Posted by: kelsijo97 | August 31, 2012

September 2012

Anbalagan, Srivishnupriya, Dmitriev, Alexander, Mcshan, W. Michael, Dunman, Paul M., & Chaussee, Michael S. (2012). Growth Phase-Dependent Modulation of Rgg Binding Specificity in Streptococcus pyogenes. Journal of bacteriology, 194(15), 3961-3971.
Streptococcus pyogenes Rgg is a transcriptional regulator that interacts with the cofactor LacD.1 to control growth phase-dependent expression of genes, including speB, which encodes a secreted cysteine protease. LacD.1 is thought to interact with Rgg when glycolytic intermediates are abundant in a manner that prevents Rgg-mediated activation of speB expression via binding to the promoter region. When the intermediates diminish, LacD.1 dissociates from Rgg and binds to the speB promoter to activate expression. The purpose of this study was to determine if Rgg bound to chromatin during the exponential phase of growth and, if so, to identify the binding sites. Rgg bound to 62 chromosomal sites, as determined by chromatin immunoprecipitation coupled with DNA microarrays. Thirty-eight were within noncoding DNA, including sites upstream of the genes encoding the M protein (M49), serum opacity factor (SOF), fibronectin-binding protein (SfbX49), and a prophage-encoded superantigen, SpeH. Each of these sites contained a promoter that was regulated by Rgg, as determined with transcriptional fusion assays. Purified Rgg also bound to the promoter regions of emm49, sof, and sfbX49 in vitro. Results obtained with a lacD.1 mutant showed that both LacD.1 and Rgg were necessary for the repression of emm49, sof, sfbX49, and speH expression. Overall, the results indicated that the DNA binding specificity of Rgg is responsive to environmental changes in a LacD.1-dependent manner and that Rgg and LacD.1 directly control virulence gene expression in the exponential phase of growth.
Basic Biomedical Sciences, Vermillion Campus.
Hansen, Keith A., & Eyster, Kathleen M. (2012). What Happened to WHI: Menopausal Hormonal Therapy in 2012. Clinical obstetrics and gynecology, 55(3), 706-712.
Menopause is characterized by amenorrhea for 1 year due to the cessation of ovarian function. The hormonal treatment of menopause has significantly altered since the publication of initial results from the Women’s Health Initiative continuous, combined, conjugated equine estrogen with medroxyprogesterone acetate study arm in 2002. Current studies suggest that treatment should be individualized and that the lowest dose of estrogen providing relief should be used for the shortest period of time in menopausal women who experience vasomotor symptoms or urogenital atrophy. Future studies into different delivery mechanisms such as transdermal applications and different agents, such as tibolone and raloxifene, will help refine the treatment of menopause.
Basic Biomedical Sciences, Vermillion Campus.
Su, Huabo, & Wang, Xuejun. (2011). p62 Stages an Interplay Between the Ubiquitin-Proteasome System and Autophagy in the Heart of Defense Against Proteotoxic Stress. Trends in cardiovascular medicine, 21(8), 224-228.
As exemplified by desmin-related cardiomyopathy and myocardial ischemia/reperfusion injury, proteasome functional insufficiency plays an essential pathogenic role in the progression of cardiac diseases with elevated proteotoxic stress. Upregulation of p62/SQSTM1 and increased selective autophagy in cardiomyocytes may protect against proteotoxic stress in the heart. p62 may serve as a proteotoxic stress sensor, promote segregation and degradation of misfolded proteins by autophagy, and mediate the cross talk between the ubiquitin-proteasome system and autophagy. Copyright 2011 Elsevier Inc. All rights reserved.
Basic Biomedical Sciences, Vermillion Campus.
Tian, Zongwen, Zheng, Hanqiao, Li, Jie, Li, Yifan, Su, Huabo, & Wang, Xuejun. (2012). Genetically induced moderate inhibition of the proteasome in cardiomyocytes exacerbates myocardial ischemia-reperfusion injury in mice. Circulation research, 111(5), 532-542.
Rationale: Both cardiomyocyte-restricted proteasome functional enhancement and pharmacological proteasome inhibition (PSMI) were shown to attenuate myocardial ischemia/reperfusion (I/R) injury. The role of cardiac proteasome dysfunction during I/R and the perspective to diminish I/R injury by manipulating proteasome function remain unclear. Objectives: We sought to determine proteasome adequacy in I/R hearts, create a mouse model of cardiomyocyte-restricted PSMI (CR-PSMI), and test CR-PSMI impact on I/R injury. Methods and Results: Myocardial I/R were modeled by ligation (30 minutes) and subsequent release of the left anterior descending artery in mice overexpressing GFPdgn, a validated surrogate proteasome substrate. At 24 hours of reperfusion, myocardial proteasome activities were significantly lower whereas total ubiquitin conjugates and GFPdgn protein levels were markedly higher in all regions of the I/R hearts than the sham controls, indicative of proteasome functional insufficiency. CR-PSMI in intact mice was achieved by transgenic (tg) overexpression of a peptidase-disabled mouse beta5 subunit (T60A-beta5) driven by an attenuated mouse mhc6 promoter. Overexpressed T60A-beta5 can replace endogenous beta5 and inhibits proteasome chymotrypsin-like activities in the heart. Mice with moderate CR-PSMI showed no abnormalities at the baseline but displayed markedly more pronounced structural and functional damage during I/R, compared with non-tg littermates. The exacerbation of I/R injury by moderate CR-PSMI was associated with significant increases in the protein level of PTEN and protein kinase Cdelta (PKCdelta), decreased Akt activation, and reduced PKCepsilon. Conclusions: Myocardial I/R causes proteasome functional insufficiency in cardiomyocytes and moderate CR-PSMI augments PTEN and PKCdelta, suppresses Akt and PKCepsilon, increases cardiomyocyte apoptosis, and aggravates I/R injury in mice.
Basic Biomedical Sciences, Vermillion Campus.
Yuan, Sharleen, & Burrell, Brian D. (2012). Long-term depression of nociceptive synapses by non-nociceptive afferent activity: Role of endocannabinoids, Ca2+, and calcineurin. Brain Research, 1460, 1-11.
Activity in non-nociceptive afferents is known to produce long-lasting decreases in nociceptive signaling, often referred to as gate control, but the cellular mechanisms mediating this form of neuroplasticity are poorly understood. In the leech, activation of non-nociceptive touch (T) mechanosensory neurons induces a heterosynaptic depression of nociceptive (N) synapses that is endocannabinoid-dependent. This heterosynaptic, endocannabinoid-dependent long-term depression (ecLTD) is observed where the T- and N-cells converge on a common postsynaptic target, in this case the motor neuron that innervates the longitudinal muscles (L-cells) that contributes to a defensive withdrawal reflex. Depression in the nociceptive synapse required both presynaptic and postsynaptic increases in intracellular Ca2+. Activation of the Ca2+-sensitive protein phosphatase calcineurin was also required, but only in the presynaptic neuron. Heterosynaptic ecLTD was unaffected by antagonists for NMDA or metabotropic glutamate receptors, but was blocked by the 5-HT2 receptor antagonist ritanserin. Depression was also blocked by the CB1 receptor antagonist rimonabant, but this is thought to represent an effect on a TRPV-like receptor. This heterosynaptic, endocannabinoid-dependent modulation of nociceptive synapses represents a novel mechanism for regulating how injury-inducing or painful stimuli are transmitted to the rest of the central nervous system. (C) 2012 Elsevier B.V. All rights reserved.
Basic Biomedical Sciences, Vermillion Campus.
Lesbarreres, D., Balseiro, A., Brunner, J., Kerby, Jacob, Miller, D. L., Robert, J., et al. (2012). Ranavirus: past, present and future. Biology Letters, 8(4), 481-483.
Emerging infectious diseases are a significant threat to global biodiversity. While historically overlooked, a group of iridoviruses in the genus Ranavirus has been responsible for die-offs in captive and wild amphibian, reptile and fish populations around the globe over the past two decades. In order to share contemporary information on ranaviruses and identify critical research directions, the First International Symposium on Ranaviruses was held in July 2011 in Minneapolis, MN, USA. Twenty-three scientists and veterinarians from nine countries examined the ecology and evolution of ranavirus-host interactions, potential reservoirs, transmission dynamics, as well as immunological and histopathological responses to infection. In addition, speakers discussed possible mechanisms for die-offs, and conservation strategies to control outbreaks.
Biology Department.
Lancaster, Susan, Kakade, Sandeep, & Mani, Gopinath. (2012). Microrough cobalt-chromium alloy surfaces for Paclitaxel delivery: preparation, characterization, and in vitro drug release studies. Langmuir : the ACS journal of surfaces and colloids, 28(31), 11511-11526.
Cobalt-chromium (Co-Cr) alloys have extensive biomedical applications including drug-eluting stents (DES). This study investigates the use of eight different microrough Co-Cr alloy surfaces for delivering paclitaxel (PAT) for potential use in DES. The eight different surfaces include four bare microrough and four self-assembled monolayer (SAM) coated microrough surfaces. The bare microrough surfaces were prepared by grit blasting Co-Cr with glass beads (50 and 100 mum in size) and Al(2)O(3) (50 and 110 mum). The SAM coated surfaces were prepared by depositing a -COOH terminated phosphonic acid monolayer on the different microrough surfaces. PAT was then deposited on all the bare and SAM coated microrough surfaces. The surfaces were characterized using scanning electron microscopy (SEM), 3D optical profilometry, and Fourier transform infrared spectroscopy (FTIR). SEM showed the different morphologies of microrough surfaces without and with PAT coating. An optical profiler showed the 3D topography of the different surfaces and the changes in surface roughness and surface area after SAM and PAT deposition. FTIR showed ordered SAMs were formed on glass bead grit blasted surfaces, while the molecules were disordered on Al(2)O(3) grit blasted surfaces. Also, FTIR showed the successful deposition of PAT on these surfaces. The PAT release was investigated for up to two weeks using high performance liquid chromatography. Al(2)O(3) grit blasted bare microrough surfaces showed sustained release profiles, while the glass bead grit blasted surfaces showed burst release profiles. All SAM coated surfaces showed biphasic drug release profiles, which is an initial burst release followed by a slow and sustained release. SAM coated Al(2)O(3) grit blasted surfaces prolonged the sustained release of PAT in a significant amount during the second week of drug elution studies, while this behavior was not observed for any other surfaces used in this study. Thus, this study demonstrates the use of different microrough Co-Cr alloy surfaces for delivering PAT for potential applications in DES and other medical devices.
Biomedical Engineering Program, Sioux Falls Campus.
Mariappan, Kadarkaraisamy, Caple, Gerald, Basa, Prem N., & Sykes, Andrew G. (2012). Preparation of onium salts of a reduced anthracenone crown ether macrocycle: a reactivity series involving pyridine, phosphine, thiophene, nitrile and primary amide nucleophiles. Journal of Physical Organic Chemistry, 25(8), 686-692.
Reaction of mineral acids with a cyclic macromolecule containing a secondary alcohol produces ammonium, phosphonium, thiophene, and amide adducts via a carbocation intermediate. X-ray crystallography confirms the structures of the products, including those when two competing nucleophiles are present. A reactivity series that mirrors the nucleophilicity index, where reactivity decreases in the order thiophene >?pyridine >?primary amides >?alkyl nitriles >> aromatic nitriles (unreactive), results. Addition of metal ions to ammonium adducts dissolved in acetonitrile produces secondary amides via the Ritter amide synthesis. Copyright (C) 2012 John Wiley & Sons, Ltd.
Chemistry Department.
Son, Jung-Ho, & Hoefelmeyer, James D. (2012). 1,2-Nucleophilic addition of 2-(picolyl)organoboranes to nitrile, aldehyde, ketone, and amide. Organic & biomolecular chemistry, 10(33), 6656-6664.
A series of 2-(picolyl)borane molecules were synthesized as products of the reaction between 2-(picolyl)lithium and R(2)BOMe (R = ethyl, 9-BBN, phenyl, 9-borafluorenyl). The 2-(picolyl)boranes were dimeric; whereas, monomers coordinated to LiOMe could be isolated when the synthesis was carried out in the presence of TMEDA and THF. The 2-(picolyl)boranes undergo reaction with nitriles, ketones, aldehydes, and amides with apparent 1,2-addition of the B-C(picolyl) bond to the unsaturated bond. Theoretical models reveal the presence of a donor orbital on the 2-(picolyl)borane with significant electron density at the benzylic carbon that we conclude was involved in nucleophilic attack on the electrophilic center of unsaturated organic functional groups.
Chemistry Department.
Lee, R. Alton. (2012). The Populist Dream of a “Wrong Way” Transcontinental. Kansas History, 35(2), 74-89.
The article discusses the efforts by the Populists of the Great Plains to have a north to south transcontinental railroad built during the 1890s, which is also referred to as a “wrong way” transcontinental. An overview of the Populists’ political philosophy, including in having government provide assistance for the poor, lowering property taxes, enacting railroad reform, raising the price of agricultural products, weakening the currency and combating monopolies, is provided. The role that the Populist leaders Alonzo Wardall and Henry Loucks played in achieving political reforms in the U.S. is discussed.
History Department [Emeritus].
Bumgarner, John, & Newswander, Chad B. (2012). Governing Alone and With Partners: Presidential Governance in a Post-NPM Environment. Administration & Society, 44(5), 546-570.
Seeking to close the gap between expectations and capacity, presidents have utilized a broad interpretation of executive power to control administrative affairs. However, the emergence of a post–New Public Management environment characterized by loosely constructed networks and a surge of governmental activity has required an evolution in the tools needed to govern. In exploring this dynamic through a constitutional governance model, it becomes evident that a new ethos of presidential governance is starting to develop that is marked by a mixture of governing alone and governing with partners. This dynamic potentially enables more effective and responsible execution of public laws.
Political Science and Criminal Justice Department.
Wray, Tyler B., Simons, Jeffrey S., Dvorak, Robert D., & Gaher, Raluca M. (2012). Trait-based affective processes in alcohol-involved “risk behaviors”. Addictive behaviors, 37(11), 1230-1239.
This study tested a theoretical model of alcohol use, markers of extreme intoxication, and risk behavior as a function of trait affect, distress tolerance, and affect-based behavior dysregulation. Positive affective pathways to risk behavior were primarily expected to be indirect via high levels of alcohol use, while negative affect paths were expected to be more directly associated with engagement in risk behavior. In addition, we expected trait affectivity and distress tolerance would primarily exhibit relationships with alcohol use and problems through behavioral dysregulation occurring during extreme affective states. To evaluate these hypotheses, we tested a SEM with three alcohol-related outcomes: “Typical” alcohol use, “blackout” drinking, and risk behavior. High trait negative affect and low tolerance for affective distress contribute to difficulty controlling behavior when negatively aroused and this is directly associated with increased risk behavior when drinking. In contrast, associations between positive urgency and risk behaviors are indirect via increased alcohol consumption. Positive affectivity exhibited both inverse and positive effects in the model, with the net effect on alcohol outcomes being insignificant. These findings contribute important information about the distinct pathways between affect, alcohol use, and alcohol-involved risk behavior among college students. Copyright 2012 Elsevier Ltd. All rights reserved.
Psychology Department.
Kruer, Michael C., Paudel, Reema, Wagoner, Wendy, Sanford, Lynn, Kara, Eleanna, Gregory, Allison, et al. (2012). Analysis of ATP13A2 in large neurodegeneration with brain iron accumulation (NBIA) and dystonia-parkinsonism cohorts. Neuroscience letters, 523(1), 35-38.
Several causative genes have been identified for both dystonia-parkinsonism and neurodegeneration with brain iron accumulation (NBIA), yet many patients do not have mutations in any of the known genes. Mutations in the ATP13A2 lead to Kufor Rakeb disease, a form of autosomal recessive juvenile parkinsonism that also features oromandibular dystonia. More recently, evidence of iron deposition in the caudate and putamen have been reported in patients with ATP13A2 mutations. We set out to determine the frequency of ATP13A2 mutations in cohorts of idiopathic NBIA and dystonia-parkinsonism. We screened for large deletions using whole genome arrays, and sequenced the entire coding region in 92 cases of NBIA and 76 cases of dystonia-parkinsonism. A number of coding and non-coding sequence variants were identified in a heterozygous state, but none were predicted to be pathogenic based on in silico analyses. Our results indicate that ATP13A2 mutations are a rare cause of both NBIA and dystonia-parkinsonism. Copyright 2012 Elsevier Ireland Ltd. All rights reserved.
Sanford School of Medicine, Sioux Falls Campus
Harris, William S., Pottala, James V., Vasan, R. S., Larson, M. G., & Robins, S. J. (2012). Changes in Erythrocyte Membrane Trans and Marine Fatty Acids between 1999 and 2006 in Older Americans. Journal of Nutrition, 142(7), 1297-1303.
Over the last several years, national programs to lower the content of industrially produced (IP) C18:1 and C18:2 trans fatty acids in foods have been implemented, but whether this has resulted in lower blood trans fatty acid levels is unknown. Likewise, an increased perception of the health benefits of fish oils rich in EPA and DHA may have resulted in an increase in consumption and blood levels of these fatty acids. To explore these issues, we analyzed the changes in RBC fatty acid composition between the 7th (1998-2001) and 8th (2005-2007) examination cycles in a random sample of the Framingham Offspring cohort. This was a retrospective cohort study of 291 participants from whom blood was drawn at both examinations and for whom complete covariate data were available. Overall, the proportion of trans fatty acids in RBC changed by -23% (95% Cl: -26 to -21%). RBC EPA+DHA proportions increased by 41% (95% Cl: 31 to 52%) in 38 individuals who were taking fish oil supplements at examination 8, but in 253 participants not taking fish oil, the proportion of RBC EPA+DHA did not change. In conclusion, in a random subsample of Framingham Offspring participants with serial observations over 6.7 y, the proportion of trans fatty acids in RBC decreased. Those of EPA+DHA increased in people taking fish oil supplements. These changes could potentially translate into a lower risk for cardiovascular disease. J. Nutr. 142: 1297-1303, 2012.
Sanford School of Medicine, Sioux Falls Campus.
Hu, Yueshan, Ehli, Erik A., Kittelsrud, Julie, Ronan, Patrick J., Munger, Karen, Downey, Terry, et al. (2012). Lipid-lowering effect of berberine in human subjects and rats. Phytomedicine : international journal of phytotherapy and phytopharmacology, 19(10), 861-867.
Due to serious adverse effects and the limited effectiveness of currently available pharmacological therapies for obesity, many research efforts have focused on the development of drugs from natural products. Our previous studies demonstrated that berberine, an alkaloid originally isolated from traditional Chinese herbs, prevented fat accumulation in vitro and in vivo. In this pilot study, obese human subjects (Caucasian) were given 500mg berberine orally three times a day for twelve weeks. The efficacy and safety of berberine treatment was determined by measurements of body weight, comprehensive metabolic panel, blood lipid and hormone levels, expression levels of inflammatory factors, complete blood count, and electrocardiograph. A Sprague-Dawley rat experiment was also performed to identify the anti-obesity effects of berberine treatment. The results demonstrate that berberine treatment produced a mild weight loss (average 5lb/subject) in obese human subjects. But more interestingly, the treatment significantly reduced blood lipid levels (23% decrease of triglyceride and 12.2% decrease of cholesterol levels) in human subjects. The lipid-lowering effect of berberine treatment has also been replicated in the rat experiment (34.7% decrease of triglyceride and 9% decrease of cholesterol level). Cortisol, calcitriol, ACTH, TSH, FT4, and SHBG levels were not significantly changed following 12 weeks of berberine treatment. However, there was interestingly, an increase in calcitriol levels seen in all human subjects following berberine treatment (mean 59.5% increase, p=0.11). Blood inflammatory factors (CRP, IL-6, TNFalpha, COX-2) and erythrocyte sedimentation rate (ESR) were not significantly affected by treatment with berberine. Tests of hematological, cardiovascular, liver, and kidney function following berberine treatment showed no detrimental side effects to this natural compound. Collectively, this study demonstrates that berberine is a potent lipid-lowering compound with a moderate weight loss effect, and may have a possible potential role in osteoporosis treatment/prevention. Copyright 2012 Elsevier GmbH. All rights reserved.
Sanford School of Medicine, Sioux Falls Campus.
Keenan, A. H., Pedersen, T. L., Fillaus, Kristi, Larson, M. K., Shearer, Gregory C., & Newman, J. W. (2012). Basal omega-3 fatty acid status affects fatty acid and oxylipin responses to high-dose n3-HUFA in healthy volunteers. Journal of Lipid Research, 53(8), 1662-1669.
A subject’s baseline FA composition may influence the ability of dietary highly unsaturated omega-3 FAs (n3-HUFA) to change circulating profiles of esterified FAs and their oxygenated metabolites. This study evaluates the influence of basal n3-HUFA and n3-oxylipin status on the magnitude of response to n3-HUFA consumption. Blood was collected from fasting subjects (n = 30) before and after treatment (4 weeks; 11 +/- 2 mg/kg/day n3-HUFA ethyl esters). Esterified FAs were quantified in erythrocytes, platelets, and plasma by GC-MS. Esterified oxylipins were quantified in plasma by LC-MS/MS. Treatment with n3-HUFAs increased n3-HUFAs and decreased n6-HUFAs in all reservoirs and increased plasma n3-oxylipins without significantly changing n6-oxylipin concentrations. As subject basal n3-HUFAs increased, treatment-associated changes decreased, and this behavior was reflected in the percentage of 20:5n3 + 22:6n3 in red blood cell membrane FAs (i.e., the omega-3 index). To maintain an omega-3 index of 8% and thus reduce cardiovascular disease risk, our analyses suggest a maintenance dose of 7 mg/kg/day n3-HUFA ethyl esters for a 70-kg individual.(jlr) These results suggest that the basal n3 index may have clinical utility to establish efficacious therapeutic experimental feeding regimens and to evaluate the USDA Dietary Guidelines recommendations for n3-HUFA consumption.-Keenan, A. H., T. L. Pedersen, K.i Fillaus, M. K. Larson, G. C. Shearer, and J. W. Newman. Basal omega-3 fatty acid status affects fatty acid and oxylipin responses to high-dose n3-HUFA in healthy volunteers. J. Lipid Res. 2012. 53: 1662-1669.
Sanford School of Medicine, Sioux Falls Campus.
Kobayashi, Satoru, Xu, Xianmin, Chen, Kai, & Liang, Qiangrong. (2012). Suppression of autophagy is protective in high glucose-induced cardiomyocyte injury. Autophagy, 8(4), 577-592.
Hyperglycemia is linked to increased heart failure among diabetic patients. However, the mechanisms that mediate hyperglycemia-induced cardiac damage remain poorly understood. Autophagy is a cellular degradation pathway that plays important roles in cellular homeostasis. Autophagic activity is altered in the diabetic heart, but its functional role has been unclear. In this study, we determined if mimicking hyperglycemia in cultured cardiomyocytes from neonatal rats and adult mice could affect autophagic activity and myocyte viability. High glucose (17 or 30 mM) reduced autophagic flux compared with normal glucose (5.5 mM) as indicated by the difference in protein levels of LC3-II (microtubule-associated protein 1 light chain 3 form II) or the changes of punctate fluorescence patterns of GFP-LC3 and mRFP-LC3 in the absence and presence of the lysosomal inhibitor bafilomycin A 1. Unexpectedly, the inhibited autophagy turned out to be an adaptive response that functioned to limit high glucose cardiotoxicity. Indeed, suppression of autophagy by 3-methyladenine or short hairpin RNA-mediated silencing of the Becn1 or Atg7 gene attenuated high glucose-induced cardiomyocyte death. Conversely, upregulation of autophagy with rapamycin or overexpression of Becn1 or Atg7 predisposed cardiomyocytes to high glucose toxicity. Mechanistically, the high glucose-induced inhibition of autophagy was mediated at least partly by increased mTOR signaling that likely inactivated ULK1 through phosphorylation at serine 467. Together, these findings demonstrate that high glucose inhibits autophagy, which is a beneficial adaptive response that protects cardiomyocytes against high glucose toxicity. Future studies are warranted to determine if autophagy plays a similar role in diabetic heart in vivo.
Sanford School of Medicine, Sioux Falls Campus.
Kovacs, Attila D., Saje, Angelika, Wong, Andrew, Ramji, Serena, Cooper, Jonathan D., & Pearce, David A. (2012). Age-dependent therapeutic effect of memantine in a mouse model of juvenile Batten disease. Neuropharmacology, 63(5), 769-775.
Currently there is no treatment for juvenile Batten disease, a fatal childhood neurodegenerative disorder caused by mutations in the CLN3 gene. The Cln3-knockout (Cln3(Deltaex1-6)) mouse model recapitulates several features of the human disorder. Cln3(Deltaex1-6) mice, similarly to juvenile Batten disease patients, have a motor coordination deficit detectable as early as postnatal day 14. Previous studies demonstrated that acute attenuation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-type glutamate receptor activity by the non-competitive AMPA antagonist, EGIS-8332, in both 1- and 6-7-month-old Cln3(Deltaex1-6) mice results in improvement in motor coordination. Here we show that acute inhibition of N-methyl-d-aspartate (NMDA)-type glutamate receptors by memantine (1 and 5mg/kg i.p.) had no effecton the impaired motor coordination of one-month-old Cln3(Deltaex1-6) mice. At a later stage of the disease, in 6-7-month-old Cln3(Deltaex1-6) mice, memantine induced a delayed but extended (8 days) improvement of motor skills similarly to that observed previously with EGIS-8332 treatment. An age-dependent therapeutic effect of memantine implies that the pathomechanism in juvenile Batten disease changes during disease progression. In contrast to acute treatment, repeated administration of memantine or EGIS-8332 (1mg/kg, once a week for 4 weeks) to 6-month-old Cln3(Deltaex1-6) mice had no beneficial effect on motor coordination. Moreover, repeated treatments did not impact microglial activation or the survival of vulnerable neuron populations. Memantine did not affect astrocytosis in the cortex. EGIS-8332, however, decreased astrocytic activation in the somatosensory barrelfield cortex. Acute inhibition of NMDA receptors can induce a prolonged therapeutic effect, identifying NMDA receptors as a new therapeutic target for juvenile Batten disease. Copyright 2012 Elsevier Ltd. All rights reserved.
Sanford School of Medicine, Sioux Falls Campus.
Messerschmidt, Kimberly A., Johnson, Brandon R., & Khan, Malik A. (2012). Encephalopathy associated with metoclopramide use in a patient with Parkinson’s disease. American Journal of Health-System Pharmacy, 69(15), 1303-1306.
Purpose. The case of a patient with Parkinson’s disease (PD) who experienced profound encephalopathy after short-term exposure to metoclopramide is described. Summary. A 79-year-old man with PD received metoclopramide (10 mg i.v. every six hours) for stimulation of gastric motility after a colon resection; the first of three doses of the drug was administered about 30 minutes after completion of the afternoon procedure. The evening after surgery, the patient appeared to be resting comfortably without pain, although he was somewhat agitated; two more metoclopramide doses were administered during the night. Over the next several hours his mental status deteriorated, and the next morning he was found to be unresponsive and could not be aroused. Although the patient had received minimal narcotics, naloxone was administered but failed to produce an improvement in the patient’s mental status. The results of laboratory tests, computer tomography scanning, and other diagnostic studies ruled out cardiac ischemia, infectious disease, and other potential causes of the abrupt change in mental status. Within eight days of the discontinuation of metoclopramide use, the patient gradually returned to his baseline mental status. The application of the algorithm of Naranjo et al. in this case indicated a possible adverse reaction to metoclopramide as the cause of acute metabolic encephalopathy, with the patient’s underlying PD and PD-related dementia suspected to have been contributing factors. Conclusion. A 79-year-old man with long-term PD developed acute encephalopathy after the administration of i.v. metoclopramide.
Sanford School of Medicine, Sioux Falls Campus.
Nie, J., Sun, C., Faruque, O., Ye, G. M., Li, J., Liang, Qiangrong, et al. (2012). Synapses of Amphids Defective (SAD-A) Kinase Promotes Glucose-stimulated Insulin Secretion through Activation of p21-activated Kinase (PAK1) in Pancreatic beta-Cells. Journal of Biological Chemistry, 287(31), 26435-26444.
The p21-activated kinase-1 (PAK1) is implicated in regulation of insulin exocytosis as an effector of Rho GTPases. PAK1 is activated by the onset of glucose-stimulated insulin secretion (GSIS) through phosphorylation of Thr-423, a major activation site by Cdc42 and Rac1. However, the kinase(s) that phosphorylates PAK1 at Thr-423 in islet beta-cells remains elusive. The present studies identified SAD-A (synapses of amphids defective), a member of AMP-activated protein kinase-related kinases exclusively expressed in brain and pancreas, as a key regulator of GSIS through activation of PAK1. We show that SAD-A directly binds to PAK1 through its kinase domain. The interaction is mediated by the p21-binding domain (PBD) of PAK1 and requires both kinases in an active conformation. The binding leads to direct phosphorylation of PAK1 at Thr-423 by SAD-A, triggering the onset of GSIS from islet beta-cells. Consequently, ablation of PAK1 kinase activity or depletion of PAK1 expression completely abolishes the potentiating effect of SAD-A on GSIS. Consistent with its role in regulating GSIS, overexpression of SAD-A in MIN6 islet beta-cells significantly stimulated cytoskeletal remodeling, which is required for insulin exocytosis. Together, the present studies identified a critical role of SAD-A in the activation of PAK1 during the onset of insulin exocytosis.
Sanford School of Medicine, Sioux Falls Campus.
Pottala, James V., Espeland, Mark A., Polreis, Jason, Robinson, Jennifer, & Harris, William S. (2012). Correcting the Effects of -20°C Storage and Aliquot Size on Erythrocyte Fatty Acid Content in the Women’s Health Initiative. Lipids, 47(9), 835-846.
Red blood cell (RBC) fatty acid (FA) patterns have been shown to predict risk for cardiovascular and other chronic diseases. As part of a project analyzing RBC samples from the Women’s Health Initiative Memory Study (WHIMS) we observed implausibly low levels of highly unsaturated fatty acids (HUFA) suggestive of degradation. This was hypothesized to be due to short term storage (<1month) at -20°C during sample aliquoting. The purpose of this study was to measure the extent of degradation that occurs under these conditions, and then to use regression calibration equations with multiple imputations to correct the biases. Samples from the Women’s Health Initiative that had always been stored at -80°C were obtained and subjected to similar conditions as the WHIMS samples. General linear mixed models were used to develop bias-corrected calibration equations for each fatty acid. Sample degradation occurred at -20°C with the average HUFA loss of 3.5 to 5.9% per week depending on aliquot size (250 and 80L, respectively). Using the ratio of HUFA to saturated fatty acids (HUFA/SAT) as a marker of degradation, this bias-correction method raised the HUFA/SAT from 0.70 to 0.81, which was similar to that (0.78) seen in another large study with optimal processing. In summary, RBC samples should always be stored at -80°C. The FA compositions of the degraded RBC samples from WHIMS were rehabilitated by application of regression calibration equations and multiple imputations, and these imputed datasets should be used in all future WHIMS studies.
Sanford School of Medicine, Sioux Falls Campus.
Bright, Larry K., & Mahdi, Ghada S. (2012). U.S./ Arab Reflections on Our Tolerance for Ambiguity. Adult Learning, 23(2), 86-89.
The article focuses on the acceptance for ambiguity that should be increased in order to reduce the agonies of prejudice. It states that increasing knowledge and educating people is the only way in which one can resolve prejudice. A poem related to the acceptance for ambiguity which can help people to learn important skills on ambiguity tolerance is also presented.
School of Education.
Burton, D., & Gillham, Andy. (2012). Exploring the Potential of Assessment Efficacy in Sports Coaching: A Commentary. International Journal of Sports Science & Coaching, 7(2), 207-210.

School of Education.
Hulac, David M., Dejong, Kayla, & Benson, Nicholas. (2012). Can students run their own interventions?: A selfadministered math fluency intervention. Psychology in the Schools, 49(6), 526-538.
Manipulating the ratio of known to unknown items has been shown to improve student ontask behavior and increase the desirability of schoolwork. Although many intervention protocols manipulate ratios of known to unknown items, these frequently require extensive adult cuing. School psychologists recommending such interventions may face resistance from teachers who find the work to be too time intensive. Selfadministered interventions whereby the students act as primary interventionists may alleviate this concern. A modified multiple baseline design across a group of 11 students identified by their teachers as having difficulty mastering multiplication facts was used to evaluate a selfadministered foldingin technique. As hypothesized, for the overall sample, stronger effects were observed on math curriculumbased measures (CBM) than on a control reading task (Maze CBM). Individually, 7 of the 11 students demonstrated higher levels of growth during the intervention phase than during the baseline phase. No student demonstrated higher Maze CBM growth rates during the intervention phase relative to the baseline phase. In contrast, of the 4 students for whom a link between the intervention and the baseline could not be established, 3 demonstrated higher levels of performance on math CBMs following the intervention phase. Results are discussed in light of a responsetointervention model. (PsycINFO Database Record (c) 2012 APA, all rights reserved) (journal abstract)
School of Education.
Matthew, James, & Karen, Card. (2012). Factors contributing to institutions achieving environmental sustainability. International Journal of Sustainability in Higher Education, 13(2), 166-176.
Purpose – The purpose of this paper is to determine what factors contributed to three universities achieving environmental sustainability. Design/methodology/approach – A case study methodology was used to determine how each factor contributed to the institutions’ sustainability. Site visits, fieldwork, document reviews, and interviews with administration, faculty, staff, and students from the participating institutions were employed as primary data collection strategies. Findings – The six factors identified in the literature as contributing to environmental sustainability were present at all three institutions: green campus operation measures; campus administration, organization, and leadership; teaching, research, and service; campus-wide actions and activities; institutional assessment of campus sustainability measures; and established methods for overcoming barriers. Research limitations/implications – This study was delimited to the six factors that were identified in the literature and the three institutions that participated in this study. The research will add to the literature on creating sustainable campuses and will also provide a foundation for further study on the progress and impact of campus sustainability efforts. Originality/value – A number of individual case studies have described what certain institutions have done. A smaller number of case studies have identified what factors have contributed to certain institutions’ achieved environmental sustainability.

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