To help us in our roles as liaison to several USD departments,we keep tabs on the research of USD. We also are responsible for keeping the departments up-to-date about the library.

This blog exists for organizing and sharing that information. Check out the tabs above for month-by-month publications.

Email us if you have any questions.  Danielle Loftus   Steve Johnson

The Cr(3+).:KSc(WO(4))2 crystal was grown by top seed solution method. The absorption and luminescence spectra were investigated. The absorption cross section sigma(a) is 1.16 x 10(-19) cm(-2) at 469 nm for the (4)A(2) -> (4)T(1) transition and 4.98 x 10(-20) cm-2 at 684 nm for the (4)A(2) -> (4)T(2) transition, respectively. The emission cross section sigma(a) of (4)T(2) -> (4)A(2) transition is 4.86 x 10(-20) cm(2) at 916 nm with FWHM of 200 nm and fluorescence lifetime is 19.83 mu s. Based on the absorption and emission spectra, the crystal field strength Dq, the Racah parameters B and C, the effective phonon energy tico and the Huang-Rhys factor S were calculated. Cr(3+) ions in Ksc(WO(4))(2) crystal occupy the weak crystal field sites and have stronger coupling to crystal lattice. Published by Elsevier B.V.

Physics Department.

Venesky, M. D., Wilcoxen, T. E., Rensel, M. A., Rollins-Smith, L., Kerby, Jacob L., & Parris, M. J. (2012). Dietary protein restriction impairs growth, immunity, and disease resistance in southern leopard frog tadpoles. Oecologia, 169(1), 23-31.

The immune system is a necessary, but potentially costly, defense against infectious diseases. When nutrition is limited, immune activity may consume a significant amount of an organism’s energy budget. Levels of dietary protein affect immune system function; high levels can enhance disease resistance. We exposed southern leopard frog [Lithobates sphenocephalus (=Rana sphenocephala)] tadpoles to high and low protein diets crossed with the presence or absence of the pathogenic amphibian chytrid fungus (Batrachochytrium dendrobatidis; Bd) and quantified: (1) tadpole resistance to Bd; (2) tadpole skin-swelling in response to phytohaemagglutinin (PHA) injection (a measure of the T cell-mediated response of the immune system); (3) bacterial killing ability (BKA) of tadpole blood (a measure of the complement-mediated cytotoxicity of the innate immune system); and (4) tadpole growth and development. Tadpoles raised on a low-protein diet were smaller and less developed than tadpoles on a high-protein diet. When controlled for developmental stage, tadpoles raised on a low-protein diet had reduced PHA and BKA responses relative to tadpoles on a high-protein diet, but these immune responses were independent of Bd exposure. High dietary protein significantly increased resistance to Bd. Our results support the general hypothesis that host condition can strongly affect disease resistance; in particular, fluctuations in dietary protein availability may change how diseases affect populations in the field.

Biology Department.

Sundram, Vasudha, Chauhan, Subhash C., Ebeling, Mara, & Jaggi, Meena. (2012). Curcumin Attenuates beta-catenin Signaling in Prostate Cancer Cells through Activation of Protein Kinase D1. PloS one, 7(4), e35368.

Prostate cancer is the most commonly diagnosed cancer affecting 1 in 6 males in the US. Understanding the molecular basis of prostate cancer progression can serve as a tool for early diagnosis and development of novel treatment strategies for this disease. Protein Kinase D1 (PKD1) is a multifunctional kinase that is highly expressed in normal prostate. The decreased expression of PKD1 has been associated with the progression of prostate cancer. Therefore, synthetic or natural products that regulate this signaling pathway can serve as novel therapeutic modalities for prostate cancer prevention and treatment. Curcumin, the active ingredient of turmeric, has shown anti-cancer properties via modulation of a number of different molecular pathways. Herein, we have demonstrated that curcumin activates PKD1, resulting in changes in beta-catenin signaling by inhibiting nuclear beta-catenin transcription activity and enhancing the levels of membrane beta-catenin in prostate cancer cells. Modulation of these cellular events by curcumin correlated with decreased cell proliferation, colony formation and cell motility and enhanced cell-cell aggregation in prostate cancer cells. In addition, we have also revealed that inhibition of cell motility by curcumin is mediated by decreasing the levels of active cofilin, a downstream target of PKD1. The potent anti-cancer effects of curcumin in vitro were also reflected in a prostate cancer xenograft mouse model. The in vivo inhibition of tumor growth also correlated with enhanced membrane localization of beta-catenin. Overall, our findings herein have revealed a novel molecular mechanism of curcumin action via the activation of PKD1 in prostate cancer cells.

Sanford School of Medicine, Sioux Falls Campus.

Sun, Y., Thiel, C. W., & Cone, R. L. (2012). Optical decoherence and energy level structure of 0.1% Tm3+:LiNbO3. Physical Review B, 85(16).

We report the energy level structure of the H-3(6) and H-3(4) multiplets for Tm3+ doped congruent LiNbO3, as well as the decoherence properties and their temperature dependencies for the H-3(6)(1) <-> H-3(4)(1a) transition at 794 nm. It is shown that this material provides very significant improvements in bandwidth, time-bandwidth product, and sensitivity for spatial-spectral holographic signal processing devices and quantum memories based on spectral hole burning. The available signal processing bandwidth for 0.1% Tm3+: LiNbO3 is 300 GHz versus 20 GHz for Tm3+ YAG. The peak absorption coefficient for 0.1% Tm3+: LiNbO3 is 15 cm(-1) at 794.5 nm compared with 1.7 cm(-1) for 0.1% Tm:YAG at 793 nm, and the total absorption strength is eighty times stronger. The oscillator strength for Tm3+: LiNbO3 is about twenty-five times larger than that for Tm3+: YAG, making the material five times more sensitive for processing high-bandwidth analog signals. The homogeneous linewidth, which determines processing time or spectrum analyzer resolution, is 30 kHz at 1.6 K and 350 kHz at 6 K, as measured by photon echoes. Those values establish potential time-bandwidth products of 10(7) and 7 x 10(5), respectively. The temperature dependence of the homogeneous linewidth was explained by observation of a 7.8 cm(-1) crystal field level in the ground multiplet and direct phonon coupling. The excited state H-3(4) lifetime T-1 is 152 mu s and the bottleneck lifetime of the lowest F-3(4) level is 7 ms from photon echo measurements. These factors combine to provide a surprisingly large increase in key parameters that determine material performance for spatial-spectral holography, quantum information, and other spectral hole burning applications.

Physics Department.

Simons, Jeffrey S., Dvorak, Robert D., Merrill, J. E., & Read, J. P. (2012). Dimensions and severity of marijuana consequences: Development and validation of the Marijuana Consequences Questionnaire (MACQ). Addictive Behaviors, 37(5), 613-621.

The Marijuana Consequences Questionnaire (MACQ) is a 50-item self-report measure modeled after the Young Adult Alcohol Consequences Questionnaire (YAACQ). College students (n = 315) completed questionnaires online. A confirmatory factor analysis supported the hypothesized 8-factor structure. The results indicate good convergent and discriminant validity of the MACQ. A brief, unidimensional, 21-item version (B-MACQ) was developed by a Rasch model. Comparison of item severity estimates of the B-MACQ items and the corresponding items from the YAACQ indicates that the severity of alcohol- and marijuana-problems is defined by a relatively unique pattern of consequences. The MACQ and B-MACQ provide promising new alternatives to assessing marijuana-related problems. (c) 2012 Elsevier Ltd. All rights reserved.

Psychology Department.

Shinozaki, Gen, Romanowicz, Magdalena, Kung, Simon, Rundell, James, & Mrazek, David. (2012). Investigation of serotonin transporter gene (SLC6A4) by child abuse history interaction with body mass index and diabetes mellitus of White female depressed psychiatric inpatients. Psychiatric genetics, 22(3), 109-114.

BACKGROUND: The serotonin transporter gene promoter polymorphism (5HTTLPR) and child abuse have been associated with an increased risk for depression. We previously reported the long/long (l/l) genotype of 5HTTLPR being associated with higher heart rate among patients with a history of child abuse compared with those without a history of child abuse, whereas the short allele carriers did not have heart rate differences dependent on child abuse history. This time, we extended our investigation to other outcomes with body mass index (BMI), and diabetes mellitus (DM) diagnosis.METHODS: A retrospective chart review identified 185 White female depressed inpatients who were genotyped for 5HTTLPR. Child abuse history, BMI, and DM diagnosis were recorded. The relationship between 5HTTLPR, child abuse, and BMI, as well as a prevalence of DM were analyzed.RESULTS: Among the l/l genotype group, patients with a history of child abuse had a higher prevalence of DM (14.3 vs. 0%, P=0.06), and higher BMI (32.3 vs. 27.3 kg/m, P=0.03) compared with those without. Patients with the short allele (s/s or s/l) had fewer differences on the basis of abuse history.CONCLUSION: A potential interaction between 5HTTLPR and child abuse influenced metabolic profiles of White female depressed inpatients. In contrast with the widely recognized ‘reactivity’ associated with the short allele of 5HTTLPR, our White female depressed psychiatric inpatients with the l/l genotype showed relatively greater clinical pathology in metabolic profiles if they have a history of child abuse than inpatients with at least one short allele who had a history of child abuse.

Sanford School of Medicine, Sioux Falls Campus.

Shearer, Gregory C., Savinova, Olga V., & Harris, William S. (2012). Fish oil – How does it reduce plasma triglycerides? Biochimica Et Biophysica Acta-Molecular and Cell Biology of Lipids, 1821(5), 843-851.

Long chain omega-3 fatty acids (FAs) are effective for reducing plasma triglyceride (TG) levels. At the pharmaceutical dose, 3.4 g/day, they reduce plasma TG by about 25-50% after one month of treatment, resulting primarily from the decline in hepatic very low density lipoprotein (VLDL-TG) production, and secondarily from the increase in VLDL clearance. Numerous mechanisms have been shown to contribute to the TG overproduction, but a key component is an increase in the availability of FAs in the liver. The liver derives FAs from three sources: diet (delivered via chylomicron remnants), de novo lipogenesis, and circulating non-esterified FAs (NEFAs). Of these, NEFAs contribute the largest fraction to VLDL-TG production in both normotriglyceridemic subjects and hypertriglyceridemic, insulin resistant patients. Thus reducing NEFA delivery to the liver would be a likely locus of action for fish oils (FO). The key regulator of plasma NEFA is intracellular adipocyte lipolysis via hormone sensitive lipase (HSL), which increases as insulin sensitivity worsens. FO counteracts intracellular lipolysis in adipocytes by suppressing adipose tissue inflammation. In addition, FO increases extracellular lipolysis by lipoprotein lipase (LpL) in adipose, heart and skeletal muscle and enhances hepatic and skeletal muscle beta-oxidation which contributes to reduced FA delivery to the liver. FO could activate transcription factors which control metabolic pathways in a tissue specific manner regulating nutrient traffic and reducing plasma TG. This article is part of a Special Issue entitled Triglyceride Metabolism and Disease. (C) 2011 Elsevier B.V. All rights reserved.

Sanford School of Medicine, Sioux Falls Campus.

Schlenker, Evelyn H. (2012). Effects of hypothyroidism on the respiratory system and control of breathing: Human studies and animal models. Respiratory Physiology & Neurobiology, 181(2), 123-131.

Abstract: Hypothyroidism, subclinical hypothyroidism and euthyroid sick syndrome, are prevalent disorders that affect all body systems including the respiratory system and control of breathing. The purpose of this review article is to discuss the regulation of thyroid hormone production and their function at the cellular level; the many causes of hypothyroidism; the effects of hypothyroidism on the respiratory system and on control of ventilation in hypothyroid patients; the variety of ways animal models of hypothyroidism are induced; and how in animal models hypothyroidism affects the respiratory system and control of breathing including neurotransmitters that influence breathing. Finally, this review will present controversies that exist in the field and thus encourage new research directions. Because of the high prevalence of hypothyroidism and subclinical forms of hypothyroidism and their influence on ventilation and the respiratory system, understanding underlying molecular mechanisms is necessary to ascertain how and sometimes why not thyroid replacement may normalize function.

Biomedical Sciences, Vermillion Campus.

Puumala, Susan E., Nelson, H. H., Ross, J. A., Nguyen, R. H. N., Damario, M. A., & Spector, L. G. (2012). Similar DNA methylation levels in specific imprinting control regions in children conceived with and without assisted reproductive technology: a cross-sectional study. BMC Pediatrics, 12.

Background: While a possible link between assisted reproductive technology ( ART) and rare imprinting disorders has been found, it is not clear if this is indicative of subtler disruptions of epigenetic mechanisms. Results from previous studies have been mixed, but some methylation differences have been observed. Methods: Children conceived through ART and children conceived spontaneously were recruited for this cross-sectional study. Information about reproductive history, demographic factors, birth characteristics, and infertility treatment was obtained from maternal interview and medical records. Peripheral blood lymphocytes and buccal cell samples were collected from participating children. Methylation analysis was performed on five loci using pyrosequencing. Statistical analysis of methylation differences was performed using linear regression with generalized estimating equations. Results are reported as differences with 95% confidence intervals (CI). Results: A total of 67 ART children and 31 spontaneously conceived (SC) children participated. No significant difference in methylation in lymphocyte samples was observed between groups for any loci. Possible differences were found in buccal cell samples for IGF2 DMR0 (Difference: 2.07; 95% confidence interval (CI): -0.28, 4.42; p = 0.08) and IGF2R (Difference: -2.79; 95% CI: -5.74, 0.16; p = 0.06). Subgroup analysis indicated potential lower methylation in those whose parents used ART for unexplained infertility. Conclusions: Observed differences in methylation between the ART and SC groups were small for all loci in the two sample types examined and no statistical differences were observed. It is still unclear whether or not small differences observed in several studies represent a real difference between groups and if this difference is biologically meaningful. Larger studies with long term follow-up are needed to fully answer these questions.

Sanford School of Medicine, Sioux Falls Campus.

Pottala, J. V., Talley, J. A., Churchill, S. W., Lynch, D. A., Von Schacky, C., & Harris, William S. (2012). Red blood cell fatty acids are associated with depression in a case-control study of adolescents. Prostaglandins, leukotrienes, and essential fatty acids, 86(4-5), 161-165.

INTRODUCTION: Epidemiological studies suggest that reduced intakes and/or blood levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are associated with increased risk for depression in adults, but data on adolescents are scarce. The objective of this study was to determine whether red blood cell (RBC) levels of EPA+DHA (the omega-3 index) and/or the overall RBC fatty acid profile differ between depressed adolescents (cases) and non-depressed adolescents (controls).PATIENTS AND METHODS: We measured the RBC fatty acid composition of cases admitted to the hospital for depression (n=150) and compared it to that of controls (n=161).RESULTS: Cases and controls had similar ages, gender proportions, and body mass index (BMI) distributions, but there was a significant difference in racial/ethnic composition due to differences in recruitment sites. The unadjusted odds ratio for case status was 0.72 (95% CI; 0.55-0.95) for a 1% absolute increase in the omega-3 index. A multivariable logistic regression model was used to determine which fatty acids were useful in classifying cases and controls; BMI, age, gender, and race/ethnicity were forced into the model. Seven fatty acids were selected (DHA, myristic, stearic, oleic, trans linoleic, trans palmitoleic, and alpha-linolenic acids) to optimize the model fit to the data. In the adjusted model, the odds ratio was 0.67 (95% CI; 0.49-0.93) for a 1 SD increase in DHA. Adding the seven fatty acid profile to the basic model increased the area under the ROC curve by 12.6% (7.5%-17.6%).DISCUSSION AND CONCLUSION: These findings support the hypothesis that adolescent depression is associated with a perturbed RBC fatty acid pattern which includes a reduced omega-3 index. Intervention studies with EPA and DHA should be conducted in this vulnerable population for which few, safe therapeutic options currently exist. Copyright 2012 Elsevier Ltd. All rights reserved.

Sanford School of Medicine, Sioux Falls Campus.

Pfefferbaum, B., Schonfeld, D., Flynn, B. W., Norwood, A. E., Jacobs, Gerald A., Hobfoll, S. E., et al. (2012). The H1N1 Crisis: A Case Study of the Integration of Mental and Behavioral Health in Public Health Crises. Disaster Medicine and Public Health Preparedness, 6(1), 67-71.

In substantial numbers of affected populations, disasters adversely affect well-being and influence the development of emotional problems and dysfunctional behaviors. Nowhere is the integration of mental and behavioral health into broader public health and medical preparedness and response activities more crucial than in disasters such as the 2009-2010 H1N1 influenza pandemic. The National Biodefense Science Board, recognizing that the mental and behavioral health responses to H1N1 were vital to preserving safety and health for the country, requested that the Disaster Mental Health Subcommittee recommend actions for public health officials to prevent and mitigate adverse behavioral health outcomes during the H1N1 pandemic. The subcommittee’s recommendations emphasized vulnerable populations and concentrated on interventions, education and training, and communication and messaging. The subcommittee’s H1N1 activities and recommendations provide an approach and template for identifying and addressing future efforts related to newly emerging public health and medical emergencies. The many emotional and behavioral health implications of the crisis and the importance of psychological factors in determining the behavior of members of the public argue for a programmatic integration of behavioral health and science expertise in a comprehensive public health response. (Disaster Med Public Health Preparedness. 2012;6:67-71)

Psychology Department.

Pfefferbaum, B., Flynn, B. W., Schonfeld, D., Brown, L. M., Jacobs, Gerald A., Dodgen, Daniel, et al. (2012). The Integration of Mental and Behavioral Health Into Disaster Preparedness, Response, and Recovery. Disaster Medicine and Public Health Preparedness, 6(1), 60-66.

The close interplay between mental health and physical health makes it critical to integrate mental and behavioral health considerations into all aspects of public health and medical disaster management. Therefore, the National Biodefense Science Board (NBSB) convened the Disaster Mental Health Subcommittee to assess the progress of the US Department of Health and Human Services (HHS) in integrating mental and behavioral health into disaster and emergency preparedness and response activities. One vital opportunity to improve integration is the development of clear and directive national policy to firmly establish the role of mental and behavioral health as part of a unified public health and medical response to disasters. Integration of mental and behavioral health into disaster preparedness, response, and recovery requires it to be incorporated in assessments and services, addressed in education and training, and founded on and advanced through research. Integration must be supported in underlying policies and administration with clear lines of responsibility for formulating and implementing policy and practice. (Disaster Med Public Health Preparedness. 2012;6:60-66)

Psychology Department.

Parayil, Sreenivasan Koliyat, Kibombo, Harrison S., Wu, Chia-Ming, Peng, Rui, Baltrusaitis, Jonas, & Koodali, Ranjit T. (2012). Enhanced photocatalytic water splitting activity of carbon-modified TiO2 composite materials synthesized by a green synthetic approach. International Journal of Hydrogen Energy, 37(10), 8257-8267.

Abstract: We report a green and facile approach for the preparation of carbon-modified (C-modified) TiO2 composite materials by hydrothermal synthesis followed by pyrolytic treatment. The resultant materials were characterized by powder X-ray diffraction (XRD), nitrogen physisorption studies, Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), diffuse reflectance spectroscopy (DRS), photoluminescence (PL) spectroscopy, and transmission electron microscopy (TEM). The photocatalytic performances of these materials were evaluated by calculating the amount of hydrogen evolved from the decomposition of water under solar simulated irradiation conditions. An improvement was achieved from no H2 evolution at all with the bare TiO2, to an evolution of 0.21mLg−1 h−1 from a composite material modified with an optimum carbon loading of 3.62%. These results suggested that the interaction of carbon with predominantly rutile form of TiO2 can promote shallow trapping of photogenerated electrons in the oxygen vacancies. This phenomenon consequently enhances the photocatalytic activity by minimizing charge carrier recombination, a characteristic demonstrated by fluorescence quenching of the TiO2 emission.

Chemistry Department.

Padmanabhuni, Ravathi V., Luo, Jie, Cao, Zhengbing B., & Sun, Yu Yu. (2012). Preparation and Characterization of N-Halamine-Based Antimicrobial Fillers. Industrial & Engineering Chemistry Research, 51(14), 5148-5156.

The purpose of this study was to demonstrate that the surface of CaCO3 fillers can be coated with an N-halamine-based fatty acid to make the filler surface organophilic and simultaneously achieve antibacterial activity, rendering the resulting polymer filler composites antimicrobial. Thus, a new bifunctional compound, 4,4-dimethylhydantoin undecanoic acid (DMH-UA), was synthesized by treating the potassium salt of dimethylhydantoin (DMH) with 11-bromoundecanoic acid (BUA). Upon chlorination treatment with dilute bleach, DMH-UA was transformed into 3-chloro-4,4-dimethylhydantoin undecanoic acid (Cl-DMH-UA). Alternatively, DMH-UA could be coated onto the surface of CaCO3 to obtain the corresponding calcium salt, 4,4-dimethylhydantoin undecanoic acid calcium carbonate (DMH-UA-CaCO3). In the presence of dilute chlorine bleach, the DMH-UA coated on the surface of CaCO3 was transformed into Cl-DMH-UA, leading to the formation of Cl-DMH-UA-CaCO3. The reactions were characterized by FT-IR, NMR, UV, DSC, and SEM analyses. Both Cl-DMH-UA and Cl-DMH-UA-CaCO3 were used as antimicrobial additives for cellulose acetate (CA). The antimicrobial efficacy of the resulting samples was evaluated against both Escherichia coli (Gram-negative bacteria) and Staphylococcus aureus (Gram-positive bacteria). It was found that, for the same additive content, CA samples with Cl-DMH-UA-CaCO3 and Cl-DMH-UA had very similar antimicrobial and biofilm-controlling activities, but the former released less active chlorine into the surrounding environment than the latter.

Biomedical Engineering Program, Sioux Falls Campusw

Meyer, Danielle L., Davies, Daniel R., Barr, Jeffrey L., Manzerra, Pasquale, & Forster, Gina L. (2012). Mild traumatic brain injury in the rat alters neuronal number in the limbic system and increases conditioned fear and anxiety-like behaviors. Experimental neurology, 235(2), 574-587.

Recent reports suggest that experiencing a mild closed head trauma or mild traumatic brain injury (mTBI) is associated with a greater incidence of anxiety disorders. Dysfunction of limbic structures, such as the medial prefrontal cortex, amygdala and hippocampus, is associated with the symptoms of anxiety disorders. Therefore, the goal of the current studies was to characterize the consequences of closed mTBI on these limbic structures and associated fear and anxiety-related behaviors. A weight-drop procedure was employed to induce mTBI in male rats. Rats were transcardically perfused 4 or 9days following exposure to mTBI or control procedures, and neuronal number, brain region area, and the number of apoptotic cells in each region were determined. In separate groups of rats, the effects of mTBI on anxiety-like behaviors, motor function, nociception, and acquisition, retention and extinction of contextual fear were also assessed. Findings suggest that mTBI was associated with significant neuronal cell loss in the CA1 region of the dorsal hippocampus and increased cell number in subregions of the amygdala, both of which appear to be related to alterations to apoptosis in these regions following mTBI. Furthermore, mTBI increased expression of anxiety-like behaviors and conditioned fear, with no effect on motor performance or nociception. Overall, a single impact to the skull to mimic mTBI in rats produces discrete alterations to neuronal numbers within the limbic system and specific emotional deficits, providing a potential neurobiological link between mTBI and anxiety disorders.

Basic Biomedical Sciences, Vermillion Campus.

Lawler, Michael J., Curry, Dale, Donnenwirth, Jann, Mangrich, Mary E., & Times, Tonya N. (2012). Assessing Transfer-of-Learning Potential With Human Services Professionals. Journal of Social Service Research, 38(3), 402-412.

Transfer of learning (TOL) from training to the job was examined in two different populations of human services workers using the Transfer Potential Questionnaire (TPQ). A cross-validation study was conducted to explore commonalities and differences between public welfare (PW) professionals in California (n = 459) and Child Protective Services (CPS) social workers in Ohio (n = 598). The TPQ significantly correlated with perceived TOL for both training populations and added to the amount of TOL variance explained after controlling for participant satisfaction and perceived learning. Important TOL factors identified for both groups included perceived learning and application planning. Findings suggest TPQ is a valid predictor of TOL for both PW professionals and CPS social workers, supporting a shared construct relative to TOL across human services practice areas. Future research should explore additional TOL assessment methods and seek to further validate the TPQ with other populations of human services professionals.

School of Health Sciences.

Laudenschlager, Mark, Nykamp, Verlan, Allard, Brandon, Japs, Robert, & Simmons, Jerry. (2012). Cardiac Neuroendocrine Tumor with Absence of Sustentacular Cells: Immunohistochemical and Ultrastructural Findings. Ultrastructural Pathology, 36(2), 130-133.

A 68-year-old male presented with increased shortness of breath and intermittent chest pain. Cardiac catheterization along with echocardiogram imaging demonstrated 3-vessel coronary artery disease with severe left ventricular dysfunction and critical aortic stenosis. During coronary artery bypass surgery, a tumor was identified at the sulcus between the aorta and the right atrial appendage. This highly vascular tumor extended over the right coronary artery, prompting biopsy and further resection. Light microscopic evaluation showed packets of uniform round neoplastic cells without evidence of necrosis or increased mitotic figures. Immunohistochemical studies were positive for synaptophysin and weakly positive for chromogranin. Pankeratin, S-100, and GFAP stains were all negative. Ultrastructural examination of the neoplasm demonstrated numerous electron-dense secretory granules within the cytoplasm of the tumor cells. These secretory granules varied in size from 60 to 210 nm, with halos encircling many of them, suggesting the likelihood of epinephrine or norepinephrine granules. Within the specimen, abundant vascular spaces were identified, but no sustentactular cells were present. The patient agreed to undergo genetic testing, and a mutation in the succinate dehydrogenase complex subunit B (SDHB) was identified. This confirmed the molecular diagnosis of hereditary paraganglioma/pheochromocytoma syndrome. Now two years out from surgery, this patient continues to be asymptomatic in spite of the fact that his tumor was only partially resected.

Sanford School of Medicine, Sioux Falls Campus.

Kruer, Michael C., Boddaert, N., Schneider, S. A., Houlden, H., Bhatia, K. P., Gregory, A., et al. (2012). Neuroimaging Features of Neurodegeneration with Brain Iron Accumulation. American Journal of Neuroradiology, 33(3), 407-414.

NBIA characterizes a class of neurodegenerative diseases that feature a prominent extrapyramidal movement disorder, intellectual deterioration, and a characteristic deposition of iron in the basal ganglia. The diagnosis of NBIA is made on the basis of the combination of representative clinical features along with MR imaging evidence of iron accumulation. In many cases, confirmatory molecular genetic testing is now available as well. A number of new subtypes of NBIA have recently been described, with distinct neuroradiologic and clinical features. This article outlines the known subtypes of NBIA, delineates their clinical and radiographic features, and suggests an algorithm for evaluation.

Sanford School of Medicine, Sioux Falls Campus.

Kim, Young Yun, & Mckay-Semmler, Kelly. (2012). Social engagement and cross-cultural adaptation: An examination of direct- and mediated interpersonal communication activities of educated non-natives in the United States. International Journal of Intercultural Relations, x(x), x-x.

This study explores whether or not technology-mediated interpersonal communication activities with co-ethnics weakens the vital role that direct social engagements with members of the host society play in the cross-cultural adaptation process. Grounded in Kim’s integrative theory of cross-cultural adaptation, this study addresses this question through a detailed examination of the extent to which non-natives participate in face-to-face and mediated “host interpersonal communication” and “ethnic interpersonal communication” through dyadic relationships and organizational affiliations. The analysis utilizes portions of the quantitative and qualitative data obtained from in-depth interviews with 51 relatively well-educated foreign-born residents in the United States. The results indicate that: (1) technology-mediated forms of communication such as email and the Internet serve as the primary means for maintaining contacts with family and friends who remain in the country of origin; (2) non-natives are engaged predominantly in activities of host interpersonal communication rather than ethnic interpersonal communication; and (3) non-natives’ involvements in direct host interpersonal communication, but not their ethnic interpersonal communication, are significantly correlated with their functional and psychological well-being. These and related findings suggest the continuing primacy of non-natives’ direct social engagement with members of the host society in the cross-cultural adaptation process.

Communication Studies Department.

Goyeneche, Alicia A., Seidel, Erin E., & Telleria, Carlos M. (2012). Growth inhibition induced by antiprogestins RU-38486, ORG-31710, and CDB-2914 in ovarian cancer cells involves inhibition of cyclin dependent kinase 2. Investigational new drugs, 30(3), 967-980.

Antiprogestins have been largely utilized in reproductive medicine, yet their repositioning for oncologic use is rapidly emerging. In this study we investigated the molecular mediators of the anti-ovarian cancer activity of the structurally related antiprogestins RU-38486, ORG-31710 and CDB-2914. We studied the responses of wt p53 OV2008 and p53 null SK-OV-3 cells to varying doses of RU-38486, ORG-31710 and CDB-2914. The steroids inhibited the growth of both cell lines with a potency of RU-38486 > ORG-31710 > CDB-2914, and were cytostatic at lower doses but lethal at higher concentrations. Antiprogestin-induced lethality associated with morphological features of apoptosis, hypodiploid DNA content, DNA fragmentation, and cleavage of executer caspase substrate PARP. Cell death ensued despite RU-38486 caused transient up-regulation of anti-apoptotic Bcl-2, ORG-31710 induced transient up-regulation of inhibitor of apoptosis XIAP, and CDB-2914 up-regulated both XIAP and Bcl-2. The antiprogestins induced accumulation of Cdk inhibitors p21(cip1) and p27(kip1) and increased association of p21(cip1) and p27(kip1) with Cdk-2. They also promoted nuclear localization of p21(cip1) and p27(kip1), reduced the nuclear abundances of Cdk-2 and cyclin E, and blocked the activity of Cdk-2 in both nucleus and cytoplasm. The cytotoxic potency of the antiprogestins correlated with the magnitude of the inhibition of Cdk-2 activity, ranging from G1 cell cycle arrest towards cell death. Our results suggest that, as a consequence of their cytostatic and lethal effects, antiprogestin steroids of well-known contraceptive properties emerge as attractive new agents to be repositioned for ovarian cancer therapeutics.

Basic Biomedical Sciences, Vermillion Campus.

Dixon, Mark D., Johnson, W. Carter, Scott, Michael L., Bowen, Daniel E., & Rabbe, Lisa A. (2012). Dynamics of Plains Cottonwood (Populus deltoides) Forests and Historical Landscape Change along Unchannelized Segments of the Missouri River, USA. Environmental management, 49(5), 990-1008.

Construction of six large dams and reservoirs on the Missouri River over the last 50-75years has resulted in major landscape changes and alterations in flow patterns, with implications for riparian forests dominated by plains cottonwood (Populus deltoides). We quantified changes in land cover from 1892-1950s and the 1950s-2006 and the current extent and age structure of cottonwood forests on seven segments (two reservoir and five remnant floodplain) comprising 1127km (53%) of the unchannelized upper two-thirds of the Missouri River. Riparian forest area declined by 49%; grassland 61%; shrubland 52%; and sandbar habitat 96%; while agricultural cropland increased six-fold and river/reservoir surface area doubled from 1892 to 2006. Net rates of erosion and accretion declined between the 1892-1950s and 1950s-2006 periods. Accretion exceeded erosion on remnant floodplain segments, resulting in declines in active channel width, particularly in 1950s-2006. Across all study segments in 2006, most cottonwood stands (67%) were >50years old, 22% were 25-50years old, and only 10% were <25years old. Among stands <50years old, the higher proportion of 25-50year old stands represents recruitment that accompanied initial post-dam channel narrowing; while declines in sandbar and shrubland area and the low proportion of stands <25years old suggest declines in geomorphic dynamism and limited recruitment under recent river management. Future conservation and restoration efforts should focus both on limiting further loss of remnant cottonwood stands and developing approaches to restore river dynamics and cottonwood recruitment processes.

Biology Department.

Casais, M., Vallcaneras, S. S., Arbocco, F. C. V., Delgado, S. M., Hapon, M. B., Sosa, Z., et al. (2012). Estradiol Promotes Luteal Regression Through a Direct Effect on the Ovary and an Indirect Effect From the Celiac Ganglion via the Superior Ovarian Nerve. Reproductive Sciences, 19(4), 416-422.

There is evidence suggesting that estradiol (E(2)) regulates the physiology of the ovary and the sympathetic neurons associated with the reproductive function. The objective of this study was to investigate the effect of E(2) on the function of late pregnant rat ovaries, acting either directly on the ovarian tissue or indirectly via the superior ovarian nerve (SON) from the celiac ganglion (CG). We used in vitro ovary (OV) or ex vivo CG-SON-OV incubation systems from day 21 pregnant rats. Various concentrations of E(2) were added to the incubation media of either the OV alone or the ganglion compartment of the CG-SON-OV system. In both experimental schemes, we measured the concentration of progesterone in the OV incubation media by radioimmunoassay at different times. Luteal messenger RNA (mRNA) expression of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) and 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSD) enzymes, respectively, involved in progesterone synthesis and catabolism, and of antiapoptotic B-cell lymphoma 2 (Bcl-2) and proapoptotic Bcl-2-associated X protein (Bax), were measured by reverse transcriptase-polymerase chain reaction (RT-PCR) at the end of the incubation period. Estradiol added directly to the OV incubation or to the CG of the CG-SON-OV system caused a decline in the concentration of progesterone accumulated in the incubation media. In addition, E(2), when added to the OV incubation, decreased the expression of 3 beta-HSD and the ratio of Bcl-2/Bax. We conclude that through a direct effect on the OV, E(2) favors luteal regression at the end of pregnancy in rats, in association with neural modulation from the CG via the SON.

Basic Biomedical Sciences, Vermillion Campus.

Brouwer, Kyle L. (2012). Writing motivation of students with language impairments. Child Language Teaching & Therapy, 28(2), 189-210.

This study compared the writing motivation of students with language impairments (LI) and their typically developing (TD) peers. For the study 272 students (33 students with language impairments, 242 TD peers) aged 8–10 years, in 11 elementary schools, were sampled. The two groups completed self-report measures of writing motivation and 20 grade-appropriate spelling words from a standardized measure. Multiple regression analyses were used to examine the hypothesis that perceived writing competence – a self-evaluative judgment of writing competence – mediates the relationship between LI status (LI or TD) and intrinsic forms of writing motivation. Statistical analyses indicated that (1) students with specific language impairments reported lower levels of perceived writing competence and intrinsic writing motivation; (2) LI status was a significant predictor of perceived competence after spelling, grade and gender were controlled; and (3) when spelling, grade and gender were controlled, perceived writing competence was a significant predictor of intrinsic writing motivation, but LI status was not. Future research is necessary to further describe external influences on the writing motivation of students with LI and appropriate motivational supports.

Communications Disorders Department.

Resveratrol is a plant-derived polyphenol that can attenuate the cardiotoxic effects of doxorubicin (DOX), a powerful antibiotic widely used in cancer chemotherapy. However, the underlying protective mechanisms of resveratrol remain elusive. Here, we show that resveratrol inhibited DOX-induced autophagy and cardiomyocyte death, and autophagy suppression is an important mechanism that mediates the ability of resveratrol to protect against DOX cardiotoxicity. Indeed, resveratrol, 3-methyladenine (3-MA), and a short hairpin RNA directed against autophagy gene beclin 1 (shBCN1) each was able to attenuate DOX-induced autophagy and cardiomyocyte death, but resveratrol did not provide additional protection in the presence of 3-MA or shBCN1. In contrast, up-regulation of autophagy by beclin 1 overexpression not only exacerbated DOX cardiotoxicity but also abolished the protective effects of resveratrol. Intriguingly, p70 S6 kinase 1 (S6K1) was activated by DOX, which was prevented by resveratrol. Knocking down S6K1 with small interfering RNA diminished DOX-induced autophagy and cardiotoxicity, but resveratrol failed to exert an additive effect. In addition, S6K1 overexpression impaired the ability of resveratrol to antagonize DOX-induced autophagy and cardiomyocyte death. Taken together, our data indicate that the protective effect of resveratrol against DOX cardiotoxicity largely depends on its ability to suppress DOX-induced autophagy via the inhibition of S6K1.

Sanford School of Medicine, Sioux Fals Campus.

Wright, Casey D., Wu, Steven C., Dahl, Erika F., Sazama, Alan J., & O’connell, Timothy D. (2012). Nuclear localization drives alpha 1-adrenergic receptor oligomerization and signaling in cardiac myocytes. Cellular Signalling, 24(3), 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.

Worthington, Amy M., Berns, Chelsea M., & Swallow, John G. (2012). Size matters, but so does shape: quantifying complex shape changes in a sexually selected trait in stalk-eyed flies (Diptera: Diopsidae). Biological Journal of the Linnean Society, 106(1), 104-113.

The elaborate morphologies of sexually selected ornaments are ubiquitous across the animal kingdom. In studies investigating these traits, ornament size is frequently the focus, and empirical evidence supports its positive correlation with fitness. Yet shape plays an important role and, surprisingly, is often overlooked. Shape frequently changes with size, influenced by biomechanical, developmental, or performance constraints. Therefore, shape can provide additional insights into the morphological differences between individuals and the potential limits on sexual trait exaggeration. Here, we used landmark-based geometric morphometric methods on a sexually dimorphic species of stalk-eyed fly ( Teleopsis dalmanni) to examine patterns of sexual shape dimorphism. Our analyses reveal a significant difference in head shape between the sexes, with males exhibiting smaller eye bulbs, thinner stalks, and smaller heads than females. Additionally, as eyestalk length increases within each sex, a similar pattern of shape change was observed as that observed between sexes. This pattern of shape change may be the result of constraints acting against further ornament exaggeration, and we suggest that this may significantly impact the whole-organism performance in stalk-eyed flies.

Biology Department.

Whaley, Katie, Winter, Jordan, Eyster, Kathleen M., & Hansen, Keith A. (2012). Mullerian agenesis with hypohidrotic ectodermal dysplasia syndrome.Fertility and sterility, 97(4), 948-949.

To describe the association of mullerian agenesis with hypohidrotic ectodermal dysplasia. Case report. University medical center. A 17-year-old woman with hypohidrotic ectodermal dysplasia referred for evaluation of primary amenorrhea. History, physical examination, and ultrasound. Physical findings of these two syndromes. Physical examination and ultrasound demonstrated mullerian agenesis with findings of hypohidrotic ectodermal dysplasia. This is the first description of the association of mullerian agenesis with ectodermal dysplasia. This rare case might provide further insight into the development of the uterus and the ectoderm as well as its derivatives. Copyright A 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Sanford School of Medicine, Sioux Falls Campus.

Weber, Amanda S., Grady, Anne M., & Koodali, Ranjit T. (2012). Lanthanide modified semiconductor photocatalysts CATALYSIS SCIENCE & TECHNOLOGY, 2(4), 683-693.

Lanthanide ion modified semiconductor photocatalysts have been explored for photocatalytic degradation of organic pollutants, dye molecules, for photo-splitting of water under both ultra-violet (UV) and visible light conditions. This review provides an in-depth analysis of lanthanide ion semiconductor photocatalysts with focus on titania based photocatalysts. The emphasis is on delineating the underlying factors responsible for the enhanced activities observed by several research groups and in providing guidance to researchers in this area.

Wang, Guojian, Huang, Yisheng, Zhang, Lizhen, Lin, Zhoubin, & Wang, Guofu. (2012). Growth and spectroscopic characteristics of Cr³⁺:KSc( WO₄) ₂ Crystal. Optical Materials, 34(7), 1120-1123.

Abstract: The Cr³⁺:KSc(WO₄)₂ crystal was grown by top seed solution method. The absorption and luminescence spectra were investigated. The absorption cross section σ _a is 1.16×10⁻¹⁹ cm⁻² at 469nm for the ⁴A₂ → ⁴T₁ transition and 4.98×10⁻²⁰ cm⁻² at 684nm for the ⁴A₂ → ⁴T₂ transition, respectively. The emission cross section σ _e of ⁴T₂ → ⁴A₂ transition is 4.86×10⁻²⁰ cm² at 916nm with FWHM of 200nm and fluorescence lifetime is 19.83μs. Based on the absorption and emission spectra, the crystal field strength Dq, the Racah parameters B and C, the effective phonon energy ħω and the Huang-Rhys factor S were calculated. Cr³⁺ ions in KSc(WO₄)₂ crystal occupy the weak crystal field sites and have stronger coupling to crystal lattice.

Physics Department.

Venesky, Matthew, Wilcoxen, Travis, Rensel, Michelle, Rollins-Smith, Louise, Kerby, Jacob, & Parris, Matthew. (2012). Dietary protein restriction impairs growth, immunity, and disease resistance in southern leopard frog tadpoles.Oecologia, 169(1), 23-31.

The immune system is a necessary, but potentially costly, defense against infectious diseases. When nutrition is limited, immune activity may consume a significant amount of an organism’s energy budget. Levels of dietary protein affect immune system function; high levels can enhance disease resistance. We exposed southern leopard frog [ Lithobates sphenocephalus (= Rana sphenocephala)] tadpoles to high and low protein diets crossed with the presence or absence of the pathogenic amphibian chytrid fungus ( Batrachochytrium dendrobatidis; Bd) and quantified: (1) tadpole resistance to Bd; (2) tadpole skin-swelling in response to phytohaemagglutinin (PHA) injection (a measure of the T cell-mediated response of the immune system); (3) bacterial killing ability (BKA) of tadpole blood (a measure of the complement-mediated cytotoxicity of the innate immune system); and (4) tadpole growth and development. Tadpoles raised on a low-protein diet were smaller and less developed than tadpoles on a high-protein diet. When controlled for developmental stage, tadpoles raised on a low-protein diet had reduced PHA and BKA responses relative to tadpoles on a high-protein diet, but these immune responses were independent of Bd exposure. High dietary protein significantly increased resistance to Bd. Our results support the general hypothesis that host condition can strongly affect disease resistance; in particular, fluctuations in dietary protein availability may change how diseases affect populations in the field.

Biology Department.

Swanson, David L, Thomas, Nathan E, Liknes, Eric T, & Cooper, Sheldon J (2012). Intraspecific correlations of Basal and maximal metabolic rates in birds and the aerobic capacity model for the evolution of endothermy. . PloS one, 7(3), e34271+.

The underlying assumption of the aerobic capacity model for the evolution of endothermy is that basal (BMR) and maximal aerobic metabolic rates are phenotypically linked. However, because BMR is largely a function of central organs whereas maximal metabolic output is largely a function of skeletal muscles, the mechanistic underpinnings for their linkage are not obvious. Interspecific studies in birds generally support a phenotypic correlation between BMR and maximal metabolic output. If the aerobic capacity model is valid, these phenotypic correlations should also extend to intraspecific comparisons. We measured BMR, M(sum) (maximum thermoregulatory metabolic rate) and MMR (maximum exercise metabolic rate in a hop-flutter chamber) in winter for dark-eyed juncos (Junco hyemalis), American goldfinches (Carduelis tristis; M(sum) and MMR only), and black-capped chickadees (Poecile atricapillus; BMR and M(sum) only) and examined correlations among these variables. We also measured BMR and M(sum) in individual house sparrows (Passer domesticus) in both summer, winter and spring. For both raw metabolic rates and residuals from allometric regressions, BMR was not significantly correlated with either M(sum) or MMR in juncos. Moreover, no significant correlation between M(sum) and MMR or their mass-independent residuals occurred for juncos or goldfinches. Raw BMR and M(sum) were significantly positively correlated for black-capped chickadees and house sparrows, but mass-independent residuals of BMR and M(sum) were not. These data suggest that central organ and exercise organ metabolic levels are not inextricably linked and that muscular capacities for exercise and shivering do not necessarily vary in tandem in individual birds. Why intraspecific and interspecific avian studies show differing results and the significance of these differences to the aerobic capacity model are unknown, and resolution of these questions will require additional studies of potential mechanistic links between minimal and maximal metabolic output.

Biology Department.

Suarez-Pinzon, Wilma L., & Rabinovitch, A. (2011). Combination Therapy With a Dipeptidyl Peptidase-4 Inhibitor and a Proton Pump Inhibitor Induces beta-Cell Neogenesis From Adult Human Pancreatic Duct Cells Implanted in Immunodeficient Mice. Cell Transplantation, 20(9), 1343-1349.

Combination therapy with a dipeptidyl peptidase-4 inhibitor (DPP-4i) and a proton pump inhibitor (PPI) raises endogenous levels of GLP-1 and gastrin, respectively, and restores pancreatic beta-cell mass and normoglycemia in nonobese diabetic (NOD) mice with autoimmune diabetes. The aim of this study was to determine whether a DPP-4i and PPI combination could increase beta-cell mass in the adult human pancreas. Pancreatic cells from adult human pancreas donors were implanted in NOD-severe combined immunodeficient (NOD-scid) mice and the mice were treated with a DPP-4i and a PPI for 16 weeks. Human grafts were examined for insulin content and insulin-stained cells. Graft beta-cell function was assessed by intravenous glucose tolerance tests (IVGTT) and by glucose control in human cell-engrafted mice treated with streptozotocin (STZ) to delete mouse pancreatic beta-cells. Plasma GLP-1 and gastrin levels were raised to two- to threefold in DPP-4i- and PPI-treated mice. Insulin content and insulin-stained cells in human pancreatic cell grafts were increased 9- to 13-fold in DPP-4i and PPI-treated mice and insulin-stained cells were colocalized with pancreatic exocrine duct cells. Plasma human C-peptide responses to IVGTT were significantly higher and STZ-induced hyperglycemia was more completely prevented in DPP-4i- and PPI-treated mice with grafts than in vehicle-treated mice with grafts. In conclusion, DPP-4i and PPI combination therapy raises endogenous levels of GLP-1 and gastrin and greatly expands the functional beta-cell mass in adult human pancreatic cells implanted in immunodeficient mice, largely from pancreatic duct cells. This suggests that a DPP-4i and PPI combination treatment may provide a pharmacologic therapy to correct the beta-cell deficit in type I diabetes.

Sanford School of Medicine, Sioux Falls Campus.

Stoebner, Susan E., & Mani, Gopinath. (2012). Effect of processing methods on drug release profiles of anti-restenotic self-assembled monolayers. Applied Surface Science, 258(12), 5061-5072.

The use of anti-restenotic self-assembled monolayers (ARSAMs) has been previously demonstrated for delivering drugs from stents without polymeric carriers. ARSAMs have been prepared by coating an anti-restenotic drug (paclitaxel – PAT) on -COOH terminated phosphonic acid self-assembled monolayers (SAMs) coated Co-Cr alloy specimens. This study investigates the effect of different processing methods on the percentage of drug release from ARSAMs. The different methods that were used in this study to process ARSAMs include room temperature (RT) treatment, heat treatment (HT), cold treatment (CT) and quenching. The changes in polymorphism, chemical structure, morphology, and distribution of PAT on SAMs coated specimens were investigated using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and atomic force microscopy (AFM), respectively. DSC showed dihydrate, dehydrated dihydrate, semi-crystalline, and mixed (amorphous and dihydrate) forms of PAT for RT, HT, CT, and quenched specimens, respectively. FTIR showed that the chemical structure of PAT was unaltered in all the specimens processed by various methods employed in this study. SEM showed a mixture of spherical, ovoid, and bean-shaped morphologies of PAT on RT, HT, and CT while particle-like and needle-shaped morphologies of PAT were observed on quenched specimens. AFM showed PAT was uniformly distributed on RT, HT and CT specimens while particle-like PAT was well distributed and needle-shaped PAT was sparsely distributed on quenched specimens. CT specimens showed greater density of PAT crystals when compared to other methods. Thus, this study demonstrated that processing methods have significant influence on the polymorphism, morphology, and distribution of PAT on SAMs coated Co-Cr alloy specimens. The in vitro drug elution studies for up to 56 days showed sustained release for all the different groups of specimens. CT showed lesser percentage of drug release when compared to that of other methods on the first day. The treatment at high temperatures (HT-100 degrees C or HT-140 degrees C) improved the stability of PAT on alloy surfaces and showed lesser percentage of drug release when compared to that of RT or HT-70 degrees C at different time points. Large data scatter was observed for the release profiles of quenched specimens. No other major differences in the percentage of drug release were observed for the specimens prepared by different processing methods. These factors should be taken into consideration when drug delivery platforms are developed for stents or other medical devices. (C) 2012 Elsevier B. V. All rights reserved.

Biomedical Engineering Program, Sioux Falls Campus.

Simons, Jeffrey S., Dvorak, Robert D., Merrill, Jennifer E., & Read, Jennifer P. (2012). Dimensions and severity of marijuana consequences: Development and validation of the Marijuana Consequences Questionnaire (MACQ). Addictive Behaviors, 37(5), 613-621.

Abstract: The Marijuana Consequences Questionnaire (MACQ) is a 50-item self-report measure modeled after the Young Adult Alcohol Consequences Questionnaire (YAACQ). College students (n =315) completed questionnaires online. A confirmatory factor analysis supported the hypothesized 8-factor structure. The results indicate good convergent and discriminant validity of the MACQ. A brief, unidimensional, 21-item version (B-MACQ) was developed by a Rasch model. Comparison of item severity estimates of the B-MACQ items and the corresponding items from the YAACQ indicates that the severity of alcohol- and marijuana-problems is defined by a relatively unique pattern of consequences. The MACQ and B-MACQ provide promising new alternatives to assessing marijuana-related problems.

Psychology Department.

Shinozaki, Gen. (2012). The integrated model of serotonin transporter gene variation (5HTTLPR) and the glial cell transporter in stress vulnerability and depression. Medical Hypotheses, 78(3), 410-414.

The serotonin transporter gene (SLC6A4) promoter polymorphism (5HTTLPR) has been associated with individual stress responses such that individuals with childhood abuse history have higher rates of depression in later life if they are homozygous short (s/s) of the gene. It is hypothesized that these findings could be explained by an integrated model of a role of the glial cell transporter and a functional difference of 5HTTLPR in the capacity of absorbing serotonin from the synapse. A hypothetical integrated model of the SLC6A4 function and the role of glial cells are put forward to explain accumulating results of recent investigations exploring the relationship between the gene and the diverse mental activities including depression and stress response. A model based on SLC6A4 variation is proposed to explain individual differences in stress vulnerability/resilience. The role of the glial cell transporter surrounding the synapse is integrated in the model to understand the modulation of the neurotransmission. It is hypothesized that a synapse with less serotonin transporter contributes to unstable processing in neurotransmission as compared to a synapse with more serotonin transporter. As such, based on functional differences of 5HTTLPR in the expression of the serotonin transporter, it is asserted that individuals with the s/s genotype process neurotransmission differently and in a reactive way. This integrated model of 5HTTLPR and glial cells suggests that the efficacy of serotonin reuptake in the synapse may play a crucial role in variability of neurotransmission, which can lead to differences in the stress response and the pathophysiology of depression. (C) 2011 Published by Elsevier Ltd.

Sanford School of Medicine, Sioux Falls Campus.

Shearer, Gregory C., Savinova, Olga V., & Harris, William S. (2012). Fish oil — How does it reduce plasma triglycerides? BBA – Molecular & Cell Biology of Lipids, 1821(5), 843-851.

Abstract: Long chain omega-3 fatty acids (FAs) are effective for reducing plasma triglyceride (TG) levels. At the pharmaceutical dose, 3.4g/day, they reduce plasma TG by about 25–50% after one month of treatment, resulting primarily from the decline in hepatic very low density lipoprotein (VLDL-TG) production, and secondarily from the increase in VLDL clearance. Numerous mechanisms have been shown to contribute to the TG overproduction, but a key component is an increase in the availability of FAs in the liver. The liver derives FAs from three sources: diet (delivered via chylomicron remnants), de novo lipogenesis, and circulating non-esterified FAs (NEFAs). Of these, NEFAs contribute the largest fraction to VLDL-TG production in both normotriglyceridemic subjects and hypertriglyceridemic, insulin resistant patients. Thus reducing NEFA delivery to the liver would be a likely locus of action for fish oils (FO). The key regulator of plasma NEFA is intracellular adipocyte lipolysis via hormone sensitive lipase (HSL), which increases as insulin sensitivity worsens. FO counteracts intracellular lipolysis in adipocytes by suppressing adipose tissue inflammation. In addition, FO increases extracellular lipolysis by lipoprotein lipase (LpL) in adipose, heart and skeletal muscle and enhances hepatic and skeletal muscle β-oxidation which contributes to reduced FA delivery to the liver. FO could activate transcription factors which control metabolic pathways in a tissue specific manner regulating nutrient traffic and reducing plasma TG. This article is part of a Special Issue entitled Triglyceride Metabolism and Disease.

Sanford School of Medicine, Sioux Falls Campus.

Sereda, Grigoriy, Marshall, Christopher, Libera, Joseph, Dreessen, James, Grady, Anne, & Turner, Mark. (2012). Effect of Atomic Layer Deposition Support Thickness on Structural Properties and Oxidative Dehydrogenation of Propane on Alumina- and Titania-Supported Vanadia. Catalysis Letters, 142(4), 399-407.

Engineered solid supports for vanadium catalysts were prepared by atomic layer deposition (ALD) of alumina and titania layers on silica. The thickness of these layers was found to have a significant effect on the structure of the solid supports, their interaction with vanadia, and their catalytic performance with regard to oxidative dehydrogenation of propane. The catalytic performance of supported vanadia catalysts is reported for both ALD-engineered and conventional solid supports (γ-AlO and TiO). The analysis results indicated that the engineered supports behave as a separate phase rather than a cross between the base silica and the deposited alumina or titania.

Chemistry Department.

Sereda, Grigoriy A., Moorthy, Ramkumar, Basa, Prem N., Sykes, Andrew G., Purohit, Kaushalkumar, Rajpara, Vikul B., et al. (2012). Unexpected Diastereoselective Acetylation of 1,8-Dimethoxyanthracene Adducts with Maleic Anhydride and Dimethyl Maleate EUROPEAN JOURNAL OF ORGANIC CHEMISTRY /(4), 810-816.

FriedelCrafts acetylation of adducts between 1,8-dimethoxyanthracene and maleic anhydride or dimethyl maleate proceeds with a strong preference toward the syn diastereomer. This stereoselectivity is especially prominent for the anhydride counterpart. Dependence of the observed selectivity on the adduct structure is rationalized by the analysis of computed HOMO energies of the reactants and relative energies of the intermediate s-complexes. The possible undesired intermolecular condensation of the anhydride did not take place because of steric hindrance. Structures of the reaction products were unambiguously confirmed by single-crystal X-ray diffraction (XRD). The reported stereoselectivity of acetylation provides facile access to compounds with the functionalized benzene ring in a syn arrangement with respect to the pendant carboxyl substituents.

Chemistry Department.

Roux, Kyle. J., Kim, Doe In, Raida, M., & Burke, B. (2012). A promiscuous biotin ligase fusion protein identifies proximal and interacting proteins in mammalian cells. Journal of Cell Biology, 196(6), 801-810.

We have developed a new technique for proximity-dependent labeling of proteins in eukaryotic cells. Named BiolD for proximity-dependent biotin identification, this approach is based on fusion of a promiscuous Escherichia coil biotin protein ligase to a targeting protein. BiolD features proximity-dependent biotinylation of proteins that are near-neighbors of the fusion protein. Biotinylated proteins may be isolated by affinity capture and identified by mass spectrometry. We apply BiolD to lamin-A (LaA), a well-characterized intermediate filament protein that is a constituent of the nuclear lamina, an important structural element of the nuclear envelope (NE). We identify multiple proteins that associate with and/or are proximate to LaA in vivo. The most abundant of these include known interactors of LaA that are localized to the NE, as well as a new NE-associated protein named SLAP75. Our results suggest BiolD is a useful and generally applicable method to screen for both interacting and neighboring proteins in their native cellular environment.

Sanford School of Medicine, Sioux Falls Campus.

Quinn, S. N., Bakos, G. A., Hartman, J., Torres, G., …., Perumpilly, Gopan, et al. (2012). HAT-P-25b: A HOT-JUPITER TRANSITING A MODERATELY FAINT G STAR. Astrophysical Journal, 745(1).

We report the discovery of HAT-P-25b, a transiting extrasolar planet orbiting the V = 13.19 G5 dwarf star GSC 1788-01237, with a period P = 3.652836 +/- 0.000019 days, transit epoch T-c = 2455176.85173 +/- 0.00047 (BJD-barycentric Julian dates throughout the paper are calculated from Coordinated Universal Time, UTC), and transit duration 0.1174 +/- 0.0017 days. The host star has a mass of 1.01 +/- 0.03 M-circle dot, radius of 0.96(-0.04)(+0.05)R(circle dot), effective temperature 5500 +/- 80 K, and metallicity [Fe/H] = +0.31 +/- 0.08. The planetary companion has a mass of 0.567 +/- 0.022 M-J and radius of 1.190(-0.056)(+0.081) R-J yielding a mean density of 0.42 +/- 0.07 g cm(-3).

Physics Department.

Parodi, Claudia, Luna, Kenneth V., & Helmer, Ángela. (2012). El leísmo en América y en España: bifurcación de una norma. Bulletin of Hispanic Studies (1475-3839), 89(3), 217-236.

En el presente trabajo, analizamos la trayectoria del leísmo en América Latina. En España, la distribución dialectal así como la historia del leísmo han sido estudiadas a fondo, mientras que la diacronía del leísmo en América es poco conocida y apenas existen trabajos sobre el tema. Por medio de un análisis sistemático de textos tanto españoles, pertenecientes a los siglos XII-XVIII, como latinoamericanos, específicamente mexicanos y peruanos de los siglos XVI-XXI, hemos seguido el recorrido de este fenómeno en Latinoamérica desde su inicio hasta su (casi) desaparición en el español estándar latinoamericano. En el estudio, tomamos también en cuenta la norma académica y su influencia en el habla de América, así como las razones sociales que pudieron haber conllevado a su eliminación.

Modern Languages Department.

Lynch, Douglas W., Verma, Rashmi, Larson, Eric, Geis, Michael C., & Jassim, Ali D.(2012). Primary cutaneous mantle cell lymphoma with blastic features: report of a rare case with special reference to staging and effectiveness of chemotherapy. Journal of cutaneous pathology, 39(4), 449-453.

We describe a case of blastic primary cutaneous mantle cell lymphoma (MCL) in an 83-year-old male with a complex medical history. The patient presented to his primary care physician with a nodular erythematous skin eruption on his thighs. Histopathologic examination showed a diffuse lymphoid infiltrate of intermediate to large cells that involved the dermis and subcutis but spared the epidermis. Immunohistochemical staining showed expression of CD20, CD5 and cyclin-D1. The lymphoma cells were negative for CD10 and CD23. Fluorescence in situ hybridization (FISH) analysis revealed a characteristic translocation [t(11;14)(q13;q32)], which is diagnostic of MCL. Cutaneous involvement by MCL is typically secondary because of widespread disease, and primary cutaneous MCL can only be diagnosed in the absence of extracutaneous involvement. Primary cutaneous MCL is extremely rare and requires proper clinical staging. In this case, clinical staging revealed no evidence of bone marrow or peripheral blood involvement, and positron emission tomography (PET) scan revealed weak, abnormal uptake only in a few cervical lymph nodes. Because of the lack of disseminated involvement, we favor the lesion to be a primary cutaneous MCL. Lynch DW, Verma R, Larson E, Geis MC, Jassim AD. Primary cutaneous mantle cell lymphoma with blastic features: report of a rare case with special reference to staging and effectiveness of chemotherapy. Copyright 2011 John Wiley & Sons A/S.

Sanford School of Medicine, Sioux FallsCampus.

Li, W., & Keifer, Joyce. (2012). RAPID ENRICHMENT OF PRESYNAPTIC PROTEIN IN BOUTONS UNDERGOING CLASSICAL CONDITIONING IS MEDIATED BY BRAIN-DERIVED NEUROTROPHIC FACTOR. Neuroscience, 203, 50-58.

Presynaptic structural modifications are thought to accompany activity-dependent synaptic plasticity and learning. This may involve the conversion of nonfunctional synapses into active ones or the generation of entirely new synapses. Here, using an in vitro neural analog of classical conditioning, we investigated presynaptic structural changes restricted to auditory nerve synapses that convey the conditioned stimulus (CS) by tract tracing using fluorescent tracers combined with immunostaining for the synaptic vesicle-associated protein synaptophysin. The results show that the size of presynaptic auditory boutons increased and the area and fluorescence intensity of punctate staining for synaptophysin were enhanced after conditioning. This occurred only for auditory nerve boutons apposed to the dendrites but not the somata of abducens motor neurons. Conditioning increased the percentage of boutons that were immunopositive for synaptophysin and enhanced the number of synaptophysin puncta they contained. Pretreatment with antibodies against brain-derived neurotrophic factor (BDNF) inhibited these conditioning-induced structural changes. There was also a net increase in the number of boutons apposed to abducens motor neurons after conditioning or BDNF treatment. These data indicate that the rapid enrichment of presynaptic boutons with proteins required for neurotransmitter recycling and release occurs during classical conditioning and that these processes are mediated by BDNF. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Basic Biomedical Sciences, Vermillon Campus.

Lauritzen, B., Timoney, N., Gisin, N., Afzelius, M., De Riedmatten, H., Sun, Y., et al. (2012). Spectroscopic investigations of Eu3+:Y2SiO5 for quantum memory applications. Physical Review B, 85(11).

Rare-earth-ion-doped solids are promising materials as light-matter interfaces for quantum applications. Europium doped into an yttrium orthosilicate crystal in particular has interesting coherence properties and a suitable ground-state energy-level structure for a quantum memory for light. In this paper we report on spectroscopic investigations of this material from the perspective of implementing an atomic frequency comb (AFC)-type quantum memory with spin-wave storage. For this goal we determine the order of the hyperfine levels in the F-7(0) ground state and D-5(0) excited state, and we measure the relative strengths of the optical transitions between these levels. We also apply spectral hole burning techniques in order to prepare the system as a well-defined Lambda system, as required for further quantum memory experiments. Furthermore, we measure the optical Rabi frequency on one of the strongest hyperfine transitions, a crucial experimental parameter for the AFC protocol. From this we also obtain a value for the transition dipole moment which is consistent with that obtained from absorption measurements.

Physics Department.

Kruer, M. C., Boddaert, N., Schneider, S. A., Houlden, H., Bhatia, K. P., Gregory, A., et al. (2012). Neuroimaging features of neurodegeneration with brain iron accumulation. AJNR. American journal of neuroradiology, 33(3), 407-414.

SUMMARY: NBIA characterizes a class of neurodegenerative diseases that feature a prominent extrapyramidal movement disorder, intellectual deterioration, and a characteristic deposition of iron in the basal ganglia. The diagnosis of NBIA is made on the basis of the combination of representative clinical features along with MR imaging evidence of iron accumulation. In many cases, confirmatory molecular genetic testing is now available as well. A number of new subtypes of NBIA have recently been described, with distinct neuroradiologic and clinical features. This article outlines the known subtypes of NBIA, delineates their clinical and radiographic features, and suggests an algorithm for evaluation.

Sanford School of Medicine, Sioux Falls Campus.

Kovash, Curtiss S., Hoefelmeyer, James D., & Logue, Brian A. (2012). TiO2 compact layers prepared by low temperature colloidal synthesis and deposition for high performance dye-sensitized solar cells. Electrochimica Acta, 67, 18-23.

Abstract: Compact layers are used in dye-sensitized solar cells (DSSCs) to passivate transparent conducting oxides (TCOs). TCO passivation increases DSSC performance by reducing electrical loss from recombination at the TCO-electrolyte interface and by improving electrical contact between the TCO and TiO2 photoelectrode. A novel process for synthesis of 4.5nm colloidal TiO2 compact layer particles via acid hydrolysis of titanium isopropoxide was developed. DSSCs fabricated with the colloidal TiO2 compact layer, with no compact layer, and those with an RF-sputtered compact layer were evaluated. Relative to a DSSC with no compact layer, the colloidal compact layer improved the short-circuit current density, fill factor, and solar energy conversion efficiency by 17.6%, 4.4%, and 25.3%, respectively. Relative to the sputtered compact layer, the colloidal compact layer improved the short-circuit current density and solar energy conversion efficiency by 5.5% and 5.3%, respectively, with no significant change in the fill factor. The improved DSSC characteristics were attributed to increased shunt resistance due to decreased electrolyte reduction at the TCO-electrolyte interface and decreased series resistance due to improved electrical contact between the TCO and the TiO2 photoelectrode.

Chemistry Department.

Jang, Yuri, Park, Nan Sook, Kim, Giyeon, Kwag, Kyung Hwa, Roh, Soonhee, & Chiriboga, David A. (2012). The association between self-rated mental health and symptoms of depression in Korean American older adults. Aging & Mental Health, 16(4), 481-485.

Objective: The study examined the association of self-rated mental health (SRMH) with three measures of depressive symptoms (the short form CES-D, GDS-SF, and PHQ-9) in Korean American older adults. Method: The sample consisted of 420 community-dwelling Korean American older adults (M age = 71.6, SD = 7.59) in the New York City metropolitan area. Hierarchical regression models of SRMH were estimated with an array of predictors: (a) sociodemographic characteristics, (b) physical health-related variables, and (c) each of the three depressive symptom measures. Results: The three measures of depressive symptoms were interrelated, and each of them made a significant contribution to the multivariate models of SRMH. The amount of variance explained by the short-form CES-D, GDS-SF, and PHQ-9 was 11%, 10%, and 16%, respectively. Conclusion: Findings show a moderately strong linkage between the measures of depressive symptoms and SRMH and invite further research on SRMH in diverse populations.

School of Health Sciences.

Han, Yulun, Dai, Fengrong, Sykes, Andrew G., May, P. Stanley, Berry, Mary T., Meng, Qingguo, et al. (2012). catena-Poly 1-butyl-3-methyl-imidazolium dichlorido(methanol-kappaO)(propan-2-ol-kappaO)lanthanate(III) -di-mu-chlorido. Acta crystallographica. Section E, Structure reports online, 68(Pt 3), m292-293.

The title compound, (C(8)H(15)N(2))[LaCl(4)(CH(3)OH)(C(3)H(7)OH)], consists of one 1-butyl-3-methyl-imidazolium (BMI(+)) cation and one hexa-hedral tetra-chlorido(methanol)(propan-2-ol)lanthanate anion. The La(III) ion is eight-coordinate, with the La(III) ion bridged by a pair of Cl atoms, so forming chains propagating along the a-axis direction. Each La(III) ion is further coordinated by two isolated Cl atoms, one methanol and one propan-2-ol mol-ecule. The coordinated methanol and propan-2-ol mol-ecules of the anion form O-H⋯Cl hydrogen bonds with the Cl atoms of inversion-related anions. The BMI(+) cation froms C-H⋯Cl hydrogen bonds with the Cl atoms of the anion. The anions are located in the C faces of the triclinic unit cell, with an inversion center in the middle of the La(2)Cl(2) ring of the polymeric chain.

Chemistry Department.

Fiegen, Michael M., Benson, Kevin D., Hanson, Jessica D., Prasek, Jennifer, Hansen, Keith A., & Vaneerden, Peter. (2012). The prevalence of urinary incontinence in American Indian women from a South Dakota tribe. International urogynecology journal, 23(4), 473-479.

The purpose of this pilot study was to evaluate the prevalence and associated risk factors for urinary incontinence in a Northern Plains tribe of American Indian women. The Urogenital Distress Inventory-Short Form was used to assess urinary incontinence in a sample of American Indian women from one tribe. This was a cross-sectional convenience sampling of 234 eligible participants. Participant’s ages ranged from 18 to 80years. Stata/Se 9.1 software was used in statistical analysis. The overall prevalence of urinary stress incontinence was 15.4%, urgency incontinence 2.14%, and mixed incontinence 20.5%. Both stress and urgency incontinence was found to be low in this sample population. A reduced prevalence of stress and urgency incontinence is seen in our sample. Our study group showed a high prevalence of known risk factors associated with urinary incontinence. We intend to extend our study for further understanding of this patient population.

Sanford School of Medicine, Sioux Falls Campus.

Cwach, Kevin T., Sandbulte, Heather R., Klonoski, Joshua M., & Huber, Victor C.(2012). Contribution of murine innate serum inhibitors toward interference within influenza virus immune assays. Influenza and Other Respiratory Viruses, 6(2), 127-135.

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 (56 degrees C) 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: 56 degrees C alone, RDE alone, or RDE + 56 degrees C, 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.

Basic Biomedical Sciences, Vermillion Campus.

Berdahl, John P., Fleischman, David, Zaydlarova, Jana, Stinnett, Sandra, Allingham, R. Rand, & Fautsch, Michael P. (2012). Body mass index has a linear relationship with cerebrospinal fluid pressure. Investigative ophthalmology & visual science, 53(3), 1422-1427.

Purpose. To examine the relationship between body mass index (BMI) and cerebrospinal fluid pressure (CSFP), as low BMI and low CSFP have recently been described as risk factors for primary open-angle glaucoma (POAG). Methods. This was a retrospective review of the electronic medical records of patients who had CSFP measured by lumbar puncture and data to calculate BMI at the Mayo Clinic (Rochester, MN). Exclusion criteria included diagnoses, surgical procedures and medications known to affect CSFP. Mean CSFP for each unit BMI was calculated. The probabilities were two-tailed, and the alpha level was set at P < 0.05. Patients with documented BMI, CSFP, and intraocular pressure (IOP) were analyzed for the relationship between IOP and BMI. Results. A total of 4235 patients, primarily of Caucasian descent, met the entry criteria. Median BMI was 26 and the mean CSFP was 10.9 2.6 mm Hg. The increase in CSFP with increasing BMI was linear with an r(2) = 0.20 (P < 0.001). CSFP increased by 37.7% from BMI 18 (8.6 2.1 mm Hg) to BMI 39 (14.1 2.5 mm Hg). The r(2) (0.21) of the model of BMI and sex was similar to the r(2) of a BMI-only model (0.20). There was no relation between IOP and BMI within a subgroup of the study population (r (2) = 0.005; P = 0.14). Conclusions. CSFP has a positive, linear relationship with BMI. IOP is not influenced by BMI. If CSFP influences the risk for POAG, then individuals with a lower BMI may have an increased risk for developing POAG. Similarly, a higher BMI may be protective.

Sanford School of Medicine, Sioux Falls Campus.

Baugh, Lee A., & Flanagan, J. R. (2012). Motor Memory: When Plans Speak Louder Than Actions. Current Biology, 22(5), R155-R157.

A new study demonstrates that separate motor memories can be learned and remembered for two physically identical movements, provided that those movements have different goals.

Basic Biomedical Sciences, Vermillion Campus.

Åse, Fagerlund, Ilona, Autti-Rämö, Mirjam, Kalland, Pekka, Santtila, Eugene, Hoyme, Sarah, Mattson, et al. (2012). Adaptive behaviour in children and adolescents with foetal alcohol spectrum disorders: a comparison with specific learning disability and typical development. European Child & Adolescent Psychiatry, 21(4), 221-231.

Foetal alcohol spectrum disorders (FASD) is a leading cause of intellectual disability in the western world. Children and adolescents with FASD are often exposed to a double burden in life, as their neurological sequelae are accompanied by adverse living surroundings exposing them to further environmental risk. In the present study, the adaptive abilities of a group of children and adolescents with FASD were examined using the Vineland Adaptive Behaviour Scales (VABS) and compared to those of a group of IQ-matched children with specific learning disorder (SLD) as well as with typically developing controls (CON). The results showed significantly different adaptive abilities among the groups: Children with FASD performed worse than IQ-matched children with SLD, who in turn performed worse than typically developing children on all domains (communication, daily living skills and socialization) on the VABS. Compared to the other groups, social skills declined with age in the FASD group. These results support previous studies of adaptive behaviour deficits in children with FASD and provide further evidence of the specificity of these deficits. On a societal level, more efforts and resources should be focused on recognizing and diagnosing FASD and supporting communication skills, daily living skills and most of all social skills across diagnostic groups within FASD. Without adequate intervention, adolescents and young adults with FASD run a great risk of marginalization and social maladjustment, costly not only to society but also to the lives of the many young people with FASD.

Sanford School of Medicine, Sioux Falls Campus.

Akerib, D. S., Bai, X., …., Mei, D., …, & Zhang, C. (2012). Data acquisition and readout system for the LUX dark matter experiment. Nuclear Instruments & Methods in Physics Research Section a-Accelerators Spectrometers Detectors and Associated Equipment, 668, 1-8.

LUX is a two-phase (liquid/gas) xenon time projection chamber designed to detect nuclear recoils from interactions with dark matter particles. Signals from the LUX detector are processed by custom-built analog electronics which provide properly shaped signals for the trigger and data acquisition (DAQ) systems. The DAQ is composed of commercial digitizers with firmware customized for the LUX experiment. Data acquisition systems in rare-event searches must accommodate high rate and large dynamic range during precision calibrations involving radioactive sources, while also delivering low threshold for maximum sensitivity. The LUX DAQ meets these challenges using real-time baseline suppression that allows for a maximum event acquisition rate in excess of 1.5 kHz with virtually no deadtime. This paper describes the LUX DAQ and the novel acquisition techniques employed in the LUX experiment. (C) 2011 Elsevier B.V. All rights reserved.

Physics Department.

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.

Gold nanorods have great potential in a variety of applications because of their unique physical properties. In this article, we present the layer-by-layer (LbL) assembly of thin films containing positively charged gold nanorods that are covalently functionalized by cationic thiol molecules. The cationic gold nanorods are uniformly distributed in ultrathin nanocomposite LbL thin films. We studied the collective surface plasmon resonance coupling in the LbL films via UV-visible spectroscopy and evaluated their application in the surface-enhanced Raman scattering detection of rhodarnine 6G probe molecules. Furthermore, we successfully manufactured freestanding nanoscale thin films containing multilayers of gold nanorods with a total thickness of less than 50 nrn. The surface morphology and their optical and mechanical properties were systematically investigated, and the polycationic gold nanorods were found to play an important role in manipulating the properties of the nanocomposite thin films. Our findings reveal that such nanorods are excellent building blocks for constructing functional LbL films with tunable plasmonic behavior and robust mechanical properties.

Chemistry Department.

Chauhan, Subash C., Ebeling, Mara C., Maher, Diane M., Koch, Michael D., Watanabe, Akira, Aburatani, Hiroyuki, Lio, Yuhlong L., and Jaggi, Meena. “Muc13 Mucin Augments Pancreatic Tumorigenesis.” Molecular Cancer Therapeutics 11, no. 1 (2012): 24-33.

The high death rate of pancreatic cancer is attributed to the lack of reliable methods for early detection and underlying molecular mechanisms of its aggressive pathogenesis. Although MUC13, a newly identified transmembrane mucin, is known to be aberrantly expressed in ovarian and gastro-intestinal cancers, its role in pancreatic cancer is unknown. Herein, we investigated the expression profile and functions of MUC13 in pancreatic cancer progression. The expression profile of MUC13 in pancreatic cancer was investigated using a recently generated monoclonal antibody (clone PPZ0020) and pancreatic tissue microarrays. The expression of MUC13 was significantly (P < 0.005) higher in cancer samples compared with normal/nonneoplastic pancreatic tissues. For functional analyses, full-length MUC13 was expressed in MUC13 null pancreatic cancer cell lines, MiaPaca and Panc1. MUC13 overexpression caused a significant (P < 0.05) increase in cell motility, invasion, proliferation, and anchorage-dependent or -independent clonogenicity while decreasing cell-cell and cell-substratum adhesion. Exogenous MUC13 expression significantly (P < 0.05) enhanced pancreatic tumor growth and reduced animal survival in a xenograft mouse model. These tumorigenic characteristics correlated with the upregulation/phosphorylation of HER2, p21-activated kinase 1 (PAK1), extracellular signal-regulated kinase (ERK), Akt, and metastasin (S100A4), and the suppression of p53. Conversely, suppression of MUC13 in HPAFII pancreatic cancer cells by short hairpin RNA resulted in suppression of tumorigenic characteristics, repression of HER2, PAK1, ERK, and S100A4, and upregulation of p53. MUC13 suppression also significantly (P < 0.05) reduced tumor growth and increased animal survival. These results imply a role of MUC13 in pancreatic cancer and suggest its potential use as a diagnostic and therapeutic target. Mol Cancer Ther; 11(1); 24-33. (C) 2011 AACR.

Sanford School of Medicine, Sioux Falls Campus.

Dement-Brown, J., Newton, C. S., Ise, T., Damdinsuren, B., Nagata, Satoshi, and Tolnay, M. “Fc Receptor-Like 5 Promotes B Cell Proliferation and Drives the Development of Cells Displaying Switched Isotypes.” Journal of Leukocyte Biology 91, no. 1 (2012): 59-67.

The biological roles of B cell membrane proteins in the FCRL family are enigmatic. FCRL proteins, including FCRL5, were shown to modulate early BCR signaling, although the subsequent, functional consequences of receptor engagement are poorly understood. We found that FCRL5 surface protein itself was induced temporarily upon BCR stimulation of human, naive B cells, indicating precise control over timing of FCRL5 engagement. Cross-linking of FCRL5 on cells induced to express FCRL5 enhanced B cell proliferation significantly. This enhancement required costimulation of the BCR and TLR9, two signals required for optimal proliferation of naive B cells, whereas T cell help in the form of anti-CD40 and IL-2 was dispensable. In addition, we found that FCRL5 stimulation generated a high proportion of cells displaying surface IgG and IgA. Optimal development of cells expressing switched isotypes required T cell help, in addition to stimuli found necessary for enhanced proliferation. Surprisingly, cells that developed upon FCRL5 stimulation simultaneously displayed surface IgM, IgG, and IgA. Cells expressing multiple Ig isotypes were described in hairy cell leukemia, a disease in which FCRL5 is overexpressed. Enhanced proliferation and downstream isotype expression upon FCRL5 stimulation could reflect a physiological role for FCRL5 in the expansion and development of antigen-primed B cells. In addition, FCRL5 may promote growth of malignant cells in hairy cell leukemia and other FCRL5-expressing tumors. J. Leukoc. Biol. 91: 59-67; 2012.

Sanford School of Medicine, Sioux Falls Campus.

Ehli, Erik A., Hu, Y., Lengyel-Nelson, T., Hudziak, J. J., and Davies, Garreth E. “Identification and Functional Characterization of Three Novel Alleles for the Serotonin Transporter-Linked Polymorphic Region.” Molecular psychiatry 17, no. 2 (2012): 185-92.

A promoter polymorphism in the serotonin transporter gene (5-HTTLPR) has been reported to confer relative risk for phenotypes (depression/anxiety) and endophenotypes (amygdala reactivity). In this report, we identify and characterize three rare 5-HTTLPR alleles not previously described in the human literature. The three novel alleles were identified while genotyping 5-HTTLPR in a family-based attention deficit hyperactivity disorder clinical population. Two of the novel alleles are longer than the common 16-repeat long (L) allele (17 and 18 repeats) and the third is significantly smaller than the 14-repeat short (S) allele (11 repeats). The sequence and genetic architecture of each novel allele is described in detail. We report a significant decrease in the expression between the XL(17) (17r) allele and the L(A) (16r) allele. The XS(11) (11r) allele showed similar expression with the S (14r) allele. A 1.8-fold increase in expression was observed with the L(A)(16r) allele compared with the L(G) (16r) allele, which replicates results from earlier 5-HTTLPR expression experiments. In addition, transcription factor binding site (TFBS) analysis was performed using MatInspector (Genomatix) that showed the presence or absence of different putative TFBSs between the novel alleles and the common L (16r) and S (14r) alleles. The identification of rare variants and elucidation of their functional impact could potentially lead to understanding the contribution that the rare variant may have on the inheritance/susceptibility of multifactorial common diseases.

Sanford School of Medicine, Sioux Falls Campus.

Gillies, P. J., Harris, William S., and Kris-Etherton, P. M. “Omega-3 Fatty Acids in Food and Pharma: The Enabling Role of Biotechnology.” Current Atherosclerosis Reports 13, no. 6 (2011): 467-73.

Omega-3 fatty acid research, which began as an epidemiologic curiosity, has generated perhaps the strongest dataset for any nutrient in regard to cardiovascular disease risk reduction. Although once a relatively descriptive field, advances in analytic techniques have opened up the biochemistry of omega-3 fatty acids and nutritional genomics in plants and man and have taken the field into the “omic” era. Despite this progress, fundamental questions remain unanswered, such as which fatty acid or metabolite thereof drives a given health benefit, how much of a given fatty acid should we consume, and how do we best source the requisite fatty acids? Of these questions, the ability to source omega-3 fatty acids in order to meet dietary guidelines has become a practical concern. The advent of novel oils from plants and single cell organisms as enabled by biotechnology may provide a solution to this problem and in the process open up new uses for omega-3 fatty acids in dietary supplements and drugs.

Snford School of Medicine, Sioux Falls Campus.

Gustafson, J. D., Fox, J. P., Ouellette, J. R., Hellan, M., Termuhlen, P., McCarthy, M. C., and Thambi-Pillai, Thavam. “Open Versus Laparoscopic Liver Resection: Looking Beyond the Immediate Postoperative Period.” Surgical Endoscopy and Other Interventional Techniques 26, no. 2 (2012): 468-72.

Laparoscopic liver resection for malignant disease has shown short-term benefit. This study aimed to compare in-house, 30-day, and 1-year morbidity between laparoscopic and open liver resections. The charts for all patients who underwent liver resection for malignant disease between April 2006 and October 2009 were reviewed. Patient, operative, and outcomes data at 30 days and 1 year were collected. For 76 patients, 49 open and 27 laparoscopic resections were performed. The two groups were similar in terms of age, gender, body mass index (BMI), extent of liver resection, use of ablation therapy, and tumor pathology (P > 0.05). The laparoscopic group had less blood loss (P = 0.004) and shorter hospital stays (P = 0.002). During their hospital stay, patients treated laparoscopically had fewer complications, but the difference was not significant. Home disposition was similar in the laparoscopic (96%) and open (90%) groups. More patients were readmitted at 30 days (2 vs. 9; P = 0.31) and 1 year (4 vs. 19; P = 0.04) in the open group. The all-cause 1-year mortality rates were similar between the laparoscopic and open groups (14.8% vs. 10.2%). The benefits of laparoscopic liver resection may extend beyond the initial postoperative period, with fewer readmissions despite shorter hospital stays. This also may suggest lower long-term hospital costs.

Sanford School of Medicine, Sioux Falls Campus.

Hanson, Jessica D. “Understanding Prenatal Health Care for American Indian Women in a Northern Plains Tribe.” Journal of Transcultural Nursing 23, no. 1 (2012): 29-37.

Early and regular prenatal care appointments are imperative for the health of both the mother and baby to help prevent complications associated with pregnancy and birth. American Indian women are especially at risk for health disparities related to pregnancy and lack of prenatal health care. Previous research has outlined a basic understanding of the reasons for lack of prenatal care for women in general; however, little is known about care received by pregnant women at Indian Health Service hospitals. Qualitative interviews were carried out with 58 women to better understand the prenatal health experiences of American Indian women from one tribe in the Northern Plains. Several themes related to American Indian women’s prenatal health care experiences were noted, including communication barriers with physicians, institutional barriers such as lack of continuity of care, and sociodemographic barriers. Solutions to these barriers, such as a nurse midwife program, are discussed.

Sanford School of Medicine, Sioux Falls Campus.

Harris, Wiliiam S. “Stearidonic Acid as a ‘Pro-Eicosapentaenoic Acid’.” Current Opinion in Lipidology 23, no. 1 (2012): 30-34.

Purpose of review omega-3 Fatty acids continue to be promoted as cardioprotective, generating an increased demand for these nutrients. Ocean-based supplies are limited, and so land-based sources are being sought. Stearidonic acid-fortified soybean oil may help to meet this demand. Recent findings Stearidonic acid has been shown in animal and human studies to be more effective than its precursor, alpha-linolenic acid, in enriching membranes with eicosapentaenoic acid. Hence, stearidonic acid can serve as a ‘pro-eicosapentaenoic acid’. Summary Stearidonic acid-fortified soybean oil may be able to help close the gap between actual and recommended intakes of omega-3 fatty acids in an environmentally friendly manner.

Sanford School of Medicine, Sioux Falls Campus.

Kerby, Jacob L., Hart, A. J., and Storfer, A. “Combined Effects of Virus, Pesticide, and Predator Cue on the Larval Tiger Salamander (Ambystoma Tigrinum).” Ecohealth 8, no. 1 (2012): 46-54.

Emerging diseases and environmental contamination are two of the leading hypotheses for global amphibian declines. Yet few studies have examined the influence of contaminants on disease susceptibility, and even fewer have incorporated the role of natural stressors such as predation. We performed a factorial study investigating the interaction of the insecticide carbaryl, dragonfly predator cue, and the emerging pathogen Ambystoma tigrinum virus (ATV) on fitness correlates and disease susceptibility in tiger salamander larvae. Four week old larvae were exposed for 22 days in a 2 (0, 500 mu g/l carbaryl) x 2 (control, predator cue water) x 2 (0, 1 x 10(4) pfu ATV) factorial designed laboratory study. Results show significant impacts to survival of larvae for both virus and predator cue treatments, as well as an interactive effect between the two, in which predator cue strongly exacerbated disease-driven mortality. There was a clear pattern of reduced survival with the addition of stressors, with those where all three stressors were present exhibiting the worst effects (a decrease in survival from 93 to 60%). On those that survived, we also detected several sub-lethal impacts in mass, SVL, and development. Predator cue and pesticide treatments significantly reduced both SVL and mass. Virus and predator treatments significantly slowed development. Stressors also exhibited opposing effects on activity. Predator cue caused a significant reduction in activity, whereas virus caused a significant increase in activity over time. These results highlight the importance of examining combined natural and introduced stressors to understand potential impacts on amphibian species. Such stressors may contribute to the emergence of ATV in particular regions, raising concerns about the influence of pesticides on disease emergence in general.

Biology Department.

Li, W., and Keifer, Joyce. “Rapid Enrichment of Presynaptic Protein in Boutons Undergoing Classical Conditioning Is Mediated by Brain-Derived Neurotrophic Factor.” Neuroscience 203 (2012): 50-8.

Presynaptic structural modifications are thought to accompany activity-dependent synaptic plasticity and learning. This may involve the conversion of nonfunctional synapses into active ones or the generation of entirely new synapses. Here, using an in vitro neural analog of classical conditioning, we investigated presynaptic structural changes restricted to auditory nerve synapses that convey the conditioned stimulus (CS) by tract tracing using fluorescent tracers combined with immunostaining for the synaptic vesicle-associated protein synaptophysin. The results show that the size of presynaptic auditory boutons increased and the area and fluorescence intensity of punctate staining for synaptophysin were enhanced after conditioning. This occurred only for auditory nerve boutons apposed to the dendrites but not the somata of abducens motor neurons. Conditioning increased the percentage of boutons that were immunopositive for synaptophysin and enhanced the number of synaptophysin puncta they contained. Pretreatment with antibodies against brain-derived neurotrophic factor (BDNF) inhibited these conditioning-induced structural changes. There was also a net increase in the number of boutons apposed to abducens motor neurons after conditioning or BDNF treatment. These data indicate that the rapid enrichment of presynaptic boutons with proteins required for neurotransmitter recycling and release occurs during classical conditioning and that these processes are mediated by BDNF. Copyright 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Basic Biomedical Sciences, Vermillion 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 ~5weeks of age male and female SHR underwent sham operation, orchidectomy, or ovariectomy (OVX). At 20-23weeks 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 1644: Ovariecttomy 1593mm Hg). MAP was reduced by orchidectomy (Sham 1895:Orchidectomy 1672mm 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.

Mize, Erica L., Tsao, J. I., and Maurer, B. A. “Habitat Correlates with the Spatial Distribution of Ectoparasites on Peromyscus Leucopus in Southern Michigan.” Journal of Vector Ecology 36, no. 2 (2011): 308-20.

The goal of this study was to evaluate the role of habitat in determining ectoparasite distribution of Peromyscus leucopus. We tested the hypothesis that ectoparasite occurrence is associated with particular host environments and this association is stronger for ectoparasites with limited interactions (i.e., ticks) than those with frequent interactions (i.e., lice). Ectoparasites from three different groups (Acari, Siphonaptera, and Phthiraptera) were collected from P. leucopus inhabiting a number of forested habitats in southern Michigan. Measurements of plant species structure and composition were collected and models were developed using quadratic discriminant function analysis to determine if habitats associated with ectoparasite presence were different from those associated with their absence. Mice parasitized by ticks were more likely to be found in areas having undergone a recent disturbance. Mice parasitized by ticks, fleas, and lice were more likely to be found in areas having tree species associated with dry soils. Our results show there is a distinct difference in habitats associated with the presence of ectoparasites, though we did not observe a stronger association of host habitat for ticks than for fleas or lice. This implies habitat should be included as an important component of assessments of the spatial distribution of ectoparasites.

Biology Department.

Mroch, Amelia R., Laudenschlager, Mark, and Flanagan, Jason D. “Detection of a Novel Fh Whole Gene Deletion in the Propositus Leading to Subsequent Prenatal Diagnosis in a Sibship with Fumarase Deficiency.” American Journal of Medical Genetics Part A 158A, no. 1 (2012): 155-58.

Fumarase deficiency is a rare autosomal recessive metabolic condition. We report on a sibship with molecularly confirmed fumarase deficiency. Prenatal findings included agenesis of the corpus callosum, ventriculomegaly, and ventriculoseptal defect. The postnatal course was significant for metabolic acidosis ultimately leading to death around 3 weeks of age. Postmortem findings were noted including swollen mitochondria with abnormal cristae on electron microscopy within the liver. Molecular testing revealed a novel whole gene deletion in conjunction with a point mutation. While the point mutation has been previously reported, the detection of a whole gene deletion has not been described to date in an individual with fumarase deficiency. (C) 2011 Wiley Periodicals, Inc.

Sanford School of Medicine, Sioux Falls Campus.

Patacsil, D., Osayi, S., Tran, A. T., Saenz, F., Yimer, L., Shajahan, A. N., Gokhale, P. C., Verma, M., Clarke, R., Chauhan, Subhash C., and Kumar, D. “Vitamin E Succinate Inhibits Survivin and Induces Apoptosis in Pancreatic Cancer Cells.” Genes and Nutrition 7, no. 1 (2012): 83-89.

Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States. Identifying novel chemotherapeutic and chemopreventive approaches is critical in the prevention and treatment of cancers such as pancreatic cancer. Vitamin E succinate (VES) is a redox-silent analog of the fat-soluble vitamin alpha-tocopherol. In the present study, we explored the antiproliferative action of VES and its effects on inhibitor of apoptosis proteins in pancreatic cancer cells. We show that VES inhibits cell proliferation and induces apoptosis in pancreatic cancer cells. Further, we demonstrate that VES downregulates the expression of survivin and X-linked inhibitor of apoptosis proteins. The apoptosis induced by VES was augmented by siRNA-mediated inhibition of survivin in PANC-1 cells. In summary, our results suggest that VES targets survivin signaling and induces apoptosis in pancreatic cancer cells.

Sanford School of Medicine, Sioux Falls Campus.

Randall, Brad, Donelan, Kent, Koponen, Mark, Sens, Mary Ann, and Krous, Henry 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): 34-9.

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.

Shinozaki, Gen, Jowsey, S., Amer, H., Biernacka, J. M., Colby, C., Walker, D., Black, J., Rundell, J., Stegall, M., and Mrazek, D. A. “Relationship between Fkbp5 Polymorphisms and Depression Symptoms among Kidney Transplant Recipients.” Depression and Anxiety 28, no. 12 (2011): 1111-18.

Background: Several polymorphisms in FK506 Binding Protein gene (FKBP5) and a history of child abuse have been shown to be associated with an increased risk for posttraumatic stress disorder (PTSD). It has also been demonstrated that the same polymorphisms of FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment. However, there are only limited numbers of studies replicating the polymorphisms as vulnerability factors for the development of mental illnesses, such as PTSD and depression after stressful life event, especially with a specific incidence, such as kidney transplant surgery. Methods: A retrospective analysis was conducted using the electronic medical records of 131 adult kidney transplant recipients. Depression severity after kidney transplantation was measured by PHQ-9, and stored blood was genotyped for variants in the Serotonin Transporter (SLC6A4), Brain-Derived Neurotrophic Factor, Catecholamine-O-Methyltransferase, Corticotropin-Releasing Hormone Receptor, and FKBP5 genes. Spearman correlations were used to test for association between genetic variants and depression severity. Results: The rare alleles at three out of four SNPs in FKBP5 (rs1360780, rs9296158, and rs9470080) were associated with increased PHQ-9 scores (P<.05), whereas the last FKBP5 SNP (rs3800373) showed a trend of association (P<.10). All four FKBP5 SNPs are in strong linkage disequilibrium. Although in a subgroup of Caucasian non-Hispanic subjects the association was not statistically significant, the direction of association was consistent with that observed in the entire sample as well as in previous studies. Polymorphisms in genes other than FKBP5 were not associated with PHQ-9 scores. Conclusions: Polymorphisms in FKBP5 may be associated with higher depression scores in kidney transplant recipients. Depression and Anxiety, 2011. (C) 2011 Wiley Periodicals, Inc.

Sanford School of Medicine, Sioux Falls Campus.

Suen, Chen S., and Burn, Paul. “The Potential of Incretin-Based Therapies in Type 1 Diabetes.” Drug discovery today 17, no. 1-2 (2012): 89-95.

Finding a cure for type 1 diabetes (T1D) has been elusive. Incretin-based therapies, since their approval, have demonstrated their clinical utilities in type 2 diabetes (T2D). Yet, their potential clinical benefits in T1D remain to be appraised. GLP-1, in addition to its insulinotropic action in alleviating hyperglycemia, possesses beneficial effects in protecting progressive impairment of pancreatic beta-cell function, preservation of beta-cell mass and suppression of glucagon secretion, gastric emptying and appetite. Preclinical data using incretin-based therapies in diabetic NOD mice demonstrated additional effects including immuno-modulation, anti-inflammation and beta-cell regeneration. Thus, data accumulated hold the promise that incretin-based therapies may be effective in delaying the new-onset, halting the further progression, or reversing T1D in subjects with newly diagnosed or long-standing, established disease. Copyright 2011 Elsevier Ltd. All rights reserved.

Sanford School of Medicine, Sioux Falls Campus.

Vaags, A. K., Lionel, A. C., Sato, D., Goodenberger, M., Stein, Quinn P., Curran, S., Ogilvie, C., Ahn, J. W., Drmic, I., Senman, L., Chrysler, C., Thompson, A., Russell, C., Prasad, A., Walker, S., Pinto, D., Marshall, C. R., Stavropoulos, D. J., Zwaigenbaum, L., Fernandez, B. A., Fombonne, E., Bolton, P. F., Collier, D. A., Hodge, J. C., Roberts, W., Szatmari, P., and Scherer, S. W. “Rare Deletions at the Neurexin 3 Locus in Autism Spectrum Disorder.” American Journal of Human Genetics 90, no. 1 (2012): 133-41.

The three members of the human neurexin gene family, neurexin 1 (NRXN1), neurexin 2 (NRXN2), and neurexin 3 (NRXN3), encode neuronal adhesion proteins that have important roles in synapse development and function. In autism spectrum disorder (ASD), as well as in other neurodevelopmental conditions, rare exonic copy-number variants and/or point mutations have been identified in the NRXN1 and NRXN2 loci. We present clinical characterization of four index cases who have been diagnosed with ASD and who possess rare inherited or de novo microdeletions at 14q24.3-31.1, a region that overlaps exons of the alpha and/or beta isoforms of NRXN3. NRXN3 deletions were found in one father with subclinical autism and in a carrier mother and father without formal ASD diagnoses, indicating issues of penetrance and expressivity at this locus. Notwithstanding these clinical complexities, this report on ASD-affected individuals who harbor NRXN3 exonic deletions advances the understanding of the genetic etiology of autism, further enabling molecular diagnoses.

Sanford School of Medicine, Sioux Falls Campus.

Vermeer, Paola D., Bell, Megan, Lee, Kimberly, Vermeer, Daniel W., Wieking, Byrant G., Bilal, Erhan, Bhanot, Gyan, Drapkin, Ronny I., Ganesan, Shridar, Klingelhutz, Aloysius J., Hendriks, Wiljan J., and Lee, John H. “Erbb2, Ephrinb1, Src Kinase and Ptpn13 Signaling Complex Regulates Map Kinase Signaling in Human Cancers.” PloS one 7, no. 1 (2012): e30447.

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.

Wang, Xuejun J., Li, Jie, Zheng, Hanqiao Q., Su, Huabo, and Powell, S. R. “Proteasome Functional Insufficiency in Cardiac Pathogenesis.” American Journal of Physiology-Heart and Circulatory Physiology 301, no. 6 (2011): H2207-H19.

Wang X, Li J, Zheng H, Su H, Powell SR. Proteasome functional insufficiency in cardiac pathogenesis. Am J Physiol Heart Circ Physiol 301: H2207-H2219, 2011. First published September 23, 2011; doi:10.1152/ajpheart.00714.2011.-The ubiquitin-proteasome system (UPS) is responsible for the degradation of most cellular proteins. Alterations in cardiac UPS, including changes in the degradation of regulatory proteins and proteasome functional insufficiency, are observed in many forms of heart disease and have been shown to play an important role in cardiac pathogenesis. In the past several years, remarkable progress in understanding the mechanisms that regulate UPS-mediated protein degradation has been achieved. A transgenic mouse model of benign enhancement of cardiac proteasome proteolytic function has been created. This has led to the first demonstration of the necessity of proteasome functional insufficiency in the genesis of important pathological processes. Cardiomyocyte-restricted enhancement of proteasome proteolytic function by overexpression of proteasome activator 28 alpha protects against cardiac proteinopathy and myocardial ischemia-reperfusion injury. Additionally, exciting advances have recently been achieved in the search for a pharmacological agent to activate the proteasome. These breakthroughs are expected to serve as an impetus to further investigation into the involvement of UPS dysfunction in molecular pathogenesis and to the development of new therapeutic strategies for combating heart disease. An interplay between the UPS and macroautophagy is increasingly suggested in noncardiac systems but is not well understood in the cardiac system. Further investigations into the interplay are expected to provide a more comprehensive picture of cardiac protein quality control and degradation.

Basic Biomedical Sciences, Vermillion Campus.

Watson, Kendra D., Arendt, K. W., Watson, W. J., and Volcheck, G. W. “Systemic Mastocytosis Complicating Pregnancy.” Obstetrics and Gynecology 119, no. 2 (2012): 486-89.

BACKGROUND: Systemic mastocytosis is a rare medical disorder in which an increased number of mast cells can precipitate immediate hypersensitivity reactions, leading to hypotension, shock, and death. It is characterized by persistent elevated serum tryptase levels. The few published reports on pregnancy complicated by systemic mastocytosis indicate favorable maternal and fetal outcomes in gravidas known to have systemic mastocytosis. CASE: A pregnant woman treated with terbutaline at 31 weeks of gestation developed severe hypotension which resulted in fetal demise; this was initially diagnosed to be an anaphylactic reaction. The finding of persistently high maternal tryptase levels led to the diagnosis of systemic mastocytosis. In her subsequent pregnancy she was treated with an H1 blocker. Hypotension during her cesarean delivery was managed with steroid and epinephrine therapy. CONCLUSION: Exacerbations of systemic mastocytosis during pregnancy can lead to significant maternal and fetal complications. Treatment with H1 blockers, and when indicated, steroids and epinephrine, can reduce these complications. (Obstet Gynecol 2012;119:486-9) DOI: 10.1097/AOG.0b013e318242d3c5

Basic Biomedical Sciences, Vermillion Campus.

Wolf, S. L., Thompson, Paul A., Estes, E., Lonergan, T., Merchant, R., and Richardson, N. “The Excite Trial: Analysis of “Noncompleted” Wolf Motor Function Test Items.” Neurorehabilitation and Neural Repair 26, no. 2 (2012): 178-87.

Objective. This is the first study to examine Wolf Motor Function Test (WMFT) tasks among EXCITE Trial participants that could not be completed at baseline or 2 weeks later. Methods. Data were collected from participants who received constraint-induced movement therapy (CIMT) immediately at the time of randomization (CIMT-I, n = 106) and from those for whom there was a delay of 1 year in receiving this intervention (CIMT-D, n = 116). Data were collected at baseline and at a 2-week time point, during which the CIMT-I group received the CIMT intervention and the CIMT-D group did not. Generalized estimating equation (GEE) analyses were used to examine repeated binary data and count values. Group and visit interactions were assessed, adjusting for functional level, affected side, dominant side, age, and gender covariates. Results. In CIMT-I participants, there was an increase in the proportion of completed tasks at posttest compared with CIMT-D participants, particularly with respect to those tasks requiring dexterity with small objects and total incompletes (P < .0033). Compared with baseline, 120 tasks governing distal limb use for CIMT-I and 58 tasks dispersed across the WMFT for CIMT-D could be completed after 2 weeks. Common movement components that may have contributed to incomplete tasks include shoulder stabilization and flexion, elbow flexion and extension, wrist pronation, supination and ulnar deviation, and pincer grip. Conclusion. CIMT training should emphasize therapy for those specific movement components in patients who meet the EXCITE criteria for baseline motor control.

Sanford School of Medicine, Sioux Falls Campus.

Xie, K. Q., Ge, S. C., Collins, Victoria E., Haynes, C. L., Renner, Kenneth J., Meisel, R. L., Lujan, R., and Martemyanov, K. A. “G Beta 5-Rgs Complexes Are Gatekeepers of Hyperactivity Involved in Control of Multiple Neurotransmitter Systems.” Psychopharmacology 219, no. 3 (2012): 823-34.

Our knowledge about genes involved in the control of basal motor activity that may contribute to the pathology of the hyperactivity disorders, e.g., attention deficit hyperactivity disorder (ADHD), is limited. Disruption of monoamine neurotransmitter signaling through G protein-coupled receptors (GPCR) is considered to be a major contributing factor to the etiology of the ADHD. Genetic association evidence and functional data suggest that regulators of G protein signaling proteins of the R7 family (R7 RGS) that form obligatory complexes with type 5 G protein beta subunit (G beta 5) and negatively regulate signaling downstream from monoamine GPCRs may play a role in controlling hyperactivity. To test this hypothesis, we conducted behavioral, pharmacological, and neurochemical studies using a genetic mouse model that lacked G beta 5, a subunit essential for the expression of the entire R7 RGS family. Elimination of G beta 5-RGS complexes led to a striking level of hyperactivity that far exceeds activity levels previously observed in animal models. This hyperactivity was accompanied by motor learning deficits and paradoxical behavioral sensitization to a novel environment. Neurochemical studies indicated that G beta 5-RGS-deficient mice had higher sensitivity of inhibitory GPCR signaling and deficits in basal levels, release, and reuptake of dopamine. Surprisingly, pharmacological treatment with monoamine reuptake inhibitors failed to alter hyperactivity. In contrast, blockade of NMDA receptors reversed the expression of hyperactivity in G beta 5-RGS-deficient mice. These findings establish that G beta 5-RGS complexes are critical regulators of monoamine-NMDA receptor signaling cross-talk and link these complexes to disorders that manifest as hyperactivity, impaired learning, and motor dysfunctions.

Biology Department

Xu, T. T., Yan, M., Hoefelmeyer, James D., and Qiao, Q. Q. “Exciton Migration and Charge Transfer in Chemically Linked P3ht-Tio(2) Nanorod Composite.” Rsc Advances 2, no. 3 (2012): 854-62.

Exciton migration and charge transfer in the chemically linked P3HT-TiO(2) nanorod composite (P3HT-Si-nr-TiO(2)) solution were investigated in comparison with pristine P3HT and physically mixed P3HT/LA-nr-TiO(2) solutions. The chemically linked P3HT-Si-nr-TiO(2) was made by covalently linking in situ polymerized P3HT onto nr-TiO(2) using triethoxy-2-thienylsilane as a linker to replace the initial linoleic acid (LA) capping agent on nr-TiO(2). The physically mixed P3HT/LA-nr-TiO(2) was prepared by adding ex situ synthesized P3HT into the LA-capped nr-TiO(2) solution. In the chemically linked sample, charge transfer from P3HT to TiO(2) nanorods was found to occur evidenced by photoluminescence (PL) quenching and ultrafast decay dynamics with a timescale of 0.75 ps. However, both the emission spectra and femtosecond dynamics in physically mixed sample overlapped very well with those from pristine P3HT solution, indicating no PL quenching or charge transfer from P3HT to nr-TiO(2). In addition, blue shift in absorbance and PL spectra, larger Stokes shift, and structureless PL spectra found in the chemically linked sample indicated that P3HT formed a more coil-like conformation with more twisted torsion disorders than those in pristine P3HT and physically mixed samples. This is consistent with the femtosecond measurement result that torsional relaxation occurred with a longer decay time and higher amplitude. Moreover, intersystem crossings (ISC) from singlet state (S(1)) to triplet state (T(1)) in P3HT of the three samples were all found to occur in a comparable timescale of similar to 1 ns and showed no dependence on conformational disorders such as torsional defects.

Chemisty Department.

Yallapu, Murali M., Jaggi, Meena, and Chauhan, Subhash C. “Curcumin Nanoformulations: A Future Nanomedicine for Cancer.” Drug discovery today 17, no. 1-2 (2012): 71-80.

Curcumin, a natural diphenolic compound derived from turmeric Curcuma longa, has proven to be a modulator of intracellular signaling pathways that control cancer cell growth, inflammation, invasion and apoptosis, revealing its anticancer potential. In this review, we focus on the design and development of nanoparticles, self-assemblies, nanogels, liposomes and complex fabrication for sustained and efficient curcumin delivery. We also discuss the anticancer applications and clinical benefits of nanocurcumin formulations. Only a few novel multifunctional and composite nanosystem strategies offer simultaneous therapy as well as imaging characteristics. We also summarize the challenges to developing curcumin delivery platforms and up-to-date solutions for improving curcumin bioavailability and anticancer potential for therapy. Copyright 2011 Elsevier Ltd. All rights reserved.

Sanford School of Medicine, Sioux Falls Campus.

Epping, Lori L., and Mark Wilder, W. “U.S.-Listed Foreign Firms’ Non-GAAP Financial Performance Disclosure Behavior.” Journal of International Accounting Research 10, no. 2 (2011): 77-96.

The purpose of this study is to observe the extent to which U.S.-listed foreign firms report non-GAAP financial performance measures and to compare the characteristics of these disclosures to those of U.S. firms. Using a matched-sample design, this research compares U.S.-listed foreign firm and U.S. firm non-GAAP disclosure frequency, non-GAAP disclosure adjustment characteristics, and reconciliation quality. Tests of the hypotheses indicate similar disclosure frequencies for U.S. firms and U.S.-listed foreign firms. Analyses of non-GAAP disclosure and adjustment characteristics provide evidence consistent with the interpretation that U.S. firms engage in aggressive non-GAAP reporting behaviors (reporting income-increasing adjustments and adjusting GAAP numbers with a greater magnitude and with a higher number of adjustments) equally or more so than U.S.-listed foreign firms. However, the quality of U.S. firm reconciliations to U.S. GAAP is equal to or greater than that of U.S.- listed foreign firms.

 Beacom School of Business.

Erford, Bradley T., Schein, Hallie, and Duncan, Kelly. “Technical Analysis of Scores on the Self-Efficacy Self-Report Scale.” Assessment for Effective Intervention 37, no. 1 (2011): 58-64.

The purpose of this study was to provide preliminary analysis of reliability and validity of scores on the Self-Efficacy Self-Report Scale, which was designed to assess general self-efficacy in students aged 10 to 17 years. Confirmatory factor analysis on cross-validated samples was conducted revealing a marginal fit of the data to the 19-item unidimensional scale. Studies of internal consistency and test–retest reliability revealed adequate levels of total scale consistency. Criterion-related validity estimates were moderate to strong. Norms and a test protocol are provided to encourage free use of the scale for student assessment and research purposes. (PsycINFO Database Record (c) 2012 APA, all rights reserved) (journal abstract)

 School of Education.

Hovland, Michelle R., Gapp, Susan C., and Theis, Becky L. “Look: Examining the Concept of Learning to Look at Print.” Reading Improvement 48, no. 3 (2011): 128-38.

The purpose of this observation case study was to understand pre-school and kindergarten teachers’ perceptions of what “distinguishing the characteristics of print” means and to identify strategies pre-school and kindergarten teachers employ to assist young children in learning to distinguish the characteristics. This study used questionnaires, analysis of children’s writing samples, and classroom observations from pre-school and kindergarten teachers in rural locations in the Midwest. Data was separated into three categories: (a) questionnaire data, (b) writing sample analysis data, and (c) observational notes. A multistep analysis was conducted to identify patterns among participant responses. The distinguishing characteristics of print perceived by pre-school and kindergarten teachers included print has a purpose, pictures correspond to words, letters/words convey a message, sounds can be represented by letters, recognition and formation of letters, letters make words, letter sequence, directionality, spacing, capital and lowercase letters, letter order within words, writing is used for various purposes. The teaching strategies pre-school and kindergarten teachers used to assist young children distinguish the characteristics of print included promoting a safe risk free environment, reading aloud, emphasizing reading for meaning by discussing stories, making predictions, and making connection, providing opportunities for shared writing and shared reading activities, emphasizing letters, providing writing opportunities, practice writing letters, handwriting program, literacy centers, word work, emphasizing letter-sound associations by teaching students how to say words slowly. The teachers in this study showed evidence of providing effective instruction in general in learning to look at print. However, the majority of instructional decisions revolved around reading and overlooked the inclusion of writing to support learning to look at print.

 School of Education.

Li, Xiaolin, and Ghosh, Suvankar. “Power-Dependence and Reseller Influence on Smes’ Continued Use of Online Direct Sales Channels: An Empirical Study.” Journal of Organizational Computing & Electronic Commerce 22, no. 1 (2012): 87-106.

A dual-channel model with a physical sales channel and an online direct sales channel (ODSC) frequently causes channel conflicts. Small- and medium-sized enterprises (SMEs) using such a model may be forced to suspend ODSC to ease conflicts and maintain traditional resellers. From a channel conflict perspective, this study investigates a few critical factors underlying SMEs’ intention to continue with an existing ODSC. We develop a research model by integrating power-dependence theory and the technology acceptance model. Then we construct and administer a survey to a sample of US SMEs currently using the dual-channel model. Partial least squares regression is employed to analyze the data and evaluate the impact of four key factors on SMEs’ continuance of ODSCs: perceived business value of ODSCs, perceived ease of continuance with ODSCs, reseller dependence, and reseller forceful actions. Findings of the study contribute to the understanding of supplier-reseller relationships and continued use of information technologies among SMEs.

Beacom School of Business.

Olagundoye, Stacy Shwartz, and Lawler, Michael J. “Building Effective Program Strategies for Youth-Adult Partnerships: Reflections and Guidance on Promising Practices.” Relational Child & Youth Care Practice 24, no. 4 (2011): 63-73.

Youth-serving organizations today often employ youth-adult partnerships (YAPs) to strengthen the overall effectiveness of their mission and to provide more enriching leadership experiences for young people. This study explores YAPs — a mutually beneficial relationship in which both parties have shared voice and decision- making power — across six nominated California county 4-H Youth Development Programs. The adults and youth interviewed provided reflections on promising practices of youth-adult partnerships, and their reflections were shared with a focus group of local youth development experts in a small study. Taken together, both groups’ reflections suggested a five step strategy for creating youth- friendly environments for YAPs. This study reveals the critical conditions that the interviewees described, as well as explores the varied ways by which young people can achieve richer forms of youth participation through YAPs.

 School of Health Sciences.

Sørensen, Christina, Nilsson, Göran E., Summers, Cliff H., and Øverli, Øyvind. “Social Stress Reduces Forebrain Cell Proliferation in Rainbow Trout (Oncorhynchus Mykiss).” Behavioural Brain Research 227, no. 2 (2012): 311-18.

Abstract: Compared to mammals, teleost fish have a very high rate of adult brain cell proliferation. Still little is known about how this process is regulated in comparative models, and what its functional implications are. We investigated the effect of stressful social interaction on brain cell proliferation in size matched rainbow trout pairs after the formation of stable social hierarchies. After 4 days of interaction, socially subordinate fish displayed common signs of chronic stress including reduced feeding behaviour, elevated plasma cortisol levels, and up-regulated brain stem 5-HT activity. The number of newborn cells in the telencephalon was quantified using immunohistochemistry for the exogenously administered S-phase marker BrdU. Subordinate fish had 40% fewer BrdU-positive telencephalic cells compared to isolated controls, while dominant individuals showed a non-significant tendency towards reduced cell proliferation. Cell proliferation in subordinate animals correlated negatively with aggression received immediately after hierarchy formation, indicating that the level of cell division suppression is related to the severity of the social stressor. These findings are comparable to findings in mammalian models of psychosocial stress, indicating that the suppressive effect of social stress on brain cell proliferation is conserved, and thus likely confers adaptive benefits throughout the vertebrate subphylum.

 Biology Department.

Stoltenberg, Scott F., Lehmann, Melissa K., Christ, Christa C., Hersrud, Samantha L., and Davies, Gareth E. “Associations among Types of Impulsivity, Substance Use Problems and Neurexin-3 Polymorphisms.” Drug and Alcohol Dependence 119, no. 3 (2011): e31-e38.

Background: Some of the genetic vulnerability for addiction may be mediated by impulsivity. This study investigated relationships among impulsivity, substance use problems and six neurexin-3 (NRXN3) polymorphisms. Neurexins (NRXNs) are presynaptic transmembrane proteins that play a role in the development and function of synapses. Methods: Impulsivity was assessed with the Barratt Impulsiveness Scale Version 11 (BIS-11), the Boredom Proneness Scale (BPS) and the TIME paradigm; alcohol problems with the Michigan Alcoholism Screening Test (MAST); drug problems with the Drug Abuse Screening Test (DAST-20); and regular tobacco use with a single question. Participants (n = 439 Caucasians, 64.7% female) donated buccal cells for genotyping. Six NRXN3 polymorphisms were genotyped: rs983795, rs11624704, rs917906, rs1004212, rs10146997 and rs8019381. A dual luciferase assay was conducted to determine whether allelic variation at rs917906 regulated gene expression. Results: In general, impulsivity was significantly higher in those who regularly used tobacco and/or had alcohol or drug problems. In men, there were modest associations between rs11624704 and attentional impulsivity (p = 0.005) and between rs1004212 and alcohol problems (p = 0.009). In women, there were weak associations between rs10146997 and TIME estimation (p = 0.03); and between rs1004212 and drug problems (p = 0.03). The dual luciferase assay indicated that C and T alleles of rs917906 did not differentially regulate gene expression in vitro. Conclusions: Associations between impulsivity, substance use problems and polymorphisms in NRXN3 may be gender specific. Impulsivity is associated with substance use problems and may provide a useful intermediate phenotype for addiction. (PsycINFO Database Record (c) 2012 APA, all rights reserved) (journal abstract)

 Basic Biomedical Sciences, Vermillion Campus.

Suen, Chen S., and Burn, Paul. “The Potential of Incretin-Based Therapies in Type 1 Diabetes.” Drug Discovery Today 17, no. 1/2 (2012): 89-95.

Finding a cure for type 1 diabetes (T1D) has been elusive. Incretin-based therapies, since their approval, have demonstrated their clinical utilities in type 2 diabetes (T2D). Yet, their potential clinical benefits in T1D remain to be appraised. GLP-1, in addition to its insulinotropic action in alleviating hyperglycemia, possesses beneficial effects in protecting progressive impairment of pancreatic β-cell function, preservation of β-cell mass and suppression of glucagon secretion, gastric emptying and appetite. Preclinical data using incretin-based therapies in diabetic NOD mice demonstrated additional effects including immuno-modulation, anti-inflammation and β-cell regeneration. Thus, data accumulated hold the promise that incretin-based therapies may be effective in delaying the new-onset, halting the further progression, or reversing T1D in subjects with newly diagnosed or long-standing, established disease.

Sanford School of Medicine, Sioux Falls Campus.

Vaags, Andrea K, Lionel, Anath C, Sato, Daisuke, Goodenberger, McKinsey, and Stein, Quinn P. “Rare Deletions at the Neurexin 3 Locus in Autism Spectrum Disorder.” American Journal of Human Genetics 90, no. 1 (2012): 133-41.

The three members of the human neurexin gene family, neurexin 1 (NRXN1), neurexin 2 (NRXN2), and neurexin 3 (NRXN3), encode neuronal adhesion proteins that have important roles in synapse development and function. In autism spectrum disorder (ASD), as well as in other neurodevelopmental conditions, rare exonic copy-number variants and/or point mutations have been identified in the NRXN1 and NRXN2 loci. We present clinical characterization of four index cases who have been diagnosed with ASD and who possess rare inherited or de novo microdeletions at 14q24.3–31.1, a region that overlaps exons of the alpha and/or beta isoforms of NRXN3. NRXN3 deletions were found in one father with subclinical autism and in a carrier mother and father without formal ASD diagnoses, indicating issues of penetrance and expressivity at this locus. Notwithstanding these clinical complexities, this report on ASD-affected individuals who harbor NRXN3 exonic deletions advances the understanding of the genetic etiology of autism, further enabling molecular diagnoses.

Sanford School of Medicine, Sioux Falls Campus.

To help us in our roles as liaison to several USD departments,we keep tabs on the research of USD. We also are responsible for keeping the departments up-to-date about the library.

This blog exists for organizing and sharing that information. Check out the tabs above for month-by-month publications.

Email us if you have any questions.  Danielle Loftus   Steve Johnson

Components of the brain’s dopaminergic system, such as dopamine receptors, undergo final maturation in adolescence. Exposure to social stress during human adolescence contributes to substance abuse behaviors. We utilized a rat model of adolescent social stress to investigate the neural mechanisms underlying this correlation. Rats exposed to repeated social defeat in adolescence (P35-P39) exhibited increased conditioned place preference (CPP) for amphetamine (1 mg/kg) in adulthood (P70). In contrast, rats experiencing foot-shock during the same developmental period exhibited amphetamine CPP levels similar to non-stressed controls. Our previous experiments suggested adolescent defeat alters dopamine activity in the mesocorticolimbic system. Furthermore, dopamine receptors have been implicated in the expression of amphetamine CPP. Therefore, we hypothesized that alteration to dopamine receptor expression in the mesocorticolimbic system may be associated with to heightened amphetamine CPP of adult rats exposed to adolescence defeat. We measured D1 and D2 dopamine receptor protein content in the medial prefrontal cortex, nucleus accumbens (NAc), and dorsal striatum following either adolescent social defeat or foot-shock stress and then adult amphetamine CPP. In controls, amphetamine CPP training reduced D2 receptor protein content in the NAc core. However, this down-regulation of NAc core D2 receptors was blocked by exposure to social defeat but not foot-shock stress in adolescence. These results suggest social defeat stress in adolescence alters the manner in which later amphetamine exposure down-regulates D2 receptors. Furthermore, persistent alterations to adult D2 receptor expression and amphetamine responses may depend on the type of stress experienced in adolescence. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Basic Biomedical Sciences, Vermillion Campus.

Johnson, C. M., Haemig, H. H. A., Chatterjee, A., Hu, W. S., Weaver, Keith E., and Dunny, G. M. (2011).  “Rna-Mediated Reciprocal Regulation between Two Bacterial Operons Is Rnase Iii Dependent.” Mbio. 2 (Sep-Oct, no. 5): x.

In bacteria, RNAs regulate gene expression and function via several mechanisms. An RNA may pair with complementary sequences in a target RNA to impact transcription, translation, or degradation of the target. Control of conjugation of pCF10, a pheromone response plasmid of Enterococcus faecalis, is a well-characterized system that serves as a model for the regulation of gene expression in bacteria by intercellular signaling. The prgQ operon, whose products mediate conjugation, is negatively regulated by two products of the prgX operon, Anti-Q, a small RNA, and PrgX, the transcriptional repressor of the prgQ promoter. Here we show that Qs, an RNA from the 5′ end of the prgQ operon, represses expression of PrgX by targeting prgX mRNA for cleavage by RNase III. Our results demonstrate that the prgQ and prgX operons each use RNAs to negatively regulate gene expression from the opposing operon by different mechanisms. Such reciprocal regulation between two operons using RNAs has not been previously demonstrated. Furthermore, these results show that Qs is an unusually versatile RNA, serving three separate functions in the regulation of conjugation. Understanding the potential versatility of RNAs and their various roles in gene regulatory networks will allow us to better understand how cells regulate complex behavior. IMPORTANCE Bacteria use RNA to regulate gene expression by a variety of mechanisms. The prgQ and prgX operons of pCF10, a conjugative plasmid of Enterococcus faecalis, have been shown to negatively regulate one another by a variety of mechanisms. One of these mechanisms involves Anti-Q, a small RNA from the prgX operon that prevents gene expression from the prgQ operon. In this work, we find that Qs, an RNA from the prgQ operon, negatively regulates gene expression from the prgX operon. These findings have a number of implications. (i) The Anti-Q and Qs RNAs act by different mechanisms, highlighting the variety of ways in which bacteria can regulate gene expression using RNAs. (ii) Reciprocal regulation between operons mediated by small RNAs has not been previously described, deepening our understanding of how bacteria regulate complex behavior. (iii) Additional roles for Qs have been described, demonstrating the versatility of this RNA.

Basic Biomedical Sciences, Vermillion Campus.

Su, Huabo B., Li, F. Q., Ranek, Mark J., Wei, N., and Wang, Xuejun J. (2011).  “Cop9 Signalosome Regulates Autophagosome Maturation.” Circulation. 124 (Nov, no. 19): 2117-U199.

Background-Autophagy is essential to intracellular homeostasis and is involved in the pathophysiology of a variety of diseases. Mechanisms regulating selective autophagy remain poorly understood. The COP9 signalosome (CSN) is a conserved protein complex consisting of 8 subunits (CSN1 through CSN8), and is known to regulate the ubiquitin-proteasome system. However, it is unknown whether CSN plays a role in autophagy. Methods and Results-Marked increases in the LC3-II and p62 proteins were observed on Csn8 depletion in the cardiomyocytes of mouse hearts with cardiomyocyte-restricted knockout of the gene encoding CSN subunit 8 (CR-Csn8KO). The increases in autophagosomes were confirmed by probing with green fluorescent protein-LC3 and electron microscopy. Autophagic flux assessments revealed that defective autophagosome removal was the cause of autophagosome accumulation and occurred before a global ubiquitin-proteasome system impairment in Csn8-deficient hearts. Analyzing the prevalence of different stages of autophagic vacuoles revealed defective autophagosome maturation. Downregulation of Rab7 was found to colocalize strikingly with the autophagosome accumulation at the individual cardiomyocyte level. A significantly higher percent of cardiomyocytes with autophagosome accumulation underwent necrosis in CR-Csn8KO hearts. Long-term lysosomal inhibition with chloroquine induced cardiomyocyte necrosis in mice. Rab7 knockdown impaired autophagosome maturation of nonselective and selective autophagy and exacerbated cell death induced by proteasome inhibition in cultured cardiomyocytes. Conclusions-Csn8/CSN is a central regulator in not only the proteasomal proteolytic pathway, but also selective autophagy. Likely through regulating the expression of Rab7, Csn8/CSN plays a critical role in autophagosome maturation. Impaired autophagosome maturation causes cardiomyocytes to undergo necrosis. (Circulation. 2011;124:2117-2128.)

Basic Biomedical Sciences, Vermillion Campus.

Zheng, Hong, Liu, Xuefei F., Li, Y. F., Sharma, N. M., and Patel, K. P. (2011).  “Gene Transfer of Neuronal Nitric Oxide Synthase to the Paraventricular Nucleus Reduces the Enhanced Glutamatergic Tone in Rats with Chronic Heart Failure.” Hypertension. 58 (Nov, no. 5): 966-U592.

Our previous studies have shown that the decreased NO and increased glutamatergic mechanisms on sympathetic regulation within the paraventricular nucleus (PVN) may contribute to the elevated sympathoexcitation during chronic heart failure (CHF). In the present study, we investigated the effects of neuronal NO synthase (nNOS) gene transfer on N-methyl-D-aspartic acid receptor subunit NR(1) in the rats with a coronary ligation model of CHF. Adenovirus vectors encoding nNOS (AdnNOS) or adenovirus vectors encoding beta-galactosidase were transfected into the PVN in vivo. Five days after application of AdnNOS, the increased expression of nNOS within the PVN was confirmed by NADPH-diaphorase staining, real-time PCR, and Western blot. In anesthetized rats, AdnNOS treatment significantly enhanced the blunted renal sympathetic nerve activity, blood pressure, and heart rate responses to NO synthase inhibitor N(G)-monomethyl-L-arginine in the rats with CHF compared with CHF-adenovirus vectors encoding beta-galactosidase group. AdnNOS significantly decreased the enhanced renal sympathetic nerve activity, blood pressure, and heart rate responses to N-methyl-D-aspartic acid in the rats with CHF (renal sympathetic nerve activity: 44 +/- 2% versus 79 +/- 6%; P < 0.05) compared with CHF-adenovirus vectors encoding the beta-galactosidase group. AdnNOS transfection significantly reduced the increased NR(1) receptor mRNA expression (Delta 35+/-5%) and protein levels (Delta 24+/-4%) within the PVN in CHF rats. Furthermore, in neuronal NG-108 cells, NR(1) receptor protein expression decreased in a dose-dependent manner after AdnNOS transfection. According to our results, nNOS downregulation enhances glutamate transmission in the PVN by increasing NR(1) subunit expression. This mechanism may enhance renal sympathetic nerve activity in CHF rats. (Hypertension. 2011; 58: 966-973.). Online Data Supplement

Basic Biomedical Sciences, Vermillion Campus.

Husak, Jerald F., Ribak, G., Wilkinson, G. S., and Swallow, John G. (2011).  “Sexual Dimorphism in Wing Beat Frequency in Relation to Eye Span in Stalk-Eyed Flies (Diopsidae).” Biological Journal of the Linnean Society. 104 (Nov, no. 3): 670-79.

Although male ornaments may provide benefits to individuals bearing them, such structures may also entail fitness costs. Selection should favour aspects of the phenotype that act to reduce such costs, yet such compensatory traits are often ignored in studies of sexual selection. If a male ornament increases predation risk via reduced locomotor performance, then there may be selection for changes in morphological traits to compensate for behavioural or biomechanical changes in how individuals use their morphology (or both). We took a comparative approach aiming to test whether changes in wing beat frequency are evolutionarily correlated with increases in male ornamentation across stalk-eyed fly species. Previous studies have shown that increased male eye span is evolutionarily correlated with increased wing size; thus, we tested whether there is additional compensation via increases in size-adjusted wing beat frequency. The results obtained revealed that relative wing beat frequency is negatively related to relative eye span in males, and sexual dimorphism in wing beat frequency is negatively related to dimorphism in eye span. These findings, in addition to our finding that eye span dimorphism is positively related to aspect ratio dimorphism, suggest that male stalk-eyed flies compensate primarily by increasing wing size and shape, which may then have resulted in the subsequent evolutionary reduction in wing beat frequency. Thus, exaggerated ornaments can result in evolutionary modifications in wing morphology, which in turn lead to adjustments in flapping kinematics, illustrating the tight envelope of trade-offs when compensating for exaggerated ornaments. (C) 2011 The Linnean Society of London, Biological Journal of the Linnean Society, 2011, 104, 670-679.

Biology Department.

Liknes, Eric T., and Swanson, David L. (2011).  “Phenotypic Flexibility in Passerine Birds: Seasonal Variation of Aerobic Enzyme Activities in Skeletal Muscle.” Journal of Thermal Biology. 36 (Oct, no. 7): 430-36.

Improved winter cold tolerance is widespread among small passerines resident in cold climates and is generally associated with elevated summit metabolic rate (M(sum)=maximum thermoregulatory metabolic rate) and improved shivering endurance with increased reliance on lipids as fuel. Elevated M(sum) and improved cold tolerance may result from greater metabolic intensity, due to mass-specific increase in oxidative enzyme capacity, or increase in the masses of thermogenic tissues. To examine the mechanisms underlying winter increases in M(sum), we investigated seasonal changes in mass-specific and total activities of the key aerobic enzymes citrate synthase (CS) and beta-hydroxyacyl CoA-dehydrogenase (HOAD) in pectoralis, supracoracoideus and mixed leg muscles of three resident passerine species, black-capped chickadee (Poecile atricapillus), house sparrow (Passer domesticus), and white-breasted nuthatch (Sitta carolinensis). Activities of CS were generally higher in winter than in summer muscles for chickadees and house sparrows, but not nuthatches. Mass-specific HOAD activity was significantly elevated in winter relative to summer in all muscles for chickadees, but did not vary significantly with season for sparrows or nuthatches, except for sparrow leg muscle. These results suggest that modulation of substrate flux and cellular aerobic capacity in muscle contribute to seasonal metabolic flexibility in some species and tissues, but such changes play varying roles among small passerines resident in cold climates. (C) 2011 Elsevier Ltd. All rights reserved.

Biology Department.

Riley, Lynn, McGlaughlin, Mitchell E., and Helenurm, Kaius. (2011).  “Microsatellite Primers for the Narrowly Endemic Shrub Eriogonum Giganteum (Polygonaceae).” American journal of botany. 98 (2011, no. 12): e352-5.

Premise of the study: Microsatellite primers were designed for Eriogonum giganteum var. formosum, an endemic shrub of San Clemente Island, to investigate population structure, genetic diversity, and demographic history. Methods and Results: Twelve polymorphic microsatellite loci were isolated from the California Channel Island endemic Eriogonum and were screened for variability. The primers amplified one to eight alleles in the target taxon. Many primers also amplified in conspecific and congeneric (E. arborescens, E. fasciculatum, E. grande, E. latifolium, and E. parvifolium) taxa and in the closely related Chorizanthe valida. The total number of alleles per locus for all taxa screened ranged from three to 24. Conclusions: These primers will be useful for conservation genetic and evolutionary studies within the California Channel Island endemic Eriogonum.

Biology Department.

Koepsell, Laura, Remund, Tyler, Bao, Jing, Neufeld, Daniel, Fong, H., and Deng, Ying. (2011).  “Tissue Engineering of Annulus Fibrosus Using Electrospun Fibrous Scaffolds with Aligned Polycaprolactone Fibers.” Journal of Biomedical Materials Research Part A. 99A (Dec, no. 4): 564-75.

In tissue engineering, it is important to fabricate a three-dimensional scaffold that resemble the extracellular matrix (ECM) and topographical appearance of native tissue. The aim of this study is to test the hypothesis that varying microstructures of electrospun fibrous scaffolds by manipulating the relative degree of fiber alignment would influence the behaviors of porcine annulus fibrosus cells. Five types of electrospun fibrous scaffolds with polycaprolactone fibers having random or partially aligned arrangements have been prepared and investigated. The scaffold microstructures have been examined, and in vitro experiments have been carried out to assess cell-material interaction, cell proliferation, and ECM production. The results indicate that the scaffold with oriented fibers provides strong guidance to the cell orientation and ECM distribution. In addition, albeit the tensile moduli of electrospun fibrous scaffolds are lower than that of native tissue, they are comparable to those reported in literature; hence, the constructs cultured with optimized conditions including the scaffold material selection and dynamic mechanical conditioning would have the potential to possess the moduli closer to that of native tissue. (C) 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 99A: 564-575, 2011.

Biomedical Engineering, Sioux Falls Campus.

He, H. S., Zhong, Y. H., Si, Liping P., and Sykes, Andrew. (2011).  “Structural, Photophysical and Theoretical Studies of Two Dodecachlorinated Porphyrins.” Inorganica Chimica Acta. 378 (Nov, no. 1): 30-35.

Two dodecachlorinated porphyrins, 2,3,7,8,12,13,17,18-octachloro-5,10,15,20-tetra(4-chlorophenyl)porphyrin free base (TCl(12)PPH(2)) and its nickel compound (TCl(12)PPNi), have been synthesized. Single-crystal X-ray diffraction analysis shows that porphyrin rings are heavily distorted and exhibit saddled conformations. The Soret and Q bands of two compounds are red-shifted compared to their non-chlorinated counterparts. Theoretical calculations reveal that the optical band gap of TCl(12)PPH(2) is reduced, whereas that of TCl(12)PPNi remains almost the same as to its non-chlorinated nickel compound due to the concurrent lowering of HOMO and LUMO energy levels. The frontier molecular orbitals are degenerated due to the decrease of symmetry of the molecules. (C) 2011 Elsevier B.V. All rights reserved.

Chemistry Department.

Kilina, S. V., Kilin, Dmitri S., Prezhdo, V. V., and Prezhdo, O. V. (2011).  “Theoretical Study of Electron-Phonon Relaxation in Pbse and Cdse Quantum Dots: Evidence for Phonon Memory.” Journal of Physical Chemistry C. 115 (Nov, no. 44): 21641-51.

We have combined analytical theory with ab initio nonadiabatic molecular dynamics to study the phonon-induced relaxation of photoexcited charge carriers in PbSe and CdSe semiconductor quantum dots (QDs). Density functional theory calculations show dense distributions of electronic levels near the energy gap, attributed to the reconstruction and lack of absolute symmetry of the QD surface. Most of these states are optically dark but they do couple to phonons and facilitate charge carrier relaxation. The time-domain simulations show a complex, nonexponential relaxation, in agreement with the observed non-Lorenzian spectral line shapes. The relaxation accelerates at higher photoexcitation energies due to both a higher density of carrier states and a larger nonadiabatic electron-phonon coupling Over time, carrier relaxation changes from Gaussian to exponential. The Gaussian component is larger in smaller dots; this may be a manifestation of the phonon bottleneck. effect. Since Markovian rate models give exponential decay, we suggest that the more complex form of the carrier relaxation, observed in our simulations, can be attributed to phonon memory. The analytic theory developed within the framework of quantized Hamilton dynamics rationalizes this observation. It shows that a detailed description of the phonon modes is more important than a model for the electronic States.

Chemistry Department.

Gonzalez-Olivares, E., Gonzalez-Yanez, B., Lorca, J. M., Rojas-Palma, A., and Flores, Jose D. (2011).  “Consequences of Double Allee Effect on the Number of Limit Cycles in a Predator-Prey Model.” Computers & Mathematics with Applications. 62 (Nov, no. 9): 3449-63.

The main goal of this work is to show a comparative analysis of simple continuous time predator-prey models considering the Allee effect affecting the prey population, also known as depensation in fisheries sciences. This phenomenon may be expressed by different mathematical forms, yielding a distinct number of limit cycles surrounding a positive equilibrium point, when two of these different formalizations are considered in the same system. It is known that the Volterra predation model, using the most usual form to express the Allee effect, has a unique limit cycle. In this work, considering a more complex mathematical expression, the existence of two limit cycles is proved, by means of the Lyapunov quantities. We argue that the second equation explains the existence of two Allee effects affecting the same population, which could justify the difference observed between the models. These results imply that the election of mathematical formulation can have consequences on the fit of the observed data, thus leading to mistakes for ecologists. We conclude that the oscillatory behaviors and overall dynamics depend strongly on the algebraic expression of the Allee effect, making difficult the proposition of general results. Nevertheless, the techniques reviewed in this paper emerge as key tools to analyze the existence of limit cycles in the presence of multiple Allee effects. (C) 2011 Elsevier Ltd. All rights reserved.

Mathematics Department.

Zadeh, Neda, Bernstein, Jonathan A., Niemi, Ann K., Dugan, Sarah, Kwan, Andrea, Liang, D., Hyland, J. C., Hoyme, H. Eugene, Hudgins, Louanne, and Manning, Melanie A. (2011).  “Ectopia Lentis as the Presenting and Primary Feature in Marfan Syndrome.” American Journal of Medical Genetics Part A. 155A (Nov, no. 11): 2661-68.

Marfan syndrome (MFS) is a multisystem connective tissue disorder with primary involvement of the ocular, cardiovascular, and skeletal systems. We report on eight patients, all presenting initially with bilateral ectopia lentis (EL) during early childhood. These individuals did not have systemic manifestations of MFS, and did not fulfill the revised Ghent diagnostic criteria. However, all patients had demonstratable, disease-causing missense mutations in the FBN1 gene. Based on molecular results, cardiovascular imaging was recommended and led to the identification of mild aortic root changes in seven of the eight patients. The remaining patient had mitral valve prolapse with a normal appearing thoracic aorta. The findings presented in this paper validate the necessity of FBN1 gene testing in all individuals presenting with isolated EL. As we observed, these individuals are at increased risk of cardiovascular complications. Furthermore, we also noted that the majority of our patient cohort’s mutations occurred in the 50 portion of the FBN1 gene, and were found to affect highly conserved cysteine residues, which may indicate a possible genotype-phenotype correlation. We conclude that in patients with isolated features of EL, FBN1 mutation analysis is necessary to aid in providing prompt diagnosis, and to identify patients at risk for potentially life-threatening complications. Additionally, knowledge of the type and location of an FBN1 mutation may be useful in providing further clinical correlation regarding phenotypic progression and appropriate medical management. (C) 2011 Wiley Periodicals, Inc.

Sanford School of Medicine, Sioux Fall Campus.

Savinova, Olga V., and Gerdes, A. Martin. (2012).  “Myocyte Changes in Heart Failure.” Heart failure clinics. 8 (2012 Jan (Epub 2011 Oct, no. 1): 1-6.

Structural remodeling is a major feature of heart failure and typically precedes the development of symptomatic disease. Structural remodeling of the heart reflects changes in myocyte morphology. Disproportional myocyte growth is observed in pathologic concentric hypertrophy (myocyte thickening) and in eccentric dilated hypertrophy (myocyte lengthening). Alterations in myocyte shape lead to changes in chamber geometry and wall stress. Human and animal studies indicate that changes in myocyte morphology are reversible. Normalization or reversal of maladaptive cardiomyocyte remodeling should be a therapeutic aim that can prevent deterioration or improve cardiac function in heart failure. Copyright 2012 Elsevier Inc. All rights reserved.

Sanford School of Medicine, Sioux Falls Campus.

Gulseth, Michael P., Wittkowsky, Ann K., Fanikos, John, Spinler, Sarah A., Dager, William E., and Nutescu, Edith A. (2011).  “Dabigatran Etexilate in Clinical Practice: Confronting Challenges to Improve Safety and Effectiveness.” Pharmacotherapy. 31 (2011, no. 12): 1232-49.

Abstract A number of novel anticoagulants are moving through various stages of drug development. Recently, the United States Food and Drug Administration approved the oral direct thrombin inhibitor dabigatran etexilate to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Although dabigatran offers a number of advantages over existing oral and parenteral anticoagulants, challenges exist for clinicians who must ensure its safe and effective use. Limited data are available on dabigatran use in patients with renal dysfunction and in obese patients, or in combination with other drugs. Clinical experience is lacking in populations for whom anticoagulants are routinely used, such as patients with a previous stroke, acute coronary syndromes, or pregnancy-associated thrombosis, or those requiring ablation therapy. More important, clinicians will be faced with incorporating dabigatran into hospital guidelines for transitioning between oral and parenteral anticoagulants, measuring anticoagulant intensity, managing anticoagulant-related hemorrhage, ensuring safe use around neuraxial anesthesia, and implementing computer-based alert or warning systems. Since anticoagulants are ubiquitously used in the prevention or treatment of venous and arterial thrombosis, both clinicians and patients must be provided structured education on dabigatran’s benefits and limitations. In this article, our goal was to provide practical advice to enhance clinician understanding of dabigatran, identify clinical and operational challenges to its use, and offer system improvements that can ensure safe and effective use of dabigatran.

Sanford School of Medicine, Sioux Falls Campus.

Harmon, Erin B., Harmon, Michelle L., Larsen, Tricia D., Yang, Jie, Glasford, Joseph W., and Perryman, M. Benjamin. (2011).  “Myotonic Dystrophy Protein Kinase Is Critical for Nuclear Envelope Integrity.” Journal of Biological Chemistry. 286 (Nov, no. 46): 40296-306.

Myotonic dystrophy 1 (DM1) is a multisystemic disease caused by a triplet nucleotide repeat expansion in the 3′ untranslated region of the gene coding for myotonic dystrophy protein kinase (DMPK). DMPK is a nuclear envelope (NE) protein that promotes myogenic gene expression in skeletal myoblasts. Muscular dystrophy research has revealed the NE to be a key determinant of nuclear structure, gene regulation, and muscle function. To investigate the role of DMPK in NE stability, we analyzed DMPK expression in epithelial and myoblast cells. We found that DMPK localizes to the NE and coimmunoprecipitates with Lamin-A/C. Overexpression of DMPK in HeLa cells or C2C12 myoblasts disrupts Lamin-A/C and Lamin-B1 localization and causes nuclear fragmentation. Depletion of DMPK also disrupts NE lamina, showing that DMPK is required for NE stability. Our data demonstrate for the first time that DMPK is a critical component of the NE. These novel findings suggest that reduced DMPK may contribute to NE instability, a common mechanism of skeletal muscle wasting in muscular dystrophies.

Sanford School of Medicine, Sioux Falls Campus.

Krajcer, Z., Nelson, P. R., Bianchi, C., Rao, V., Morasch, M. D., and Bacharach, J. Michael. (2011).  “Percutaneous Endovascular Abdominal Aortic Aneurysm Repair: Methods and Initial Outcomes from the First Prospective, Multicenter Trial.” Journal of Cardiovascular Surgery. 52 (Oct, no. 5): 651-59.

Aim. A totally percutaneous approach to endovascular abdominal aortic aneurysm repair (PEVAR) has been shown in multiple single center reports to be feasible. Nonetheless, questions regarding the broader applicability of the approach remain due to the lack of a randomized multicenter trial, thus preventing more widespread adoption. We report the methods and outcomes from the roll-in phase of the first prospective, multicenter trial of PEVAR. Methods. Among 19 institutions participating in the PEVAR Trial (NCT01070069), 38 consecutive patients with abdominal aortic aneurysm were enrolled in a roll-in phase between April 2010 and May 2011. PEVAR procedures with adjunctive “pre-close” of the common femoral arteries (CFAs) targeted for large sheath access using the ProGlide or Prostar XL closure devices were performed using the Endologix IntuiTrak System. All patients were followed periprocedurally and to 30 days for major adverse events and access-related vascular complications. Results. Patients presented at a mean age of 71 years with mean aneurysm sac diameter of 5.6cm. Technical success of the pre-close procedure was 97% (37/38 patients). In one patient, ProGlide devices failed to achieve ipsilateral CFA hemostasis, leading to bleeding requiring transfusion and surgical vascular repair. All endovascular repairs were successful. No mortality or major adverse events occurred. Other pre-close related complications occurring within 30 days included pseudoaneurysm, lower extremity ischemia, and blood transfusion. Conclusion. PEVAR with adjunctive ‘pre-close’ techniques using the Pro Glide or Prostar XL devices is safe and feasible as applied in this multicenter experience. Continued evaluation in the prospective, randomized trial is warranted.

Sanford School of Medicine, Sioux Falls Campus.

Loganathan, G., Dawra, R. K., Pugazhenthi, S., Guo, Zhiguang G., Soltani, S. M., Wiseman, A., Sanders, M. A., Papas, K. K., Velayutham, K., Saluja, A. K., Sutherland, D. E. R., Hering, B. J., and Balamurugan, A. N. (2011).  “Insulin Degradation by Acinar Cell Proteases Creates a Dysfunctional Environment for Human Islets before/after Transplantation: Benefits of Alpha-1 Antitrypsin Treatment.” Transplantation. 92 (Dec, no. 11): 1222-30.

Background. Pancreatic acinar cells are commonly cotransplanted along with islets during auto-and allotransplantations. The aims of this study were to identify how acinar cell proteases cause human islet cell loss before and after transplantation of impure islet preparations and to prevent islet loss and improve function with supplementation of alpha-1 antitrypsin (A1AT). Methods. Acinar cell protease activity, insulin levels, and percent islet loss were measured after culture of pure and impure clinical islet preparations. The effect of proteases on ultrastructure of islets and beta-cell insulin granules were examined by transmission electron microscopy. The number of insulin granules and insulin-labeled immunogold particles were counted. The in vivo effect of proteases on islet function was studied by transplanting acinar cells adjacent to islet grafts in diabetic mice. The effects of A1AT culture supplementation on protease activity, insulin levels, and islet function were assessed in pure and impure islets. Results. Islet loss after culture was significantly higher in impure relative to pure preparations (30% vs. 14%, P < 0.04). Lower islet purity was associated with increased protease activity and decreased insulin levels in culture supernatants. Reduced beta-cell insulin granules and insulin degradation by proteases were confirmed by transmission electron microscopy. Transplantations in mice showed delayed islet graft function when acinar cells were transplanted adjacent to the islets under the kidney capsule. Supplementation of A1AT to impure islet cultures maintained islet cell mass, restored insulin levels, and preserved islet functional integrity. Conclusion. Culture of impure human islet fractions in the presence of A1AT prevents insulin degradation and improves islet recovery.

Sanford School of Medicine, Sioux Falls Campus.

Perrone, R. D., Abebe, K. Z., Schrier, R. W., Thompson, Paul A., Miller, J. P., Meyers, C. M., Bae, K. T., and Grp, Halt Pkd Study. (2011).  “Cardiac Magnetic Resonance Assessment of Left Ventricular Mass in Autosomal Dominant Polycystic Kidney Disease.” Clinical Journal of the American Society of Nephrology. 6 (Oct, no. 10): 2508-15.

Background and objectives Autosomal dominant polycystic kidney disease (ADPKD) is associated with a substantial cardiovascular disease burden including early onset hypertension, intracranial aneurysms, and left ventricular hypertrophy (LVH). A 41% prevalence of LVH has been reported in ADPKD, using echocardiographic assessment of LV mass (LVM). The HALT PKD study was designed to assess the effect of intensive angiotensin blockade on progression of total kidney volume and LVM. Measurements of LVM were performed using cardiac magnetic resonance (MR). Design, setting, participants, & measurements Five hundred forty-three hypertensive patients with GFR >60 ml/min per 1.73 m(2) underwent MR assessment of LVM at baseline. LVM was adjusted for body surface area and expressed as LVM index (LVMI; g/m(2)). Results Baseline BP was 125.1 +/- 14.5/79.3 +/- 11.6 mmHg. Average duration of hypertension was 5.79 years. Prior use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers was present in 59.5% of patients. The prevalence of LVH assessed using nonindexed LVM (g) was 3.9% (n = 21, eight men and 13 women) and 0.93% (n = 5, one man and four women) using LVMI (g/m(2)). In exploratory analyses, the prevalence of LVH using LVM indexed to H(2.7), and the allometric index ppLVmass(HW), ranged from 0.74% to 2.23% (n = 4 to 12). Multivariate regression showed significant direct associations of LVMI with systolic BP, serum creatinine, and albuminuria; significant inverse associations with LVMI were found with age and female gender. Conclusions The prevalence of LVH in hypertensive ADPKD patients <50 years of age with short duration of hypertension, and prior use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers is low. Early BP intervention in ADPKD may have decreased LVH and may potentially decrease cardiovascular mortality. Clin J Am Soc Nephrol 6: 2508-2515, 2011. doi: 10.2215/CJN.04610511

Sanford School of Medicine, Sioux Falls Campus.

Yallapu, Murali Mohan, Ebeling, Mara C., Chauhan, Neeraj, Jaggi, Meena, and Chauhan, Subhash C. (2011).  “Interaction of Curcumin Nanoformulations with Human Plasma Proteins and Erythrocytes.” International journal of nanomedicine. 6 (2011 (Epub 2011 Nov, 2779-90.

Recent studies report curcumin nanoformulation(s) based on polylactic-co-glycolic acid (PLGA), beta-cyclodextrin, cellulose, nanogel, and dendrimers to have anticancer potential. However, no comparative data are currently available for the interaction of curcumin nanoformulations with blood proteins and erythrocytes. The objective of this study was to examine the interaction of curcumin nanoformulations with cancer cells, serum proteins, and human red blood cells, and to assess their potential application for in vivo preclinical and clinical studies. The cellular uptake of curcumin nanoformulations was assessed by measuring curcumin levels in cancer cells using ultraviolet-visible spectrophotometry. Protein interaction studies were conducted using particle size analysis, zeta potential, and Western blot techniques. Curcumin nanoformulations were incubated with human red blood cells to evaluate their acute toxicity and hemocompatibility. Cellular uptake of curcumin nanoformulations by cancer cells demonstrated preferential uptake versus free curcumin. Particle sizes and zeta potentials of curucumin nanoformulations were varied after human serum albumin adsorption. A remarkable capacity of the dendrimer curcumin nanoformulation to bind to plasma protein was observed, while the other formulations showed minimal binding capacity. Dendrimer curcumin nanoformulations also showed higher toxicity to red blood cells compared with the other curcumin nanoformulations. PLGA and nanogel curcumin nanoformulations appear to be very compatible with erythrocytes and have low serum protein binding characteristics, which suggests that they may be suitable for application in the treatment of malignancy. These findings advance our understanding of the characteristics of curcumin nanoformulations, a necessary component in harnessing and implementing improved in vivo effects of curcumin.

Sanford School of Medicine, Sioux Falls Campus.

Yi, Q. Y., Zhao, X. Y., Huang, Y., Ma, T. L., Zhang, Y. Y., Hou, H. L., Cooke, H. J., Yang, Da Qing, Wu, M. A., and Shi, Q. H. (2011).  “P53 Dependent Centrosome Clustering Prevents Multipolar Mitosis in Tetraploid Cells.” Plos One. 6 (Nov, no. 11):

Background: p53 abnormality and aneuploidy often coexist in human tumors, and tetraploidy is considered as an intermediate between normal diploidy and aneuploidy. The purpose of this study was to investigate whether and how p53 influences the transformation from tetraploidy to aneuploidy. Principal Findings: Live cell imaging was performed to determine the fates and mitotic behaviors of several human and mouse tetraploid cells with different p53 status, and centrosome and spindle immunostaining was used to investigate centrosome behaviors. We found that p53 dominant-negative mutation, point mutation, or knockout led to a 2 similar to 33-fold increase of multipolar mitosis in N/TERT1, 3T3 and mouse embryonic fibroblasts (MEFs), while mitotic entry and cell death were not significantly affected. In p53(-/-) tetraploid MEFs, the ability of centrosome clustering was compromised, while centrosome inactivation was not affected. Suppression of RhoA/ROCK activity by specific inhibitors in p53(-/-) tetraploid MEFs enhanced centrosome clustering, decreased multipolar mitosis from 38% to 20% and 16% for RhoA and ROCK, respectively, while expression of constitutively active RhoA in p53(+/+) tetraploid 3T3 cells increased the frequency of multipolar mitosis from 15% to 35%. Conclusions: p53 could not prevent tetraploid cells entering mitosis or induce tetraploid cell death. However, p53 abnormality impaired centrosome clustering and lead to multipolar mitosis in tetraploid cells by modulating the RhoA/ROCK signaling pathway.

Sanford School of Medicine, Sioux Falls Campus.

Ikiugu, Moses N., and Smallfield, Stacy. (2011).  “Ikiugu’s Eclectic Method of Combining Theoretical Conceptual Practice Models in Occupational Therapy.” Australian occupational therapy journal. 58 (2011 Dec (Epub 2011 Oct, no. 6): 437-46.

Background/aim: Occupational therapists are often reluctant to use single theoretical conceptual practice models to guide practice because they recognise the limitation of individual models in addressing clients’ occupational performance issues. However, there is a dearth of eclectic methods of guiding theoretical model combination in the profession. The effectiveness of one such newly developed method in guiding combination of models by students working on a case study was investigated. Methods: This was a mixed methods study with experimental and phenomenological designs in which forty-three occupational therapy students participated. Results: There was increased confidence in ability to apply theory in a case study for all research participants. The improvement was significantly higher for participants in the experimental group, who had been introduced to the eclectic method. Participants in the experimental group were more capable of combining models systematically in a case study compared with those in the control group. Conclusions: Adopting Ikiugu’s eclectic method of combining theoretical conceptual practice models may help students learn how to combine them systematically and increase their likelihood of using theory effectively to guide clinical practice in their future as occupational therapists. 2011 The Authors. Australian Occupational Therapy Journal 2011 Occupational Therapy Australia.

School of Health Sciences.

Background: It has been suggested that, in order to validate a diagnosis of (C)APD (central auditory processing disorder), testing using direct cross-modal analogs should be performed to demonstrate that deficits exist solely or primarily in the auditory modality (McFarland and Cacace, 1995; Cacace and McFarland, 2005). This modality-specific viewpoint is controversial and not universally accepted (American Speech-Language-Hearing Association [ASHA], 2005; Musiek et al, 2005). Further, no such analogs have been developed to date, and neither the feasibility of such testing in normally functioning individuals nor the concurrent validity of cross-modal analogs has been established. Purpose: The purpose of this study was to investigate the feasibility of cross-modal testing by examining the performance of normal adults and children on four tests of central auditory function and their corresponding visual analogs. In addition, this study investigated the degree to which concurrent validity of auditory and visual versions of these tests could be demonstrated. Research Design: An experimental repeated measures design was employed. Study Sample: Participants consisted of two groups (adults, n=10; children, n=10) with normal and symmetrical hearing sensitivity, normal or corrected-to-normal visual acuity, and no family or personal history of auditory/otologic, language, learning, neurologic, or related disorders. Data Collection and Analysis: Visual analogs of four tests in common clinical use for the diagnosis of (C)APD were developed (Dichotic Digits [Musiek, 1983]; Frequency Patterns [Pinheiro and Ptacek, 1971]; Duration Patterns [Pinheiro and Musiek, 1985]; and the Random Gap Detection Test [RGDT; Keith, 2000]). Participants underwent two 1 hr test sessions separated by at least 1 wk. Order of sessions (auditory, visual) and tests within each session were counterbalanced across participants. ANOVAs (analyses of variance) were used to examine effects of group, modality, and laterality (for the Dichotic/Dichoptic Digits tests) or response condition (for the auditory and visual Frequency Patterns and Duration Patterns tests). Pearson product-moment correlations were used to investigate relationships between auditory and visual performance. Results: Adults performed significantly better than children on the Dichotic/Dichoptic Digits tests.Results also revealed a significant effect of modality, with auditory better than visual, and a significant modality × laterality interaction, with a right-ear advantage seen for the auditory task and a left-visual-field advantage seen for the visual task. For the Frequency Patterns test and its visual analog, results revealed a significant modality × response condition interaction, with humming better than labeling for the auditory version but the reversed effect for the visual version. For Duration Patterns testing, visual performance was significantly poorer than auditory performance. Due to poor test-retest reliability and ceiling effects for the auditory and visual gap-detection tasks, analyses could not be performed. No cross-modal correlations were observed for any test. Conclusions: Results demonstrated that cross-modal testing is at least feasible using easily accessible computer hardware and software. The lack of any cross-modal correlations suggests independent processing mechanisms for auditory and visual versions of each task. Examination of performance in individuals with central auditory and pan-sensory disorders is needed to determine the utility of cross-modal analogs in the differential diagnosis of (C)APD.

Communication Disorders Department.

Bellis, Teri James, Billiet, Cassie, and Ross, Jody. “The Utility of Visual Analogs of Central Auditory Tests in the Differential Diagnosis of (Central) Auditory Processing Disorder and Attention Deficit Hyperactivity Disorder.” Journal of the American Academy of Audiology 22, no. 8 (2011).

Background: Cacace and McFarland (2005) have suggested that the addition of cross-modal analogs will improve the diagnostic specificity of (C)APD (central auditory processing disorder) by ensuring that deficits observed are due to the auditory nature of the stimulus and not to supra-modal or other confounds. Others (e.g., Musiek et al, 2005) have expressed concern about the use of such analogs in diagnosing (C)APD given the uncertainty as to the degree to which cross-modal measures truly are analogous and emphasize the nonmodularity of the CANs (central auditory nervous system) and its function, which precludes modality specificity of (C)APD. To date, no studies have examined the clinical utility of cross-modal (e.g., visual) analogs of central auditory tests in the differential diagnosis of (C)APD. Purpose: This study investigated performance of children diagnosed with (C)APD, children diagnosed with ADHD (attention deficit hyperactivity disorder), and typically developing children on three diagnostic tests of central auditory function and their corresponding visual analogs. The study sought to determine whether deficits observed in the (C)APD group were restricted to the auditory modality and the degree to which the addition of visual analogs aids in the ability to differentiate among groups. Research Design: An experimental repeated measures design was employed. Study Sample: Participants consisted of three groups of right-handed children (normal control, n=10; ADHD, n=10; (C)APD, n=7) with normal and symmetrical hearing sensitivity, normal or corrected-tonormal visual acuity, and no family or personal history of disorders unrelated to their primary diagnosis. Participants in Groups 2 and 3 met current diagnostic criteria for ADHD and (C)APD. Data Collection and Analysis: Visual analogs of three tests in common clinical use for the diagnosis of (C)APD were used (Dichotic Digits [Musiek, 1983]; Frequency Patterns [Pinheiro and Ptacek, 1971]; and Duration Patterns [Pinheiro and Musiek, 1985]). Participants underwent two 1 hr test sessions separated by at least 1 wk. Order of sessions (auditory, visual) and tests within each session were counterbalanced across participants. ANCOVAs (analyses of covariance) were used to examine effects of group, modality, and laterality (Dichotic/Dichoptic Digits) or response condition (auditory and visual patterning). In addition, planned univariate ANCOVAs were used to examine effects of group on intratest comparison measures (REA, HLD [Humming-Labeling Differential]). Results: Children with both ADHD and (C)APD performed more poorly overall than typically developing children on all tasks, with the (C)APD group exhibiting the poorest performance on the auditory and visual patterns tests but the ADHD and (C)APD group performing similarly on the Dichotic/Dichoptic Digits task. However, each of the auditory and visual intratest comparison measures, when taken individually, was able to distinguish the (C)APD group from both the normal control and ADHD groups, whose performance did not differ from one another. Conclusions: Results underscore the importance of intratest comparison measures in the interpretation of central auditory tests (American Speech-Language-Hearing Association [ASHA], 2005; American Academy of Audiology [AAA], 2010). Results also support the “non-modular” view of (C)APD in which cross-modal deficits would be predicted based on shared neuroanatomical substrates. Finally, this study demonstrates that auditory tests alone are sufficient to distinguish (C)APD from supra-modal disorders, with cross-modal analogs adding little if anything to the differential diagnostic process.

Communication Disorders Department.

Burke, A. R., Watt, Michael J., and Forster, Gina L. “Adolescent Social Defeat Increases Adult Amphetamine Conditioned Place Preference and Alters D2 Dopamine Receptor Expression.” Neuroscience 197 (2011): 269-79.

Components of the brain’s dopaminergic system, such as dopamine receptors, undergo final maturation in adolescence. Exposure to social stress during human adolescence contributes to substance abuse behaviors. We utilized a rat model of adolescent social stress to investigate the neural mechanisms underlying this correlation. Rats exposed to repeated social defeat in adolescence (P35-P39) exhibited increased conditioned place preference (CPP) for amphetamine (1 mg/kg) in adulthood (P70). In contrast, rats experiencing foot-shock during the same developmental period exhibited amphetamine CPP levels similar to non-stressed controls. Our previous experiments suggested adolescent defeat alters dopamine activity in the mesocorticolimbic system. Furthermore, dopamine receptors have been implicated in the expression of amphetamine CPP. Therefore, we hypothesized that alteration to dopamine receptor expression in the mesocorticolimbic system may be associated with to heightened amphetamine CPP of adult rats exposed to adolescence defeat. We measured D1 and D2 dopamine receptor protein content in the medial prefrontal cortex, nucleus accumbens (NAc), and dorsal striatum following either adolescent social defeat or foot-shock stress and then adult amphetamine CPP. In controls, amphetamine CPP training reduced D2 receptor protein content in the NAc core. However, this down-regulation of NAc core D2 receptors was blocked by exposure to social defeat but not foot-shock stress in adolescence. These results suggest social defeat stress in adolescence alters the manner in which later amphetamine exposure down-regulates D2 receptors. Furthermore, persistent alterations to adult D2 receptor expression and amphetamine responses may depend on the type of stress experienced in adolescence. Copyright A 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Basic Biomedical Sciences, Vermillion Campus.

Elhai, Jon D., Naifeh, James A., Forbes, David, Ractliffe, Kendra C., and Tamburrino, Marijo. “Heterogeneity in Clinical Presentations of Posttraumatic Stress Disorder among Medical Patients: Testing Factor Structure Variation Using Factor Mixture Modeling.” Journal of Traumatic Stress 24, no. 4 (2011): 435-43.

The present study used factor mixture modeling to explore empirically defined subgroups of psychological trauma victims based on confirmatory factor analysis (CFA) and latent class analysis of posttraumatic stress disorder (PTSD) symptoms. We sampled 310 medical patients with a history of trauma exposure. Confirmatory factor analysis revealed that the 4-factor emotional numbing PTSD model yielded the best model fit. Using latent factor means derived from this model and the 4-factor dysphoria PTSD model (indexing severity on PTSD factors), 3 latent classes of participants were identified using factor mixture modeling. The 3-class model fit the data very well and was validated against external measures of anxiety and rumination. (PsycINFO Database Record (c) 2011 APA, all rights reserved) (journal abstract)

Psychology Department.

Elias, A. F., Dunn, Joel, and Huntington, Mark K. “Tuberculosis and Profound Hypovitaminosis D in an Infant.” Pediatric Infectious Disease Journal 30, no. 11 (2011): 1008-10.

A young infant presented with a febrile respiratory illness, irritability, and failure to thrive. Clinical evaluation identified that he had profound hypovitaminosis D with severe hypocalcemia and active pulmonary tuberculosis. We review the literature and discuss the current state of knowledge of the interrelationship between Mycobacterium infection and vitamin D status, and its implication to pediatricians.

Sanford School of Medicine, Sioux Falls Campus.

Fayer, Liz, Zalud, Garreth, Baron, Mark, Anderson, Cynthia M., and Duggan, Timothy J. “Student Perceptions of the Use of Inquiry Practices in a Biology Survey Laboratory Course.” Journal of College Science Teaching 41, no. 2 (2011): 82-88.

Extensive research has shown inquiry in science education to be best practice; however , most universities currently do not include inquiry practices in their coursework. The purpose of this study was to determine the level of inquiry that students in a Biology Survey Laboratory course considered to be the most supportive of their learning at a small, rural, midwestern university. A survey instrument, developed using the inquiry level rubric designed by Bruck, Bretz, and Towns (2008) and consisting of 36 Likert-scale items plus four demographic items, was used to collect data (N = 190). When considering the most appropriate level of inquiry to support their learning of biology, students perceived that they would learn best with open or authentic inquiry levels.

School of Education.

Flynn, Stephen V., and Black, Linda L. “An Emergent Theory of Altruism and Self-Interest.” Journal of Counseling & Development 89, no. 4 (2011): 459-69.

Beliefs about altruism and self-interest of 25 participants were examined through a grounded theory methodology. Altruism was defined as the promotion of needs of others and self-interest as the promotion of needs of self. Data sources included interviews, focus group, journal analysis, artifacts, and a measure of altruism. The relationship between altruism and self-interest emerged and was composed of 12 themes. Themes described a dynamic theory that was systemic, values oriented, and interactional. (PsycINFO Database Record (c) 2011 APA, all rights reserved) (journal abstract)

School of Education.

He, H. S., Zhong, Yihan H., Si, Liping P., and Sykes, Andrew. “Structural, Photophysical and Theoretical Studies of Two Dodecachlorinated Porphyrins.” Inorganica Chimica Acta 378, no. 1 (2011): 30-35.

Two dodecachlorinated porphyrins, 2,3,7,8,12,13,17,18-octachloro-5,10,15,20-tetra(4-chlorophenyl)porphyrin free base (TCl(12)PPH(2)) and its nickel compound (TCl(12)PPNi), have been synthesized. Single-crystal X-ray diffraction analysis shows that porphyrin rings are heavily distorted and exhibit saddled conformations. The Soret and Q bands of two compounds are red-shifted compared to their non-chlorinated counterparts. Theoretical calculations reveal that the optical band gap of TCl(12)PPH(2) is reduced, whereas that of TCl(12)PPNi remains almost the same as to its non-chlorinated nickel compound due to the concurrent lowering of HOMO and LUMO energy levels. The frontier molecular orbitals are degenerated due to the decrease of symmetry of the molecules. (C) 2011 Elsevier B.V. All rights reserved.

Chemistry Department.

Johnson, K. J., Carozza, S. E., Mueller, B. A., Puumala, Susan E., Reynolds, P., Von Behren, J., and Spector, L. G. “Birth Characteristics and Childhood Carcinomas.” British Journal of Cancer 105, no. 9 (2011): 1396-401.

Background:Carcinomas in children are rare and have not been well studied.Methods:We conducted a population-based case-control study and examined associations between birth characteristics and childhood carcinomas diagnosed from 28 days to 14 years during 1980-2004 using pooled data from five states (NY, WA, MN, TX, and CA) that linked their birth and cancer registries. The pooled data set contained 57 966 controls and 475 carcinoma cases, including 159 thyroid and 126 malignant melanoma cases. We used unconditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs).Results:White compared with ‘other’ race was positively associated with melanoma (OR=3.22, 95% CI 1.33-8.33). Older maternal age increased the risk for melanoma (OR_{per 5-year age increase}=1.20, 95% CI 1.00-1.44), whereas paternal age increased the risk for any carcinoma (OR=1.10_{per 5-year age increase}, 95% CI 1.01-1.20) and thyroid carcinoma (OR_{per 5-year age increase}=1.16, 95% CI 1.01-1.33). Gestational age <37 vs 37-42 weeks increased the risk for thyroid carcinoma (OR=1.87, 95% CI 1.07-3.27). Plurality, birth weight, and birth order were not significantly associated with childhood carcinomas.Conclusion:This exploratory study indicates that some birth characteristics including older parental age and low gestational age may be related to childhood carcinoma aetiology.

Sanford School of Medicine, Sioux Falls Campus.

Koepsell, Laura, Remund, Tyler, Bao, Jing, Neufeld, Daniel, Fong, Hao, and Deng, Ying. “Tissue Engineering of Annulus Fibrosus Using Electrospun Fibrous Scaffolds with Aligned Polycaprolactone Fibers.” Journal of biomedical materials research. Part A 99, no. 4 (2011): 564-75.

In tissue engineering, it is important to fabricate a three-dimensional scaffold that resemble the extracellular matrix (ECM) and topographical appearance of native tissue. The aim of this study is to test the hypothesis that varying microstructures of electrospun fibrous scaffolds by manipulating the relative degree of fiber alignment would influence the behaviors of porcine annulus fibrosus cells. Five types of electrospun fibrous scaffolds with polycaprolactone fibers having random or partially aligned arrangements have been prepared and investigated. The scaffold microstructures have been examined, and in vitro experiments have been carried out to assess cell-material interaction, cell proliferation, and ECM production. The results indicate that the scaffold with oriented fibers provides strong guidance to the cell orientation and ECM distribution. In addition, albeit the tensile moduli of electrospun fibrous scaffolds are lower than that of native tissue, they are comparable to those reported in literature; hence, the constructs cultured with optimized conditions including the scaffold material selection and dynamic mechanical conditioning would have the potential to possess the moduli closer to that of native tissue. 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2011. Copyright 2011 Wiley Periodicals, Inc.

Biomedical Engineering, Sioux Falls Campus.

Lubbers, Charles A. (2011). An assessment of predictors of student peer evaluations of team work in the capstone campaigns course. Public Relations Review, 37(5), 492-498.

Abstract: The role of peer evaluations of team work in the capstone, campaigns class is investigated. An assessment of the scores on a 16-item, quantitative assessment of student contributions to their team in a campaigns class indicated that students are extremely positive when evaluating their team members. Means for the 16 evaluation items ranged from 1.44 to 2.19 on a 1–7 scale. The evaluation items were regressed with two overall evaluation measures in the form of the “pay” students would receive from other individuals or the group mean payment. The statistically significant predictors for both dependent variables are identified.

Contemporary Media Department.

May, Philip A., Tabachnick, Barbara G., Gossage, J. Phillip, Kalberg, Wendy O., Marais, Anna-Susan, Robinson, Luther K., Manning, Melanie, Buckley, David, and Hoyme, H. Eugene. “Maternal Risk Factors Predicting Child Physical Characteristics and Dysmorphology in Fetal Alcohol Syndrome and Partial Fetal Alcohol Syndrome.” Drug & Alcohol Dependence 119, no. 1/2 (2011): 18-27.

Abstract: Background: Previous research in South Africa revealed very high rates of fetal alcohol syndrome (FAS), of 46–89 per 1000 among young children. Maternal and child data from studies in this community summarize the multiple predictors of FAS and partial fetal alcohol syndrome (PFAS). Method: Sequential regression was employed to examine influences on child physical characteristics and dysmorphology from four categories of maternal traits: physical, demographic, childbearing, and drinking. Then, a structural equation model (SEM) was constructed to predict influences on child physical characteristics. Results: Individual sequential regressions revealed that maternal drinking measures were the most powerful predictors of a child”s physical anomalies (R ² =.30, p <.001), followed by maternal demographics (R ² =.24, p <.001), maternal physical characteristics (R ² =.15, p <.001), and childbearing variables (R ² =.06, p <.001). The SEM utilized both individual variables and the four composite categories of maternal traits to predict a set of child physical characteristics, including a total dysmorphology score. As predicted, drinking behavior is a relatively strong predictor of child physical characteristics (β =0.61, p <.001), even when all other maternal risk variables are included; higher levels of drinking predict child physical anomalies. Conclusions: Overall, the SEM model explains 62% of the variance in child physical anomalies. As expected, drinking variables explain the most variance. But this highly controlled estimation of multiple effects also reveals a significant contribution played by maternal demographics and, to a lesser degree, maternal physical and childbearing variables.

Sanford School of Medicine, Sioux Falls Campus.

Ranek, Mark J., Cotten, S. W., and Willis, M. S. “Albert Szent-Gyorgyi, Md, Phd Discoverer of Vitamin C and a Pioneer of Cellular Respiration, Muscle Physiology, and Cancer Development.” Labmedicine 42, no. 11 (2011): 694-98.

Basic Biomedicine, Vermillion Campus.

Roh, Soonhee, Jang, Yuri, Chiriboga, David, Kwag, Kyung, Cho, Sunhee, and Bernstein, Kunsook. “Perceived Neighborhood Environment Affecting Physical and Mental Health: A Study with Korean American Older Adults in New York City.” Journal of Immigrant & Minority Health 13, no. 6 (2011): 1005-12.

This study examined how subjective perceptions of the neighborhood environment (e.g., perceived ethnic density, safety, social cohesion, and satisfaction) influenced the physical and mental health of Korean American older adults. Using data from 420 residents of the New York City metropolitan area ( M = 71.6, SD = 7.59), health perceptions and depressive symptoms were estimated with hierarchical regression models entered in the order of (1) demographics and acculturation, (2) health-related variables, and (3) perceived neighborhood environment. After controlling for the effects of the individual-level variables, perceived neighborhood environment was found to make a significant contribution to both outcomes. Individuals less satisfied with their overall neighborhood environment were more likely to have negative perceptions of health and depressive symptoms. A strong linkage between perceived neighborhood safety and depressive symptoms was also observed. Findings from the study highlight the importance of subjective evaluations of neighborhood environment and provide implications for health promotion.

Scholl of Health Sciences.

Sharma, Neeru M., Zheng, Hong, Mehta, Parmender P., Li, Yi-Fan, and Patel, Kaushik P. “Decreased Nnos in the Pvn Leads to Increased Sympathoexcitation in Chronic Heart Failure: Role for Capon and Ang Ii.” Cardiovascular Research 92, no. 2 (2011): 348-57.

Aims Previously, we showed an enhanced excitatory (N-methyl d-aspartate receptor-NR1) and decreased inhibitory neuronal nitric oxide (NO) synthase (nNOS) influence within the paraventricular nucleus (PVN) of rats with chronic heart failure (CHF). Although NR1 and nNOS are normally linked, they can be disconnected by nNOS sequestering with nNOS-associated protein (CAPON). The aim of this study was to elucidate the underlying mechanism for the disconnection between increased expression of NR1 and decreased nNOS in the PVN of rats with CHF which leads to enhanced sympathoexcitation. Methods and results CAPON expression was augmented while nNOS expression was decreased in the PVN of rats with CHF (6–8 weeks after left coronary artery ligation). Angiotensin II (Ang II) type I receptor (AT1) antagonist losartan (Los) treatment in rats with CHF reduced renal sympathetic nerve activity with concomitant normalization of protein expression of CAPON and nNOS in the PVN. Los treatment also reversed the blunting of endogenous NO-mediated sympatho-inhibition in rats with CHF. Moreover, Ang II-induced increase in CAPON expression in NG108 neuronal cells was also ameliorated by Los. Conclusion Blocking AT1 receptors prevents the overexpression of CAPON and concomitant decrease in nNOS in the PVN, resulting in attenuation of sympathoexcitation commonly observed in CHF. Taken together, our data highlight the importance of altered expression and subsequent interaction of nNOS and CAPON within the PVN, leading to increased sympathoexcitation in CHF. Identifying this crucial nNOS/CAPON interaction regulated by AT1 receptors may provide an important potential therapeutic target in CHF.

Basic Biomedical Sciences, Vermillion Campus.

Su, Huabo, and Wang, Xuejun. “Autophagy and P62 in Cardiac Protein Quality Control.” Autophagy 7, no. 11 (2011): 1382-3.

This is an addendum to a recent report which demonstrates for the first time that autophagic flux is increased in the heart of a well-established mouse model of cardiac proteinopathy and p62 is transcriptionally upregulated in cardiomyocytes and hearts overexpressing human cardiomyopathy-linked misfolded proteins. The p62 plays a critical and protective role in aggresome formation and autophagic activation in cardiomyocytes overexpressing misfolded proteins.

Basic Biomedical Sciences, Vermillion Campus.

This review discusses selected classical works and contemporary research on recovery of contralesional fine hand motor function following lesions to motor areas of the cerebral cortex in non-human primates. Findings from both the classical literature and contemporary studies show that lesions of cortical motor areas induce paresis initially, but are followed by remarkable recovery of fine hand/digit motor function that depends on lesion size and post-lesion training. Indeed, in recent work where considerable quantification of fine digit function associated with grasping and manipulating small objects has been observed, very favorable recovery is possible with minimal forced use of the contralesional limb. Studies of the mechanisms underlying recovery have shown that following small lesions of the digit areas of primary motor cortex (M1), there is expansion of the digit motor representations into areas of M1 that did not produce digit movements prior to the lesion. However, after larger lesions involving the elbow, wrist and digit areas of M1, no such expansion of the motor representation was observed, suggesting that recovery was due to other cortical or subcortical areas taking over control of hand/digit movements. Recently, we showed that one possible mechanism of recovery after lesion to the arm areas of M1 and lateral premotor cortex is enhancement of corticospinal projections from the medially located supplementary motor area (M2) to spinal cord laminae containing neurons which have lost substantial input from the lateral motor areas and play a critical role in reaching and digit movements. Because human stroke and brain injury patients show variable, and usually poorer, recovery of hand motor function than that of nonhuman primates after motor cortex damage, we conclude with a discussion of implications of this work for further experimentation to improve recovery of hand function in human stroke patients.

Basic Biomedical Sciences, Vermillion Campus.

Li, Qin, and Burrell, Brian D. “Associative, Bidirectional Changes in Neural Signaling Utilizing Nmda Receptor- and Endocannabinoid-Dependent Mechanisms.” Learning & Memory 18, no. 9 (2011).

Persistent, bidirectional changes in synaptic signaling (that is, potentiation and depression of the synapse) can be induced by the precise timing of individual pre- and postsynaptic action potentials. However, far less attention has been paid to the ability of paired trains of action potentials to elicit persistent potentiation or depression. We examined plasticity following the pairing of spike trains in the touch mechanosensory neuron (T cell) and S interneuron (S cell) in the medicinal leech. Long-term potentiation (LTP) of T to S signaling was elicited when the T-cell spike train preceded the S-cell train. An interval 0 to +1 sec between the T- and S-cell spike trains was required to elicit long-term potentiation (LTP), and this potentiation was NMDA receptor (NMDAR)-dependent. Long-term depression (LTD) was elicited when S-cell activity preceded T-cell activity and the interval between the two spike trains was -0.2 sec to -10 sec. This surprisingly broad temporal window involved two distinct cellular mechanisms; an NMDAR-mediated LTD (NMDAR-LTD) when the pairing interval was relatively brief (<-1 sec) and an endocannabinoid-mediated LTD (eCB-LTD) when longer pairing intervals were used (-1 to -10 sec). This eCB-LTD also required activation of a presynaptic transient receptor potential vanilloid (TRPV)-like receptor, presynaptic Ca(2+) release from intracellular stores and activation of voltage-gated Ca(2+) channels (VGCCs). These findings demonstrate that the pairing of spike trains elicits timing-dependent forms of LTP and LTD that are supported by a complex set of cellular mechanisms involving NMDARs and endocannabinoid activation of TRPV-like receptors.

Basic Biomedical Sciences, Vermillion Campus.

Timms, Barry G., and Hofkamp, Luke E. “Prostate Development and Growth in Benign Prostatic Hyperplasia.” Differentiation; research in biological diversity 82, no. 4-5 (2011).

The etiology of benign prostatic hyperplasia [BPH] in elderly men has intrigued anatomists, pathologists and scientists for centuries. Studies of morbid anatomy, clinical observations and contemporary cellular biology have contributed to an evolving interpretation of the causality of the disease. Insights into the detailed microanatomy and ductal architecture of the prostate during stages of fetal and early postnatal development suggest that mechanisms involved in the early growth period become aberrantly expressed in elderly men. Age, hormones and epithelial-mesenchymal interactions are all contributing factors to the pathogenesis of BPH. Control of the microenvironment in normal and abnormal growth is a multifactorial process. Susceptibility to the disease may include clinical comorbid diseases, region-specific changes in cell-cell interactions and a variety of signaling pathways including a novel hypothesis regarding the role of the primary cilium as a regulator of signal transduction mechanisms. Recent work in animal models has shown that there are region-specific differences within the prostate that may be significant because of the dynamic and intricate interplay between the epithelium and mesenchyme. Because of the focal nature of BPH a closer examination of normal morphogenesis patterns, which defines the gland’s architecture, may facilitate a detailed understanding of the atypical growth patterns. Copyright 2011 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

Basic Biomedical Sciences, Vermillion Campus.

Zheng, Yuhuan, and Miskimins, W. Keith. “Far Upstream Element Binding Protein 1 Activates Translation of P27<Sup>Kip1</Sup> Mrna through Its Internal Ribosomal Entry Site.” International Journal of Biochemistry & Cell Biology 43, no. 11 (2011).

Abstract: The cyclin dependent kinase inhibitor p27 plays an important role in controlling the eukaryotic cell cycle by regulating progression through G1 and entry into S phase. It is often elevated during differentiation and under conditions of cellular stress. In contrast, it is commonly downregulated in cancer cells and its levels are generally inversely correlated with favorable prognosis. The cellular levels of p27 are regulated, in part, by translational control mechanisms. The 5′-untranslated region (5′-UTR) of the p27 mRNA harbors an internal ribosome entry site (IRES) which may facilitate synthesis of p27 in certain conditions. In this study, Far Upstream Element (FUSE) Binding Protein 1 (FBP1) was shown to directly bind to the human p27 5′-UTR and to promote IRES activity. An eight-nucleotide element downstream of a U-rich region within the 5′-UTR was important for FBP1 binding and p27 IRES activity. Overexpression of FBP1 enhanced endogenous p27 levels and stimulated translation initiation. In contrast, repression of FBP1 by siRNA transfection downregulated endogenous p27 protein levels. Using rabbit reticulocyte lysates, FBP1 stimulated p27 mRNA translation in vitro. The central domain of FBP1, containing four K homology motifs, was required for p27 5′-UTR RNA binding and the N terminal domain was important for translational activation. These findings indicate that FBP1 is a novel activator of p27 translation upon binding to the 5′-UTR.

Basic Biomedical Sciences, Vermillion Campus.

Husak, Jerry F., Ribak, G. A. L., Wilkinson, Gerald S., and Swallow, John G. “Sexual Dimorphism in Wing Beat Frequency in Relation to Eye Span in Stalk-Eyed Flies (Diopsidae).” Biological Journal of the Linnean Society 104, no. 3 (2011).

Although male ornaments may provide benefits to individuals bearing them, such structures may also entail fitness costs. Selection should favour aspects of the phenotype that act to reduce such costs, yet such compensatory traits are often ignored in studies of sexual selection. If a male ornament increases predation risk via reduced locomotor performance, then there may be selection for changes in morphological traits to compensate for behavioural or biomechanical changes in how individuals use their morphology (or both). We took a comparative approach aiming to test whether changes in wing beat frequency are evolutionarily correlated with increases in male ornamentation across stalk-eyed fly species. Previous studies have shown that increased male eye span is evolutionarily correlated with increased wing size; thus, we tested whether there is additional compensation via increases in size-adjusted wing beat frequency. The results obtained revealed that relative wing beat frequency is negatively related to relative eye span in males, and sexual dimorphism in wing beat frequency is negatively related to dimorphism in eye span. These findings, in addition to our finding that eye span dimorphism is positively related to aspect ratio dimorphism, suggest that male stalk-eyed flies compensate primarily by increasing wing size and shape, which may then have resulted in the subsequent evolutionary reduction in wing beat frequency. Thus, exaggerated ornaments can result in evolutionary modifications in wing morphology, which in turn lead to adjustments in flapping kinematics, illustrating the tight envelope of trade-offs when compensating for exaggerated ornaments.

Biology Department.

Liknes, Eric. T., and Swanson, David L. “Phenotypic Flexibility of Body Composition Associated with Seasonal Acclimatization in Passerine Birds.” Journal of Thermal Biology 36, no. 6 (2011).

Improved winter cold tolerance is widespread among small birds overwintering in cold climates and is associated with improved shivering endurance and elevated summit metabolic rate (M(sum)). Phenotypic flexibility resulting in elevated M(sum), could result from either increased skeletal muscle mass (perhaps with support from similar adjustments in “nutritional organs”) and/or cellular metabolic intensity. We investigated seasonal changes in body composition of three species of passerine birds resident in cold winter climates, all of which show large seasonal variations in M(sum) ( > 25%); white-breasted nuthatch (Sitta carolinensis), black-capped chickadee (Poecile atricapillus), and house sparrow (Passer domesticus). All three species displayed significant winter increases in pectoralis and heart masses, and supracor-acoideus mass also increased in winter chickadees. Gizzard mass increased in winter for all three species, but masses of other nutritional organs did not vary consistently with season. These data suggest that winter increases in pectoralis and heart masses are important contributors to elevated thermogenic capacity and cold tolerance, but seasonal variation in nutritional organ masses, other than gizzard, which is likely associated with dietary changes, are not universally associated with seasonal phenotypes. The winter increases in pectoralis and heart masses are consistent with data from other small passerines showing marked seasonal changes in cold tolerance and support the Variable Maximum Model of seasonal phenotypic flexibility, where physiological adjustments that promote improved cold tolerance, also result in elevated M(sum). (C) 2011 Elsevier Ltd. All rights reserved.

Biology Department.

Venesky, M. D., Kerby, Jacob L., Storfer, A., and Parris, M. J. “Can Differences in Host Behavior Drive Patterns of Disease Prevalence in Tadpoles?” Plos One 6, no. 9 (2011).

Differences in host behavior and resistance to disease can influence the outcome of host-pathogen interactions. We capitalized on the variation in aggregation behavior of Fowler’s toads (Anaxyrus [ = Bufo] fowleri) and grey treefrogs (Hyla versicolor) tadpoles and tested for differences in transmission of Batrachochytrium dendrobatidis (Bd) and host-specific fitness consequences (i.e., life history traits that imply fitness) of infection in single-species amphibian mesocosms. On average, A. fowleri mesocosms supported higher Bd prevalences and infection intensities relative to H. versicolor mesocosms. Higher Bd prevalence in A. fowleri mesocosms may result, in part, from higher intraspecific transmission due to the aggregation of tadpoles raised in Bd treatments. We also found that, independent of species, tadpoles raised in the presence of Bd were smaller and less developed than tadpoles raised in disease-free conditions. Our results indicate that aggregation behavior might increase Bd prevalence and that A. fowleri tadpoles carry heavier infections relative to H. versicolor tadpoles. However, our results demonstrate that Bd appears to negatively impact larval growth and developmental rates of A. fowleri and H. versicolor similarly, even in the absence of high Bd prevalence.

Biology Department.

Eyster, Kathleen M., Appt, S. E., Mark-Kappeler, Connie J., Chalpe, Alpha, Register, T. C., and Clarkson, T. B. “Gene Expression Signatures Differ with Extent of Atherosclerosis in Monkey Iliac Artery.” Menopause-the Journal of the North American Menopause Society 18, no. 10 (2011).

Objective: The aim of this study was to evaluate global gene expression patterns in the common iliac arteries of monkeys with a varied extent of atherosclerosis. Methods: The left common iliac artery was removed from ovariectomized cynomolgus monkeys (n = 12) after 6.5 years of consuming a diet containing fat and cholesterol at levels comparable with those consumed in Western populations. Arterial gene expression was analyzed using DNA microarray and real-time reverse transcription-polymerase chain reaction. Results: Significant differential expression of 986 genes was observed in iliac arteries containing moderate to large atherosclerotic plaques compared with normal/minimally affected reference group arteries. Atherosclerosis-associated genes included cytokines, chemokines, components of signal transduction pathways, and transcriptional activators and repressors, as well as other functional categories. Real-time reverse transcription-polymerase chain reaction confirmed a differential expression of genes chosen from a variety of functional categories. Specifically, the expression of genes for estrogen receptor-1, claudin 11, and brain heart protocadherin 7 was reduced, whereas the expression of genes for apolipoprotein E, growth differentiation factor 15, superoxide dismutase-2, SET domain bifurcated 2, phospholipase A2 group IIA, phospholipase A2 group VII, and ring finger protein 149 was increased in atherosclerotic arteries. Conclusions: The gene expression environment in arteries containing atherosclerotic plaques is profoundly different from that of relatively unaffected arteries and reflects the cellular and molecular complexity of atherosclerosis and associated arterial remodeling processes.

Biomedical Sciences, Vermillion Campus.

Basa, Prem N., Bhowmick, Arundhati, Schulz, Mariah M., and Sykes, Andrew G. “Site-Selective Imination of an Anthracenone Sensor: Selective Fluorescence Detection of Barium(Ii).” The Journal of organic chemistry 76, no. 19 (2011).

Site-selective imination of anthraquinone-based macrocyclic crown ethers using titanium tetrachloride as the catalyst yields imines where only the external carbonyl group of the anthraquinone forms Schiff-bases. The following aromatic amines yield monomeric compounds (aniline, 4-nitroaniline, 4-pyrrolaniline, and 1,3-phenylenediamine). Reaction of 2 equiv of the macrocyclic anthraquinone host with 1,2- and 1,4-phenylenediamine yields dimeric imine compounds. The 1,2-diimino host acts as a luminescence sensor, exhibiting enhanced selectivity for Ba(II) ion. Spectroscopic data indicate that two barium ions coordinate to the sensor. Due to E/Z isomerization of the imine, the monomeric complexes are nonluminescent. Restricted rotation about the 1,2 oriented C═N groups or other noncovalent/coordinate-covalent interactions acting between neighboring crown ether rings may inhibit E/Z isomerization in this example, which is different from current examples that employ coordination of a metal cation with a chelating imine nitrogen atom to suppress E/Z isomerization and activate luminescence. The 1,4-diimino adduct, where the crown rings remain widely separated, remains nonluminescent.

Chemistry Department.

He, H. S., Dubey, M., Zhong, Y. H., Shrestha, M., and Sykes, Andrew G. “2-(1-Acetyl-2-Oxopropyl)-5,10,15,20-Tetraphenylporphyrin and Its Transition-Metal Complexes.” European Journal of Inorganic Chemistry, no. 25 (2011).

The 2-(1-acetyl-2-oxopropyl)-5,10,15,20-tetraphenylporphyrin free base (H(2)TPP-AOP) and its transition-metal complexes (MTPP-AOP, M = Cu(2+), Zn(2+)) have been synthesized. Single-crystal X-ray diffraction analysis revealed that the 1-acetyl-2-oxopropyl (AOP) group is attached to a beta-pyrrolic position through the methylene group. The mean plane of the AOP is almost perpendicular to the porphyrin ring. The zinc(II) complex crystallizes as a five-coordinate species with one methanol/water solvate in the axial position, whereas the copper(II) complex is four-coordinate. These compounds exhibit strong absorption in the UV and visible regions. The fluorescence lifetimes are 1.85 and 8.0 ns for the free base and zinc(II) complex, respectively. Density functional calculations indicate that these porphyrins are energetically suitable for electron injection from their lowest-unoccupied molecular orbitals to the conduction band of the titanium dioxide semiconductor. However, the energy conversion efficiencies of the three porphyrin-sensitized solar cells are low, that is, 0.14, 0.015 and 0.021% for ZnTPP-AOP, CuTPP-AOP and H(2)TPP-AOP, respectively. The poor photovoltaic performance is ascribed to the low dye-loading of these porphyrins on the titanium dioxide surface. The neighbouring phenyl groups exert sufficient steric hindrance on the AOP to limit its binding to the TiO(2) semiconductor.

Chemistry Department.

Paudel, H. P., Zhong, L. L., Bayat, K., Baroughi, M. F., Smith, S., Lin, Culkon K., Jiang, Chaoyang Y., Berry, Mary T., and May, P. Stanley. “Enhancement of near-Infrared-to-Visible Upconversion Luminescence Using Engineered Plasmonic Gold Surfaces.” Journal of Physical Chemistry C 115, no. 39 (2011).

An engineered plasmonic gold surface, specifically designed to couple with 980 nm radiation, is shown to enhance near-infrared-to-visible upconversion luminescence from a monolayer of beta-NaYF(4): 17%Yb, 3%Er nanocrystals in poly(methyl methacrylate) on that gold surface. Confocal imaging of upconversion luminescence from the surface is used to characterize the nature of the enhancement. It is shown that the luminescence data were acquired below the so-called “high power limit” for excitation, but some saturation was evident, as the observed power dependence was less than quadratic. Over the range of excitation power densities used, the intrinsic enhancement factor for upconversion from the patterned surface was greater than a factor of 3 but decreased slowly with increasing excitation power. The red and green upconversion were enhanced by similar factors, which would support the intensification of the excitation field by the plasmonic surface as being the mechanism of enhancement. In the absence of other enhancement or quenching mechanisms, the data imply an approximate 2-fold magnification of the excitation field intensity relative to smooth gold.

Chemistry Department.

Sweeney, Mark R., McDonald, Eric V., and Etyemezian, Vicken. “Quantifying Dust Emissions from Desert Landforms, Eastern Mojave Desert, USA.” Geomorphology 135, no. 1/2 (2011).

Abstract: The measurement of natural dust emissions from desert landforms is crucial in environmental hazard assessment and field checking the accuracy of global dust models. More than 500 individual dust measurements from eight common desert landforms in southern California were collected using the PI-SWERL (Portable In Situ Wind Erosion Lab). The largest emitters of dust are dry washes (13.787 to 0.007mgm⁻² s⁻¹), dunes, playa margins, distal alluvial fans, and lacustrine beaches. Low emitters include salt-crusted playas (0.692 to 0.002mgm⁻² s⁻¹), silt–clay-crusted playas, and desert pavements. High emissions are a function of saltating sand that bombards the surface, liberating dust-sized particles for entrainment. Low dust emissions are primarily a function of surface crusting, gravel armoring, and vegetation density. PI-SWERL measurements reveal that emission rates can vary by at least three orders of magnitude, reflecting local variability in soil texture and continuity of surface crusts. Shear-stress partitioning models can be applied to dust data measured by the PI-SWERL to account for large surface roughness features, such as vegetation. The results presented here give an approximation of the contributions to atmospheric dust loading by landforms in the Mojave Desert, and can potentially be used to improve atmospheric dust models.

Earth Sciences Department.

González-Olivares, Eduardo, Mena-Lorca, Jaime, Rojas-Palma, Alejandro, and Flores, José D. “Erratum to “Dynamical Complexities in the Leslie–Gower Predator–Prey Model as Consequences of the Allee Effect on Prey” [Appl. Math. Modell. (2011) 366–381].” Applied Mathematical Modelling 36, no. 2 (2012).

Abstract: The aim of this paper is to correct two mistakes in [Appl. Math. Modell. (2011) 366–381], which are: the function defining the time rescaling given and the inclusion of a parameter outside of model. For a modified Leslie–Gower type predator–prey model considering the Allee effect on prey, a change of variables and a new time rescaling generating a diffeomorphism is proved; a topologically equivalent system to the original one is obtained, which is the same studied in the mentioned paper; we claim that the results and conclusions obtained are correct and the errors have not further implications.

Mathematics Department.

Haagerup, U., and Picioroaga, Gabriel. “New Presentations of Thompson’s Groups and Applications.” Journal of Operator Theory 66, no. 1 (2011).

We find new presentations for the Thompson’s groups F, the derived group F’ and the intermediate group D. These presentations have a common ground in that their relators are the same and only the generating sets differ. As an application of these presentations we extract the following consequences: the cost of the group F’ is 1 hence the cost cannot decide the (non)amenability question of F; the II(1) factor L(F’) is inner asymptotically abelian and the reduced C*-algebra of F is not residually finite dimensional.

Mathematics Department.

Gehman, V. M., Seibert, S. R., Rielage, K., Hime, A., Sun, Y., Mei, D. M., Maassen, J., and Moore, D. “Fluorescence Efficiency and Visible Re-Emission Spectrum of Tetraphenyl Butadiene Films at Extreme Ultraviolet Wavelengths.” Nuclear Instruments & Methods in Physics Research Section A 654, no. 1 (2011).

Abstract: A large number of current and future experiments in neutrino and dark matter detection use the scintillation light from noble elements as a mechanism for measuring energy deposition. The scintillation light from these elements is produced in the extreme ultraviolet (EUV) range, from 60 to 200nm. Currently, the most practical technique for observing light at these wavelengths is to surround the scintillation volume with a thin film of tetraphenyl butadiene (TPB) to act as a fluor. The TPB film absorbs EUV photons and re-emits visible photons, detectable with a variety of commercial photosensors. Here we present a measurement of the re-emission spectrum of TPB films when illuminated with 128, 160, 175, and 250nm light. We also measure the fluorescence efficiency as a function of incident wavelength from 120 to 250nm.

Physics Department.

Boden, Daniel, Borrego, Maura, and Newswander, Lynita. “Student Socialization in Interdisciplinary Doctoral Education.” Higher Education 62, no. 6 (2011).

Interdisciplinary approaches are often seen as necessary for attacking the most critical challenges facing the world today, and doctoral students and their training programs are recognized as central to increasing interdisciplinary research capacity. However, the traditional culture and organization of higher education are ill-equipped to facilitate interdisciplinary work. This study employs a lens of socialization to study the process through which students learn the norms, values, and culture of both traditional disciplines and integrated knowledge production. It concludes that many of the processes of socialization are similar, but that special attention should be paid to overcoming organizational barriers to interdisciplinarity related to policies, space, engagement with future employers, and open discussion of the politics of interdisciplinarity.

Political Science and Criminal Justice Department.

Herman, Steve, Archambeau, Olga G., Deliramich, Aimee N., Kim, Bryan S. K., Chiu, Pearl H., and Frueh, B. Christopher. “Depressive Symptoms and Mental Health Treatment in an Ethnoracially Diverse College Student Sample.” Journal of American College Health 59, no. 8 (2011).

Objectives: To study (a) the prevalence of depressive symptoms and (b) the utilization of mental health treatment in an ethnoracially diverse sample consisting primarily of Asian Americans, European Americans, Native Hawaiians, and Pacific Islanders. Participants: Five hundred eighty-nine college students. Method: A questionnaire packet that included the Center for Epidemiological Studies Depression Scale (CES-D) was administered to students in introductory psychology courses. Results: (a) There were no differences among ethnoracial groups in levels of depressive symptoms as measured by the CES-D; (b) 71% of participants with high levels of depressive symptoms had not received any mental health treatment in the previous 12 months; and (c) European Americans were 3.7 times more likely to have received mental health treatment in the previous 12 months than other students. Conclusion: Outreach efforts designed to improve utilization of mental health treatment services by depressed college students, especially by members of ethnoracial minority groups, should be increased.

Psychology Department (student)

Wang, X. T., and Dvorak, Robert D. “Sweet Future: Fluctuating Blood Glucose Levels Affect Future Discounting.” Psychological Science 21, no. 2 (2010).

This study explored metabolic mechanisms of future (delay) discounting, a choice phenomenon where people value present goods over future goods. Using fluctuating blood glucose as an index of body-energy budget, optimal discounting should regulate choice among rewards as a function of temporal caloric requirement. We identified this novel link between blood glucose levels measured in the lab and future-discounting rates of participants, who made choices between a “smaller and sooner” reward and a “larger but later” option, with possible actual monetary rewards. A group of participants who drank a soft drink that contained sugar showed a reduced rate of future discounting afterward, when we controlled for sex, age, body mass index, and the taste of the drink. In contrast, a group of participants who drank a soft drink that contained artificial sweetener showed an increased rate of future discounting. Blood glucose levels not only varied as a result of caloric intake but also regulated the rate of future discounting, according to participants’ dynamic body-energy budget.

Psychology Department.

Alves, R. V., and Asfora, W. T. “Deep Brain Stimulation for Dejerine-Roussy Syndrome: Case Report.” Minimally Invasive Neurosurgery 54, no. 4 (2011).

Background: The term “central post-stroke pain” is more appropriate to describe neuropathic pain following a cerebrovascular accident. Most patients complain of burning and other symptoms like lacerating and shooting pain. Treatment options for central pain are limited in number and efficacy. Case Report: This paper reports on a 47-year-old man with central post-stroke pain refractory to treatment. The patient underwent insertion of a deep brain stimulator utilizing the Leksell frame. The target was the left centromedian thalamic nuclei. He had a qualitative symptomatic improvement. Conclusion: Deep brain stimulation can be a useful tool when all other modalities have failed. It is a minimally invasive neurosurgical procedure that may improve the quality of life in carefully selected (often desperate) patients with central post-stroke pain.

Sanford School of Medicine, Sioux Falls Campus.

Fagerlund, Åse, Autti-Rämö, Ilona, Hoyme, H. Eugene, Mattson, Sarah N., and Korkman, Marit. “Risk Factors for Behavioural Problems in Foetal Alcohol Spectrum Disorders.” Acta Paediatrica 100, no. 11 (2011).

Aim: To examine risk and protective factors associated with behavioural problems of children and adolescents following prenatal alcohol exposure. Methods: A total of 73 children and adolescents with foetal alcohol spectrum disorders (FASD) were assessed for internalizing, externalizing and total behavioural problems using the Child Behavior Checklist. Linear regression models were used to determine the effects of diagnostic and environmental risk and protective factors on behaviour, while controlling for age, sex and IQ. Results: Length of time spent in residential care was the most pervasive risk factor associated with internalizing, externalizing and total behavioural problems. A low dysmorphology score was related to more internalizing and total problems. Conclusions: Children and adolescents prenatally exposed to alcohol faced greater risk of substantive behavioural problems (i) if they were less visibly alcohol affected and (ii) the longer time they had spent in residential care. The results underscore the clinical importance of appropriate services and care for less visibly affected children with FASD and highlight the need to attend to children with FASD being raised in institutions.

Sanford School of Medicine, Sioux Falls Campus.

Harris, William S., Brouwer, I. A., and Mozaffarian, D. “N-6 Fatty Acids and Risk for Chd: Consider All the Evidence.” British Journal of Nutrition 106, no. 6 (2011).

Sanford School of Medicine, Sioux Falls Campus.

Jensen, Brian C., O’Connell, Timothy D., and Simpson, Paul C. “Alpha-1-Adrenergic Receptors: Targets for Agonist Drugs to Treat Heart Failure.” Journal of Molecular & Cellular Cardiology 51, no. 4 (2011).

Abstract: Evidence from cell, animal, and human studies demonstrates that α1-adrenergic receptors mediate adaptive and protective effects in the heart. These effects may be particularly important in chronic heart failure, when catecholamine levels are elevated and β-adrenergic receptors are down-regulated and dysfunctional. This review summarizes these data and proposes that selectively activating α1-adrenergic receptors in the heart might represent a novel and effective way to treat heart failure. This article is part of a special issue entitled “Key Signaling Molecules in Hypertrophy and Heart Failure.”

Sanford School of Medicine, Sioux Falls Campus.

Sironen, A., Kotaja, N., Mulhern, H., Wyatt, T. A., and Lee, Lance. “Loss of Spef2 Function in Mice Results in Spermatogenesis Defects and Primary Ciliary Dyskinesia.” Biology of Reproduction 85, no. 4 (2011).

Primary ciliary dyskinesia (PCD) results from defects in motile cilia function. Mice homozygous for the mutation big giant head (bgh) have several abnormalities commonly associated with PCD, including hydrocephalus, male infertility, and sinusitis. In the present study, we use a variety of histopathological and cell biological techniques to characterize the bgh phenotype, and we identify the bgh mutation using a positional cloning approach. Histopathological, immunofluorescence, and electron microscopic analyses demonstrate that the male infertility results from shortened flagella and disorganized axonemal and accessory structures in elongating spermatids and mature sperm. In addition, there is a reduced number of elongating spermatids during spermatogenesis and mature sperm in the epididymis. Histological analyses show that the hydrocephalus is characterized by severe dilatation of the lateral ventricles and that bgh sinuses have an accumulation of mucus infiltrated by neutrophils. In contrast to the sperm phenotype, electron microscopy demonstrates that mutant respiratory epithelial cilia are ultrastructurally normal, but video microscopic analysis shows that their beat frequency is lower than that of wild-type cilia. Through a positional cloning approach, we identified two sequence variants in the gene encoding sperm flagellar protein 2 (SPEF2), which has been postulated to play an important role in spermatogenesis and flagellar assembly. A causative nonsense mutation was validated by Western blot analysis, strongly suggesting that the bgh phenotype results from the loss of SPEF2 function. Taken together, the data in this study demonstrate that SPEF2 is required for cilia function and identify a new genetic cause of PCD in mice.

Sanford School of Medicine, Sioux Falls Campus.

A political pattern of power focused on defining enemies of the state permits administrative agencies to be grounded in framework that allows them to create meaning. In an effort to better understand how agencies act as political players in a web of power relationships, this article suggests a framework based jointly on Foucault’s concept of power and Schmitt’s understanding of the political. Although these models may at first appear to be incompatible, Foucault and Schmitt’s ideas on power and politics are in fact complementary, and together can enrich an understanding of how administration is deeply constitutive.

Political Science Department.

Boschee, Bonni F., and Boschee, Floyd. “A Profile of Homeschooling in South Dakota.” Journal of School Choice 5, no. 3 (2011).

The authors conducted a statewide study to determine which factors influenced parents’ decision making in electing to homeschool their children rather than send them to public school education in South Dakota. Analysis of data, using frequencies, percentages, means, and standard deviations revealed that the most prevalent reasons for homeschooling in South Dakota were the opportunity for parents to strengthen their relationship with their children, religion, peer pressure, public schools not teaching American values, and not aiding in character development. The major reason why parents homeschooled their children was to strengthen their family relationship. The least prevalent factors were teacher salary, ridicule by peers, physical handicap, not getting along with teachers, and racial reasons.

School of Education

Anbalagan, S., McShan, W. M., Dunman, P. M., and Chaussee, Michael S. “Identification of Rgg Binding Sites in the Streptococcus Pyogenes Chromosome.” Journal of Bacteriology 193, no. 18 (2011).

Streptococcus pyogenes Rgg is a regulatory protein that controls the transcription of 588 genes in strain NZ131 during the post-exponential phase of growth, including the virulence-associated genes encoding the extracellular SpeB protease, pullulanase A (PulA), and two extracellular nucleases (SdaB and Spd-3). Rgg binds to DNA proximally to the speB promoter (PspeB) to activate transcription; however, it is not known if Rgg binds to the promoters of other genes to influence expression, or if the perturbation of other global regulons accounts for the genome-wide changes in expression associated with the mutant. To address this issue, chromatin immunoprecipitation followed by DNA microarray analysis (ChIP-chip) was used to identify the DNA binding sites of Rgg. Rgg bound to 65 sites in the chromosome. Thirty-five were within noncoding DNA, and 43% of these were adjacent to genes previously identified as regulated by Rgg. Electrophoretic mobility shift assays were used to assess the binding of Rgg to a subset of sites bound in vivo, including the noncoding DNA upstream of speB, the genes encoding PulA, Spd-3, and a transcriptional regulator (SPY49_1113), and prophage-associated genes encoding a putative integrase (SPY49_0746) and a surface antigen (SPY49_0396). Rgg bound to all target DNAs in vitro, consistent with the in vivo results. Finally, analyses with a transcriptional reporter system showed that the DNA bound by Rgg contained an active promoter that was regulated by Rgg. Overall, the results indicate that Rgg binds specifically to multiple sites in the chromosome, including prophage DNA, to influence gene expression.

Basic Biomedical Sciences, Vermillion Campus.

Li, Jie, Horak, Kathleen M., Su, Huabo B., Sanbe, A., Robbins, J., and Wang, Xuejun J. “Enhancement of Proteasomal Function Protects against Cardiac Proteinopathy and Ischemia/Reperfusion Injury in Mice.” Journal of Clinical Investigation 121, no. 9 (2011).

The ubiquitin-proteasome system degrades most intracellular proteins, including misfolded. proteins. Proteasome functional insufficiency (PFI) has been observed in proteinopathies, such as desmin-related cardiomyopathy, and implicated in many common diseases, including dilated cardiomyopathy and ischemic heart disease. However, the pathogenic role of PFI has not been established. Here we created inducible Tg mice with cardiomyocyte-restricted overexpression of proteasome 28 subunit alpha (CR-PA28 alpha OE) to investigate whether upregulation of the 11S proteasome enhances the proteolytic function of the proteasome in mice and, if so, whether the enhancement can rescue a bona fide proteinopathy and protect against ischemia/reperfusion (I/R) injury. We found that CR-PA28 alpha OE did not alter the homeostasis of normal proteins and cardiac function, but did facilitate the degradation of a surrogate misfolded protein in the heart. By breeding mice with CR-PA28 alpha OE with mice representing a well-established model of desmin-related cardiomyopathy, we demonstrated that CR-PA28 alpha OE markedly reduced aberrant protein aggregation. Cardiac hypertrophy was decreased, and the lifespan of the animals was increased. Furthermore, PA28 alpha knockdown promoted, whereas PA28 alpha overexpression attenuated, accumulation of the mutant protein associated with desmin-related cardiomyopathy in cultured cardiomyocytes. Moreover, CR-PA28 alpha OE limited infarct size and prevented postreperfusion cardiac dysfunction in mice with myocardial I/R injury. We therefore conclude that benign enhancement of cardiac proteasome proteolytic function can be achieved by CR-PA28 alpha OE and that PFI plays a major pathogenic role in cardiac proteinopathy and myocardial I/R injury.

Basic Biomedical Sciences, Vermillion Campus.

Li, Jie, Powell, Saul R., and Wang, Xuejun. “Enhancement of Proteasome Function by Pa28α Overexpression Protects against Oxidative Stress.” FASEB Journal 25, no. 3 (2011).

The principal function of the proteasome is targeted degradation of intracellular proteins. Proteasome dysfunction has been observed in experimental cardiomyopathies and implicated in human congestive heart failure. Measures to enhance proteasome proteolytic function are currently lacking but would be beneficial in testing the pathogenic role of proteasome dysfunction and could have significant therapeutic potential. The association of proteasome activator 28 (PA28) with the 20S proteasome may play a role in antigen processing. It is unclear, however, whether the PA28 plays any important role outside of antigen presentation, although up-regulation of PA28 has been observed in certain types of cardiomyopathy. Here, we show that PA28α expression (PA28αOE) stabilized PA28β, increased 11S proteasomes, and enhanced the degradation of a previously validated proteasome surrogate substrate (GFPu) in cultured neonatal rat cardiomyocytes. PA28αOE significantly attenuated H₂O₂-induced increases in the protein carbonyls and markedly suppressed apoptosis in cultured cardiomyocytes under basal conditions or when stressed by H₂O₂-. We conclude that PA28αOE is sufficient to up-regulate 11S proteasomes, enhance proteasome-mediated removal of misfolded and oxidized proteins, and protect against oxidative stress in cardiomyocytes, providing a highly sought means to increase proteasomal degradation of abnormal cellular proteins.

Basic Biomedical Sciences, Vermillion Campus.

Lopez-Fontana, C. M., Maselli, M. E., de Di Nasso, F. E. G., Telleria, Carlos M., and Caron, R. W. “Regulation of Prolactin Secretion During the Estrus in Rats: Possible Role of Glucocorticoids.” Reproduction 142, no. 3 (2011).

Mifepristone (MIF) administration to cycling rats at proestrus induces hypersecretion of prolactin (PRL) at the following estrus. We aimed to assess whether this effect is due to the antiprogesterone or antiglucocorticoid action of MIF and to help underscore the nature of the circulating hormone(s) regulating PRL secretion at estrus. Female cycling rats in proestrus were treated with vehicle; the progesterone (Pg) and glucocorticoid receptor antagonists, MIF (5 mg/kg) or ORG-33628 (5 mg/kg); the glucocorticoid agonist dexamethasone (DEX; 27 mg/kg)+/-MIF; or the inhibitor of steroid synthesis aminoglutethimide (AG; 150 mg/kg)+/-MIF. The animals’ blood was sampled the same day at 1800 h and at 1800 h of the following day to assess for circulating PRL and Pg levels. To distinguish antiglucocorticoid from antiprogesterone effects of MIF, we administered a highly specific neutralizing antibody against Pg. None of the antagonists modified serum PRL values at proestrus but increased PRL levels at estrus. DEX decreased the secretion of PRL at proestrus, yet the effect was entirely blocked by MIF. Furthermore, DEX decreased PRL at estrus in a MIF-reversible manner, suggesting that adrenal corticoids during proestrous may regulate PRL secretion at estrus. AG increased PRL secretion at estrus, whereas its association with MIF produced an even higher response. PRL concentration at estrus was not modified by the antiprogesterone antibody, suggesting that the effect of MIF is a consequence of its antiglucocorticoid effect and not due to its antiprogesterone properties. In conclusion, PRL secretion in the afternoon of the estrus is most likely regulated by glucocorticoids through an inhibitory action. Reproduction (2011) 142 477-485

Basic Biomedical Sciences, Vermillion Campus.

Mark-Kappeler, Connie J., Martin, Douglas S., and Eyster, Kathleen M. “Estrogens and Selective Estrogen Receptor Modulators Regulate Gene and Protein Expression in the Mesenteric Arteries.” Vascular Pharmacology 55, no. 1-3 (2011).

Estrogen has both beneficial and detrimental effects on the cardiovascular system. Selective estrogen receptor modulators (SERMs) exhibit partial estrogen agonist/antagonist activity in estrogen target tissues. Gene targets of estrogen and SERMs in the vasculature are not well-known. Thus, the present study tested the hypothesis that estrogens (ethinyl estradiol, estradiol benzoate, and equilin) and SERMs (tamoxifen and raloxifene) cause differential gene and protein expression in the vasculature. DNA microarray and real-time RT-PCR were used to investigate gene expression in the mesenteric arteries of estrogen and SERM treated ovariectomized rats. The genes shown to be differentially expressed included stearoyl-CoA desaturase (SCD), soluble epoxide hydrolase (sEH), secreted frizzled related protein-4 (SFRP-4), insulin-like growth factor-1 (IGF-1), phospholipase A2 group 1B (PLA2-G1B), and fatty acid synthase (FAS). Western blot further confirmed the differential expression of sEH, SFRP-4, FAS, and SCD protein. These results reveal that estrogens and SERMs cause differential gene and protein expression in the mesenteric artery. Consequently, the use of these agents may be associated with a unique profile of functional and structural changes in the mesenteric arterial circulation. (C) 2011 Elsevier Inc. All rights reserved.

Basic Biomedical Sciences, Vermillion Campus.

Novick, Andrew M., Forster, Gina L., Tejani-Butt, Shanaz M., and Watt, Michael J. “Adolescent Social Defeat Alters Markers of Adult Dopaminergic Function.” Brain Research Bulletin 86, no. 1/2 (2011).

Abstract: Stressful experiences during adolescence can alter the trajectory of neural development and contribute to psychiatric disorders in adulthood. We previously demonstrated that adolescent male rats exposed to repeated social defeat stress show changes in mesocorticolimbic dopamine content both at baseline and in response to amphetamine when tested in adulthood. In the present study we examined whether markers of adult dopamine function are also compromised by adolescent experience of social defeat. Given that the dopamine transporter as well as dopamine D1 receptors act as regulators of psychostimulant action, are stress sensitive and undergo changes during adolescence, quantitative autoradiography was used to measure [³H]-GBR12935 binding to the dopamine transporter and [³H]-SCH23390 binding to dopamine D1 receptors, respectively. Our results indicate that social defeat during adolescence led to higher dopamine transporter binding in the infralimbic region of the medial prefrontal cortex and higher dopamine D1 receptor binding in the caudate putamen, while other brain regions analyzed were comparable to controls. Thus it appears that social defeat during adolescence causes specific changes to the adult dopamine system, which may contribute to behavioral alterations and increased drug seeking.

Basic Biomedical Sciences, Vermillion Campus.

Keifer, Joyce, and Zheng, Z. “Ampa Receptor Trafficking and Learning.” European Journal of Neuroscience 32, no. 2 (2010).

In the last few years it has become clear that AMPA-type glutamate neurotransmitter receptors are rapidly transported into and out of synapses to strengthen or weaken their function. The remarkable dynamics of AMPA receptor (AMPAR) synaptic localization provides a compelling mechanism for understanding the cellular basis of learning and memory, as well as disease states involving cognitive dysfunction. Here, we summarize the evidence for AMPAR trafficking as a mechanism underlying a variety of learned responses derived from both behavioral and cellular studies. Evidence is also reviewed supporting synaptic dysfunction related to impaired AMPAR trafficking as a mechanism underlying learning and memory deficits in Alzheimer’s disease. We conclude that emerging data support the concept of multistage AMPAR trafficking during learning and that a broad approach to include examination of all of the AMPAR subunits will provide a more complete view of the mechanisms underlying multiple forms of learning.

Basic Biomedical Sciences, Vermillion Campus.

Zhaoqing, Zheng, Sabirzhanov, Boris, and Keifer, Joyce. “Oligomeric Amyloid-Β Inhibits the Proteolytic Conversion of Brain-Derived Neurotrophic Factor (Bdnf), Ampa Receptor Trafficking, and Classical Conditioning.” Journal of Biological Chemistry 285, no. 45 (2010).

Amyloid-β (Aβ) peptide is thought to have a significant role in the progressive memory loss observed in patients with Alzheimer disease and inhibits synaptic plasticity in animal models of learning. We previously demonstrated that brain-derived neurotrophic factor (BDNF) is critical for synaptic AMPA receptor delivery in an in vitro model of eyeblink classical conditioning. Here, we report that acquisition of conditioned responses was significantly attenuated by bath application of oligomeric (200 nm), but not fibrillar, Aβ peptide. Western blotting revealed that BDNF protein expression during conditioning is significantly reduced by treatment with oligomeric Aβ, as were phosphorylation levels of cAMP-response element-binding protein (CREB), Ca²⁺/calmodulin-dependent protein kinase II (CaMKII), Ca2⁺/calmodulin-dependent protein kinase IV (CaMKIV), and ERK. However, levels of PKA and PKC·/» were unaffected, as was PDK-1. Protein localization studies using confocal imaging indicate that oligomeric Aβ, but not fibrillar or scrambled forms, suppresses colocalization of GluR1 and GluR4 AMPA receptor subunits with synaptophysin, indicating that trafficking of these subunits to synapses during the conditioning procedure is blocked. In contrast, coapplication of BDNF with oligomeric Aβ significantly reversed these findings. Interestingly, a tolloid-like metalloproteinase in turtle, tTLLs (turtle tolloid-like protein), which normally processes the precursor proBDNF into mature BDNF, was found to degrade oligomeric Aβ into small fragments. These data suggest that an Aβ-induced reduction in BDNF, perhaps due to interference in the proteolytic conversion of proBDNF to BDNF, results in inhibition of synaptic AMPA receptor delivery and suppression of the acquisition of conditioning.

Basic Biomedical Sciences, Vermillion Campus.

An, Hunter, Cook, Douglas O., and Zumpano, Leonard V. “Corporate Transparency and Firm Growth: Evidence from Real Estate Investment Trusts.” Real Estate Economics 39, no. 3 (2011).

Using a panel data set of Real Estate Investment Trusts (REITs), we find corporate transparency to be positively associated with REIT growth. These results suggest that greater transparency facilitates firm growth by relaxing information-based constraints on external financing. The magnitude of this effect is larger in the equity market than in the debt market. Moreover, the sensitivity of investment to cash flows is decreasing in transparency, evidence that transparency relaxes liquidity constraints. Finally, we find more transparent REITs are less likely to crash.

Beacom School of Business.

Egge, Alison R., and Swallow, John G. “Previous Experience Matters in the Stalk-Eyed Fly Teleopsis Dalmanni.” Behavioral Ecology and Sociobiology 65, no. 9 (2011).

Previous experiences can play a significant role in determining future behaviors. Winner and loser effects, where the outcome of previous aggressive encounters influences the behavioral approach to and outcomes of future conflicts, have been documented in many taxa and illustrate this phenomenon. These effects are prevalent in species that interact frequently because modulation of these potentially costly social interactions may influence fitness. Stalk-eyed flies of the dimorphic species Teleopsis dalmanni engage in frequent fights over food resources, as well as over access to harems of females, with larger males typically prevailing when size disparities exist. However, whether and how prior experience influences fighting decisions and outcomes remains unexplored. To test for winner and loser effects in stalk-eyed flies, sexually mature flies were paired in size-mismatched dyads to establish winning and losing experiences. After their first contest, the flies were paired with size-matched individuals and allowed to interact. We determined whether an initial winning or losing experience significantly altered the outcome probabilities in the second size-matched encounter. Initial winning experience did not significantly affect the second interaction, providing no evidence for a winner effect. However, initial losers were significantly more likely to lose a subsequent interaction which provides evidence for a loser effect in stalk-eyed flies. In addition, smaller males experienced an increased probability of losing their second interaction regardless of prior winning or losing experience. This effect was not seen in large males. Our data suggest that the loser effects we observed, which were more pronounced in small males, could result from the energetic costs of fighting that they were less able to absorb than large males.

Biology Department.

Worthington, Amy M., and Swallow, John G. “Sequential Analysis Reveals Behavioral Differences Underlying Female-Biased Predation Risk in Stalk-Eyed Flies.” Ethology 117, no. 9 (2011).

Stalk-eyed flies are classic models of how sexual selection can drive morphological and behavioral elaboration. Exaggerated ornaments born by stalk-eyed flies could impose locomotor costs and increase susceptibility to predation; however, a previous study determined that behavior, not eye span, was the major influence on predation risk. Despite the importance of behavior, relatively little is known about how these flies avoid and deter predators. We created an ethogram of behaviors and used it to score individual interactions of male and female Teleopsis dalmanni paired with an actively foraging, generalist arachnid predator ( Phidippus audax). Sequential analysis was employed to identify temporal patterns in behavior and determine how males and females differ in their approaches to avoiding predation. Our results indicate that males and females significantly differ when specific behaviors were employed. Patterns in the behavioral transitions suggest that males are more aggressive than females and are more likely to approach a predator to jab, abdomen bob, or display. Males elicited more retreat responses from the predator, whereas females elicited more attacks. Although the behavioral repertoires of male and female stalk-eyed flies are indistinguishable, their uses of the behaviors differ, particularly the sequential order of presentation, suggesting a strong sex difference in anti-predatory behavior.

Biology Department.

Luo, Jie E., Porteous, N., and Sun, Yuyu Y. “Rechargeable Biofilm-Controlling Tubing Materials for Use in Dental Unit Water Lines.” Acs Applied Materials & Interfaces 3, no. 8 (2011).

A simple and practical surface grafting approach was developed to introduce rechargeable N-halamine-based antimicrobial functionality onto the inner surfaces of continuous small-bore polyurethane (PU) dental unit waterline (DUWL) tubing. In this approach, tetrahydrofuran (THF) solution of a free-radical initiator, dicumyl peroxide (DCP), flowed through the PU tubing (inner diameter of 1/16 in., or 1.6 mm) to diffuse DCP into the tubing’s inner walls, which was used as initiator in the subsequent grafting polymerization methacrylamide (MAA) onto the tubing. Upon chlorine bleach treatment, the amide groups of the grafted MAA side chains were transformed into acyclic N-halamines. The reactions were confirmed with attenuated total reflectance infrared (ATR) spectra and iodometric titration. The mechanical properties of the tubing were not significantly affected by the grafting reactions. The biofilm-controlling function of the new N-halamine-based PU tubing Was evaluated with Pseudomonas aeruginosa (P. aeruginosa), one of the most isolated water bacteria from DUWLs, in a continuous bacterial., flow, model. Bacteria culturing and SEM studies showed that the inner surfaces of the new N-halaniine-based PU tubing completely prevented bacterial biofilm formation for at least three to four weeks. After that, bacteria began to colonize the tubing surface: However, the lost function was fully regenerated by exposing the tubing inner surfaces to diluted chlorine bleach The recharging process could be repeated periodically to further extend the biofilm-controlling duration for long-term applications.

Biomedical Engineering, Sioux Falls

Netzer, Nathan L., Qiu, Chao, Zhang, Yongyi Y., Lin, Cuikun K., Zhang, L. F., Fong, H., and Jiang, Chaoyang Y. “Gold-Silver Bimetallic Porous Nanowires for Surface-Enhanced Raman Scattering.” Chemical Communications 47, no. 34 (2011).

Highly porous bimetallic nanowires manufactured via a simple galvanic reaction have demonstrated superior activity in surface-enhanced Raman scattering, allowing ultrasensitive chemical detections on isolated porous nanowires in comparison to pristine silver nanowires.

Chemistry Department.

Sellin Jeffries, Marlo K., Abbott, Kelty I., Cowman, Tim, and Kolok, Alan S. “Occurrence and Endocrine Effects of Agrichemicals in a Small Nebraska, USA, Watershed.” Environmental Toxicology & Chemistry 30, no. 10 (2011).

The Bow Creek watershed (Nebraska, USA) is dominated by the production of beef cattle and row crops; therefore, surface waters are likely to receive runoff containing steroid hormones and pesticides. The goal of the present study was to determine the occurrence and endocrine effects of agrichemicals in this watershed. To accomplish this, four sites within the watershed-Pearl, Bow, and East Bow Creeks and a site at the confluence with the Missouri River-were selected. In June of 2008, polar organic chemical integrative samplers (POCIS) were deployed at each site, whereas in June of 2009, water and sediment samples were collected. Caged fathead minnows ( Pimephales promelas) were deployed at all of the selected sites in both years. Analysis of these samples revealed that steroid hormones were not present; however, pesticides were present in POCIS extracts and water samples. In general, the amount of pesticides was higher in POCIS retrieved from Pearl and Bow Creeks than in POCIS from East Bow Creek and the confluence. This variation between sites appeared to be related to row crop density, as row crop land cover surrounding the Pearl and Bow Creek sites was higher than that surrounding the East Bow and confluence sites. To determine the endocrine effects of agrichemicals within this watershed, the hepatic mRNA expression of vitellogenin and estrogen receptor α (ERα), as well as the gonadal expression of P450 aromatase A, was determined for the caged minnows. Females deployed at East Bow Creek and the confluence experienced decreases in the expression of ERα, suggesting that these females had been defeminized; however, this defeminization could not be attributed to any of the pesticides detected at these sites. Environ. Toxicol. Chem.

Missouri River Institute

Elhai, Jon D., Naifeh, James A., Forbes, David, Ractliffe, Kendra C., and Tamburrino, Marijo. “Heterogeneity in Clinical Presentations of Posttraumatic Stress Disorder among Medical Patients: Testing Factor Structure Variation Using Factor Mixture Modeling.” Journal of Traumatic Stress 24, no. 4 (2011).

The present study used factor mixture modeling to explore empirically defined subgroups of psychological trauma victims based on confirmatory factor analysis (CFA) and latent class analysis of posttraumatic stress disorder (PTSD) symptoms. We sampled 310 medical patients with a history of trauma exposure. Confirmatory factor analysis revealed that the 4-factor emotional numbing PTSD model yielded the best model fit. Using latent factor means derived from this model and the 4-factor dysphoria PTSD model (indexing severity on PTSD factors), 3 latent classes of participants were identified using factor mixture modeling. The 3-class model fit the data very well and was validated against external measures of anxiety and rumination.

Psychology Department.

Billman, George E., and Harris, William S. “Effect of Dietary Omega-3 Fatty Acids on the Heart Rate and the Heart Rate Variability Responses to Myocardial Ischemia or Submaximal Exercise.” American Journal of Physiology: Heart & Circulatory Physiology 69, no. 6 (2011).

The consumption of omega-3 polyunsaturated fatty acids (n-3 PUFAs) has been reported to decrease resting heart rate (HR) and increase heart rate variability (HRV). However, the effects of n-3 PUFAs on these variables in response to a physiological stress (e.g., exercise or acute myocardial ischemia), particularly in postmyocardial infarction (MI) patients, are unknown. Therefore, HR and HRV (high frequency and total R-R interval variability) were evaluated at rest, during submaximal exercise, and during a 2-min coronary artery occlusion at rest and before and 3 mo after n-3 PUFA treatment in dogs with healed MI (n = 59). The dogs were randomly assigned to either placebo (1 g/day corn oil, n = 19) or n-3 PUFA supplement (docosahexaenoic acid + eicosapentaenoic acid ethyl esters; 1 g/day, n = 6; 2 g/day, n = 12; or 4 g/day, n = 22) groups. The treatment elicited significant (P < 0.01) dose-dependent increases in right atrial n-3 PUFA levels but dose-independent reductions in resting HR and increases in resting HRV. In contrast, n-3 PUFAs did not attenuate the large changes in HR or HRV induced by either the coronary occlusion or submaximal exercise. These data demonstrate that dietary n-3 PUFA decreased resting (i.e., preexercise or preocclusion) HR and increased resting HRV but did not alter the cardiac response to physiologic challenges.

Sanford School of Medicine, Sioux Falls Campus.

Sergeant, Susan, McQuail, Joseph A., Riddle, David R., Chilton, Floyd H., Ortmeier, Steven B., Jessup, Jewell A., Groban, Leanne, and Nicolle, Michelle M. “Dietary Fish Oil Modestly Attenuates the Effect of Age on Diastolic Function but Has No Effect on Memory or Brain Inflammation in Aged Rats.” Journals of Gerontology Series A: Biological Sciences & Medical Sciences 66A, no. 5 (2011).

Fish oil (FO) mediates a number of cardioprotective benefits in patients with cardiovascular disease. In the absence of cardiovascular disease, however, the effects of FO on cardiac structure and function are not clear. In addition, it is not known if an effective dosing strategy for attenuating age-related cardiac dysfunction is also effective at limiting cognitive dysfunction. Therefore, we determined if 4 months of FO supplementation in aged rats would lessen age-related cardiac dysfunction while concomitantly preventing the cognitive decline that is normally observed in this population. The results indicate that FO initiated late in life modifies diastolic function in a small but positive way by attenuating the age-related increases in filling pressure, posterior wall thickness, and interstitial collagen without mitigating age-related deficits in memory or increases in brain inflammation. These data raise the possibility that FO supplementation for purposes of cardiac and brain protection may need to occur earlier in the life span.

Sanford School of Medicine, Sioux Falls Campus.

Stevens, Dennis C., Helseth, Carol C., Khan, M. Akram, Munson, David P., and Reid, E. J. “A Comparison of Parent Satisfaction in an Open-Bay and Single-Family Room Neonatal Intensive Care Unit.” Herd-Health Environments Research & Design Journal 4, no. 3 (2011).

Objective: The purpose of this research was to test the hypothesis that parental satisfaction with neonatal intensive care is greater in a single-family room facility as compared with a conventional open-bay neonatal intensive care unit (NICU). Methods: This investigation was a prospective cohort study comparing satisfaction survey results for parents who responded to a commercially available parent NICU satisfaction survey following the provision of NICU care in open-bay and single-family room facilities. A subset of 16 items indicative of family-centered care was also computed and compared for these two NICU facilities. Results: Parents whose babies received care in the single-family room facility expressed significantly improved survey responses in regard to the NICU environment, overall assessment of care, and total survey score than did parents of neonates in the open-bay facility. With the exception of the section on nursing in which scores in both facilities were high, nonsignificant improvement in median scores for the sections on delivery, physicians, discharge planning, and personal issues were noted. The total median item score for family-centered care was significantly greater in the single-family room than the open-bay facility. Conclusions: Parental satisfaction with care in the single-family room NICU was improved in comparison with the traditional open-bay NICU. The single-family room environment appears more conducive to the provision of family-centered care. Improved parental satisfaction with care and the potential for enhanced family-centered care need to be considered in decisions made regarding the configuration of NICU facilities in the future.

Sanford School of Medicine, Sioux Falls Campus.

Sundram, Vasudha, Chauhan, Subhash C., and Jaggi, Meena. “Emerging Roles of Protein Kinase D1 in Cancer.” Molecular Cancer Research 9, no. 8 (2011).

Protein kinase D1 (PKD1) is a serine-threonine kinase that regulates various functions within the cell, including cell proliferation, apoptosis, adhesion, and cell motility. In normal cells, this protein plays key roles in multiple signaling pathways by relaying information from the extracellular environment and/or upstream kinases and converting them into a regulated intracellular response. The aberrant expression of PKD1 is associated with enhanced cancer phenotypes, such as deregulated cell proliferation, survival, motility, and epithelial mesenchymal transition. In this review, we summarize the structural and functional aspects of PKD1 and highlight the pathobiological roles of this kinase in cancer. Mol Cancer Res; 9(8); 985-96. (C)2011 AACR.

Sanford School of Medicine, Sioux Falls Campus.

Daack-Hirsch, Sandra, Dieter, Carla, and Quinn Griffin, Mary T. “Integrating Genomics into Undergraduate Nursing Education.” Journal of nursing scholarship : an official publication of Sigma Theta Tau International Honor Society of Nursing / Sigma Theta Tau 43, no. 3 (2011).

Purpose: To prepare the next generation of nurses, faculty are now faced with the challenge of incorporating genomics into curricula. Here we discuss how to meet this challenge. Organizing Construct: Steps to initiate curricular changes to include genomics are presented along with a discussion on creating a genomic curriculum thread versus a standalone course. Ideas for use of print material and technology on genomic topics are also presented. Information is based on review of the literature and curriculum change efforts by the authors. Conclusions: In recognition of advances in genomics, the nursing profession is increasing an emphasis on the integration of genomics into professional practice and educational standards. Incorporating genomics into nurses’ practices begins with changes in our undergraduate curricula. Information given in didactic courses should be reinforced in clinical practica, and Internet-based tools such as WebQuest, Second Life, and wikis offer attractive, up-to-date platforms to deliver this now crucial content. Clinical Relevance: To provide information that may assist faculty to prepare the next generation of nurses to practice using genomics. 2011 Sigma Theta Tau International.

 School of Health Sciences.