Posted by: kelsijo97 | January 25, 2012

December 2011

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


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