Posted by: tadeterman | March 31, 2017

February 2017

Anderson, Jordan A., Remund, T., Pohlson, K., Lamichhane, Sujan, Evans, C., Evans, R., . . . Mani, Gopinath. (2017). In vitro and in vivo evaluation of effect of excipients in local delivery of paclitaxel using microporous infusion balloon catheters.Journal of Biomedical Materials Research Part B-Applied Biomaterials, 105(2), 376-390.

Drug-infusion balloons are one of the currently used local drug delivery devices for preventing restenosis after endovascular treatments. An antiproliferative drug (paclitaxel, PAT) is infused through the balloon using a cremophor-based formulation to control restenosis. However, the major limitations of this approach are poor in vivo drug uptake and a limit in the amount of PAT delivered because of cremophor toxicity. In this study, we have investigated the use of different excipients for effectively infusing PAT out of the balloon for improved drug uptake in the tissue. The excipients include nanoparticle albumin-bound PAT (nab-PAT, a nanobiomaterial used in cancer therapy), urea (a hydrophilic agent used for faster drug transfer), iodixanol (a contrast agent used for coronary angiography), and cremophor-PAT (the most commonly used PAT formulation). An in vitro drug release, smooth muscle cell (SMC) response, endothelial cell (EC) response, and in vivo drug uptake were investigated for all the different excipients of PAT infused through the balloon. The nab-PAT was as effective as cremophor in infusing out of the balloon and inhibiting SMC growth. Also, nab-PAT showed a significantly greater amount of in vivo PAT uptake than that of cremophor-PAT. Urea and iodixanol were not effective in delivering a clinically relevant dose of PAT due to the poor solubility of PAT in these excipients. Urea eradicated all the SMCs and ECs, suggesting a toxic effect, which impedes its use in balloon-based therapy. Thus, this study demonstrated that nab-PAT is an effective formulation to locally deliver PAT through infusion balloons. (C) 2015 Wiley Periodicals, Inc.

Biomedical Engineering, Sioux Falls Campus.


Burnette, Catherine Elizabeth,Soonhee, Roh, Kyoung Hag, Lee, Yeon-Shim, Lee, Newland, Lisa A., & Jung Sim, Jun. (2017). A Comparison of Risk and Protective Factors Related to Depressive Symptoms among American Indian and Caucasian Older Adults. Health & Social Work, 42(1), e15-e23.

Despite efforts to reduce health disparities, many American Indian and Alaska Native (AI/AN) populations, including older adults, experience elevated levels of depression and associated suicide. Although adverse childhood experiences (ACEs) and social support are well-documented risk and protective factors for depression in the general population, little is known about AI/AN populations, especially older adults. The purpose of this study was to examine factors related to depression among a sample of AI older adults in the Midwest. Data were collected using a self-administered survey completed by 479 AI and Caucasian respondents over the age of 50. The survey included standardized measures such as the Geriatric Depression Scale–Short Form, ACE Questionnaire, and Multidimensional Scale of Perceived Social Support. Hierarchical multivariate regression analyses were conducted to evaluate the main hypotheses of the study. Results indicate that two dimensions of ACEs (childhood neglect and household dysfunction) were positively associated with depressive symptoms; social support was negatively associated with depressive symptoms. Perceived health and living alone were also significant predictors of depressive symptoms. ACEs may play a significant role in depression among AI/AN populations across the life course and into old age. Social support offers a promising mechanism to bolster resilience among AI/AN older adults.

School of Education.


De, P., Carlson, J. H., Jepperson, T., Willis, S., Leyland-Jones, B., &Dey, Nandini. (2017). RAC1 GTP-ase signals wnt-beta-catenin pathway mediated integrin-directed metastasis-associated tumor cell phenotypes in triple negative breast cancers. Oncotarget, 8(2), 3072-3103.

The acquisition of integrin-directed metastasis-associated (ID-MA) phenotypes by Triple-Negative Breast Cancer (TNBC) cells is caused by an upregulation of the Wnt-beta-catenin pathway (WP). We reported that WP is one of the salient genetic features of TNBC. RAC-GTPases, small G-proteins which transduce signals from cell surface proteins including integrins, have been implicated in tumorigenesis and metastasis by their role in essential cellular functions like motility. The collective percentage of alteration(s) in RAC1 in ER+ve BC was lower as compared to ER-ve BC (35% vs 57%) (brca/tcga/pub2015). High expression of RAC1 was associated with poor outcome for RFS with HR= 1.48 [ CI: 1.15-1.9] p=0.0019 in the Hungarian ER-veBC cohort. Here we examined how WP signals are transduced via RAC1 in the context of ID-MA phenotypes in TNBC. Using pharmacological agents (sulindac sulfide), genetic tools (beta-catenin siRNA), WP modulators (Wnt-C59, XAV939), RAC1 inhibitors (NSC23766, W56) and WP stimulations (LWnt3ACM, Wnt3A recombinant) in a panel of 6-7 TNBC cell lines, we studied fibronectin-directed (1) migration, (2) matrigel invasion, (3) RAC1 and Cdc42 activation, (4) actin dynamics (confocal microscopy) and (5) podia-parameters. An attenuation of WP, which (a) decreased cellular levels of beta-catenin, as well as its nuclear active-form, (b) decreased fibronectin-induced migration, (c) decreased invasion, (d) altered actin dynamics and (e) decreased podia-parameters was successful in blocking fibronectin-mediated RAC1/Cdc42 activity. Both Wnt-antagonists and RAC1 inhibitors blocked fibronectin-induced RAC1 activation and inhibited the fibronectin-induced ID-MA phenotypes following specific WP stimulation by LWnt3ACM as well as Wnt3A recombinant protein. To test a direct involvement of RAC1-activation in WP-mediated ID-MA phenotypes, we stimulated brain-metastasis specific MDA-MB231BR cells with LWnt3ACM. LWnt3ACM-stimulated fibronectin-directed migration was blocked by RAC1 inhibition in MDA-MB231BR cells. In the light of our previous report that WP upregulation causes ID-MA phenotypes in TNBC tumor cells, here we provide the first mechanism based evidence to demonstrate that WP upregulation signals ID-MA tumor cell phenotypes in a RAC1-GTPase dependent manner involving exchange-factors like TIAM1 and VAV2. Our study demonstrates for the first time that betacatenin-RAC1 cascade signals integrin-directed metastasis-associated tumor cell phenotypes in TNBC.

Sanford School of Medicine, Sioux Falls Campus.


Forred, B. J., Daugaard, D. R., Titus, B. K., …., & Vitiello, Peter F.(2017). Detoxification of Mitochondrial Oxidants and Apoptotic Signaling Are Facilitated by Thioredoxin-2 and Peroxiredoxin-3 during Hyperoxic Injury. Plos One, 12(1), 20.

Mitochondria play a fundamental role in the regulation of cell death during accumulation of oxidants. High concentrations of atmospheric oxygen (hyperoxia), used clinically to treat tissue hypoxia in premature newborns, is known to elicit oxidative stress and mitochondrial injury to pulmonary epithelial cells. A consequence of oxidative stress in mitochondria is the accumulation of peroxides which are detoxified by the dedicated mitochondrial thioredoxin system. This system is comprised of the oxidoreductase activities of peroxiredoxin-3 (Prx3), thioredoxin-2 (Trx2), and thioredoxin reductase-2 (TrxR2). The goal of this study was to understand the role of the mitochondrial thioredoxin system and mitochondrial injuries during hyperoxic exposure. Flow analysis of the redox-sensitive, mitochondrial-specific fluorophore, MitoSOX, indicated increased levels of mitochondrial oxidant formation in human adenocarcinoma cells cultured in 95% oxygen. Increased expression of Trx2 and TrxR2 in response to hyperoxia were not attributable to changes in mitochondrial mass, suggesting that hyperoxic upregulation of mitochondrial thioredoxins prevents accumulation of oxidized Prx3. Mitochondrial oxidoreductase activities were modulated through pharmacological inhibition of TrxR2 with auranofin and genetically through shRNA knockdown of Trx2 and Prx3. Diminished Trx2 and Prx3 expression was associated with accumulation of mitochondrial superoxide; however, only shRNA knockdown of Trx2 increased susceptibility to hyperoxic cell death and increased phosphorylation of apoptosis signal-regulating kinase-1 (ASK1). In conclusion, the mitochondrial thioredoxin system regulates hyperoxic-mediated death of pulmonary epithelial cells through detoxification of oxidants and regulation of redox-dependent apoptotic signaling.

Sanford School of Medicine, Sioux Falls Campus.


Hansen, John. (2017). Opiates for Chronic Pain. Pain Practice, 17(1), 147-148.

The article presents ten problems that would help improve patient-centered, multidisciplinary care for chronic pain, including structured opiate prescribing when indicated, in the U.S. Topics discussed include the poor outcomes of self-care, either individually or collectively, the challenge opiate prescribing risk reduction, and the problem of substance abuse and addiction.

Sanford School of Medicine, Sioux Falls Campus.


Juber, Brian A., Harris Jackson, Kristina,Johnson, Kristopher B.Harris, William S., & Baack, Michelle L. (2017). Breast milk DHA levels may increase after informing women: a community-based cohort study from South Dakota USA. International Breastfeeding Journal, 12, 1-9.

Background: Docosahexaenoic acid (DHA), an omega-3 fatty acid found in breast milk, has many health benefits for both mother and baby. A 2007 meta-analysis found U.S. women had breast milk DHA levels (0.20% of total fatty acids) below the worldwide mean (0.32%). In 2008, international dietary recommendations were made for pregnant and lactating women to consume 200 mg of DHA per day. This community-based study aimed to define current milk DHA levels from upper Midwest USA lactating mothers and to determine if providing information about their own level along with dietary recommendations would incite changes to increase breast milk DHA content. Methods: New mothers attending lactation classes or using hospital pumping rooms in Sioux Falls, South Dakota, USA participated by providing one drop of breast milk on a card for fatty acid analysis at baseline and 1 month after initial reporting. DHA levels were analyzed by gas chromatography. Mothers received a report of their own breast milk level along with dietary recommendations on DHA intake for lactating women. Median baseline and follow-up DHA levels were determined and differences were compared by Wilcoxon signed-rank test. Results: At baseline, breast milk DHA content (n = 84) was highly variable (range 0.05 to 0.73%) with a median of 0.18% (IQR, 0.13, 0.28; mean ± SD, 0.22 ± 0.13%), well below the worldwide average (0.32%). Women who reported taking DHA supplements (n = 43) had higher levels than those who did not (0.23% vs. 0.15%, P < 0.0001). In a subset of 60 mothers who submitted a second sample, median breast milk DHA content increased from 0.19 to 0.22% (P < 0.01). Conclusions: Findings suggest that providing nursing mothers with their breast milk DHA level and education about DHA intake while breastfeeding motivates change to increase DHA levels.

Sanford School of Medicine, Sioux Falls Campus.


Jung-Ho, SonTamang, Sem Raj,Fostvedt, Jade I., &Hoefelmeyer, James D. (2017). Dehydrodechlorination of Methylene Chloride, Chloroform, and Chlorodiphenylmethane in the Presence of Ga/N Lewis Pairs.Organometallics, 36(2), 474-479.

Transmetalation occurs upon addition of GaCl3 to (quinolin-8-yl)trimethylstannane. The compound dissolves immediately in pyridine, and recrystallization gives dichloropyridinyl(quinolin-8-yl)gallium(III). In chloroform, the compound bis-μ-(quinolin-8-yl)-μ-chloro-dichlorodigallium(III) tetrachlorogallate could be isolated in small quantities; however, the major product was trichloro(quinolinium-8-yl)gallate(III) zwitterion. The zwitterion also formed upon addition of methylene chloride or chlorodiphenylmethane. We hypothesize that the highly electrophilic digallyl cation abstracts chloride to form a carbocation and that proton transfer from the carbocation to the quinoline nitrogen affords transient carbenes. In particular, diphenyl carbene forms from dehydrodechlorination of chlorodiphenylmethane in toluene/cyclohexene to give a well-defined mixture of products due to cyclopropanation and C-H insertion reactions. Dichloropyridinyl(quinolin-8-yl)gallium(III) undergoes reaction with chloroform only at elevated temperature to yield quinolinium tetrachlorogallate salt as the product. This salt also forms in the reaction of chloroform with GaCl3 and quinoline at elevated temperature. The zwitterion could be converted to quinolinium tetrachlorogallate upon heating, which supports the idea that it was formed initially as an intermediate. Thus, the Ga/N Lewis pairs appear capable of dehydrodechlorination of chloroalkanes.

Chemistry Department.


Mayhan, William G., & Arrick, Denise M. (2017). Tetrahydrobiopterin rescues impaired responses of cerebral resistance arterioles during type 1 diabetes.Diabetes & Vascular Disease Research, 14(1), 33-39.

Our goal was to test the hypothesis that administration of tetrahydrobiopterin (BH4) would improve impaired endothelial nitric oxide synthase-dependent dilation of cerebral arterioles during type 1 diabetes. In addition, we examined the influence of BH4 on levels of superoxide in brain tissue. In vivo diameter of cerebral arterioles in nondiabetic and diabetic rats was measured in response to endothelial nitric oxide synthase-dependent agonists (acetylcholine and adenosine 5-diphosphate) and an endothelial nitric oxide synthase-independent agonist (nitroglycerine) before and during application of BH4 (1.0 mu M). We also measured levels of superoxide from cortex tissue in nondiabetic and diabetic rats under basal states and during BH4. Acetylcholine and adenosine 5-diphosphate dilated cerebral arterioles in nondiabetic rats, but this vasodilation was significantly impaired in diabetic rats. In contrast, nitroglycerine produced similar vasodilation in nondiabetic and diabetic rats. Application of BH4 did not enhance vasodilation in nondiabetic rats but improved impaired cerebral vasodilation in diabetic rats. Basal superoxide levels were increased in cortex tissue from diabetic rats, and BH4 reduced these levels to that found in nondiabetic rats. Thus, BH4 is an important mediator of endothelial nitric oxide synthase-dependent responses of cerebral arterioles in diabetes and may have therapeutic potential for the treatment of cerebral vascular disease.

Basic Biomedical Sciences, Vermillion Campus.


McDougall, Matthew A.Walsh, MichaelWater, Kristina,Knigge, RyanMiller, Lindsey,Steverrner, Michalene, & Fogas, Bruce S. (2016). The effect of social networking sites on the relationship between perceived social support and depression.Psychiatry Research, 246, 223-229.

This study examined whether Social Networking Sites (SNSs) have a negative moderator effect on the established relationship between perceived social support and depression in psychiatric inpatients. Survey instruments assessing for depression, perceived social support, and SNS use, were filled out by 301 psychiatric inpatients. Additional data on age, gender, and primary psychiatric diagnosis were collected. A step-wise multiple regression analysis was performed to determine significant interactions. There was no significant interaction of SNS use on the relationship between perceived social support and depression when measured by Social Media Use Integration Scale or by hours of SNS use per day. There was a significant negative relationship between perceived social support and depression, and a significant positive relationship between hours of SNS use per day and depression, measured by the Beck Depression Inventory-II. Limitations include a gender discrepancy among participants, generalizability, recall bias, and SNS measurement. This is the first study to look at SNS use and depression in psychiatric inpatients. SNS use did not affect perceived social support or the protective relationship between perceived social support and depression. Hours of SNS use per day were correlated with depression scores. Future studies between SNS use and depression should quantify daily SNS use. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Sanford School of Medicine, Sioux Falls Campus.


McDougall, Matthew A.Walsh, MichaelWattier, Kristina,Knigge, RyanMiller, Lindsey,Stevermer, Michalene, & Fogas, Bruce S. (2016). The effect of social networking sites on the relationship between perceived social support and depression.Psychiatry Research, 246, 223-229.

This study examined whether Social Networking Sites (SNSs) have a negative moderator effect on the established relationship between perceived social support and depression in psychiatric inpatients. Survey instruments assessing for depression, perceived social support, and SNS use, were filled out by 301 psychiatric inpatients. Additional data on age, gender, and primary psychiatric diagnosis were collected. A step-wise multiple regression analysis was performed to determine significant interactions. There was no significant interaction of SNS use on the relationship between perceived social support and depression when measured by Social Media Use Integration Scale or by hours of SNS use per day. There was a significant negative relationship between perceived social support and depression, and a significant positive relationship between hours of SNS use per day and depression, measured by the Beck Depression Inventory-II. Limitations include a gender discrepancy among participants, generalizability, recall bias, and SNS measurement. This is the first study to look at SNS use and depression in psychiatric inpatients. SNS use did not affect perceived social support or the protective relationship between perceived social support and depression. Hours of SNS use per day were correlated with depression scores. Future studies between SNS use and depression should quantify daily SNS use. (PsycINFO Database Record (c) 2017 APA, all rights reserved)

Sanford School of Medicine, Sioux Falls Campus.


Meyer, M., Kovacs, Attila D., & Pearce, David A. (2017). Decreased sensitivity of palmitoyl protein thioesterase 1-deficient neurons to chemical anoxia.Metabolic Brain Disease, 32(1), 275-279.

Infantile CLN1 disease, also known as infantile neuronal ceroid lipofuscinosis, is a fatal childhood neurodegenerative disorder caused by mutations in the CLN1 gene. CLN1 encodes a soluble lysosomal enzyme, palmitoyl protein thioesterase 1 (PPT1), and it is still unclear why neurons are selectively vulnerable to the loss of PPT1 enzyme activity in infantile CLN1 disease. To examine the effects of PPT1 deficiency on several well-defined neuronal signaling and cell death pathways, different toxic insults were applied in cerebellar granule neuron cultures prepared from wild type (WT) and palmitoyl protein thioesterase 1-deficient (Ppt1 (-/-) ) mice, a model of infantile CLN1 disease. Glutamate uptake inhibition by t-PDC (L-trans-pyrrolidine-2,4-dicarboxylic acid) or Zn2+-induced general mitochondrial dysfunction caused similar toxicity in WT and Ppt1 (-/-) cultures. Ppt1 (-/-) neurons, however, were more sensitive to mitochondrial complex I inhibition by MPP+ (1-methyl-4-phenylpyridinium), and had significantly decreased sensitivity to chemical anoxia induced by the mitochondrial complex IV inhibitor, sodium azide. Our results indicate that PPT1 deficiency causes alterations in the mitochondrial respiratory chain.

Sanford School of Medicine, Sioux Falls Campus.


Min, Jia-Wei, Lü, Lanhai, Freeling, Jessica L.Martin, Doug S., &Wang, Hongmin. (2017). USP14 inhibitor attenuates cerebral ischemia/reperfusion-induced neuronal injury in mice. Journal of Neurochemistry, 140(5), 826-833.

Stroke is associated with over-production of misfolded and aggregating proteins. However, it remains largely unclear whether enhanced removal of protein aggregates following ischemic stroke is neuroprotective. Deubiquitinating enzymes ( DUBs) are a large group of proteases that regulate protein degradation. The ubiquitin-specific protease 14 ( USP14) is a DUB that is associated with the proteasome and negatively regulates proteasome activity. In this study, we examined the effect of 1-[1-(4-fluorophenyl)-2,5-dimethylpyrrol-3-yl]-2-pyrrolidin-1-ylethanone ( IU1), a specific small molecule inhibitor of USP14, on mouse focal cerebral ischemic stroke-induced neuronal injury in mice. We found that IU1 treatment attenuated ischemic stroke-caused neuronal injury, which was reflected by increased survival rate, reduced infarct volume, as well as decreased neuronal loss in the IU1-treated mice compared to the control-treated mice. Additionally, IU1 treatment is associated with reduced protein aggregates and enhanced proteasome functionality. These data not only highlight the significance of protein homeostasis in cerebral ischemia/reperfusion-induced neuronal injury but also extend the therapeutic role of DUB inhibitors.

Basic Biomedical Sciences, Vermillion Campus.


Pingree, M. J., Sole, Joshua S., O’ Brien, T. G., Eldrige, J. S., & Moeschler, S. M. (2017). Clinical Efficacy of an Ultrasound-Guided Greater Occipital Nerve Block at the Level of C2. Regional Anesthesia and Pain Medicine, 42(1), 99-104.

Background and Objectives: The purpose of this prospective open-label study was to investigate the analgesic effects of an ultrasound-guided greater occipital nerve (GON) block at the level of C2, as the nerve courses superficially to the obliquus capitis inferior muscle. Methods: Patients with a diagnosis of occipital neuralgia or cervicogenic headache were recruited for the study. Ultrasound-guided GON blocks at the level of C2 were performed by experienced clinicians according to a standardized protocol. Numeric rating scale pain scores were recorded preinjection and at 30 minutes, 2 weeks, and 4 weeks after injection. Results: A total of 14 injections were performed with a mean procedure time of 3.75 minutes. Anesthesia in the GON distribution was achieved for 86% of patients at 30 minutes postinjection. Compared with baseline, numeric rating scale scores decreased by a mean of 3.78 at 30 minutes (P < 0.001), 2.64 at 2 weeks (P = 0.006), and 2.21 at 4 weeks (P = 0.01). There were no significant adverse events reported during the study period. Conclusions: This prospective open-label study demonstrated successful blockade of the GONat the level of C2 using a novel ultrasound-guided technique. Significant reductions in pain scores were observed over the 4-week study period, and no adverse events were reported. The observations from this study provide important preliminary data for future randomized trials involving patients with occipital neuralgia and cervicogenic headache.

Sanford School of Medicine, Sioux Falls Campus.


Pitcher, Kristopher A., & Soluk, Daniel A. (2016). Inter-patch connectivity and intra-patch structure differentially alter prey consumption by multiple predators. Ecosphere, 7(11), 14.

Structural habitat complexity (SHC) and functional habitat connectivity (FHC) have important effects on predator-prey interactions and exert a strong influence on community structure/dynamics in terrestrial and aquatic ecosystems. Although these factors vary simultaneously in most systems, their interactive effects are poorly understood. Using artificial pond mesocosms and multiple prey types, we manipulated plant density (SHC: low, high) and inter-patch distance (FHC: short, long) in a full factorial design to test for potential interactive effects of these factors on competition and predation by a dragonfly larva (Anax junius) and fish predator (Lepomis cyanallus). When inter-patch distances (FHC) were short, A. junius consumed more amphipods (36% +/- 4.6%) compared with long treatments (19% +/- 4.8%). We detected no significant effects of plant density (SHC) on prey consumption by A. junius. There were significant interactive effects of FHC and SHC on Lepomis cyanellus consumption of amphipods and damselflies. The most counterintuitive of these effects was that sunfish consumed more larval damselflies at high plant density (64% +/- 6.0%) than at low plant density (38% +/- 8.6%) but only in short connection treatments. This interactive effect of SHC and FHC on damselfly predation by L. cyanellus was likely because damselflies exhibited riskier behavior at higher SHC. Prey consumption with both predators present was additive, but no significant effect of either SHC or FHC on interspecific predation was detected, suggesting compensatory foraging responses. Structural habitat complexity and FHC interactively influence predator foraging behavior in complex, non-intuitive ways that are highly dependent on the predator/prey combination in question. Structural habitat complexity and FHC are currently being influenced by anthropogenic factors in multiple ways (e.g., habitat loss, global climate change), and being able to predict the responses of biotic communities to these changes should be an important consideration in restoration and conservation efforts.

Biology Department.


Posthumus, David C. (2016). Hereditary enemies? An examination of Sioux–Arikara relations prior to 1830. Plains Anthropologist, 61(240), 361-382.

Sociology and Anthropology Department.


Puckett, Jae A., Newcomb, M. E., Ryan, D. T., Swann, G., Garofalo, R., & Mustanski, B. (2017). Internalized Homophobia and Perceived Stigma: a Validation Study of Stigma Measures in a Sample of Young Men who Have Sex with Men. Sexuality Research and Social Policy, 14(1), 1-16.

Young men who have sex with men (YMSM) experience minority stressors that impact their mental health, substance use, and sexual risk behaviors. Internalized homophobia (IH) and perceived stigma represent two of these minority stressors, and there has been limited research empirically validating measures of these constructs. We validated measures of IH and perceived stigma with a sample of 450 YMSM (mean age = 18.9) and a sample of 370 YMSM (mean age = 22.9). Results from exploratory and confirmatory factor analyses supported modifications to the IH and perceived stigma scales, ultimately revealing a three factor and one factor structure, respectively. Convergent and discriminant validity were examined utilizing correlations between IH, perceived stigma, and other variables related to minority stress (e.g., victimization). We evaluated predictive validity by examining relations with mental health, substance use, and risky sexual behaviors measured 12-months from baseline. There were mixed findings for IH, with subscales varying in their relations to mental health, drinking, and sexual risk variables. Perceived stigma was not related to mental health or substance use, but was associated with greater prevalence of STIs. Findings supported the use of these modified scales with YMSM and highlight the need for further measurement studies.

Psychology Department.


Puckett, Jae A., Newcomb, Michael E., Garofalo, Robert, & Mustanski, Brian. (2017). Examining the conditions under which internalized homophobia is associated with substance use and condomless sex in young msm: The moderating role of impulsivity. Annals of Behavioral Medicine.

Background: Internalized homophobia (IH) is the internalization of homophobic attitudes by sexual minorities due to social bias. IH has been inconsistently related to substance use and condomless sex for young men who have sex with men (YMSM).Purpose: We examined negative urgency (the tendency to act impulsively in response to negative emotional experiences), positive urgency (the tendency to act impulsively in response to positive emotional experiences), and sensation seeking as independent moderators of the association of IH with binge drinking, drug use, and condomless anal sex.Methods: Data were collected from 450 YMSM (mean age = 18.9) over the course of 18 months (baseline, 6-, 12-, and 18-month follow-up).Results: Hierarchical generalized linear modeling revealed that there was a significant moderation for binge drinking and receptive condomless anal sex, with the association between IH and these risk behaviors increased for those with higher levels of negative urgency and positive urgency.Conclusions: IH is important to the negative health outcomes of binge drinking and condomless anal sex for individuals high in negative and/or positive urgency, who may act impulsively to avoid subjective negative experiences or in the face of positive emotional experiences. Future research is needed to further establish additional conditions under which IH may be important to understanding risk behaviors in YMSM, which is essential to developing targeted prevention and intervention efforts. (PsycINFO Database Record (c) 2017 APA, all rights reserved)

Psychology Department.


Sariol, Ana M., & Abebe, Michael A. (2017). The influence of CEO power on explorative and exploitative organizational innovation. Journal of Business Research, 73, 38-45.

Despite the growing research evidence on the effect of powerful CEOs on organizational outcomes, their role in shaping the firm’s innovation agenda has received little scholarly attention. This study examines the effect of CEO power on exploratory and exploitative innovation. Drawing from core arguments of Behavioral Agency Theory, this study proposes that firms led by powerful CEOs are likely to pursue more exploratory and less exploitative innovations. Furthermore, these relationships are significantly strengthened by CEO Outsider Status. Using data from 150 U.S. firms, the results reveal a significant positive relationship between CEO power and explorative innovation. Contrary to predictions, firms led by powerful CEOs engage in more not less exploitative innovation when the CEO is appointed from outside the firm. Overall, the findings provide a more nuanced explanation of the link between CEO power and organizational innovation. Implications for research and practice are discussed.

Beacom School of Business.


Sazama, Eric J., Bosch, Michael J.,Shouldis, Carmelita S.,Ouellette, Scot P., & Wesner, Jeff S. (2017). Incidence of Wolbachia in aquatic insects.Ecology & Evolution (20457758), 7(4), 1165-1169.

Wolbachia is a genus of intracellular bacteria typically found within the reproductive systems of insects that manipulates those systems of their hosts. While current estimates of Wolbachia incidence suggest that it infects approximately half of all arthropod species, these estimates are based almost entirely on terrestrial insects. No systematic survey of Wolbachia in aquatic insects has been performed. To estimate Wolbachia incidence among aquatic insect species, we combined field-collected samples from the Missouri River (251 samples from 58 species) with a global database from previously published surveys. The final database contained 5,598 samples of 2,687 total species (228 aquatic and 2,459 terrestrial). We estimate that 52% (95% CrIs: 44%-60%) of aquatic insect species carry Wolbachia, compared to 60% (58%-63%) of terrestrial insects. Among aquatic insects, infected orders included Odonata, Coleoptera, Trichoptera, Ephemeroptera, Diptera, Hemiptera, and Plecoptera. Incidence was highest within aquatic Diptera and Hemiptera (69%), Odonata (50%), and Coleoptera (53%), and was lowest within Ephemeroptera (13%). These results indicate that Wolbachia is common among aquatic insects, but incidence varies widely across orders and is especially uncertain in those orders with low sample sizes such as Ephemeroptera, Plecoptera, and Trichoptera.

Basic Biomedical Sciences, Vermillion Campus.


Sheets, Jordan N., Iwanicki, M., Liu, J. F., Howitt, B. E., Hirsch, M. S., Gubbels, J. A. A., . . . Egland, Kristi A. (2016). SUSD2 expression in high-grade serous ovarian cancer correlates with increased patient survival and defective mesothelial clearance. Oncogenesis, 5, 12.

The cause of death among the majority of epithelial ovarian cancer (EOC) patients involves passive dissemination of cancer cells within the peritoneal cavity and subsequent implantation of cancer spheroids into adjacent organs. Thus, it is important to identify the factors that mediate EOC metastasis and implantation, including clearance of the mesothelium. Sushi domain containing 2 (SUSD2) encodes a type I transmembrane protein containing several functional domains inherent to adhesion molecules. Immunohistochemical analysis determined the presence of SUSD2 in several subtypes of EOC, with the strongest staining observed in high-grade serous ovarian carcinomas (HGSOCs). A high-density, clinically annotated HGSOC tissue microarray was stained with an anti-SUSD2 antibody. Patients with tumors that had a low percentage of SUSD2 staining cells had a shorter median survival (31.7 months) compared with patients who had tumors with extensive SUSD2 staining (49.1 months; P-value = 0.0083). To investigate the role of SUSD2 in HGSOCs, stable OVCAR3, OVSAHO and KURAMOCHI cell lines were established with knockdown (KD) or non-targeting (NT) of SUSD2. Boyden chamber and wound-healing assays demonstrated that OVCAR3, OVSAHO and KURAMOCHI SUSD2-KD cells migrated at significantly higher rates compared with their SUSD2 NT counterpart cell lines. Quantitative reverse transcription-PCR and western immunoblot analysis indicated an inverse relationship between SUSD2 and well-characterized mesenchymal proteins, including Twist-1, Zeb-1, N-cadherin, STEAP1, AHNAK, Snail-1, COL5A2 and Snail-3 in OVCAR3, OVSAHO and KURAMOCHI cell line models. In addition, OVCAR3 and KURAMOCHI SUSD2-KD spheroids displayed increased mesothelial clearance ability compared with cells that express endogenous levels of SUSD2. These data suggest that SUSD2 has a role in the inhibition of mesothelial clearance, which is required for metastasis. Altogether, our findings indicate that SUSD2 impedes migration, epithelial-to-mesenchymal transitional and mesothelial clearance of HGSOC cells, consistent with prolonged survival of patients with SUSD2-expressing tumors.

Sanford School of Medicine, Sioux Falls Campus.


Strouse, Gabrielle A., & Ganea, P. A. (2016). Are Prompts Provided by Electronic Books as Effective for Teaching Preschoolers a Biological Concept as Those Provided by Adults? Early Education and Development, 27(8), 1190-1204.

Research Findings: Prior research indicates that shared book reading is an effective method for teaching biological concepts to young children. Adult questioning during reading enhances children’s comprehension. We investigated whether adult prompting during the reading of an electronic book enhanced children’s understanding of a biological concept. Ninety-one 4-year- olds read about camouflage in 3 conditions. We varied how prompts were provided: (a) read by the book, (b) read by a researcher, or (c) given face to face by the researcher. There was an interaction between children’s initial vocabulary level and condition. Children with low vocabulary scores gave fewer camouflage responses than their high-vocabulary peers, and this effect was particularly pronounced in the book-read condition. Children’s executive function was also measured and discussed. Practice or Policy: Our findings indicate that under some circumstances electronic prompts built into touchscreen books can be as effective at supporting conceptual development as the same prompts provided by a coreading adult. However, children with low vocabulary skills may be particularly supported by adult-led prompting. We suggest that adult prompting be used to motivate children to test and revise their own biological theories. Once children have learned strategies for updating their concepts, electronic prompting may be useful for scaffolding children’s transition to using the strategies when reading alone.

School of Education.


Strouse, Gabrielle A., & Ganea, Patricia A. (2017). Toddlers’ word learning and transfer from electronic and print books.Journal of Experimental Child Psychology, 156, 129-142.

Transfer from symbolic media to the real world can be difficult for young children. A sample of 73 toddlers aged 17 to 23 months were read either an electronic book displayed on a touchscreen device or a traditional print book in which a novel object was paired with a novel label. Toddlers in both conditions learned the label within the context of the book. However, only those who read the traditional format book generalized and transferred the label to other contexts. An older group of 28 toddlers aged 24 to 30 months did generalize and transfer from the electronic book. Across ages, those children who primarily used screens to watch prerecorded video at home transferred less from the electronic book than those with more diverse home media experiences. (PsycINFO Database Record (c) 2017 APA, all rights reserved)

School of Education.


Tamang, Sem Raj, & Hoefelmeyer, James D. (2016). Direct arylation catalysis with chloro 8-(dimesitylboryl)quinoline-kappa N copper(I). Beilstein Journal of Organic Chemistry, 12, 2757-2762.

We report direct arylation of arylhalides with unactivated sp(2) C-H bonds in benzene and naphthalene using a copper(I) catalyst featuring an ambiphilic ligand, (quinolin-8-yl) dimesitylborane. Direct arylation could be achieved with 0.2 mol % catalyst and 3 equivalents of base (KO(t-Bu)) at 80 degrees C to afford TON approximate to 160-190 over 40 hours.

Chemistry Department.


Villano, Ines, Messina, Antonietta, Valenzano, Anna, …., Summers, Cliff H., & Mallick, Birendra N. (2017). Basal Forebrain Cholinergic System and Orexin Neurons: Effects on Attention.Frontiers in Behavioral Neuroscience, 11, 1-11.

The basal forebrain (BF) cholinergic system has an important role in attentive functions. The cholinergic system can be activated by different inputs, and in particular, by orexin neurons, whose cell bodies are located within the postero-lateral hypothalamus. Recently the orexin-producing neurons have been proved to promote arousal and attention through their projections to the BF. The aim of this review article is to summarize the evidence showing that the orexin system contributes to attentional processing by an increase in cortical acetylcholine release and in cortical neurons activity.

Biology Department.


Wang, X. T., & Huangfu, Gang. (2017). Glucose-specific signaling effects on delay discounting in intertemporal choice.Physiology & Behavior, 169, 195-201.

We propose that decisions related to resource management (e.g., intertemporal choice between a smaller-and-sooner reward and a larger-and-later reward) are sensitive to and regulated by fluctuating blood glucose levels. Circulating glucose affects intertemporal choice by means of signaling body energy condition instead of serving as a replenishing resource for effortful cognitive processing. We intend to dissociate calorie-supplying functions from glucose-unique anticipatory effects on behavioral resource management, measured by delay discounting in making intertemporal choices. Regarding the anticipatory functions of the glucose–insulin system in regulating the degree of delay discounting, we tested three predictions: First, we predict that the signaling effects of circulating glucose on delay discounting do not need to be dose-dependent as long as glucose fluctuation indicates a directional trend in body energy budget. Second, such effects of glucose fluctuation on delay discounting are phagic (appetite related) instead of dipsian (thirst related). Third, this glucose–insulin signaling system requires glucose as the specific input, thus is insensitive to other forms of sugar that are not insulin regulated. In Study 1, fasting participants were randomly assigned to one of five groups: water consumption, zero-consumption, and three glucose consumption (18 g, 36 g, and 72 g cane sugar/250 ml water) groups. The participants competed two sets of intertemporal choice questions with varying delay discounting rates before and after a beverage intervention. The results showed that the rate of delay discounting was negatively correlated to blood glucose levels. The effects of circulating glucose on delay discounting closely followed the changes in blood glucose levels showing a plateau on both dose-response curves (i.e., the sugar dose-blood glucose level curve and the sugar does-delay discounting curve). Secondly, the effects of circulating glucose on delay discounting were significant only in the glucose ingestion group, but not in the zero consumption and the water consumption groups, suggesting that the behavioral effects were in fact related to hunger-reduction instead of thirst-reduction. Study 2 revealed that glucose ingestion, but not water or another form of sugar (xylitol matched to glucose either for sweetness or for calories), reduced delay discounting, making future options more attractive. This result suggests that signaling of body energy budget is indeed glucose-unique. Our results suggest a forecasting mechanism of the glucose-insulin system for both metabolic and behavioral regulations of resource acquisition and allocation. (PsycINFO Database Record (c) 2017 APA, all rights reserved)

Psychology Department.


Wang, Z. F., Kedzierski, L., Nuessing, S., …., Huber, Victor C., Jackson, D. C., . . . Kedzierska, K. (2016). Establishment of memory CD8(+) T cells with live attenuated influenza virus across different vaccination doses. Journal of General Virology, 97, 3205-3214.

FluMist has been used in children and adults for more than 10 years. As pre-existing CD8(+) T cell memory pools can provide heterologous immunity against distinct influenza viruses, it is important to understand influenza-specific CD8(+) T cell responses elicited by different live attenuated influenza virus (LAIV) regimens. In this study, we immunized mice intranasally with two different doses of live-attenuated PR8 virus (PR8 ts, H1N1), low and high, and then assessed protective efficacy by challenging animals with heterosubtypic X31-H3N2 virus at 6 weeks post-vaccination. Different LAIV doses elicited influenza-specific CD8(+) T cell responses in lungs and spleen, but unexpectedly not in bronchoalveolar lavage. Interestingly, the immunodominance hierarchy at the acute phase after immunization varied depending on the LAIV dose; however, these differences disappeared at 6 weeks post-vaccination, resulting in generation of comparable CD8(+) T cell memory pools. After vaccination with either dose, sufficient numbers of specific CD8(+) T cells were generated for recall and protection of mice against heterosubtypic H1N1 -> H3N2 challenge. As a result, immunized mice displayed reduced weight loss, diminished inflammatory responses and lower viral titres in lungs, when compared to unvaccinated animals. Interestingly, the higher dose led to enhanced viral clearance on day 5 post-challenge, though this was not associated with increased CD8(+) T cell responses, but with higher levels of non-neutralizing antibodies against the priming virus. Our study suggests that, while different LAIV doses result in distinct immune profiles, even a low dose produces sufficient protective CD8(+) T cell memory against challenge infection, though the high dose results in more rapid viral clearance and reduced inflammation.

Basic Biomedical Sciences, Vermillion Campus.


Yao, Bin, Kolla, Praveen, Koodali, Ranjit, Ding, Yichun, Balaranjan, SelvaratnamShrestha, Sunav, & Smirnova, Alevtina. (2017). Enzymatic decomposition and electrochemical study of alkali lignin by laccase (Trametes versicolor) in the presence of a natural mediator (methyl syringate). New Journal of Chemistry, 41(3), 958-964.

The aerobic-enzymatic decomposition of alkali lignin in the presence of laccase from Trametes versicolor (LTV) and the natural mediator methyl syringate in acetic acid–sodium acetate buffer solution (pH = 4.5) at 40 °C in an oxygen-rich (aerobic) environment is studied. SEM and BET analyses are used to characterize the changes in the surface area and morphology of lignin that occurred during the exposure to the laccase–mediator system (LMS) for 72 h. The LMS interaction causes a 2-fold improvement in the surface area from 4.9 to 9.8 m2 g−1, due to significant changes in the mesoporous structure of lignin within a pore size of 2–120 nm. This could be due to an efficient interaction of the surface phenolic groups and internal mesoporous β-O-4 network of lignin with the LMS in an aerobic environment. To further understand the enzymatic degradation of lignin, electrochemical oxidation of a thin film of lignin on the surface of a glassy carbon electrode (GCE) is performed under aerobic vs. anaerobic conditions in the presence of the LMS. A synergistic lignin electrooxidation in the aerobic environment is observed due to the promotion of LMS activity by a parallel oxygen reduction reaction (ORR). Based on the electrochemical studies, a mechanism for understanding the role of oxygen in the enzymatic oxidation of lignin in an aerobic environment and the stability of the mediator radical (MSṖ) is proposed.

Chemistry Department.


Yao, Qingqing, Cosme, J. G. L., Xu, T.,Miszuk, Jacob M., Picciani, P. H. S., Fong, H., & Sun, Hongli. (2017). Three dimensional electrospun PCL/PLA blend nanofibrous scaffolds with significantly improved stem cells osteogenic differentiation and cranial bone formation.Biomaterials, 115, 115-127.

Nanofibrous scaffolds that are morphologically/structurally similar to natural ECM are highly interested for tissue engineering; however, the electrospinning technique has the difficulty in directly producing clinically relevant 3D nanofibrous scaffolds with desired structural properties. To address this challenge, we have developed an innovative technique of thermally induced nanofiber self-agglomeration (TISA) recently. The aim of this work was to prepare (via the TISA technique) and evaluate 3D electrospun PCL/PLA blend (mass ratio: 4/1) nanofibrous scaffolds having high porosity of similar to 95.8% as well as interconnected and hierarchically structured pores with sizes from sub-micrometers to similar to 300 mu m for bone tissue engineering. The hypothesis was that the incorporation of PLA (with higher mechanical stiffness/modulus and bioactivity) into PCL nanofibers would significantly improve human mesenchymal stem cells (hMSCs) osteogenic differentiation in vitro and bone formation in vivo. Compared to neat PCL-3D scaffolds, PCL/PLA-3D blend scaffolds had higher mechanical properties and in vitro bioactivity; as a result, they not only enhanced the cell viability of hMSCs but also promoted the osteogenic differentiation. Furthermore, our in vivo studies revealed that PCL/PLA-3D scaffolds considerably facilitated new bone formation in a critical-sized cranial bone defect mouse model. In summary, both in vitro and in vivo results indicated that novel 3D electrospun PCL/PLA blend nanofibrous scaffolds would be strongly favorable/desired for hMSCs osteogenic differentiation and cranial bone formation. (C) 2016 Elsevier Ltd. All rights reserved.

Biomedical Engineering, Sioux Falls Campus.


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