb coordination, manual dexterity, and running speed and agility standard scores. Conclusions: Wii game use by a child with DS may elicit improvements in highly practiced motor skills and postural control. (Pediatr Phys Ther 2012;24:78-84)

School of Health Sciences.


Cwach, Kevin T., Sandbulte, Heather R., Klonoski, Joshua M., and Huber, Victor C. “Contribution of Murine Innate Serum Inhibitors toward Interference within Influenza Virus Immune Assays.” Influenza and other respiratory viruses 6, no. 2 (2012): 127-35.

Please cite this paper as: Cwach etal. (2011) Contribution of murine innate serum inhibitors toward interference within influenza virus immune assays. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750-2659.2011.00283.x. Background Prior to detection of an antibody response toward influenza viruses using the hemagglutination inhibition assay (HAI), sera are routinely treated to inactivate innate inhibitors using both heat inactivation (56degreesC) and recombinant neuraminidase [receptor-destroying enzyme (RDE)]. Objectives We revisited the contributions of innate serum inhibitors toward interference with influenza viruses in immune assays, using murine sera, with emphasis on the interactions with influenza A viruses of the H3N2 subtype. Methods We used individual serum treatments: 56degreesC alone, RDE alone, or RDE+56degreesC, to treat sera prior to evaluation within HAI, microneutralization, and macrophage uptake assays. Results Our data demonstrate that inhibitors present within untreated murine sera interfere with the HAI assay in a manner that is different from that seen for the microneutralization assay. Specifically, the gamma class inhibitor alpha(2) -Macroglobulin (A2-M) can inhibit H3N2 viruses within the HAI assay, but not in the microneutralization assay. Based on these findings, we used a macrophage uptake assay to demonstrate that these inhibitors can increase uptake by macrophages when the influenza viruses express an HA from a 1968 H3N2 virus isolate, but not a 1997 H3N2 isolate. Conclusions The practice of treating sera to inactivate innate inhibitors of influenza viruses prior to evaluation within immune assays has allowed us to effectively detect influenza virus-specific antibodies for decades. However, this practice has yielded an under-appreciation for the contribution of innate serum inhibitors toward host immune responses against these viruses, including contributions toward neutralization and macrophage uptake. 2011 Blackwell Publishing Ltd.

Basic Biomedical Sciences, Vermillion Campus.


Deckelbaum, Richard J., Calder, Philip C., Harris, William S., Akoh, Casimir C., Maki, Kevin C., Whelan, Jay, Banz, William J., and Kennedy, Eileen. “Conclusions and Recommendations from the Symposium, Heart Healthy Omega-3s for Food: Stearidonic Acid (Sda) as a Sustainable Choice1-3.” Journal of Nutrition 142, no. 3 (2012): 641S-43S.

Faculty who had presented at the symposium “Heart Healthy Omega-3s (n-3 fatty acids) for Food: Stearidonic Acid (SDA) as a Sustainable Choice” met and agreed upon conclusions and recommendations that could be made on the basis of evidence provided at the symposium. The participants also submitted manuscripts relating to their topics and these are presented in this supplement. These manuscripts were reviewed and also contributed to the conclusions and recommendations presented herein. The three major objectives of the symposium were to: 11 increase understanding of the current and emerging knowledge regarding the health benefits of ln-3) fatty acids (FA) including a focus on stearidonic acid (SDA) and EPA; 21 evaluate the importance of increasing (n-3) FA consumption in the US and the current challenge of doing so via mainstream foods; and 3) consider the health and food application benefits of SDA as a precursor to EPA and a plant-based sustainable source of highly unsaturated (n-3) FA for mainstream foods. Specific areas for future research were defined and included in the summary and conclusions herein. Overall evidence-based conclusions included: the current evidence provides a strong rationale for increasing (n-3) FA intakes in the US and other populations; current consumption of (n-3) FA in most populations is either insufficient or not efficient at providing adequate tissue levels of the long-chain (n-3) FA EPA and DHA; SDA in soybean oil appears to be a cost-effective and sustainable plant-based source that could contribute to reaching recommended levels of (n-3) FA intake, but more research and surveillance is needed; and adding SDA-enriched soybean oil to foods should be considered as a natural fortification approach to improving (n-3) FA status in the US and other populations. References for these conclusions and recommendations can be found in the articles included in the supplement.

Sanford School of Medicine, Sioux Falls Campus.


Ekstrom, Richard A., Osborn, Roy W., Goehner, Heather M., Moen, Adam C., Ommen, Brian M., Mefferd, Michael J., Bergman, Thomas R., Molencamp, Timothy B., and Kelsey, Steven A. “Electromyographic Normalization Procedures for Determining Exercise Intensity of Closed Chain Exercises for Strengthening the Quadriceps Femoris Muscles.” Journal of Strength and Conditioning Research 26, no. 3 (2012): 766-71.

The purpose of this study was to compare the electromyographic (EMG) amplitudes of the quadriceps femoris (QF) muscles during a maximum voluntary isometric contraction (MVIC) to submaximal and maximal dynamic concentric contractions during active exercises. A secondary purpose was to provide information about the type of contraction that may be most appropriate for normalization of EMG data if one wants to determine if a lower extremity closed chain exercise is of sufficient intensity to produce a strengthening response for the QF muscles. Sixty-eight young healthy volunteers (39 female, 29 male) with no lower extremity pain or injury participated in the study. Surface electrodes recorded EMG amplitudes from the vastus medialis obliquus (VMO), rectus femoris (RF), and vastus lateralis (VL) muscles during 5 different isometric and dynamic concentric exercises. The last 27 subjects performed an additional 4 exercises from which a second data set could be analyzed. Maximum isokinetic knee extension and moderate to maximum closed chain exercises activated the QF significantly more than a MVIC. A 40-cm. lateral step-up exercise produced EMG amplitudes of the QF muscles of similar magnitude as the maximum isokinetic knee extension exercises and would be an exercise that could be considered for strengthening the QF muscles. Most published EMG studies of exercises for the QF have been performed by comparing EMG amplitudes during dynamic exercises to a MVIC. This procedure can lead one to overestimate the value of a dynamic exercise for strengthening the QF muscles. We suggest that when studying the efficacy of a dynamic closed chain exercise for strengthening the QF muscles, the exercise be normalized to a dynamic maximum muscle contraction such as that obtained with knee extension during isokinetic testing.

School of Health Sciences


Harris, William S. “Stearidonic Acid-Enhanced Soybean Oil: A Plant-Based Source of (N-3) Fatty Acids for Foods.” The Journal of nutrition 142, no. 3 (2012): 600S-4S.

Omega-3 (n-3) fatty acids have been reported to have a variety of cardiovascular and neuropsychiatric benefits. Although obtaining the preformed fatty acids EPA and DHA from their traditional source (fish) is optimal, such an approach may not be realistic for meeting the world’s growing demand for (n-3) fatty acids; therefore, a more sustainable and dependable source is needed. Stearidonic acid (SDA) is a metabolic precursor of EPA that can be provided by SDA-enhanced soybean oil. Such a product can provide a sustainable source of (n-3) fatty acids that does not endanger fish stocks. Two clinical trials have demonstrated that SDA-enhanced soybean oil can significantly improve an emerging marker of cardiovascular health, the omega-3 index (RBC EPA+DHA). The increase in the Index seen in these trials was used to estimate the potential clinical benefit of SDA consumption based on prior prospective cohort studies. In this analysis, risk for sudden cardiac death and the rate of cellular aging would both theoretically be reduced. The lower risk for major cardiac events seen in the Japan EPA Lipid Intervention Study (which used EPA supplementation) suggests that raising EPA tissue levels, independent of changes in DHA, can have clinical benefit. Thus, the consumption of foods containing SDA-enhanced soybean oil may be both a practical and sustainable approach to enriching tissues with beneficial (n-3) fatty acids.

Sanford School of Medicine, Sioux Falls Campus.


Johnson, W. C., Dixon, Mark D., Scott, M. L., Rabbe, L., Larson, G., Volke, M., and Werner, B. “Forty Years of Vegetation Change on the Missouri River Floodplain.” Bioscience 62, no. 2 (2012): 123-35.

Comparative inventories in 1969 and 1970 and in 2008 of vegetation from 30 forest stands downstream of Garrison Dam on the Missouri River in central North Dakota showed (a) a sharp decline in cottonwood regeneration; (b) a strong compositional shift toward dominance by green ash; and (c) large increases in invasive understory species, such as smooth brome, reed canary grass, and Canada thistle. These changes, and others discovered during remeasurement, have been caused by a complex of factors, some related to damming (altered hydrologic and sediment regimes, delta formation, and associated wet-dry cycles) and some not (diseases and expansion of invasive plants). Dominance of green ash, however, may be short lived, given the likelihood that the emerald ash borer will arrive in the Dakotas in 5-10 years, with potentially devastating effects. The prospects for recovery of this valuable ecosystem, rich in ecosystem goods and services and in American history, are daunting.

Biology Department.


Kenyon, Denyelle Baete, Kubik, Martha Y., Davey, Cynthia, Sirard, John, and Fulkerson, Jayne A. “Alternative High School Students’ Physical Activity: Role of Self-Efficacy.” American journal of health behavior 36, no. 3 (2012): 300-10.

To examine physical activity self-efficacy as a mediator of the association between perceived barriers to PA and moderate-to-vigorous physical activity (MVPA) among alternative high school (AHS) students. Students (N=145) from 6 AHS completed self-report questionnaires. Mediation analyses revealed partial mediation of PA self-efficacy on relationships between general barriers to PA and MVPA (b = -.39 reduced b = -.33) among females (47.6% of sample). Interventions with female AHS students should include a component on building PA self-efficacy. However, results suggest the broader environment may have greater impact on MVPA than individual-level psycho-social factors.

Sanford School of Medicine, Sioux Falls Campus.


Kiesow, Alyssa. M., Wallace, Lisa E., and Britten, Hugh B. “Characterization and Isolation of Five Microsatellite Loci in Northern Flying Squirrels, Glaucomys Sabrinus (Sciuridae, Rodentia).” Western North American Naturalist 71, no. 4 (2011): 553-56.

Northern flying squirrels (Glaucomys sabrinus) are found in boreal forests of northern and northwestern North America, but a small population is isolated to the Black Hills of South Dakota and Wyoming. Few microsatellite primers have been developed for this species, though they are needed to examine the genetic structure of these populations. Thus, we isolated and characterized 5 microsatellite loci in northern flying squirrels through a series of steps involving microbiology, molecular biology, and genetic techniques. Data analyses with these primers indicated that the northern flying squirrel population found in the Black Hills may have low heterozygosity and significant departure from Hardy Weinberg equilibrium. The development of these primers not only provides additional data for analyzing a small, disjunct population but also serves as a mechanism for understanding population dynamics and assisting with overall management and conservation of unique populations.

Biology Department.


Krul, E. S., Lemke, S. L., Mukherjea, R., Harris, William S., and Maki, K. C. “Effects of Duration of Treatment and Dosage of Eicosapentaenoic Acid and Stearidonic Acid on Red Blood Cell Eicosapentaenoic Acid Content.” Prostaglandins Leukotrienes and Essential Fatty Acids 86, no. 1-2 (2012): 51-59.

Objective: The purpose of this randomized, controlled, parallel group study was to characterize the relationships between dosages of stearidonic acid (SDA) and eicosapentaenoic acid (EPA), and incorporation of EPA into red blood cell (RBC) membranes over time. Methods: Healthy subjects (n = 131) received capsules with placebo (safflower oil), SDA (0.43, 1.3, 2.6, or 5.2 g/d) or EPA (0.44, 1.3, or 2.7 g/d) for 12 weeks. RBC fatty acids were analyzed biweekly. Results: RBC %EPA increased in all EPA and SDA groups (p < 0.02 vs. control) except the 0.43 g/d SDA group (p = 0.187). For theoretical intakes of EPA of 0.25, 0.5, and 0.89 g/d, the amounts of SDA needed to achieve equivalent RBC EPA enrichment were 0.61, 1.89, and 5.32 g/d (conversion efficiencies of 41%, 26%, and 17%), respectively. Conclusions: SDA increased RBC %EPA in a dosage and time-dependent manner at intakes as low as 1.3 g/d. (C) 2011 Elsevier Ltd. All rights reserved.

Sanford School of Mediine, Sioux Falls Campus.


Martin, Douglas S., Klinkova, Olga, and Eyster, Kathleen M. “Regional Differences in Sexually Dimorphic Protein Expression in the Spontaneously Hypertensive Rat (Shr).” Molecular and Cellular Biochemistry 362, no. 1-2 (2012): 103-14.  

Hypertension is sexually dimorphic and modified by removal of endogenous sex steroids. This study tested the hypothesis that endogenous gonadal hormones exert differential effects on protein expression in the kidney and mesentery of SHR. At similar to 5 weeks of age male and female SHR underwent sham operation, orchidectomy, or ovariectomy (OVX). At 20-23 weeks of age, mean arterial pressure (MAP) was measured in conscious rats. The mesenteric arterial tree and kidneys were collected, processed for Western blots, and probed for Cu Zn superoxide dismutase (SOD1), soluble epoxide hydrolase (sEH), and Alpha 2A adrenergic receptor (A2AR) expression. MAP was unaffected by ovariectomy (Sham 164 +/- A 4: Ovariecttomy 159 +/- A 3 mm Hg). MAP was reduced by orchidectomy (Sham 189 +/- A 5:Orchidectomy 167 +/- A 2 mm Hg). In mesenteric artery, SOD1 expression was greater in male versus female SHR. Orchidectomy increased while ovariectomy decreased SOD1 expression. The kidney exhibited a different pattern of response. SOD1 expression was reduced in male compared to female SHR but gonadectomy had no effect. sEH expression was not significantly different among the groups in mesenteric artery. In kidney, sEH expression was greater in males compared to females. Ovariectomy but not orchidectomy increased sEH expression. A2AR expression was greater in female than male SHR in mesentery artery and kidney. Gonadectomy had no effect in either tissue. We conclude that sexually dimorphic hypertension is associated with regionally specific changes in expression of three key proteins involved in blood pressure control. These data suggest that broad spectrum inhibition or stimulation of these systems may not be the best approach for hypertension treatment. Instead regionally targeted manipulation of these systems should be investigated.

Basic Biomedical Sciences, Vermillion Campus.


Morecraft, Robert J., Stilwell-Morecraft, Kimberly S., Cipolloni, P. B., Ge, Jizhil, McNeal, David W., and Pandya, D. N. “Cytoarchitecture and Cortical Connections of the Anterior Cingulate and Adjacent Somatomotor Fields in the Rhesus Monkey.” Brain Research Bulletin 87, no. 4/5 (2012): 457-97.

Abstract: The cytoarchitecture and cortical connections of the anterior cingulate, medial and dorsal premotor, and precentral region are investigated using the Nissl and NeuN staining methods and the fluorescent retrograde tract tracing technique. There is a gradual stepwise laminar change in the cytoarchitectonic organization from the proisocortical anterior cingulate region, through the lower and upper banks of the cingulate sulcus, to the dorsolateral isocortical premotor and precentral motor regions of the frontal lobe. These changes are characterized by a gradational emphasis on the lower stratum layers (V and VI) in the proisocortical cingulate region to the upper stratum layers (II and III) in the premotor and precentral motor region. This is accompanied by a progressive widening of layers III and VI, a poorly delineated border between layers III and V and a sequential increase in the size of layer V neurons culminating in the presence of giant Betz cells in the precentral motor region. The overall patterns of corticocortical connections paralleled the sequential changes in cytoarchitectonic organization. The proisocortical areas have connections with cingulate motor, supplementary motor, premotor and precentral motor areas on the one hand and have widespread connections with the frontal, parietal, temporal and multimodal association cortex and limbic regions on the other. The dorsal premotor areas have connections with the proisocortical areas including cingulate motor areas and supplementary motor area on the one hand, and premotor and precentral motor cortex on the other. Additionally, this region has significant connections with posterior parietal cortex and limited connections with prefrontal, limbic and multimodal regions. The precentral motor cortex also has connections with the proisocortical areas and premotor areas. Its other connections are limited to the somatosensory regions of the parietal lobe. Since the isocortical motor areas on the dorsal convexity mediate voluntary motor function, their close connectional relationship with the cingulate areas form a pivotal limbic–motor interface that could provide critical sources of cognitive, emotional and motivational influence on complex motor function.

Basic Biomedical Sciences, Vermillion Campus.


Newland, Lisa A., Gapp, Susan C., Jacobs, Gera M., Reisetter, Marcy F., Syed, Daniela Cambetas, and Wu, Chih-Hsiu. “Mothers’ Beliefs and Involvement: Links with Preschool Literacy Development.” International Journal of Psychology: A Biopsychosocial Approach 9 (2011): 67-90.

Background: Parents play a crucial role in early literacy development, by initiating and supporting literacy-rich activities with children. Purpose: This study examined mothers’ beliefs in relation to involvement in literacy activities and child literacy skills. Material and methods: Mothers (n = 75) completed surveys measuring their efficacy, attributions, motivation for involvement, frequency and interactive nature of literacy activities, and preschoolers’ literacy outcomes. An adaptation of Hoover- Dempsey and Sandler’s 1995 theoretical model was tested using correlations and structural equation modeling to examine direct and indirect effects. Results: Results showed that mothers’ efficacy, motivation to read for pleasure, and self-attributions were related to the frequency and quality of home literacy interactions. In addition, facilitative reading and frequent writing activities had the strongest direct effects on children’s literacy, while efficacy had an indirect effect through reading and writing activities. The interactive nature of book reading was more predictive than the simple frequency of reading books in home settings. Conclusions: This study has implications for parents and educators who work with parents and children. (PsycINFO Database Record (c) 2012 APA, all rights reserved) (journal abstract)

School of Education.


Padilla-Lopez, Sergio, Langager, Deanna, Chan, Chun-Hung, and Pearce, David A. “Btn1, the Saccharomyces Cerevisiae Homolog to the Human Batten Disease Gene, Is Involved in Phospholipid Distribution.” Disease models & mechanisms 5, no. 2 (2012): 191-9.

BTN1, the yeast homolog to human CLN3 (which is defective in Batten disease), has been implicated in the regulation of vacuolar pH, potentially by modulating vacuolar-type H(+)-ATPase (V-ATPase) activity. However, we report that Btn1p and the V-ATPase complex do not physically interact, suggesting that any influence that Btn1p has on V-ATPase is indirect. Because membrane lipid environment plays a crucial role in the activity and function of membrane proteins, we investigated whether cells lacking BTN1 have altered membrane phospholipid content. Deletion of BTN1 (btn1-Delta) led to a decreased level of phosphatidylethanolamine (PtdEtn) in both mitochondrial and vacuolar membranes. In yeast there are two phosphatidylserine (PtdSer) decarboxylases, Psd1p and Psd2p, and these proteins are responsible for the synthesis of PtdEtn in mitochondria and Golgi-endosome, respectively. Deletion of both BTN1 and PSD1 (btn1-Delta psd1-Delta) led to a further decrease in levels of PtdEtn in ER membranes associated to mitochondria (MAMs), with a parallel increase in PtdSer. Fluorescent-labeled PtdSer (NBD-PtdSer) transport assays demonstrated that transport of NBD-PtdSer from the ER to both mitochondria and endosomes and/or vacuole is affected in btn1-Delta cells. Moreover, btn1-Delta affects the synthesis of PtdEtn by the Kennedy pathway and impairs the ability of psd1-Delta cells to restore PtdEtn to normal levels in mitochondria and vacuoles by ethanolamine addition. In summary, lack of Btn1p alters phospholipid levels and might play a role in regulating their subcellular distribution.

Sanford School of Medicine, Sioux Falls Campus.


Peng, Rui, Zhao, D., Dimitrijevic, N. M., Rajh, T., and Koodali, Ranjit T. “Room Temperature Synthesis of Ti-Mcm-48 and Ti-Mcm-41 Mesoporous Materials and Their Performance on Photocatalytic Splitting of Water.” Journal of Physical Chemistry C 116, no. 1 (2012): 1605-13.

Two sets of titania containing MCM-48 and MCM-41 photocatalysts were prepared at room temperature. Powder X-ray diffraction (XRD), transmission electron microscopy (TEM), nitrogen adsorption isotherms, UV-visible diffuse reflectance spectroscopy (DRS), and electron paramagnetic resonance (EPR) spectroscopy were utilized to characterize the Ti-MCM-48 and Ti-MCM-41 mesoporous materials. The photocatalytic hydrogen evolution results carried out under UV light irradiation indicated that the photocatalytic activity decreased with an increase of Ti-loading in Ti-MCM-48 and Ti-MCM-41 samples. The photocatalytic activity was found to be dependent on the coordination of Ti-and most importantly on the pore geometry, that is, cubic MCM-48 with interpenetrating network of pores exhibiting higher activity than uni-dimensional hexagonal pores in MCM-41.

Chemistry Department.


Randall, Brad, Donelan, K., Koponen, M., Sens, M. A., and Krous, H. F. “Application of a Classification System Focusing on Potential Asphyxia for Cases of Sudden Unexpected Infant Death.” Forensic Science Medicine and Pathology 8, no. 1 (2012): 34-39.

Current classification schemes for sudden unexpected infant death (SUID) may not be optimal for capturing scene events that potentially predispose to asphyxia. (1) To compare causes of death in a group of SUID cases assigned by multiple reviewers using our recently published classification scheme for SUID that is based on asphyxial risk at the death scene, and (2) To compare these newly assigned causes of death to that originally assigned by the medical examiners of record who performed the autopsies. Five reviewers independently assigned causes of death for 117 cases of SUID, including 83 originally diagnosed as sudden infant death syndrome (SIDS), accessioned into the San Diego SIDS/SUDC Research Project from the San Diego County Medical Examiner’s Office. The diagnostic categories are: A: SIDS; B: Unexplained-Potentially Asphyxia; C: Unexplained-Other Potential Causes of Death; D: Unclassified-Other; E: Unclassified; and F: Known Cause of Death. The reviewers collectively opined that conditions at the death scene contributed to or caused death in 32-50% of all of the 117 cases as well as in 40-59% of the 83 originally diagnosed SIDS cases. Another cause of death was considered plausible in 2-12% of the SIDS cases. Application of this new classification system resulted in 55-69% decrease in SIDS diagnoses. Asphyxia as a potential contributor to, or as the specific cause of death, appears to exist in a large percentage of cases designated as SIDS using other classification schemes. When certifiers use a classification system that focuses upon potential asphyxia in determining the cause of death the incidence of SIDS dramatically declines.

Sanford School of Medicine, Sioux Falls Campus.


Shearer, Gregory C., Carrero, J. J., Heimburger, O., Barany, P., and Stenvinkel, P. “Plasma Fatty Acids in Chronic Kidney Disease: Nervonic Acid Predicts Mortality.” Journal of Renal Nutrition 22, no. 2 (2012): 277-83.

Although the value of red blood cell fatty acids (FAs) in estimating risk for acute coronary syndrome in the general population is evident, the value of FAs in chronic kidney disease (CKD) is unknown. Here, we provide a pilot analysis in a spectrum of CKD patients. Plasma samples were obtained from 20 incident dialysis patients (CKD stage 5), matched with samples from 10 CKD stage 3-4 patients, and 10 control subjects. Whole plasma FAs were measured using gas chromatography. Whereas neither linoleic acid nor arachidonate acid were altered in CKD, metabolic intermediates of arachidonate synthesis (gamma-linolenate and dihomo gamma-linolenate) were reduced in CKD. Demming (orthogonal) correlation of FA abundance with estimated GFR identified several saturated and unsaturated FAs in addition to the intermediates; again, neither linoleate nor arachidonate were related. Follow-up data within the CKD stage 5 patients revealed that nervonic acid, a component of membrane sphingolipids and phosphatidylethanolamines, was a significant predictor of all-cause mortality; the age-adjusted relative risk for a 0.15% change is 2.1 (1.4, 3.7; 95% CI; P = .0008). These findings support the exploration of FAs in larger studies for validation of the role FAs in cardiovascular risk and mortality in CKD. (C) 2012 by the National Kidney Foundation, Inc. All rights reserved.

Sanford School of Medicine, Sioux Falls Campus.


Spicer, P., LaFramboise, T., Grayson, Liane, and Sarche, M. “Toward an Applied Developmental Science for Native Children, Families, and Communities.” Child Development Perspectives 6, no. 1 (2012): 49-54.

This article summarizes current knowledge in applied developmental science for Native children and adolescents. Included are brief reviews of research documenting disparities in health and education, exploring cultural factors in development, and moving toward evidence-based interventions for Native children. Opportunities for campuscommunity partnerships are made evident, especially in the area of intervention development that seeks to bridge cultural knowledge and strengths to address persistent disparities in health and development.

Communication Disorders Department [Former Faculty Member]


Sun, Xinbo, Cao, Zhengbing, Porteous, Nuala, and Sun, Yuyu. “An N-Halamine-Based Rechargeable Antimicrobial and Biofilm Controlling Polyurethane.” Acta biomaterialia 8, no. 4 (2012): 1498-506.

An N-halamine precursor, 5,5-dimethylhydantoin (DMH), was covalently linked to the surface of polyurethane (PU) with 1,6-hexamethylene diisocyanate (HDI) as the coupling agent. The reaction pathways were investigated using propyl isocyanate (PI) as a model compound. The results suggested that the imide and amide groups of DMH have very similar reactivities toward the isocyanate groups on PU surfaces activated with HDI. After bleach treatment the covalently bound DMH moieties were transformed into N-halamines. The new N-halamine-based PU provided potent antimicrobial effects against Staphylococcus aureus (Gram-positive bacterium), Escherichia coli (Gram-negative bacterium), methicillin-resistant Staphylococcus aureus (MRSA, drug-resistant Gram-positive bacterium), vancomycin-resistant Enterococcus faecium (VRE, drug-resistant Gram-positive bacterium), and Candida albicans (fungus), and successfully prevented bacterial and fungal biofilm formation. The antimicrobial and biofilm controlling effects were stable for longer than 6months under normal storage in open air. Furthermore, if the functions were lost due to prolonged use they could be recharged by another chlorination treatment. The recharging could be repeated as needed to achieve long-term protection against microbial contamination and biofilm formation. Copyright A 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Biomedical Engineering, Sioux Falls.


Tan, Z. S., Harris, William S., Beiser, A. S., Au, R., Himali, J. J., Debette, S., Pikula, A., DeCarli, C., Wolf, P. A., Vasan, R. S., Robins, S. J., and Seshadri, S. “Red Blood Cell Omega-3 Fatty Acid Levels and Markers of Accelerated Brain Aging.” Neurology 78, no. 9 (2012): 658-64.

Objective: Higher dietary intake and circulating levels of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have been related to a reduced risk for dementia, but the pathways underlying this association remain unclear. We examined the cross-sectional relation of red blood cell (RBC) fatty acid levels to subclinical imaging and cognitive markers of dementia risk in a middle-aged to elderly community-based cohort. Methods: We related RBC DHA and EPA levels in dementia-free Framingham Study participants (n = 1,575; 854 women, age 67 +/- 9 years) to performance on cognitive tests and to volumetric brain MRI, with serial adjustments for age, sex, and education (model A, primary model), additionally for APOE is an element of 4 and plasma homocysteine (model B), and also for physical activity and body mass index (model C), or for traditional vascular risk factors (model D). Results: Participants with RBC DHA levels in the lowest quartile (Q1) when compared to others (Q2-4) had lower total brain and greater white matter hyperintensity volumes (for model A: beta +/- SE = -0.49 +/- 0.19; p = 0.009, and 0.12 +/- 0.06; p = 0.049, respectively) with persistence of the association with total brain volume in multivariable analyses. Participants with lower DHA and omega-3 index (RBC DHA + EPA) levels (Q1 vs Q2-4) also had lower scores on tests of visual memory (beta +/- SE = -0.47 +/- 0.18; p = 0.008), executive function (beta +/- SE = -0.07 +/- 0.03; p = 0.004), and abstract thinking (beta +/- SE = -0.52 +/- 0.18; p = 0.004) in model A, the results remaining significant in all models. Conclusion: Lower RBC DHA levels are associated with smaller brain volumes and a “vascular” pattern of cognitive impairment even in persons free of clinical dementia. Neurology (R) 2012;78:658-664

SanfordSchool of Medicine, Sioux Falls Campus.


Vermeer, Paoloa D., Bell, Megan, Lee, Kimberly, Vermeer, Daniel, Wieking, Bryant G., Bilal, E., Bhanot, G., Drapkin, R. I., Ganesan, S., Klingelhutz, A. J., Hendriks, W. J., and Lee, Johnh. “Erbb2, Ephrinb1, Src Kinase and Ptpn13 Signaling Complex Regulates Map Kinase Signaling in Human Cancers.” Plos One 7, no. 1 (2012).

In non-cancerous cells, phosphorylated proteins exist transiently, becoming de-phosphorylated by specific phosphatases that terminate propagation of signaling pathways. In cancers, compromised phosphatase activity and/or expression occur and contribute to tumor phenotype. The non-receptor phosphatase, PTPN13, has recently been dubbed a putative tumor suppressor. It decreased expression in breast cancer correlates with decreased overall survival. Here we show that PTPN13 regulates a new signaling complex in breast cancer consisting of ErbB2, Src, and EphrinB1. To our knowledge, this signaling complex has not been previously described. Co-immunoprecipitation and localization studies demonstrate that EphrinB1, a PTPN13 substrate, interacts with ErbB2. In addition, the oncogenic V660E ErbB2 mutation enhances this interaction, while Src kinase mediates EphrinB1 phosphorylation and subsequent MAP Kinase signaling. Decreased PTPN13 function further enhances signaling. The association of oncogene kinases (ErbB2, Src), a signaling transmembrane ligand (EphrinB1) and a phosphatase tumor suppressor (PTPN13) suggest that EphrinB1 may be a relevant therapeutic target in breast cancers harboring ErbB2-activating mutations and decreased PTPN13 expression.

Sanford School of Medicine, Sioux Falls Campus.


Wright, Casey D., Wu, Steven C., Dahl, Erika F., Sazama, Alan J., and O’Connell, Timothy D. “Nuclear Localization Drives Alpha 1-Adrenergic Receptor Oligomerization and Signaling in Cardiac Myocytes.” Cellular Signalling 24, no. 3 (2012): 794-802.

Conventional models of G-protein coupled receptor (GPCR) signaling describe cell surface receptors binding to external ligands, such as hormones or circulating peptides, to induce intracellular signaling and a physiologic response. However, recent studies identify new paradigms indicating that GPCRs localize to and signal at the nucleus and that GPCR oligomers can influence receptor function. Previously, we reported that endogenous alpha 1-adrenergic receptors (alpha 1-ARs) localize to and signal at the nuclei in adult cardiac myocytes. In this study, we examined the mechanisms behind alpha 1-AR nuclear localization and how nuclear localization impacted receptor function. We verified that endogenous alpha 1-ARs localized to the nuclear membrane of intact nuclei isolated from wild-type adult cardiac myocytes. Next, we identified and disrupted putative nuclear localization sequences in both the alpha 1A- and alpha 1B-adrenergic receptors, which led to mis-localization of alpha 1-ARs in cultured adult cardiac myocytes. Using these mutants, we demonstrated that nuclear localization was required for alpha 1-signaling in adult cardiac myocytes. We also found that the nuclear export inhibitor leptomycin B inhibited alpha 1-AR signaling, indicating alpha 1-AR signaling must arise in the nucleus in adult cardiac myocytes. Finally, we found that co-localization of the alpha 1-subtypes at the nuclei in adult cardiac myocytes facilitated the formation of receptor oligomers that could affect receptor signaling. In summary, our data indicate that alpha 1-AR nuclear localization can drive the formation of receptor oligomers and regulate signaling in adult cardiac myocytes. (C) 2011 Elsevier Inc. All rights reserved.

Sanford School of Medicine, Sioux Falls Campus.


Yallapu, Murali M., Dobberpuhl, Mitch R., Maher, Diane M., Jaggi, Meena, and Chauhan, Subhash C. “Design of Curcumin Loaded Cellulose Nanoparticles for Prostate Cancer.” Current Drug Metabolism 13, no. 1 (2012): 120-28.

Prostate cancer (PC) is the most frequently diagnosed disease in men in the United States. Curcumin (CUR), a natural diphenol, has shown potent anti-cancer efficacy in various types of cancers. However, suboptimal pharmacokinetics and poor bioavailability limit its effective use in cancer therapeutics. Several successful CUR nanoformulations have recently been reported which improve upon these features; however, there is no personalized safe nanoformulation for prostate cancer. This study contributes two important scientific aspects of prostate cancer therapeutics. The first objective was to investigate the comparative cellular uptake and cytotoxicity evaluation of beta-cyclodextrin (CD), hydroxypropyl methylcellulose (cellulose), poly(lactic-co-glycolic acid) (PLGA), magnetic nanoparticles (MNP), and dendrimer based CUR nanoformulations in prostate cancer cells. Curcumin loaded cellulose nanoparticles (cellulose-CUR) formulation exhibited the highest cellular uptake and caused maximum ultrastructural changes related to apoptosis (presence of vacuoles) in prostate cancer cells. Secondly, the anti-cancer potential of the cellulose-CUR formulation was evaluated in cell culture models using cell proliferation, colony formation and apoptosis (7-AAD staining) assays. In these assays, the cellulose-CUR formulation showed improved anti-cancer efficacy compared to free curcumin. Our study shows, for the first time, the feasibility of cellulose-CUR formulation and its potential use in prostate cancer therapy.

Sanford School of Medicine, Sioux Falls Campus.


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