Posted by: kelsijo97 | January 24, 2014

December 2013

Bhuiyan, Md Shenuarin, J. Scott Pattison, Hanna Osinska, Jeanne James, James Gulick, Patrick M. McLendon, . . . Jeffrey Robbins. (2013). Enhanced autophagy ameliorates cardiac proteinopathy. Journal of Clinical Investigation, 123(12), 5284-5297.
Basal autophagy is a crucial mechanism in cellular homeostasis, underlying both normal cellular recycling and the clearance of damaged or misfolded proteins, organelles and aggregates. We showed here that enhanced levels of autophagy induced by either autophagic gene overexpression or voluntary exercise ameliorated desmin-related cardiomyopathy (DRC). To increase levels of basal autophagy, we generated an inducible Tg mouse expressing autophagy-related 7 (Atg7), a critical and rate-limiting autophagy protein. Hearts from these mice had enhanced autophagy, but normal morphology and function. We crossed these mice with CryABR120G mice, a model of DRC in which autophagy is significantly attenuated in the heart, to test the functional significance of autophagy activation in a proteotoxic model of heart failure. Sustained Atg7-induced autophagy in the CryABR120G hearts decreased interstitial fibrosis, ameliorated ventricular dysfunction, decreased cardiac hypertrophy, reduced intracellular aggregates and prolonged survival. To determine whether different methods of autophagy upregulation have additive or even synergistic benefits, we subjected the autophagy-deficient CryAB mice and the Atg7-crossed CryABR120G mice to voluntary exercise, which also upregulates autophagy. The entire exercised Atg7-crossed CryABR120G cohort survived to 7 months. These findings suggest that activating autophagy may be a viable therapeutic strategy for improving cardiac performance under proteotoxic conditions.
Basic Biomedical Sciences, Vermillion Campus.
Li, Shuai, Xuejun Wang, Yifan Li, Curtis K. Kost, Jr., & Douglas S. Martin. (2013). Bortezomib, a Proteasome Inhibitor, Attenuates Angiotensin II-Induced Hypertension and Aortic Remodeling in Rats. PloS one, 8(10), e78564.
BACKGROUND: Hypertension is a highly prevalent disorder and a major risk factor for cardiovascular diseases. Hypertensive vascular remodeling is the pathological mal-adaption of blood vessels to the hypertensive condition that contributes to further development of high blood pressure and end-organ damage. Hypertensive remodeling involves, at least in part, changes in protein turnover. The ubiquitin proteasome system (UPS) is a major protein quality and quantity control system. This study tested the hypothesis that the proteasome inhibitor, bortezomib, would attenuate AngII-induced hypertension and its sequelae such as aortic remodeling in rats.; METHODOLOGY/PRINCIPAL FINDINGS: Male Sprague Dawley rats were subjected to AngII infusion for two weeks in the absence or presence of bortezomib. Mean arterial pressure was measured in conscious rats. Aortic tissue was collected for estimation of wall area, collagen deposition and expression of tissue inhibitors of matrix metalloproteases (TIMP), Ki67 (a marker of proliferation), reactive oxygen species (ROS) and VCAM-1 (a marker of inflammation). AngII infusion increased arterial pressure significantly (1604 mmHg vs. vehicle treatment 1332 mmHg). This hypertensive response was attenuated by bortezomib (1385 mmHg). AngII hypertension was associated with significant increases in aortic wall to lumen ratio (29%), collagen deposition (14%) and expression of TIMP1 and TIMP2. AngII also increased MMP2 activity, proteasomal chymotrypsin-like activity, Ki67 staining, ROS generation and VCAM-1 immunoreactivity. Co-treatment of AngII-infused rats with bortezomib attenuated these AngII-induced responses.; CONCLUSIONS: Collectively, these data support the idea that proteasome activity contributes to AngII-induced hypertension and hypertensive aortic vascular remodeling at least in part by modulating TIMP1/2 and MMP2 function. Preliminary observations are consistent with a role for ROS, inflammatory and proliferative mechanisms in this effect. Further understanding of the mechanisms by which the proteasome is involved in hypertension and vascular structural remodeling may reveal novel targets for pharmacological treatment of hypertension, hypertensive remodeling or both.
Basic Biomedical Sciences, Vermillion Campus.
Morgan, Jeremy P., Helen Magee, Andrew Wong, Tarah Nelson, Bettina Koch, Jonathan D. Cooper, & Jill M. Weimer. (2013). A murine model of variant late infantile ceroid lipofuscinosis recapitulates behavioral and pathological phenotypes of human disease. PloS one, 8(11), e78694.
Neuronal ceroid lipofuscinoses (NCLs; also known collectively as Batten Disease) are a family of autosomal recessive lysosomal storage disorders. Mutations in as many as 13 genes give rise to 10 variants of NCL, all with overlapping clinical symptomatology including visual impairment, motor and cognitive dysfunction, seizures, and premature death. Mutations in CLN6 result in both a variant late infantile onset neuronal ceroid lipofuscinosis (vLINCL) as well as an adult-onset form of the disease called Type A Kufs. CLN6 is a non-glycosylated membrane protein of unknown function localized to the endoplasmic reticulum (ER). In this study, we perform a detailed characterization of a naturally occurring Cln6 mutant (Cln6(nclf)) mouse line to validate its utility for translational research. We demonstrate that this Cln6(nclf) mutation leads to deficits in motor coordination, vision, memory, and learning. Pathologically, we demonstrate loss of neurons within specific subregions and lamina of the cortex that correlate to behavioral phenotypes. As in other NCL models, this model displays selective loss of GABAergic interneuron sub-populations in the cortex and the hippocampus with profound, early-onset glial activation. Finally, we demonstrate a novel deficit in memory and learning, including a dramatic reduction in dendritic spine density in the cerebral cortex, which suggests a reduction in synaptic strength following disruption in CLN6. Together, these findings highlight the behavioral and pathological similarities between the Cln6(nclf) mouse model and human NCL patients, validating this model as a reliable format for screening potential therapeutics.
Basic Biomedical Sciences, Vermillion Campus.
Blanchard, D. Caroline, Cliff H. Summers, & Robert J. Blanchard. (2013). The role of behavior in translational models for psychopathology: Functionality and dysfunctional behaviors. Neuroscience and Biobehavioral Reviews, 37(8), 1567-1577.
The history of science has frequently included a problem-based impetus toward research that can be translated expeditiously into solutions. A current problem is that psychopathologies, typically chronic, contribute hugely to the economic and social burden of medical care, especially in the United States. For behavioral neuroscientists a psychopathology-aimed translational research emphasis particularly involves animal models to facilitate the experimental and invasive work necessary to an understanding of the biology of normal and aberrant behavior. When the etiology of a particular psychopathology is unknown, and there are no specific biomarkers, behavioral parallels between the focal disorder and its putative models become crucial elements in assessing model validity. Evaluation of these parallels is frequently neglected, reflecting in part the lack of a systematic conceptualization of the organization of behavior and how this may be conserved across species. Recent work specifically attempting to bridge this gap suggests that analysis of behaviors that are functional—adaptive in crucial situations such as danger or social contexts—can facilitate an understanding of the parallels between behaviors of human and nonhuman species, including the dysfunctional behaviors of psycho pathologies. As research with animal models comes to provide a more systematic analysis of particular behaviors and their adaptive functions, cross-talk between model and focal psychopathology may be advantageous to understanding both. (PsycINFO Database Record (c) 2013 APA, all rights reserved) (journal abstract)
Biology Department.
Feller, K. D., T. W. Cronin, S. T. Ahyong, & Megan L. Porter. (2013). Morphological and molecular description of the late-stage larvae of Alima Leach, 1817 (Crustacea: Stomatopoda) from Lizard Island, Australia. Zootaxa, 3722(1), 22-32.
Alima pacifica and A. orientalis are stomatopods commonly found at Lizard Island, Great Barrier Reef, Australia. There are currently no descriptions that link the larvae to the adult morphotype despite the frequent occurrence of the last larval stage of these two species. We used DNA barcoding of the cytochrome oxidase I (COI) gene to link the last stage larvae of A. pacifica and A. orientalis to the respective adult morphotype. Detailed morphological descriptions of the late larva of each species are provided and compared to other described last- stage Alima larvae. These data support previous studies that suggest paraphyly of the genus Alima.
Biology Department.
Kats, Lee B., Gary Bucciarelli, Thomas L. Vandergon, ….., Jacob L. Kerby, & Robert N. Fisher. (2013). Effects of natural flooding and manual trapping on the facilitation of invasive crayfish-native amphibian coexistence in a semi-arid perennial stream. Journal of Arid Environments, 98, 109-112.
Abstract: Aquatic amphibians are known to be vulnerable to a myriad of invasive predators. Invasive crayfish are thought to have eliminated native populations of amphibians in some streams in the semi-arid Santa Monica Mountains of southern California. Despite their toxic skin secretions that defend them from native predators, newts are vulnerable to crayfish attacks, and crayfish have been observed attacking adult newts, and eating newt egg masses and larvae. For 15 years, we have observed invasive crayfish and native California newts coexisting in one stream in the Santa Monica Mountains. During that period, we monitored the densities of both crayfish and newt egg mass densities and compared these to annual rainfall totals. After three seasons of below average rainfall, we reduced crayfish numbers by manual trapping. Our long-term data indicated that crayfish did not fare well in years when rainfall is above the historic average. This invasive predator did not evolve with high velocity streams, and observations indicated that southern California storm events washed crayfish downstream, killing many of them. Newts exhibit increased reproduction in years when crayfish numbers were reduced. A comparison with a nearby stream that does not contain crayfish indicated that newt reproduction positively responded to increased rainfall, but that fluctuations were much greater in the stream that contains crayfish. We suggest that rainfall patterns help explain invasive crayfish/newt coexistence and that management for future coexistence may benefit from manual trapping.
Biology Department.
Siler, Cameron D., T. Alex Dececchi, Chris L. Merkord, Drew R. Davis, Tony J. Christiani, & Rafe M. Brown. (2014). Cryptic diversity and population genetic structure in the rare, endemic, forest-obligate, slender geckos of the Philippines. Molecular Phylogenetics & Evolution, 70, 204-209.
Abstract: Recent studies of forest lizards in Southeast Asia have highlighted spectacular morphological and cryptic genetic diversity in several poorly known clades. Unfortunately, many of the included species have microhabitat preferences for forested environments, and therefore they are threatened by extensive forest destruction throughout the region. This is particularly true in the Philippines, an archipelago with a strikingly high proportion (84%) of endemic geckos. Abundances inferred from historical museum collections suggests that we are in a critical period where apparent declines in population viability and species’ abundance have taken place faster than the growth in our understanding of alpha diversity. This phenomenon is exemplified in the exceedingly rare Philippine slender forest geckos of the genus Pseudogekko. Most of the known species are rarely encountered by field biologists, and species boundaries are unclear; this poor state of knowledge impedes effective conservation measures. Using the first multilocus phylogeny for these taxa, and phylogenetic and population genetic approaches, we elucidate evolutionary lineages and delimit species-level conservation targets in this unique radiation of endemic Philippine geckos. The results support the presence of widespread cryptic diversity in the genus, providing a framework for the re-evaluation of conservation priorities aimed at protecting these rare, forest-obligate species.
Biology Department.
Lamichhane, Sujan, Susan Lancaster, Eagappanath Thiruppathi, & Gopinath Mani. (2013). Interaction of endothelial and smooth muscle cells with cobalt-chromium alloy surfaces coated with Paclitaxel deposited self-assembled monolayers. Langmuir : the ACS journal of surfaces and colloids, 29(46), 14254-14264.
The use of self-assembled monolayers (SAMs) as a polymer-free platform to deliver an antiproliferative drug, paclitaxel (PAT), from a stent material cobalt-chromium (CoCr) alloy has been previously demonstrated. In this study, the interaction of human aortic endothelial cells (ECs) and human aortic smooth muscle cells (SMCs) with CoCr alloy surfaces coated with SAMs- (SAMs-CoCr) and PAT-deposited SAMs (PAT-SAMs-CoCr) was investigated. A polished CoCr with no coatings was used as a control. The viability, proliferation, morphology, and phenotype of ECs and SMCs were investigated on these samples. SAMs-CoCr significantly enhanced the growth of ECs. Also, the ECs were well spreading with its typical morphological features and showed stronger PECAM-1 expression on SAMs-CoCr. This showed that the SAMs-CoCr surface is conducive to endothelialization. For PAT-SAMs-CoCr, although the adhesion of ECs was lower, the cells continued to proliferate with some degree of spreading and limited PECAM-1 expression. For SMCs, a significant decrease in the cell proliferation was observed on SAMs-CoCr when compared with that of Control-CoCr. PAT-SAMs-CoCr showed maximum inhibitory effect on the proliferation of SMCs. Also, the SMCs on PAT-SAMs-CoCr displayed a poorly spread discoid morphology with disarranged alpha-actin filaments. This showed that the PAT released from the SAMs platform successfully inhibited the growth of SMCs. Thus, this study showed the interaction of ECs and SMCs with SAMs-CoCr and PAT-SAMs-CoCr for potential uses in stents and other cardiovascular medical devices.
Biomedical Engineering, Sioux Falls Campus.
Bao, Ying, H. Fong, & Chaoyang Jiang. (2013). Manipulating the Collective Surface Plasmon Resonances of Aligned Gold Nanorods in Electrospun Composite Nanofibers. Journal of Physical Chemistry C, 117(41), 21490-21497.
Surface plasmon resonance (SPR) is an interesting optical property that has been intensively studied in recent years. Herein, we report that the SPRs of gold nanorods (Au NRs) embedded in electrospun poly(vinyl alcohol) nanofibrous films can be manipulated via several approaches such as the change of Au NR percentage in the composite nanofibers, swelling-induced refractive index decrease of local environment, and swelling-induced increase of inter-rod distances among the embedded Au NRs. The electrospun composite nanofibrous films exhibit excellent sensing ability to the swelling solvents with short responsible time and remarkable reversibility. This study advances the fundamental understandings of plasmonic properties for electrospun composite nanofibrous films; thus, it can benefit the novel design of smart nanomaterials for broad sensing and nanophotonic applications.
Chemistry Department.
Chen, Jiangchao, Andrew Schmitz, T. Inerbaev, Q. G. Meng, S. Kilina, S. Tretiak, & Dmitri S. Kilin. (2013). First-Principles Study of p-n-Doped Silicon Quantum Dots: Charge Transfer, Energy Dissipation, and Time-Resolved Emission. Journal of Physical Chemistry Letters, 4(17), 2906-2913.
Electron-phonon coupling controls nonradiative relaxation dynamics of the photoexcited electron-hole pair in semiconductor nanostructures. Here the optoelectronic properties for Al- and P-codoped silicon quantum dots (QDs) are calculated by combining time-dependent density matrix methodology and ab initio electronic structure methods. The energy-band landscape of the codoped Si QD is elucidated via time evolution of population density distributions in energy and in coordinate space. Multiple nonradiative relaxation pathways result in a specific charge-separated state, where a hole and an electron are localized on Al and P dopants, respectively. Analysis of the simulated nonradiative decay shows that high-energy photoexcitation relaxes to the band gap edge within 10 ps, forming the final charge-transfer state. We also simulate time-resolved emission spectra of the codoped Si QD that reveals optical and IR emissions below the optical band gap. These emission features are attributed to the intraband transitions introduced by doping.
Chemistry Department.
Hanson, Elizabeth K., David R. Beukelman, & Kathryn M. Yorkston. (2013). Communication Support through Multimodal Supplementation:A Scoping Review. Augmentative and alternative communication (Baltimore, Md. : 1985), 29(4), 310-321.
Abstract Speech supplementation strategies improve spoken communication for people with motor speech disorders who experience reduced speech intelligibility. The purpose of this review was to summarize the literature on traditional supplementation strategies (e.g., alphabet supplementation, topic supplementation, and gestural supplementation) and to expand the definition of speech supplementation to include additional modalities, such as augmenting speech with pictures via mobile technology, and conversation management strategies. Results showed that studies of traditional supplementation consistently reported positive outcomes, including increased intelligibility, decreased speech rate, and positive attitudes toward speakers. New modalities, such as supplementing speech through digital photos, may come to be integrated with traditional approaches, given the proliferation of digital photography and mobile tablet technologies. In addition, new research is exploring the role of communication partners in dyads where one speaker has dysarthria, as well as strategies that communication partners employ to understand dysarthric speech.
Communication Disorders Department.
Struckman-Johnson, David, Cindy Struckman-Johnson, Justin D. Kruse, Pamela M. Gross, & Brady J. Sumners. (2013). A Pre-PREA Survey of Inmate and Correctional Staff Opinions on How to Prevent Prison Sexual Assault. Prison Journal, 93(4), 429-452.
This study is a content analysis of inmate and staff free responses to a question about good ways to prevent prison sexual assault. Data from 1,094 inmates and 373 correctional staff were abstracted from a 1998 survey of Midwestern prisons. A total of 2,689 distinctive ideas ( 1,830 from inmates and 859 from staff) were distributed across 12 prevention categories. Inmates’ top solutions were classification of inmates and increased sexual outlets. Staff s top choices were increasing security and hiring more and better staff. Similarities and disparities in inmate and staff solutions are discussed in light of Prison Rape Elimination Act-based policies.
Computer Science Department.
Psychology Department.
Sweeney, Mark R., & J. A. Mason. (2013). Mechanisms of dust emission from Pleistocene loess deposits, Nebraska, USA. Journal of Geophysical Research-Earth Surface, 118(3), 1460-1471.
Saltation bombardment is commonly believed to be the primary mechanism by which large quantities of dust can be generated. Direct entrainment of silt, on the other hand, is thought to generate minimal quantities of dust. If so, loess landscapes should rarely be major sources of dust unless disturbed by human activity. To test the mechanisms by which loess can be eroded by the wind, we used the Portable In-Situ Wind Erosion Lab (PI-SWERL). PI-SWERL tests were conducted on benches that were carved into loess at field locations. Coarse to fine loess was also collected and tested in a controlled setting using (1) dry, unconsolidated loess and (2) crusted loess. Results indicate that in most cases, the threshold friction velocity for silt is less than that for sand and that most dust generation occurs by direct entrainment of dust. Saltation, even in coarse loess, was nonexistent to intermittent. In a few cases, saltation of sand or soil aggregates preceded dust generation or enhanced emissions after direct entrainment began. Emission fluxes of loess are potentially high in both proximal and distal settings, suggesting that loess is easily entrainable if vegetation density is low. We hypothesize that an arid and windy climate of the late Pleistocene, paired with lower vegetation density, facilitated large-scale erosion of Peoria Loess in Nebraska to generate wind-aligned ridges and troughs. More broadly, our results indicate that loess landscapes have the potential to be major sources as well as sinks of dust.
Earth Sciences Department.
Aguirre, Pablo, José D. Flores, & Eduardo González-Olivares. (2014). Bifurcations and global dynamics in a predator–prey model with a strong Allee effect on the prey, and a ratio-dependent functional response. Nonlinear Analysis: Real World Applications, 16, 235-249.
Abstract: We extend a previous study of a predator–prey model with strong Allee effect on the prey in which the functional response is a function of the ratio of prey to predator. We prove that the solutions are always bounded and non-negative, and that the species can always tend to long-term extinction. By means of bifurcation analysis and advanced numerical techniques for the computation of invariant manifolds of equilibria, we explain the consequences of the (dis)appearance of limit cycles, homoclinic orbits, and heteroclinic connections in the global arrangement of the phase plane near a Bogdanov–Takens bifurcation. In particular, we find that the Allee threshold in the two-dimensional system is given as the boundary of the basin of attraction of an attracting positive equilibrium, and determine conditions for the mutual extinction or survival of the populations.
Mathematics Department.
Georgescu, Catalin, & Gabriel Picioroaga. (2014). FUGLEDE-KADISON DETERMINANTS FOR OPERATORS IN THE VON NEUMANN ALGEBRA OF AN EQUIVALENCE RELATION. Proceedings of the American Mathematical Society, 142(1), 173-180.
We calculate the Fuglede-Kadison determinant for operators of the form Sigma(n)(i=1) MfiLgi, where L-gi are unitaries or partial isometries coming from Borel (partial) isomorphisms g(i) on a probability space which generate an ergodic equivalence relation and where M-fi are multiplication operators. We obtain formulas for the cases when the relation is treeable or the f(i)’s and g(i)’s satisfy some restrictions.
Mathematics Department.
Leviner, L. E., C. E. Aalseth, M. W. Ahmed, F. T. Avignone, ….., & D. M. Mei. (2014). A segmented, enriched N-type germanium detector for neutrinoless double beta-decay experiments. Nuclear Instruments & Methods in Physics Research Section A, 735, 66-77.
Abstract: We present data characterizing the performance of the first segmented, N-type Ge detector, isotopically enriched to 85% 76Ge. This detector, based on the Ortec PT6×2 design and referred to as SEGA (Segmented, Enriched Germanium Assembly), was developed as a possible prototype for neutrinoless double beta-decay measurements by the Majorana collaboration. We present some of the general characteristics (including bias potential, efficiency, leakage current, and integral cross-talk) for this detector in its temporary cryostat. We also present an analysis of the resolution of the detector, and demonstrate that for all but two segments there is at least one channel that reaches the Majorana resolution goal below 4keV FWHM at 2039keV, and all channels are below 4.5keV FWHM.
Physics Department.
Wang, Guojian, X. F. Long, L. Z. Zhang, Z. B. Lin, & G. F. Wang. (2013). Growth and spectral properties of Nd3+:Ba2LiNb5O15 crystal. Optical Materials, 35(12), 2703-2706.
Nd3+ doped Ba2LiNb5O15 single crystals with dimension Phi 10 x 30 mm(3) were grown by the Czochralski technique. The refractive indexes were measured. The polarized absorption spectra, polarized fluorescence spectra and fluorescence decay curve were measured at 300 K and the spectral parameters were calculated according to Judd-Ofelt theory. These results indicate that Nd3+:Ba2LiNb5O15 crystal can be regarded as a laser crystal. (C) 2013 Elsevier B.V. All rights reserved.
Physics Department.
Zhang, C., D. M. Mei, P. Davis, B. Woltman, & F. Gray. (2013). Measuring fast neutrons with large liquid scintillation detector for ultra-low background experiments. Nuclear Instruments & Methods in Physics Research Section a-Accelerators Spectrometers Detectors and Associated Equipment, 729, 138-146.
We developed a 12-liter volume neutron detector filled with the liquid scintillator EJ301 that measures neutrons in an underground laboratory where dark matter and neutrino experiments are located. The detector target is a cylindrical volume coated on the inside with reflective paint (95% reflectivity) that significantly increases the detector’s light collection. We demonstrate several calibration techniques using point sources and cosmic-ray muons for energies up to 20 MeV for this large liquid scintillation detector. Neutron-gamma separation using pulse shape discrimination with a few MeV neutrons to hundreds of MeV neutrons is shown for the first time using a large liquid scintillator. Published by Elsevier B.V.
Physics Department.
Contractor, Ateka A., Jon D. Elhai, Kendra C. Ractliffe, & David Forbes. (2013). PTSD’s underlying symptom dimensions and relations with behavioral inhibition and activation. Journal of Anxiety Disorders, 27(7), 645-651.
Highlights: [•] We examined the relation between PTSD factors and BIS/BAS dimensions in a primary care sample. [•] PTSD’s avoidance and dysphoria factor had a significantly greater association with BIS compared to BAS. [•] PTSD’s re-experiencing factor related more to BIS than BAS. [•] PTSD’s avoidance significantly mediated the relation between BIS/BAS and PTSD’s dysphoria.
Psychology Department.
Callahan, Leah B., Kristi E. Tschetter, & Patrick J. Ronan. (2013). Inhibition of corticotropin releasing factor expression in the central nucleus of the amygdala attenuates stress-induced behavioral and endocrine responses. Frontiers in neuroscience, 7, 195.
Corticotropin releasing factor (CRF) is a primary mediator of endocrine, autonomic and behavioral stress responses. Studies in both humans and animal models have implicated CRF in a wide-variety of psychiatric conditions including anxiety disorders such as post-traumatic stress disorder (PTSD), depression, sleep disorders and addiction among others. The central nucleus of the amygdala (CeA), a key limbic structure with one of the highest concentrations of CRF-producing cells outside of the hypothalamus, has been implicated in anxiety-like behavior and a number of stress-induced disorders. This study investigated the specific role of CRF in the CeA on both endocrine and behavioral responses to stress. We used RNA Interference (RNAi) techniques to locally and specifically knockdown CRF expression in CeA. Behavior was assessed using the elevated plus maze (EPM) and open field test (OF). Knocking down CRF expression in the CeA had no significant effect on measures of anxiety-like behavior in these tests. However, it did have an effect on grooming behavior, a CRF-induced behavior. Prior exposure to a stressor sensitized an amygdalar CRF effect on stress-induced HPA activation. In these stress-challenged animals silencing CRF in the CeA significantly attenuated corticosterone responses to a subsequent behavioral stressor. Thus, it appears that while CRF projecting from the CeA does not play a significant role in the expression stress-induced anxiety-like behaviors on the EPM and OF it does play a critical role in stress-induced HPA activation.
Sanford School of Medicine, Sioux Falls Campus.
Dey, Nandini, B. Young, M. Abramovitz, M. Bouzyk, B. Barwick, Pradip De, & Brian Leyland-Jones. (2013). Differential Activation of Wnt-beta-Catenin Pathway in Triple Negative Breast Cancer Increases MMP7 in a PTEN Dependent Manner. Plos One, 8(10).
Mutations of genes in tumor cells of Triple Negative subset of Breast Cancer (TNBC) deregulate pathways of signal transduction. The loss of tumor suppressor gene PTEN is the most common first event associated with basal-like subtype (Martins, De, Almendro, Gonen, and Park, 2012). Here we report for the first time that the functional upregulation of secreted-MMP7, a transcriptional target of Wnt-beta-catenin signature pathway in TNBC is associated to the loss of PTEN. We identified differential expression of mRNAs in several key-components genes, and transcriptional target genes of the Wnt-beta-catenin pathway (WP), including beta-catenin, FZD7, DVL1, MMP7, c-MYC, BIRC5, CD44, PPARD, c-MET, and NOTCH1 in FFPE tumors samples from TNBC patients of two independent cohorts. A similar differential upregulation of mRNA/protein for beta-catenin, the functional readout of WP, and for MMP7, a transcriptional target gene of beta-catenin was observed in TNBC cell line models. Genetic or pharmacological attenuation of beta-catenin by SiRNA or WP modulators (XAV939 and sulindac sulfide) and pharmacological mimicking of PTEN following LY294002 treatment downregulated MMP7 levels as well as enzymatic function of the secreted MMP7 in MMP7 positive PTEN-null TNBC cells. Patient data revealed that MMP7 mRNA was high in only a subpopulation of TNBC, and this subpopulation was characterized by a concurrent low expression of PTEN mRNA. In cell lines, a high expression of casein-zymograph-positive MMP7 was distinguished by an absence of functional PTEN. A similar inverse relationship between MMP7 and PTEN mRNA levels was observed in the PAM50 data set (a correlation coefficient of -0.54). The PAM50 subtype and outcome data revealed that the high MMP7 group had low pCR (25%) and High Rd (74%) in clinical stage T3 pathologic response in contrast to the high pCR (40%) and low residual disease (RD) (60%) of the low MMP7 group.
Sanford School of Medicine, Sioux Falls Campus.
Grenon, S. M., M. S. Conte, E. Nosova, H. Alley, K. Chong, William S. Harris, . . . C. D. Owens. (2013). Association between n-3 polyunsaturated fatty acid content of red blood cells and inflammatory biomarkers in patients with peripheral artery disease. Journal of Vascular Surgery, 58(5), 1283-1290.
Objective: The n-3 polyunsaturated fatty acids are dietary components derived from fish oil with beneficial cardiovascular effects that may relate in part to anti-inflammatory properties. Peripheral artery disease (PAD) is characterized by a marked proinflammatory state. We hypothesized that the n-3 polyunsaturated fatty acids content of red blood cells (omega-3 index) would be correlated with biomarkers of inflammation and vascular function in a PAD cohort. Methods: This was a cross-sectional study of subjects who presented to an outpatient vascular surgery clinic for evaluation of PAD. We used linear regression to evaluate the independent association between the omega-3 index, inflammatory biomarkers (C-reactive protein [CRP], intercellular adhesion molecule-1, interleukin-6, and tumor-necrosis-factor-alpha) and endothelial function (brachial artery flow mediated dilation). Results: 64 subjects (61 claudicants and three with critical limb ischemia) were recruited for the study. The mean CRP level was 5.0 +/- 5.0 mg/L, and the mean omega-3 index was 5.0% +/- 1.8%. In an unadjusted model, the omega- 3 index was negatively associated with CRP (38% increase in CRP for one standard deviation decrease in the omega-3 index; P = .007), which remained significant after adjustment for age, body mass index, smoking, ankle-brachial index, and high-density lipoprotein (33%; P = .04). There was also evidence for independent associations between the omega-3 index and IL-6 (P = .001). There were no significant associations between the omega-3 index and vascular function tests. Conclusions: In a cohort of patients with PAD, the omega- 3 index was inversely associated with biomarkers of inflammation even after adjustment for covariates including the ankle-brachial index. Because patients with PAD have a high inflammatory burden, further studies should be conducted to determine if manipulation of omega-3 index via dietary changes or fish oil supplementation could improve inflammation and symptoms in these patients.
Sanford School of Medicine, Sioux Falls Campus.
Harris, William S., Thomas D. Dayspring, & Terrance J. Moran. (2013). Omega-3 fatty acids and cardiovascular disease: new developments and applications. Postgraduate medicine, 125(6), 100-113.
The omega-3 fatty acids (FA) found in fish oils, eicosapentaenoic and docosahexaenoic acids (EPA and DHA, respectively), have been extensively studied therapeutically in a wide variety of disease conditions, but in none more than cardiovascular disease (CVD). Our review summarizes mechanisms of action, recent meta-analyses of CVD outcome trials, sources (fish and supplements), and recommendations for use of omega-3 FA in clinical practice. With the ability to now measure the omega-3 FA biostatus through blood tests, patients can achieve cardioprotective levels by either taking fish oil supplements or simply eating more oily fish. Two omega-3 FA formulations (both in the ethyl ester form) have been approved by the US Food and Drug Administration (FDA) for the treatment of patients with very high triglyceride levels (> 500 mg/dL); one contains both EPA and DHA, whereas the other contains only EPA. The agents have been extensively tested in 2 patient populations, those with very high triglycerides and those with triglycerides between 200 and 500 mg/dL while on background statin therapy. In general, treatment with EPA+DHA appears to lower patient triglycerides more effectively, but in those patients with very high triglyceride levels, use of EPA+DHA also raised low-density lipoprotein cholesterol levels, whereas EPA alone did not. Both formulations, at doses that do not lower triglycerides, have been shown to reduce CVD events in some, but not all, studies. Given the favorable risk-to-benefit ratio for these essentially nutritional agents, use is expected to continue to expand.
Sanford School of Medicine, Sioux Falls Campus.
Irvine, E., & Casey Williams. (2013). Treatment-, Patient-, and Disease-Related Factors and the Emergence of Adverse Events with Tyrosine Kinase Inhibitors for the Treatment of Chronic Myeloid Leukemia. Pharmacotherapy, 33(8), 868-881.
Four breakpoint cluster region (BCR)-ABL1 tyrosine kinase inhibitors ( s) are currently available for the treatment of chronic myeloid leukemia (CML): imatinib, nilotinib, dasatinib, and bosutinib. Choosing the most appropriate requires clinicians to consider a host of patient-, disease-, and treatment-related factors, not the least of which include the safety profiles of the agents. therapy, with a focus on the underlying mechanisms believed to be responsible for a number of important adverse events associated with these agents and what implications they may have for treatment choice, particularly in the setting of first-line treatment. A literature search of the PubMed database was conducted to identify articles that described the molecular mechanisms of BCR-ABL1-mediated leukemic transformation, the efficacy and safety of imatinib, nilotinib, dasatinib, and bosutinib in patients with CML, the kinase-binding spectrum of each , and evidence suggesting a link between the -binding profile and adverse events. . Clinical studies suggest that imatinib, nilotinib, dasatinib, and bosutinib have differing safety profiles, which are in part attributable to the specificity and selectivity of each agent. Although much basic research must be conducted to further illuminate the mechanisms responsible for -related adverse events, on- and off-target effects are believed to be at least partly responsible for cardiovascular toxicity, myelosuppression, fluid retention, gastrointestinal toxicity, and dermatologic toxicity. Increased understanding of the factors that affect -associated adverse events and long-term safety data will enable a more informed approach to the selection of therapy best suited to the individual needs of patients with CML.
Sanford School of Medicine, Sioux Falls Campus.
Khan, Sheema, Deepak Kumar, Meena Jaggi, & Subhash C. Chauhan. (2013). Targeting microRNAs in Pancreatic Cancer: Microplayers in the Big Game. Cancer research, 73(22), 6541-6547.
The prognosis of patients with pancreatic cancer is extremely poor, and current systemic therapies result in only marginal survival rates for patients. The era of targeted therapies has offered a new avenue to search for more effective therapeutic strategies. Recently, microRNAs (miRNA) that are small noncoding RNAs (18-24 nucleotides) have been associated with a number of diseases, including cancer. Disruption of miRNAs may have important implications in cancer etiology, diagnosis, and treatment. So far, focus has been on the mechanisms that are involved in translational silencing of their targets to fine tune gene expression. This review summarizes the approach for rational validation of selected candidates that might be involved in pancreatic tumorigenesis, cancer progression, and disease management. Herein, we also focus on the major issues hindering the identification of miRNAs, their linked pathways and recent advances in understanding their role as diagnostic/prognostic biomarkers, and therapeutic tools in dealing with this disease. miRNAs are expected to be robust clinical analytes, valuable for clinical research and biomarker discovery. Cancer Res; 73(22); 6541-7. 2013 AACR.
Sanford School of Medicine, Sioux Falls Campus.
Lal, Yasir, & J. Van Heukelom. (2013). Dabigatran: A Cause of Hematologic Emergency. American Journal of the Medical Sciences, 346(3), 190-193.
Dabigatran etexilate, a direct thrombin inhibitor, has become an alternative to warfarin for stroke prevention in patients with nonvalvular atrial fibrillation. There remains a concern about its overdose and life-threatening hemorrhage because of unavailability of appropriate coagulation tests to monitor and antidotes to reverse its effects. There are no clinical data about its safety in patients with fluctuating renal function. Multiple bleeding events reported with dabigatran have prompted the U.S. Food and Drug Administration to further investigate these reports. Four clinical cases with life-threatening bleeding, strategies that were used to achieve hemostasis and a brief literature review to demonstrate the hematologic emergency caused by dabigatran are presented in this study.
Sanford School of Medicine, Sioux Falls Campus.
Tjarks, B. Joel, Jason C. Dorman, Verle D. Valentine, Thayne A. Munce, Paul A. Thompson, Shanna L. Kindt, & Michael F. Bergeron. (2013). Comparison and utility of King-Devick and ImPACT composite scores in adolescent concussion patients. Journal of the neurological sciences, 334(1-2), 148-153.
UNLABELLED: The King-Devick (KD) oculomotor test has recently been advocated for sideline diagnosis of concussion. Although visual processing and performance are often impaired in concussion patients, the utility of KD as a concussion diagnostic tool is not validated.; PURPOSE: To examine the diagnostic value of KD, by comparing KD with post-concussion symptom scale (PCSS) and ImPACT composite scores. We hypothesized that KD would be correlated with visual motor speed/memory (VMS, VIS) and reaction time (RT), because all require cognitive visual processing. We also expected parallel changes in KD and PCSS across recovery.; METHODS: Thirty-five concussed individuals (12-19y; 18 females, 17 males) were evaluated with PCSS, ImPACT composite and KD scores over four clinical visits (V).; RESULTS: KD times improved with each visit (DeltaV1-V2: 7.8611.82; DeltaV2-V3: 9.1711.07; DeltaV3-V4: 5.307.87s) and paralleled improvements in PCSS (DeltaV1-V2: 8.9720.27; DeltaV2-V3: 8.6914.70; DeltaV3-V4: 6.317.71), RT (DeltaV1-V2: 0.050.21; DeltaV2-V3: 0.090.19; DeltaV3-V4 0.030.07) and VMS (DeltaV1-V2: -5.276.98; DeltaV2-V3: -2.616.48; DeltaV3-V4: -2.355.22). Longer KD times were associated with slower RT (r=0.67; P<0.0001) and lower VMS (r=-0.70; P<0.0001), respectively.; CONCLUSION: Cognitive visual performance testing using KD has utility in concussion evaluation. Validation would further establish KD as an effective ancillary tool in longitudinal concussion management and research. 2013 Elsevier B.V. All rights reserved.
Sanford School of Medicine, Sioux Falls Campus.
Avoseh, Mejai B. M. (2013). Proverbs as theoretical frameworks for lifelong learning in indigenous African education. Adult Education Quarterly, 63(3), 236-250.
Every aspect of a community’s life and values in indigenous Africa provide the theoretical framework for education. The holistic worldview of the traditional system places a strong emphasis on the centrality of the human element and orature in the symmetrical relationship between life and learning. This article focuses on proverbs and the words that form them as important sources of, and foundation for, indigenous African education. The article analyzes proverbs and the power of the spoken word in indigenous African pedagogy. The analysis is used to argue for an increased articulation of indigenous African knowledge into the dialogue on the inclusion of non-Western traditions in the theoretical frameworks for adult education. The article uses the traditional contexts of Ogu and Yoruba of West Africa but draws examples mostly from Yoruba proverbs to present their epistemological significance in traditional African education. (PsycINFO Database Record (c) 2013 APA, all rights reserved) (journal abstract)
School of Education.
Schweinle, Amy, Patti J. Berg, & Ashley R. Sorenson. (2013). Preadolescent perceptions of challenging and difficult course activities and their motivational distinctions. Educational Psychology, 33(7), 797-816.
The present research sought to determine if primary school students differentiate between classes that are challenging and those that are difficult, and how these distinctions relate to their motivation and achievement. Results indicated that there are three types of challenges/difficulties.Challengingclasses are those that are demanding of the students but within their ability, are important and are tied to interests; students in these classes are more likely to adopt mastery goal orientations.Purely difficultclasses are not valued, require a lot of effort, but are threatening to students’ efficacy. Classes that aredifficult compared to othersare those that are more demanding for the student than other students or other classes. These classes are not valued and are also seen as a threat to efficacy. Bothpurely difficultanddifficult compared to othersclasses were negatively related to achievement, and students in these classes are more likely to adopt performance avoidance goal orientations.
School of Education.
School of Health Sciences.
Psychology Department.
Ko, Eunjeong, Soonhee Roh, & Doreen Higgins. (2013). Do older Korean immigrants engage in end-of-life communication? Educational Gerontology, 39(8), 613-622.
End-of-life communication is an important process as it allows individuals’ treatment preferences to be known, yet not every culture is receptive to such discussions. Planning for end-of-life care is not readily supported in Asian culture, and little is known about individuals’ communication with family and health care professionals among older Korean immigrants related to end-of-life care. A cross-sectional study was conducted with 195 older Korean immigrants on end-of-life communication. Measures include end-of-life communication, attitudes toward end-of-life communication, perceived burden, number of adult children in the United States, health status, and sociodemographic variables. Overall, 21.9% (n = 42) of participants reported to have discussed their end-of-life treatment preferences with others, primarily family members. Attitudes toward end-of-life discussions, perceived burden, religiosity, and the number of children in the U.S. significantly accounted for end-of-life communication. Culturally appropriate interventions are recommended to promote dialogue regarding treatment preferences among older adults, family, and health care professionals. (PsycINFO Database Record (c) 2013 APA, all rights reserved) (journal abstract)
School of Health Sciences.
Naik, Bijayananda. (2013). INFLUENCE OF CULTURE ON LEARNING STYLES OF BUSINESS STUDENTS. International Journal of Education Research, 8(1), 129-139.
The Index of Learning Styles (ILS) instrument based on the Felder-Silverman Learning Style Model was used to investigate the influence of culture on learning style distribution of business students. Business students from three distinctly different cultures, namely, western, middle-eastern, and eastern cultures were surveyed in this research. Western culture was represented by the United States, middle-eastern culture by Egypt, and eastern culture by South Korea. Results of this study show that most business students, in all three cultures, have a balanced learning style in each of the four learning style dimensions of the Felder-Silverman model. A comparison of learning style distributions of business students belonging to the three cultures revealed small but statistically significant differences.
Beacom School of Business.
Buchwald, Dedra, Clemma Muller, Maria Bell, & Delf Schmidt-Grimminger. (2013). Attitudes Toward HPV Vaccination Among Rural American Indian Women and Urban White Women in the Northern Plains. Health Education & Behavior, 40(6), 704-711.
Background. American Indian women in the Northern Plains have a high incidence of cervical cancer. We assessed attitudes on vaccination against human papillomavirus (HPV) in this population. Method. In partnership with two tribal communities, from 2007 to 2009, we surveyed women 18 to 65 years old attending two reservation clinics (n = 118 and n = 76) and an urban clinic in the same region serving primarily White women (n = 158) on HPV knowledge, vaccine familiarity, and willingness to vaccinate children against HPV. We used chi-square tests and binary logistic regression to compare groups and identify correlates of willingness to vaccinate. Results. American Indian women were less knowledgeable about HPV than White women (p < .001), especially its role in cervical cancer. Willingness to vaccinate children was differentially distributed across the three clinic samples (p < .001), but this association did not persist after adjusting for demographics and HPV knowledge. Among all samples, more correct answers to HPV knowledge questions was the only factor positively correlated with willingness to vaccinate (odds ratios = 1.2-1.5; p < .00-.05). Conclusions. These findings underscore the importance of locally relevant educational interventions to increase HPV vaccination rates among American Indian women.
Sanford School of Medicine, Sioux Falls Campus.
Taub, Gordon E., & Nicholas Benson. (2013). Identifying the Effects of Specific CHC Factors on College Students’ Reading Comprehension. International Journal for the Scholarship of Teaching & Learning, 7(2), 1-13.
Reading comprehension is an important skill for college academic success. Much of the research pertaining to reading in general, and reading comprehension specifically, focuses on the success of primary and secondary school-age students. The present study goes beyond previous research by extending such investigation to the reading comprehension of college-age student participants. Using the Cattell-Horn-Carroll (CHC) theoretical model, this study investigates the effects of seven broad factors on the reading comprehension of college-age students. Of the seven broad factors identified within the CHC theoretical model, only crystallized intelligence and visual-spatial thinking demonstrate statistically significant direct effects on reading comprehension. Although crystallized intelligence consistently has been identified as playing an integral role in the reading comprehension of primary and secondary school-age students, this study represents the first time visualspatial thinking has been found to have a statistically significant direct effect on reading comprehension, in any population. This study provides hypotheses to explain the effects of visual-spatial thinking on college-age students’ reading comprehension and offers instructional strategies to assist faculty in improving student learning in higher education settings.
School of Education.

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