Posted by: reganenosusd | October 31, 2014

October 2014

Gupta, M. K., J. Gulick, R. J. Liu, Xuejun Wang, J. D. Molkentin, & J. Robbins. (2014). Sumo E2 Enzyme UBC9 Is Required for Efficient Protein Quality Control in Cardiomyocytes. Circulation Research, 115(8), 721-+.

Rationale: Impairment of proteasomal function is pathogenic in several cardiac proteinopathies and can eventually lead to heart failure. Loss of proteasomal activity often results in the accumulation of large protein aggregates. The ubiquitin proteasome system (UPS) is primarily responsible for cellular protein degradation, and although the role of ubiquitination in this process is well studied, the function of an ancillary post-translational modification, SUMOylation, in protein quality control is not fully understood. Objective: To determine the role of ubiquitin-conjugating enzyme 9 (UBC9), a small ubiquitin-like modifier-conjugating enzyme, in cardiomyocyte protein quality control. Methods and Results: Gain-and loss-of-function approaches were used to determine the importance of UBC9. Overexpression of UBC9 enhanced UPS function in cardiomyocytes, whereas knockdown of UBC9 by small interfering RNA caused significant accumulations of aggregated protein. UPS function and relative activity was analyzed using a UPS reporter protein consisting of a short degron, CL1, fused to the COOH-terminus of green fluorescent protein (GFPu). Subsequently, the effects of UBC9 on UPS function were tested in a proteotoxic model of desmin-related cardiomyopathy, caused by cardiomyocyte-specific expression of a mutated alpha B crystallin, CryAB(R120G). CryAB(R120G) expression leads to aggregate formation and decreased proteasomal function. Coinfection of UBC9-adenovirus with CryABR120G virus reduced the proteotoxic sequelae, decreasing overall aggregate concentrations. Conversely, knockdown of UBC9 significantly decreased UPS function in the model and resulted in increased aggregate levels. Conclusions: UBC9 plays a significant role in cardiomyocyte protein quality control, and its activity can be exploited to reduce toxic levels of misfolded or aggregated proteins in cardiomyopathy.

Baisc Biomedical Sciences, Vermillion Campus.

Klonoski, Joshua M., Heather R. Hurtig, Brian A. Juber, Margaret J. Schuneman, Thomas E. Bickett, Joshua M. Svendsen, . . . Victor C. Huber. (2014). Vaccination against the M protein of Streptococcus pyogenes prevents death after influenza virus:S. pyogenes super-infection. Vaccine, 32(40), 5241-5249.

Influenza virus infections are associated with a significant number of illnesses and deaths on an annual basis. Many of the deaths are due to complications from secondary bacterial invaders, including Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, and Streptococcus pyogenes. The beta-hemolytic bacteria S. pyogenes colonizes both skin and respiratory surfaces, and frequently presents clinically as strep throat or impetigo. However, when these bacteria gain access to normally sterile sites, they can cause deadly diseases including sepsis, necrotizing fasciitis, and pneumonia. We previously developed a model of influenza virus:S. pyogenes super-infection, which we used to demonstrate that vaccination against influenza virus can limit deaths associated with a secondary bacterial infection, but this protection was not complete. In the current study, we evaluated the efficacy of a vaccine that targets the M protein of S. pyogenes to determine whether immunity toward the bacteria alone would allow the host to survive an influenza virus:S. pyogenes super-infection. Our data demonstrate that vaccination against the M protein induces IgG antibodies, in particular those of the IgG1 and IgG2a isotypes, and that these antibodies can interact with macrophages. Ultimately, this vaccine-induced immunity eliminated death within our influenza virus:S. pyogenes super-infection model, despite the fact that all M protein-accinated mice showed signs of illness following influenza virus inoculation. These findings identify immunity against bacteria as an important component of protection against influenza virus:bacteria super-infection. (C) 2014 Elsevier Ltd. All rights reserved.

Basic Biomedical Sciences, Vermillion Campus.

Morecraft, Robert J., Kimberly S. Stilwell-Morecraft, Kathryn M. Solon-Cline, Jizhir Ge, & W. G. Darling. (2014). Cortical Innervation of the Hypoglossal Nucleus in the Non-Human Primate (Macaca mulatta). Journal of Comparative Neurology, 522(15), 3456-3484.

The corticobulbar projection to the hypoglossal nucleus was studied from the frontal, parietal, cingulate, and insular cortices in the rhesus monkey by using high-resolution anterograde tracers and stereology. The hypoglossal nucleus received bilateral input from the face/head region of the primary (M1), ventrolateral pre( LPMCv), supplementary (M2), rostral cingulate (M3), and caudal cingulate (M4) motor cortices. Additional bilateral corticohypoglossal projections were found from the dorsolateral premotor cortex (LPMCd), ventrolateral proisocortical motor area (ProM), ventrolateral primary somatosensory cortex (S1), rostral insula, and pregenual region of the anterior cingulate gyrus (areas 24/32). Dense terminal projections arose from the ventral region of M1, and moderate projections from LPMCv and rostral part of M2, with considerably fewer hypoglossal projections arising from the other cortical regions. These findings demonstrate that extensive regions of the non-human primate cerebral cortex innervate the hypoglossal nucleus. The widespread and bilateral nature of this corticobulbar connection suggests recovery of tongue movement after cortical injury that compromises a subset of these areas, may occur from spared corticohypoglossal projection areas located on the lateral, as well as medial surfaces of both hemispheres. Since functional imaging studies have shown that homologous cortical areas are activated in humans during tongue movement tasks, these corticobulbar projections may exist in the human brain. (C) 2014 Wiley Periodicals, Inc.

Basic Biomedical Sciences, Vermillion Campus.

Weltman, Nathan Y., K. Ojamaa, Evelyn H. Schlenker, Y. F. Chen, R. Zucchi, A. Saba, . . . A. M. Gerdes. (2014). Low-Dose T-3 Replacement Restores Depressed Cardiac T-3 Levels, Preserves Coronary Microvasculature and Attenuates Cardiac Dysfunction in Experimental Diabetes Mellitus. Molecular Medicine, 20, 302-312.

Thyroid dysfunction is common in individuals with diabetes mellitus (DM) and may contribute to the associated cardiac dysfunction. However, little is known about the extent and pathophysiological consequences of low thyroid conditions on the heart in DM. DM was induced in adult female Sprague Dawley (SD) rats by injection of nicotinamide (N; 200 mg/kg) followed by streptozotocin (STZ; 65 mg/kg). One month after STZ/N, rats were randomized to the following groups (N = 10/group): STZ/N or STZ/N + 0.03 g/mL T-3; age-matched vehicle-treated rats served as nondiabetic controls (C). After 2 months of T-3 treatment (3 months post-DM induction), left ventricular (LV) function was assessed by echocardiography and LV pressure measurements. Despite normal serum thyroid hormone (TH) levels, STZ/N treatment resulted in reductions in myocardial tissue content of THs (T-3 and T-4 : 39% and 17% reduction versus C, respectively). Tissue hypothyroidism in the DM hearts was associated with increased DIO3 deiodinase (which converts THs to inactive metabolites) altered TH transporter expression, reexpression of the fetal gene phenotype, reduced arteriolar resistance vessel density, and diminished cardiac function. Low-dose T-3 replacement largely restored cardiac tissue TH levels (T-3 and T-4 : 43% and 10% increase versus STZ/N, respectively), improved cardiac function, reversed fetal gene expression and preserved the arteriolar resistance vessel network without causing overt symptoms of hyperthyroidism. We conclude that cardiac dysfunction in chronic DM may be associated with tissue hypothyroidism despite normal serum TH levels. Low-dose T-3 replacement appears to be a safe and effective adjunct therapy to attenuate and/or reverse cardiac remodeling and dysfunction induced by experimental DM.

Basic Biomedical Sciences, Vermillion Campus.

Kraus, J. M., D. M. Walters, Jeff S. Wesner, C. A. Stricker, T. S. Schmidt, & R. E. Zuellig. (2014). Metamorphosis Alters Contaminants and Chemical Tracers in Insects: Implications for Food Webs. Environmental Science & Technology, 48(18), 10957-10965.

Insects are integral to most freshwater and terrestrial food webs, but due to their accumulation of environmental pollutants they are also contaminant vectors that threaten reproduction, development, and survival of consumers. Metamorphosis from larvae to adult can cause large chemical changes in insects, altering contaminant concentrations and fractionation of chemical tracers used to establish contaminant biomagnification in food webs, but no framework exists for predicting and managing these effects. We analyzed data from 39 studies of 68 analytes (stable isotopes and contaminants), and found that metamorphosis effects varied greatly. delta N-15, widely used to estimate relative trophic position in biomagnification studies, was enriched by similar to 1 parts per thousand during metamorphosis, while delta C-13 used to estimate diet, was similar in larvae and adults. Metals and polycyclic aromatic hydrocarbons (PAHs) were predominantly lost during metamorphosis leading to similar to 2 to 125-fold higher larval concentrations and higher exposure risks for predators of larvae compared to predators of adults. In contrast, manufactured organic contaminants (such as polychlorinated biphenyls) were retained and concentrated in adults, causing up to similar to 3-fold higher adult concentrations and higher exposure risks to predators of adult insects. Both food web studies and contaminant management and mitigation strategies need to consider how metamorphosis affects the movement of materials between habitats and ecosystems, with special regard for aquatic-terrestrial linkages.

Biology Department.

Swanson, David, Yufeng Zhang, & Marisa King. (2014). Mechanistic Drivers of Flexibility in Summit Metabolic Rates of Small Birds. Plos One, 9(7), 9.

Flexible metabolic phenotypes allow animals to adjust physiology to better fit ecological or environmental demands, thereby influencing fitness. Summit metabolic rate (M-sum = maximal thermogenic capacity) is one such flexible trait. Skeletal muscle and heart masses and myocyte metabolic intensity are potential drivers of M-sum flexibility in birds. We examined correlations of skeletal muscle and heart masses and pectoralis muscle citrate synthase (CS) activity (an indicator of cellular metabolic intensity) with M-sum in house sparrows (Passer domesticus) and dark-eyed juncos (Junco hyemalis) to determine whether these traits are associated with M-sum variation. Pectoralis mass was positively correlated with M-sum for both species, but no significant correlation remained for either species after accounting for body mass (M-b) variation. Combined flight and leg muscle masses were also not significantly correlated with M-sum for either species. In contrast, heart mass was significantly positively correlated with M-sum for juncos and nearly so (P = 0.054) for sparrows. Mass-specific and total pectoralis CS activities were significantly positively correlated with M-sum for sparrows, but not for juncos. Thus, myocyte metabolic intensity influences M-sum variation in house sparrows, although the stronger correlation of total (r = 0.495) than mass-specific (r = 0.378) CS activity with M-sum suggests that both pectoralis mass and metabolic intensity impact M-sum. In contrast, neither skeletal muscle masses nor pectoralis metabolic intensity varied with M-sum in juncos. However, heart mass was associated with M-sum variation in both species. These data suggest that drivers of metabolic flexibility are not uniform among bird species.

Biology Department.

Wesner, Jeff S., J. M. Kraus, T. S. Schmidt, D. M. Walters, & W. H. Clements. (2014). Metamorphosis Enhances the Effects of Metal Exposure on the Mayfly, Centroptilum triangulifer. Environmental Science & Technology, 48(17), 10415-10422.

The response of larval aquatic insects to stressors such as metals is used to assess the ecological condition of streams worldwide. However, nearly all larval insects metamorphose from aquatic larvae to winged adults, and recent surveys indicate that adults may be a more sensitive indicator of stream metal toxicity than larvae. One hypothesis to explain this pattern is that insects exposed to elevated metal in their larval stages have a reduced ability to successfully complete metamorphosis. To test this hypothesis we exposed late-instar larvae of the mayfly, Centroptilum triangulifer, to an aqueous Zn gradient (32-476 mu g/L) in the laboratory. After 6 days of exposure, when metamorphosis began, larval survival was unaffected by zinc. However, Zn reduced wingpad development at concentrations above 139 mu g/L. In contrast, emergence of subimagos and imagos tended to decline with any increase in Zn. At Zn concentrations below 105 mu g/L (hardness-adjusted aquatic life criterion), survival between the wingpad and subimago stages declined 5-fold across the Zn gradient. These results support the hypothesis that metamorphosis may be a survival bottleneck, particularly in contaminated streams. Thus, death during metamorphosis may be a key mechanism explaining how stream metal contamination can impact terrestrial communities by reducing aquatic insect emergence.

Biology Department.

Ghimire, Niranjan, Jie Luo, Ruogu Tang, Yuyu Sun, & Ying Deng. (2014). Novel anti-infective activities of chitosan immobilized titanium surface with enhanced osteogenic properties. Colloids & Surfaces B: Biointerfaces, 122, 126-133.

We have covalently immobilized chitosan onto a titanium (Ti) surface to manage implant-related infection and poor osseointegration, two of the major complications of orthopedic implants. The Ti surface was first treated with sulfuric acid (SA) and then covalently grafted with chitosan. Surface roughness, contact angle and surface zeta potential of the samples were markedly increased by the sulfuric acid treatment and the subsequent chitosan immobilization. The chitosan-immobilized Ti (SA-CS-Ti) showed two novel antimicrobial roles: it (a) prevented the invasion and internalization of bacteria into the osteoblast-like cells, and (b) significantly increased the susceptibility of adherent bacteria to antibiotics. In addition, the sulfuric acid-treated Ti (SA-Ti) and SA-CS-Ti led to significantly increased ( P < 0.05) osteoblast-like cell attachment, enhanced cell proliferation, and better osteogenic differentiation and mineralization of osteoblast-like cells.

Biomedical Engineering, Sioux Falls Campus.

Banerjee, Subhash, Soumen Payra, Arijit Saha, & Grigoriy Sereda. (2014). ZnO nanoparticles: a green efficient catalyst for the room temperature synthesis of biologically active 2-aryl-1,3-benzothiazole and 1,3-benzoxazole derivatives. Tetrahedron Letters: International Organ for the Rapid Publication of Preliminary Communications in Organic Chemistry, 55(40), 5515-5520.

A facile synthetic protocol for the synthesis of 2-aryl-1,3-benzothiazoles and 1,3-benzoxazoles has been demonstrated using ZnO nanoparticles as a mild and efficient heterogeneous catalyst. The reactions using ZnO nanoparticles were very fast (<8 min) and provided excellent yields (>90%) of the products. The catalyst was recycled and reused up to eight times without significant loss of catalytic activity. The potential application of 2-(4-hydroxyphenyl)-1,3-benzothiazole as new acid–base indicator has also been demonstrated in this Letter.

Chemistry Department.

Bartholomew, Catherine, Ashish Chakradhar, U. W. E. Burghaus, Chia-Ming Wu, R. U. I. Peng, Srujan Mishra, & Ranjit T. Koodali. (2014). REACTIVITY AND MORPHOLOGY OF , , AND – OXIDE CLUSTERS SUPPORTED ON MCM-48 TOWARD THIOPHENE HYDRODESULPHURIZATION. Surface Review & Letters, 21(5), -1.

In this paper, the morphology, chemical composition and reactivity of MCM-48 powders impregnated with , or both toward hydrodesulphurization (HDS) of thiophene were characterized. The reactivity of the catalyst was quantitatively compared with a standard industrial catalyst (from HaldorTopsoe, Denmark) and a novel 2 nanotube-based catalysts (from R. Tenne, Israel). Morphology and chemical composition were characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDX), and EDX elemental maps. Reactivity was determined in a gas-chromatograph based mini flow reactor using thiophene as a probe molecule. The sulfided MCM-48 supported catalyst showed the largest HDS activity with turnover frequencies (TOF) about half as large as for the commercial system under the test conditions used here. Presulfiding did increase activity of all MCM-48 catalysts.

Chemistry Department.

Blumenthal, Tyler, Jeevan Meruga, Jon Kellar, William Cross, Krishnamraju Ankireddy, Swathi Vunnam, . . . QuocAnh N. Luu. (2012). Patterned direct-write and screen-printing of NIR-to-visible upconverting inks for security applications. Nanotechnology, 23(18), 1-1.

Two methods of direct-write printing for producing highly resolved features of a polymer impregnated with luminescent upconversion phosphors for security applications are presented. The printed polymer structures range in shape from features to text. The thin polymer features were deposited by direct-write printing of atomized material as well as by screen-printing techniques. These films contain highly luminescent lanthanide-doped, rare-earth nanocrystals, β-NaYF4:3%Er, 17%Yb, which are capped with oleic acid. This capping agent allows the nanocrystals to disperse throughout the films for full detailing of printed features. Upconversion of deposited features was obtained using a 980 nm wavelength laser with emission of upconverted light in the visible region at both 540 and 660 nm. Features were deposited onto high bond paper, Kapton®, and glass to demonstrate possible covert and forensic security printing applications, as they are printed in various features and invisible to ‘naked-eye’ viewing at low concentrations of nanocrystals.

Chemistry Department.

Huang, Shuping, T. M. Inerbaev, & Dmitri S. Kilin. (2014). Excited State Dynamics of Ru-10 Cluster Interfacing Anatase TiO2(101) Surface and Liquid Water. Journal of Physical Chemistry Letters, 5(16), 2823-2829.

Charge transfer dynamics at the interface of supported metal nanocluster and liquid water by GGA+U calculations combined with density matrix formalism is considered. The Rum duster introduces new states into the band gap of TiO2 surface, narrows the band gap of TiO2, and enhances the absorption strength. The H2O adsorption significantly enhances the intensity of photon absorption, which is due to the formation of Ti-O(water) and Ru-O(water) bonds at the interfaces. The Ruff, cluster promotes the dissociation of water, facilitates charge transfer, and increases the relaxation rates of holes and electrons. We expect that our results are helpful in understanding basic processes contributing to photoelectrochemical water splitting.

Chemistry Department.

Huang, Shuping, & Dmitri S. Kilin. (2014). Charge Transfer, Luminescence, and Phonon Bottleneck in TiO2 Nanowires Computed by Eigenvectors of Liouville Superoperator. Journal of Chemical Theory and Computation, 10(9), 3996-4005.

A nonadiabatic excited state dynamics study of ?001? anatase TiO2 nanowire is obtained by combining density matrix in LiouvilleRedfield formalism and ab initio electronic structure calculations. The properties of eigenvectors of LiouvilleRedfield superoperator are investigated. The time evolutions of KohnSham orbital populations are obtained for different electronic excitations. The numerical solutions of the population changes over time are in agreement with the analytical results. The analytical and numerical results on the electron and hole relaxation rates are compared. The electron nonradiative relaxation to the bottom of conduction band involves Ti 3d orbitals, whereas the hole nonradiative relaxation to the top of valence band is mainly localized in surface O 2p orbitals. The rate of relaxation in nanowire is slower than in bulk TiO2 demonstrating phonon-bottleneck effect. Calculated emission spectrum has vanishing contribution from lowest energy excitation, which indicates charge transfer.

Chemistry Department.

Kibombo, Harrison S., Vagulejan Balasanthiran, Chia-Ming Wu, Rui Peng, & Ranjit T. Koodali. (2014). Exploration of room temperature synthesis of palladium containing cubic MCM-48 mesoporous materials. Microporous and Mesoporous Materials, 198, 1-8.

 

Pd-MCM-48 mesoporous materials were synthesized by a modified Stober synthesis method in 4 h at room temperature. Pd nanoparticles were prepared by using Na-2[PdCl4] and Pd(acac)(2) as Pd precursors, and their influence in the preparation of the cubic MCM-48 mesoporous phase was investigated. In addition, Pd(0) nanoparticles was prepared separately and added to the synthesis gel. The influence of varying the Pd precursor, solvent media, the time of addition of Pd precursor, and the concentration of NaBH4 reducing agent used for preparation of Pd(0) and its effect for the formation of the cubic phase were investigated. These resultant materials were characterized by powder X-ray diffraction (XRD), transmission electron microscopy (TEM), UV-Visible spectroscopy, nitrogen physisorption, and CO-Pulse titration. Reusability studies assessing a material prepared using Pd(0)-DMAP encapsulated nanoparticles that were reduced with 0.1 N NaBH4 i.e. 3%Pd-MCM-48-D-N01 indicate that the yields for the hydrogenation of trans-cinnamic acid are greater than 95% even after 8 catalytic cycles, and at which the cubic phase was maintained under our experimental conditions. (C) 2014 Elsevier Inc. All rights reserved.

Chemistry Department.

Meruga, Jeevan M., William M. Cross, P. Stanley  May, QuocAnh Luu, Grant A. Crawford, & Jon J. Kellar. (2012). Security printing of covert quick response codes using upconverting nanoparticle inks. Nanotechnology, 23(39), 1-1.

Counterfeiting costs governments and private industries billions of dollars annually due to loss of value in currency and other printed items. This research involves using lanthanide doped β-NaYF4 nanoparticles for security printing applications. Inks comprised of Yb3+/Er3+ and Yb3+/Tm3+ doped β-NaYF4 nanoparticles with oleic acid as the capping agent in toluene and methyl benzoate with poly(methyl methacrylate) (PMMA) as the binding agent were used to print quick response (QR) codes. The QR codes were made using an AutoCAD file and printed with Optomec direct-write aerosol jetting®. The printed QR codes are invisible under ambient lighting conditions, but are readable using a near-IR laser, and were successfully scanned using a smart phone. This research demonstrates that QR codes, which have been used primarily for information sharing applications, can also be used for security purposes. Higher levels of security were achieved by printing both green and blue upconverting inks, based on combinations of Er3+/Yb3+ and Tm3+/Yb3+, respectively, in a single QR code. The near-infrared (NIR)-to-visible upconversion luminescence properties of the two-ink QR codes were analyzed, including the influence of NIR excitation power density on perceived color, in term of the CIE 1931 chromaticity index. It was also shown that this security ink can be optimized for line width, thickness and stability on different substrates.

Chemistry Department.

Sathe, Ajay, Matthea A. Peck, Choumini Balasanthiran, Marjorie A. Langell, Robert M. Rioux, & James D. Hoefelmeyer. (2014). X-ray photoelectron spectroscopy of transition metal ions attached to the surface of rod-shape anatase TiO2 nanocrystals. Inorganica Chimica Acta, 422, 8-13.

X-ray photoelectron spectra were obtained for a series of M–TiO 2 samples in which transition metal ions are directly attached to the surface of anatase TiO 2 nanocrystals. The samples were prepared using CrCl 3 · n H 2 O, MnCl 2 · n H 2 O, FeCl 2 · n H 2 O, CoCl 2 · n H 2 O, NiCl 2 · n H 2 O, and CuCl 2 · n H 2 O as metal sources. We observed spontaneous air oxidation of the metal for the Mn–TiO 2 and Fe–TiO 2 samples as indicated by rapid color changes. X-ray photoelectron spectroscopy (XPS) data confirms the oxidation states of the metals Cr, Co, and Ni are unchanged from the precursor, Mn and Fe are oxidized, and Cu is in a more reduced state. The reduction of Cu likely arises during the XPS experiment – a phenomenon well-documented in the literature; whereas UV–Vis data of the Cu–TiO 2 dispersions are consistent with Cu 2+ .

Chemistry Department.

Carley, Tamara L., Calvin F. Miller, Joseph L. Wooden, …., & Brennan T. Jordan. (2014). Iceland is not a magmatic analog for the Hadean: Evidence from the zircon record. Earth & Planetary Science Letters, 405, 85-97.

Tangible evidence of Earth’s earliest (Hadean; >4.0 Ga) crust, and the processes and materials that contributed to its formation, exists almost entirely in a record of detrital zircon from Jack Hills, Western Australia, and a few other locations. Iceland, with its thick, juvenile, basaltic crust and relatively abundant silicic rocks, is considered a potential modern analog for the Hadean magmatic environment where >4 Ga zircon formed. We present the first extensive dataset for Icelandic zircon, with trace element and oxygen isotope compositions from samples that span the island’s history and full range of tectonic settings. This statistically robust zircon-based comparison between Iceland and the early Earth reveals distinctions in chemistry that suggest fundamental differences in magmatic environments. Whereas the δ 18 O signature of Hadean zircons generally exceed that of zircons equilibrated with mantle-derived magma ( 85 % ≥ 5.3 ‰ ; median 6‰), almost all Icelandic zircons are characterized by a “light” oxygen signature ( 98 % ≤ 5.3 ‰ ; median 3‰). Deviations from “juvenile” oxygen values indicate that many Hadean zircons and almost all Icelandic zircons grew from magmas with substantial contributions from materials that had interacted with surface waters. In the Hadean case, the interaction occurred at low temperatures, while in Iceland, it was a high-temperature interaction. Icelandic and Hadean zircons are also distinct in their Ti concentrations (Icelandic median concentration 12 ppm, Hadean median 5 ppm). Titanium in zircon correlates positively with temperature of crystallization, and this difference in median Ti concentration suggests a temperature difference of at least 50 °C. Other differences in trace elements compositions are consistent with the interpretation that Icelandic and Hadean zircons grew in magmas with very different origins and histories (e.g., the heavy rare earth element Yb is almost an order of magnitude higher in Icelandic zircon). A comparison with elemental data for Phanerozoic zircon from different environments demonstrates that the Hadean population is unusually depleted in Ti, but otherwise similar to zircons from continental arc settings. Zircons from Iceland, and from modern evolving rift environments where oceanic lithosphere and upwelling asthenosphere are replacing continental lithosphere, are compositionally intermediate between mid-ocean ridge and continental arc zircon populations. The elemental distinctions are consistent with fractionation of zircon-bearing magmas under hotter and drier conditions in Icelandic, mid-ocean ridge, and evolving rift environments and cooler and wetter conditions in arc and, especially, Hadean environments.

Earth Sciences Department.

Chowell, Gerardo, Lone Simonsen, Jose Flores, Mark A. Miller, & Cécile Viboud. (2014). Death Patterns during the 1918 Influenza Pandemic in Chile. Emerging Infectious Diseases, 20(11), 1803-1811.

Scarce information about the epidemiology of historical influenza pandemics in South America prevents complete understanding of pandemic patterns throughout the continent and across different climatic zones. To fill gaps with regard to spatiotemporal patterns of deaths associated with the 1918 influenza pandemic in Chile, we reviewed archival records. We found evidence that multiple pandemic waves at various times of the year and of varying intensities occurred during 1918-1921 and that influenza-related excess deaths peaked during July-August 1919. Pandemic-associated mortality rates were elevated for all age groups, including for adults ≥50 years of age; elevation from baseline was highest for young adults. Overall, the rate of excess deaths from the pandemic was estimated at 0.94% in Chile, similar to rates reported elsewhere in Latin America, but rates varied ≈10-fold across provinces. Patterns of death during the pandemic were affected by variation in host-specific susceptibility, population density, baseline death rate, and climate.

Mathematics Department.

Dutkay, Dorin E., & Gabriel Picioroaga. (2014). Generalized Walsh Bases and Applications. Acta Applicandae Mathematicae, 133(1), 1-18.

We investigate convergence properties of generalized Walsh series associated with signals faL (1)[0,1]. We also show how the dependence of the generalized Walsh bases on NxN unitary matrices allows for applications in signal encoding and encryption, provided the signals are piece-wise constant on N-adic subintervals of [0,1].

Mathematics Department.

Borrego, Maura, Daniel Boden, & Lynita K. Newswander. (2014). Sustained Change: Institutionalizing Interdisciplinary Graduate Education. Journal of Higher Education, 85(6), 858-885.

We employ Scott’s three pillars of institutions (regulative, normative, and cultural-cognitive) to investigate how higher education organizations change to support interdisciplinary graduate education. Using document analysis and case study approaches, we illustrate how strategies which address both policies and cultural norms are most successful.

Political Science Department.

Emery, Noah N., Jeffrey S. Simons, C. Joseph Clarke, & Raluca M. Gaher. (2014). Emotion differentiation and alcohol-related problems: The mediating role of urgency. Addictive Behaviors, 39(10), 1459-1463.

Deficits in emotional and behavioral regulation figure prominently in etiological models of alcohol-related problems. This study tests a model linking poor differentiation of emotion to alcohol-related problems via urgency. The sample consisted of 102 undergraduates between the ages 18 and 24 who reported moderate to heavy alcohol consumption. As hypothesized, negative urgency mediated the relationship between negative emotion differentiation and alcohol-related problems. However, contrary to hypothesis, positive urgency was not associated with either positive emotion differentiation or alcohol-related problems and the indirect effect of positive emotion differentiation via positive urgency was not significant. Instead, positive emotion differentiation exhibited a significant direct effect on alcohol-related problems. This study provides an initial examination of connections between specificity in labeling emotions, behavioral disinhibition, and problematic alcohol use. These findings suggest that poor differentiation of negative emotion may foster impulsive behavior when negatively aroused. Whereas, impulsive behavior when positively aroused may reflect heightened sensitivity to positive reinforcement, which may not be related to reflective processes underlying emotion differentiation. (C) 2014 Elsevier Ltd. All rights reserved.

Psychology Department.

Robles, Elias, Noah N. Emery, Perla A. Vargas, Araceli Moreno, Brent Marshall, Richard C. Grove, & Huateng Zhang. (2014). Patterns of responding on a balloon analogue task reveal individual differences in overall risk-taking: Choice between guaranteed and uncertain cash. Journal of General Psychology, 141(3), 207-227.

We explored the utility of analyzing within- and between-balloon response patterns on a balloon analogue task (BAT) in relation to overall risk scores, and to a choice between a small guaranteed cash reward and an uncertain reward of the same expected value. Young adults (n = 61) played a BAT, and then were offered a choice between $5 in cash and betting to win $0 to $15. Between groups, pumping was differentially influenced by explosions and by the number of successive unexploded balloons, with risk takers responding increasingly on successive balloons after an explosion. Within-balloons, risk takers showed a characteristic pattern of constant high rate, while non-risk takers showed a characteristic variable lower rate. Overall, results show that the higher number of pumps and explosions that characterize risk takers at a molar level, result from particular forms of adaptation to the positive and negative outcomes of choices seen at a molecular level. (PsycINFO Database Record (c) 2014 APA, all rights reserved). (journal abstract)

Psychology Department.

Wang, X. T., S. Li, & L. L. Rao. (2014). Conservation combats exploitation: Choices within an evolutionary framework. Behavioral and Brain Sciences, 37(4), 437-438.

Intentional change when viewed as making a risky or intertemporal choice with evolutionary relevance helps us understand its successes and its failures. To promote future-oriented ecological rationality requires establishing a linkage between nongenetic, cultural, and symbolic selections and genetic adaptations. Coupled with biophilic instinct, intentional conservation is more likely to prevail against evolved desires of environmental exploitation.

Psychology Department.

Askelson, N. M., D. L. Chi, E. Momany, R. Kuthy, C. Ortiz, Jessica D. Hanson, & P. Damiano. (2014). Encouraging early preventive dental visits for preschool-aged children enrolled in Medicaid: using the Extended Parallel Process Model to conduct formative research. Journal of Public Health Dentistry, 74(1), 64-70.

Objective: Preventive dental visits for preschool-aged children can result in better oral health outcomes, especially for children from lower income families. Many children, however, still do not see a dentist for preventive visits. This qualitative study examined the potential for the Extended Parallel Process Model (EPPM) to be used to uncover potential antecedents to parents’ decisions about seeking preventive dental care. Methods: Seventeen focus groups including 41 parents were conducted. The focus group protocol centered on constructs (perceived severity, perceived susceptibility, perceived self-efficacy, and perceived response efficacy) of the EPPM. Transcripts were analyzed by three coders who employed closed coding strategies. Results: Parents’ perceptions of severity of dental issues were high, particularly regarding negative health and appearance outcomes. Parents perceived susceptibility of their children to dental problems as low, primarily because most children in this study received preventive care, which parents viewed as highly efficacious. Parents’ self-efficacy to obtain preventive care for their children was high. However, they were concerned about barriers including lack of dentists, especially dentists who are good with young children. Conclusions: Findings were consistent with EPPM, which suggests this model is a potential tool for understanding parents’ decisions about seeking preventive dental care for their young children. Future research should utilize quantitative methods to test this model.

Sanford School of Medicine, Sioux Falls Campus.

Bergeron, Michael F. (2014). Heat Stress and Thermal Strain Challenges in Running. Journal of Orthopaedic & Sports Physical Therapy, 44(10), 831-838.

 

SYNOPSIS: Running well and safely in the heat is challenging for all runners, from recreational to elite. As environmental heat stress (heat stress modulated or augmented by air temperature, humidity, wind speed, and solar radiation) and the intensity and duration of a training run or race increase, so are metabolic heat production, the parallel need for heat transfer from the body to maintain thermal equilibrium, the consequent increase in blood flow to the skin, and the concomitant sweating response progressively and proportionally amplified. An accumulating total body-water deficit from extensive sweating and escalating level of cardiovascular and thermal strain will, in due course, considerably challenge a runner’s physiology, perception of effort, and on-course well-being and performance. However, with the appropriate preparation and modifications to planned running intensity and distance, runners can safely tolerate and effectively train and compete in a wide range of challenging environmental conditions. Clinicians play a key role in this regard as an effective resource for providing the most effective guidelines and making the best overall individual recommendations regarding training and competing in the heat.

Sanford School of Medicine, Sioux Falls Campus.

Ferris, D., R. Samakoses, S. L. Block, E. Lazcano-Ponce, J. A. Restrepo, K. S. Reisinger, . . . A. Saah. (2014). Long-term Study of a Quadrivalent Human Papillomavirus Vaccine. Pediatrics, 134(3), E657-E665.

 

BACKGROUND: We present a long-term safety, immunogenicity, and effectiveness study of a quadrivalent human papillomavirus (HPV4) vaccine. METHODS: Sexually naive boys and girls aged 9 to 15 years (N = 1781) were assigned (2:1) to receive HPV4 vaccine or saline placebo at day 1 and months 2 and 6. At month 30, the placebo group (n = 482) received HPV4 vaccine following the same regimen and both cohorts were followed through month 96. Subjects >= 16 years were eligible for effectiveness evaluations. The primary objective was to evaluate the long-term anti-HPV6/11/16/18 serological levels. The secondary objective was to estimate vaccine effectiveness against HPV6/11/16/18-related persistent infection or disease. RESULTS: For each of the HPV4 vaccine types, vaccination-induced anti-HPV response persisted through month 96. Among 429 subjects who received HPV4 vaccine at a mean age of 12, none developed HPV6/11/16/18-related disease or persistent infection of >= 12 months’ duration. Acquisition of new sexual partners (among those >= 16 years) was similar to 1 per year. Subjects receiving HPV4 vaccine at month 30 (mean age 15 years) had a similar baseline rate of seropositivity to >= 1 of the 4 HPV types to those vaccinated at day 1 (mean age 12 years; 1.9% [9 of 474] vs 1.7% [20 of 1157]); however, 4 of the 9 subjects vaccinated at the later age were seropositive to 3 vaccine types, indicating previous HPV exposure. No new significant serious adverse events were observed for 8 years postvaccination in both genders. CONCLUSIONS: When administered to adolescents, the HPV4 vaccine demonstrated durability in clinically effective protection and sustained antibody titers over 8 years.

Sanford School of Medicine, Sioux Falls Campus.

Finn, R., C. C. Evans, & Lance Lee. (2014). Strain-dependent brain defects in mouse models of primary ciliary dyskinesia with mutations in Pcdp1 and Spef2. Neuroscience, 277, 552-567.

Hydrocephalus is caused by the accumulation of cerebrospinal fluid (CSF) in the cerebral ventricular system which results in an enlargement of the cranium due to increased intraventricular pressure. The increase in pressure within the brain typically results in sloughing of ciliated ependymal cells, loss of cortical gray matter, and increased gliosis. Congenital hydrocephalus is associated with several syndromes including primary ciliary dyskinesia (PCD), a rare, genetically heterogeneous, pediatric syndrome that results from defects in motile cilia and flagella. We have examined the morphological and physiological defects in the brains of two mouse models of PCD, nm1054 and bgh , which have mutations in Pcdp1 (also known as Cfap221 ) and Spef2 , respectively. Histopathological and immunohistochemical analyses of mice with these mutations on the C57BL/6J and 129S6/SvEvTac genetic backgrounds demonstrate strain-dependent morphological brain damage. Alterations in astrocytosis, microglial activation, myelination, and the neuronal population were identified and are generally more severe on the C57BL/6J background. Analysis of ependymal ciliary clearance ex vivo and CSF flow in vivo demonstrate a physiological defect in nm1054 and bgh mice on both genetic backgrounds, indicating that abnormal cilia-driven flow is not the sole determinant of the severity of hydrocephalus in these models. These results suggest that genetic modifiers play an important role in susceptibility to severe PCD-associated hydrocephalus.

Sanford School of Medicine, Sioux Falls Campus.

Flock, M. R., A. C. Skulas-Ray, William S. Harris, T. L. Gaugler, J. A. Fleming, & P. M. Kris-Etherton. (2014). Effects of supplemental long-chain omega-3 fatty acids and erythrocyte membrane fatty acid content on circulating inflammatory markers in a randomized controlled trial of healthy adults. Prostaglandins Leukotrienes and Essential Fatty Acids, 91(4), 161-168.

The long-chain omega-3 polyunsaturated (n-3 PUFA), eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), may have anti-inflammatory effects. We evaluated the dose-response effect of EPA+DHA supplementation on circulating TNF-alpha, IL-6, and CRP and explored associations between red blood cell (RBC) membrane PUFA content and TNF-alpha, IL-6, and CRP. Young adults with low fish intake (n= 116) received one of five doses (0, 300, 600, 900, or 1,800 mg/d EPA+DHA) for 5 months. There were no significant effects of supplemental EPA+DHA on IL-6 or CRP; however, there was a marginal treatment effect for TNF-alpha (p < 0.08). At baseline, higher quartiles of RBC DHA were associated with lower TNF-alpha (p=0.001); higher quartiles of arachidonic acid were associated with higher TNF-alpha (p=0.005). EPA+DHA supplementation had no dose-response effect on TNF-alpha, IL-6, or CRP in healthy young adults; however, associations between inflammatory markers and RBC PUFA warrant further investigation. (C) 2014 Elsevier Ltd. All rights reserved.

Sanford School of Medicine, Sioux Falls Campus.

Floen, Miranda J., Benjamin J. Forred, Elliot J. Bloom, & Peter F. Vitiello. (2014). Thioredoxin-1 redox signaling regulates cell survival in response to hyperoxia. Free Radical Biology & Medicine, 75, 167-177.

 

The most common form of newborn chronic lung disease, bronchopulmonary dysplasia (BPD), is thought to be caused by oxidative disruption of lung morphogenesis, which results in decreased pulmonary vasculature and alveolar simplification. Although cellular redox status is known to regulate cellular proliferation and differentiation, redox-sensitive pathways associated with these processes in developing pulmonary epithelium are unknown. Redox-sensitive pathways are commonly regulated by cysteine thiol modifications. Therefore two thiol oxidoreductase systems, thioredoxin and glutathione, were chosen to elucidate the roles of these pathways on cell death. Studies herein indicate that thiol oxidation contributes to cell death through impaired activity of glutathione-dependent and thioredoxin (Trx) systems and altered signaling through redox-sensitive pathways. Free thiol content decreased by 71% with hyperoxic (95% oxygen) exposure. Increased cell death was observed during oxygen exposure when either the Trx or the glutathione-dependent system was pharmacologically inhibited with aurothioglucose (ATG) or buthionine sulfoximine, respectively. However, inhibition of the Trx system yielded the smallest decrease in free thiol content (1.44% with ATG treatment vs 21.33% with BSO treatment). Although Trx1 protein levels were unchanged, Trx1 function was impaired during hyperoxic treatment as indicated by progressive cysteine oxidation. Overexpression of Trx1 in H1299 cells utilizing an inducible construct increased cell survival during hyperoxia, whereas siRNA knockdown of Trx1 during oxygen treatment reduced cell viability. Overall, this indicated that a comparatively small pool of proteins relies on Trx redox functions to mediate cell survival in hyperoxia, and the protective functions of Trx1 are progressively lost by its oxidative inhibition. To further elucidate the role of Trx1, potential Trx1 redox protein–protein interactions mediating cytoprotection and cell survival pathways were determined by utilizing a substrate trap (mass action trapping) proteomics approach. With this method, known Trx1 targets were detected, including peroxiredoxin-1 as well as novel targets, including two HSP90 isoforms (HSP90AA1 and HSP90AB1). Reactive cysteines within the structure of HSP90 are known to modulate its ATPase-dependent chaperone activity through disulfide formation and S-nitrosylation. Whereas HSP90 expression is unchanged at the protein level during hyperoxic exposure, siRNA knockdown significantly increased hyperoxic cell death by 2.5-fold, indicating cellular dependence on HSP90 chaperone functions in response to hyperoxic exposure. These data support the hypothesis that hyperoxic impairment of Trx1 has a negative impact on HSP90-oxidative responses critical to cell survival, with potential implications for pathways implicated in lung development and the pathogenesis of BPD.

Sanford School of Medicine, Sioux Falls Campus.

Griffin, Kurt J., Paul A. Thompson, M. Gottschalk, J. H. Kyllo, & Alex Rabinovitch. (2014). Combination therapy with sitagliptin and lansoprazole in patients with recent-onset type 1 diabetes (REPAIR-T1D): 12-month results of a multicentre, randomised, placebo-controlled, phase 2 trial. Lancet Diabetes & Endocrinology, 2(9), 710-718.

Background Type 1 diabetes results from autoimmune destruction of pancreatic beta cells. Findings from preclinical studies suggest that dipeptidyl peptidase-4 inhibitors and proton-pump inhibitors might enhance beta-cell survival and regeneration. We postulated that sitagliptin and lansoprazole would preserve beta-cell function in patients with recentonset type 1 diabetes. Methods We did a double-blind, placebo-controlled, phase 2 trial (REPAIR-T1D). Participants aged 11-36 years, diagnosed with type 1 diabetes within the past 6 months were recruited from Sanford Health Systems (Sioux Falls, SD, USA; Fargo, ND, USA), Children’s Hospitals and Clinics of Minnesota (St Paul, MN, USA), and Rady Children’s Hospital (San Diego, CA, USA). Participants were randomly assigned (2: 1) to receive oral sitagliptin (100 mg for participants >= 18 years, 50 mg for those <18 years) and lansoprazole (60 mg for participants >= 18 years, 30 mg for those <18 years) or matched placebo for 12 months. Randomisation was done by a blocked randomisation process (blocks of three and six), with separate streams for younger (<18 years) and older (>= 18 years) participants, and males and females. All participants and personnel remained masked until after the completion of the final 12 month visit, at which time data were unmasked to the analysis team. The primary endpoint was C-peptide response to a mixed meal challenge at 12 months measured as 2 h area under curve. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01155284. Findings Between Sept 21, 2010, and May 29, 2012, 46 participants were randomly assigned to the treatment group and 22 to the placebo group; of whom 40 participants in the treatment group and 18 in the placebo group completed the 12-month treatment. At 12 months, the mean change in C-peptide area under curve was -229 pmol/L (95% CI -316 to -142) for the treatment group and -253 pmol/L (-383 to -123) for the placebo group; this difference was not significant (p= 0.77). No adverse or serious adverse events were probably or definitely related to the study treatment. Interpretation Although the expected change in the primary endpoint was not achieved, not all participants had increases in glucagon-like peptide-1 and gastrin concentrations that were expected with treatment. Although participants did not have adverse events related to study drugs, the study is not powered to address safety definitively. Further trials including these drugs might be warranted, but should be designed to ensure appropriate selection of participants and increases in these intermediary hormones.

Sanford School of Medicine, Sioux Falls Campus.

Gupta, Brij, Diane Maher, Mara Ebeling, Phillip Stephenson, Susan Puumala, Michael Koch, . . . Subhash Chauhan. (2014). Functions and regulation of MUC13 mucin in colon cancer cells. Journal of Gastroenterology, 49(10), 1378-1391.

Background: MUC13 is overexpressed and aberrantly localized in colon cancer tissue; however, the specific functions and regulation of MUC13 expression are unknown. Methods: Stable cell lines with either overexpressed or suppressed MUC13 levels were analyzed to determine cell growth, colony formation, cell migration, and cell invasion assays. The molecular mechanisms involved in MUC13 regulation were elucidated via chromatin immunoprecipitation (ChIP) and analysis of interleukin 6 (IL6) treatments. Colon cancer tissues were analyzed by immunohistochemistry (IHC) for the protein levels of MUC13 and P-STAT5 in colon cancer cells. Results: Overexpression of MUC13 increased cell growth, colony formation, cell migration, and invasion. In concordance, MUC13 silencing decreased these tumorigenic features. Overexpression of MUC13 also modulated various cancer-associated proteins, including telomerase reverse transcriptase, sonic hedgehog, B cell lymphoma murine like site 1, and GATA like transcription factor 1. Additionally, MUC13-overexpressing cells showed increased HER2 and P-ERK expression. ChIP analysis revealed binding of STAT5 to the predicted MUC13 promoter. IL6 treatment of colon cancer cells increased the expression of MUC13 via activation of the JAK2/STAT5 signaling pathway. Suppression of JAK2 and STAT5 signaling by chemical inhibitors abolished IL6-induced MUC13 expression. IHC analysis showed increased expression of both P-STAT5 and MUC13 in colon cancer as compared to adjacent normal tissue. Conclusions: The results of this study, for the first time, suggest functional roles of MUC13 in colon cancer progression and provide information regarding the regulation of MUC13 expression via JAK2/STAT5 which may reveal promising therapeutic approaches for colon cancer treatment.

Sanford School of Medicine, Sioux Falls Campus.

Haugrud, Allison B., Yongxian Zhuang, Joseph D. Coppock, & W. Keith Miskimins. (2014). Dichloroacetate enhances apoptotic cell death via oxidative damage and attenuates lactate production in metformin-treated breast cancer cells. Breast Cancer Research and Treatment, 147(3), 539-550.

 

The unique metabolism of breast cancer cells provides interest in exploiting this phenomenon therapeutically. Metformin, a promising breast cancer therapeutic, targets complex I of the electron transport chain leading to an accumulation of reactive oxygen species (ROS) that eventually lead to cell death. Inhibition of complex I leads to lactate production, a metabolic byproduct already highly produced by reprogrammed cancer cells and associated with a poor prognosis. While metformin remains a promising cancer therapeutic, we sought a complementary agent to increase apoptotic promoting effects of metformin while attenuating lactate production possibly leading to greatly improved efficacy. Dichloroacetate (DCA) is a well-established drug used in the treatment of lactic acidosis which functions through inhibition of pyruvate dehydrogenase kinase (PDK) promoting mitochondrial metabolism. Our purpose was to examine the synergy and mechanisms by which these two drugs kill breast cancer cells. Cell lines were subjected to the indicated treatments and analyzed for cell death and various aspects of metabolism. Cell death and ROS production were analyzed using flow cytometry, Western blot analysis, and cell counting methods. Images of cells were taken with phase contrast microscopy or confocal microscopy. Metabolism of cells was analyzed using the Seahorse XF24 analyzer, lactate assays, and pH analysis. We show that when DCA and metformin are used in combination, synergistic induction of apoptosis of breast cancer cells occurs. Metformin-induced oxidative damage is enhanced by DCA through PDK1 inhibition which also diminishes metformin promoted lactate production. We demonstrate that DCA and metformin combine to synergistically induce caspase-dependent apoptosis involving oxidative damage with simultaneous attenuation of metformin promoted lactate production. Innovative combinations such as metformin and DCA show promise in expanding breast cancer therapies.

Sanford School of Medicine, Sioux Falls Campus.

Miedema, Jayson, Daniel C. Zedek, Brian Z. Rayala, & E. Eugene Bain Iii. (2014). 9 tips to help prevent derm biopsy mistakes. Journal of Family Practice, 63(10), 559-564.

 

The article offers 9 tips for family physicians on how to prevent errors in conducting skin biopsy among patients.

Sanford School of Medicine, Sioux Falls Campus.

Novak, Jeanne, Wendy Parent-Johnson, Laura A. Owens, & Patricia Keul. (2014). National certification initiative for employment support professionals: Promoting quality integrated employment services. Journal of Vocational Rehabilitation, 40(2), 99-107.

 

This article describes a recent certification initiative to build an international network of professionals who have the knowledge and skills to provide quality integrated employment services to individuals with a variety of disabilities. An overview of the history and conceptual framework guiding the development of the Employment Support Professional Certification Program will be followed by a presentation of findings from a preliminary survey study of 93 professionals who have been certified. Survey respondents identified both personal and professional motivations for pursuing the Certified Employment Support Professional (CESP) designation, including the desire to (a) achieve a sense of accomplishment and personal satisfaction, (b) demonstrate a professional standard of competence and commitment to the profession, and (c) garner professional credibility and enhanced opportunities for career advancement. The authors describe ongoing efforts and recommendations for validating the credentialing program and for increasing the number of certified professionals equipped to establish and expand equitable employment opportunities for individuals with disabilities. (PsycINFO Database Record (c) 2014 APA, all rights reserved). (journal abstract)

Sanford School of Medicine, Sioux Falls Campus.

Radichev, Ilian A., Lilia V. Maneva-Radicheva, Christina Amatya, Camille Parker, Jacob Ellefson, Clive Wasserfall, . . . Alexei Y. Savinov. (2014). Nardilysin-Dependent Proteolysis of Cell-Associated VTCN1 (B7-H4) Marks Type 1 Diabetes Development. Diabetes, 63(10), 3470-3482.

T-cell responses directed against insulin-secreting pancreatic β-cells are the key events highlighting type 1 diabetes (T1D). Therefore, a defective control of T-cell activation is thought to underlie T1D development. Recent studies implicated a B7-like negative costimulatory protein, V-set domain-containing T-cell activation inhibitor-1 (VTCN1), as a molecule capable of inhibiting T-cell activation and, potentially, an important constituent in experimental models of T1D. Here, we unravel a general deficiency within the VTCN1 pathway that is shared between diabetes-prone mice and a subset of T1D patients. Gradual loss of membrane-tethered VTCN1 from antigen-presenting cells combined with an increased release of soluble VTCN1 (sVTCN1) occurs in parallel to natural T1D development, potentiating hyperproliferation of diabeto-genic T cells. Mechanistically, we demonstrate that the loss of membrane-tethered VTCN1 is linked to proteolytic cleavage mediated by the metalloproteinase nardilysin. The cleaved sVTCN1 fragment was detected at high levels in the peripheral blood of 53% T1D patients compared with only 9% of the healthy subjects. Elevated blood sVTCN1 levels appeared early in the disease progression and correlated with the aggressive pace of disease, highlighting the potential use of sVTCN1 as a new T1D biomarker, and identifying nardilysin as a potential therapeutic target.

Sanford School of Medicine, Sioux Falls Campus.

Savinova, Olga V., Kristi Fillaus, L. Jing, William S. Harris, & Gregory C. Shearer. (2014). Reduced Apolipoprotein Glycosylation in Patients with the Metabolic Syndrome. Plos One, 9(8), 9.

Objective: The purpose of this study was to compare the apolipoprotein composition of the three major lipoprotein classes in patients with metabolic syndrome to healthy controls. Methods: Very low density (VLDL), intermediate/low density (IDL/LDL, hereafter LDL), and high density lipoproteins (HDL) fractions were isolated from plasma of 56 metabolic syndrome subjects and from 14 age-sex matched healthy volunteers. The apolipoprotein content of fractions was analyzed by one-dimensional (1D) gel electrophoresis with confirmation by a combination of mass spectrometry and biochemical assays. Results: Metabolic syndrome patients differed from healthy controls in the following ways: (1) total plasma – apoA1 was lower, whereas apoB, apoC2, apoC3, and apoE were higher; (2) VLDL – apoB, apoC3, and apoE were increased; (3) LDL – apoC3 was increased, (4) HDL -associated constitutive serum amyloid A protein (SAA4) was reduced (p<0.05 vs. controls for all). In patients with metabolic syndrome, the most extensively glycosylated (di-sialylated) isoform of apoC3 was reduced in VLDL, LDL, and HDL fractions by 17%, 30%, and 25%, respectively (p<0.01 vs. controls for all). Similarly, the glycosylated isoform of apoE was reduced in VLDL, LDL, and HDL fractions by 15%, 26%, and 37% (p<0.01 vs. controls for all). Finally, glycosylated isoform of SAA4 in HDL fraction was 42% lower in patients with metabolic syndrome compared with controls (p<0.001). Conclusions: Patients with metabolic syndrome displayed several changes in plasma apolipoprotein composition consistent with hypertriglyceridemia and low HDL cholesterol levels. Reduced glycosylation of apoC3, apoE and SAA4 are novel findings, the pathophysiological consequences of which remain to be determined.

Sanford School of Medicine, Sioux Falls Campus.

Simpson, N. A., E. D. Wheeler, & David A. Pearce. (2014). Screening, diagnosis and epidemiology of Batten disease. Expert Opinion on Orphan Drugs, 2(9), 903-910.

Introduction: Batten disease, also called neuronal ceroid lipofuscinosis, describes a heterogeneous group of lysosomal storage disorders that are the most common inherited progressive neurodegenerative disorders in children. The disease is caused by mutations in the neuronal ceroid lipofusinoses (CLN) genes, which are mostly inherited in an autosomal recessive manner. Areas covered: Screening guidelines and diagnostic tools have been developed for Batten disease, and although improvements have been made to these tools they may not be widely available or accessible. While certain studies have investigated the epidemiology of Batten disease in certain geographic locations, the global prevalence of Batten disease is not well established. Expert opinion: An international patient registry may provide a mechanism to gather important data on individuals diagnosed with Batten disease and may serve as a resource that could help investigators better understand the epidemiology of the disease.

Sanford School of Medicine, Sioux Falls Campus.

Stewart, Brandie M., Jason P. Gallivan, Lee A. Baugh, & J. Randall Flanagan. (2014). Motor, not visual, encoding of potential reach targets. Current Biology, 24(19), R953-R954.

Summary We often encounter situations in which there are multiple potential targets for action, as when, for example, we hear the request “could you pass the …” at the dinner table. It has recently been shown that, in such situations, activity in sensorimotor brain areas represents competing reach targets in parallel prior to deciding between, and then reaching towards, one of these targets [1] . One intriguing possibility, consistent with the influential notion of action ‘affordances’ [2] , is that this activity reflects movement plans towards each potential target [3] . However, an equally plausible explanation is that this activity reflects an encoding of the visual properties of the potential targets (for example, their locations or directions), prior to any target being selected and the associated movement plan being formed. Notably, previous work showing spatial averaging behaviour during reaching, in which initial movements are biased towards the midpoint of the spatial distribution of potential targets [4–6] , remains equally equivocal concerning the motor versus visual encoding of reach targets. Here, using a rapid reaching task that disentangles these two competing accounts, we show that reach averaging behaviour reflects the parallel encoding of multiple competing motor plans. This provides direct evidence for theories proposing that the brain prepares multiple available movements before selecting between them [3] .

Sanford School of Medicine, Sioux Falls Campus.

Jang, Yuri, Soonhee Roh, & David A. Chiriboga. (2014). The impact of acculturation on depressive symptoms: A comparison of older Korean Americans in two areas. Asian American Journal of Psychology, 5(3), 200-205.

This study examined how the impact of acculturation on depressive symptoms varied between two samples of older Korean Americans. One sample was from west central Florida (low Korean density area; n = 672), and the other from the New York City metropolitan area (high Korean density area; n = 420). The average level of acculturation was lower among older Korean Americans in New York, compared to those living in Florida. In the hierarchical regression models with the New York sample, acculturation was initially significant in predicting depressive symptoms; however, its impact was gradually attenuated and eventually became nonsignificant with the sequential entry of control variables. On the other hand, in the Florida sample, the impact of acculturation on depressive symptoms remained significant throughout the models. The results suggest that the level and importance of acculturation may differ by geographic locations and invite further contextual research in immigrant populations.

School of Health Sciences.

Posted by: reganenosusd | September 10, 2014

September 2014

Klonoski, Joshua M., Hurtig, Heather R., Juber, Brian A., Schuneman, Margaret J., Bickett, Thomas E.,Svendsen, Joshua M., Burum, Brandon, Penfound, Thomas A., Sereda, Grigoriy,Dale, James B., Chaussee, Michael S., & Huber, Victor C. (2014). Vaccination against the M protein of Streptococcus pyogenes prevents death after influenza virus:S. pyogenes super-infection. Vaccine, 32(40), 5241-5249.

Influenza virus infections are associated with a significant number of illnesses and deaths on an annual basis. Many of the deaths are due to complications from secondary bacterial invaders, including Streptococcus pneumoniae , Staphylococcus aureus , Haemophilus influenzae , and Streptococcus pyogenes . The β-hemolytic bacteria S. pyogenes colonizes both skin and respiratory surfaces, and frequently presents clinically as strep throat or impetigo. However, when these bacteria gain access to normally sterile sites, they can cause deadly diseases including sepsis, necrotizing fasciitis, and pneumonia. We previously developed a model of influenza virus: S. pyogenes super-infection, which we used to demonstrate that vaccination against influenza virus can limit deaths associated with a secondary bacterial infection, but this protection was not complete. In the current study, we evaluated the efficacy of a vaccine that targets the M protein of S. pyogenes to determine whether immunity toward the bacteria alone would allow the host to survive an influenza virus: S. pyogenes super-infection. Our data demonstrate that vaccination against the M protein induces IgG antibodies, in particular those of the IgG1 and IgG2a isotypes, and that these antibodies can interact with macrophages. Ultimately, this vaccine-induced immunity eliminated death within our influenza virus: S. pyogenes super-infection model, despite the fact that all M protein-vaccinated mice showed signs of illness following influenza virus inoculation. These findings identify immunity against bacteria as an important component of protection against influenza virus:bacteria super-infection.

Basic Biomedical Sciences, Vermillion Campus [Everyone whose underlined except Sereda and Burum].

Chemistry Department [Sereda and Burum].

Barr, Jeffrey L., Forster, Gina L., & Unterwald, Ellen M. (2014). Repeated cocaine enhances ventral hippocampal-stimulated dopamine efflux in the nucleus accumbens and alters ventral hippocampal NMDA receptor subunit expression. Journal of Neurochemistry, 130(4), 583-590.

Dopaminergic neurotransmission in the nucleus accumbens is important for various reward-related cognitive processes including reinforcement learning. Repeated cocaine enhances hippocampal synaptic plasticity, and phasic elevations of accumbal dopamine evoked by unconditioned stimuli are dependent on impulse flow from the ventral hippocampus. Therefore, sensitized hippocampal activity may be one mechanism by which drugs of abuse enhance limbic dopaminergic activity. In this study, in vivo microdialysis in freely moving adult male Sprague-Dawley rats was used to investigate the effect of repeated cocaine on ventral hippocampus-mediated dopaminergic transmission within the medial shell of the nucleus accumbens. Following seven daily injections of saline or cocaine (20 mg/kg, ip), unilateral infusion of N-methyl- d-aspartate ( NMDA, 0.5 μg) into the ventral hippocampus transiently increased both motoric activity and ipsilateral dopamine efflux in the medial shell of the nucleus accumbens, and this effect was greater in rats that received repeated cocaine compared to controls that received repeated saline. In addition, repeated cocaine altered NMDA receptor subunit expression in the ventral hippocampus, reducing the NR2A : NR2B subunit ratio. Together, these results suggest that repeated exposure to cocaine produces maladaptive ventral hippocampal-nucleus accumbens communication, in part through changes in glutamate receptor composition.

Basic Biomedical Sciences, Vermillion Campus.

Tian, Zongwen, Wang, Changhua,Hu, Chengjun, Tian, Yihao, Liu, J. B., & Wang, Xuejun. (2014). Autophagic-Lysosomal Inhibition Compromises Ubiquitin-Proteasome System Performance in a p62 Dependent Manner in Cardiomyocytes. Plos One, 9(6).

Intracellular protein degradation is primarily performed by the ubiquitin-proteasome system (UPS) and the autophagic-lysosomal pathway (ALP). The interplay between these two pathways has been rarely examined in intact animals and the mechanism underlying the interplay remains unclear. Hence, we sought to test in vivo and in vitro the impact of inhibition of the ALP on UPS proteolytic performance in cardiomyocytes and to explore the underlying mechanism. Transgenic mice ubiquitously expressing a surrogate UPS substrate (GFPdgn) were treated with bafilomycin-A1 (BFA) to inhibit the ALP. Myocardial and renal GFPdgn protein levels but not mRNA levels were increased at 24 hours but not 3 hours after the first injection of BFA. Myocardial protein abundance of key proteasome subunits and the activities of proteasomal peptidases were not discernibly altered by the treatment. In cultured neonatal rat ventricular myocytes (NRVMs), the surrogate UPS substrate GFPu and a control red fluorescence protein (RFP) were co-expressed to probe UPS performance. At 12 hours or 24 hours after ALP inhibition by 3-methyladenine (3-MA) or BFA, GFPu/RFP protein ratios and the protein half-life of GFPu were significantly increased, which is accompanied by increases in p62 proteins. Similar findings were obtained when ALP was inhibited genetically via silencing Atg7 or Rab7. ALP inhibition-induced increases in GFPu and p62 are co-localized in NRVMs. siRNA-mediated p62 knockdown prevented ALP inhibition from inducing GFPu accumulation in NRVMs. We conclude that in a p62-dependent fashion, ALP inhibition impairs cardiac UPS proteolytic performance in cardiomyocytes in vitro and in vivo.

Basic Biomedical Sciences, Vermillion Campus.

Ghose, Sonia L., Donnelly, Maureen A., Kerby, Jacob,& Whitfield, Steven M. (2014). Acute toxicity tests and meta-analysis identify gaps in tropical ecotoxicology for amphibians. Environmental Toxicology & Chemistry, 33(9), 2114-2119.

Amphibian populations are declining worldwide, particularly in tropical regions where amphibian diversity is highest. Pollutants, including agricultural pesticides, have been identified as a potential contributor to decline, yet toxicological studies of tropical amphibians are very rare. The present study assesses toxic effects on amphibians of 10 commonly used commercial pesticides in tropical agriculture using 2 approaches. First, the authors conducted 8-d toxicity assays with formulations of each pesticide using individually reared red-eyed tree frog ( Agalychnis callidryas) tadpoles. Second, they conducted a review of available data for the lethal concentration to kill 50% of test animals from the US Environmental Protection Agency’s ECOTOX database to allow comparison with their findings. Lethal concentration estimates from the assays ranged over several orders of magnitude. The nematicides terbufos and ethoprophos and the fungicide chlorothalonil were very highly toxic, with evident effects within an order of magnitude of environmental concentrations. Acute toxicity assays and meta-analysis show that nematicides and fungicides are generally more toxic than herbicides yet receive far less research attention than less toxic herbicides. Given that the tropics have a high diversity of amphibians, the findings emphasize the need for research into the effects of commonly used pesticides in tropical countries and should help guide future ecotoxicological research in tropical regions.

Biology Department.

Monroe, E. M., & Britten, Hugh B. (2014). Conservation in Hine’s sight: the conservation genetics of the federally endangered Hine’s emerald dragonfly, Somatochlora hineana. Journal of Insect Conservation, 18(3), 353-363.

Hine’s emerald dragonfly (Somatochlora hineana) is distributed in discrete fen and wet meadow habitats over its range from Ontario, Canada, to Missouri, USA. Habitat destruction in the vicinity of Chicago, IL, and other areas lead to its designation as an US federal endangered species in 1995. Our main goal was to delineate the population genetic structure of the species within the northern recovery unit centered on the Door Peninsula in Wisconsin and the southern recovery unit in the Des Plaines River Valley near Chicago, IL. Sites on the Door Peninsula, WI, are in a matrix of agricultural development and second-growth forest and were used as a best available approximation of a pristine system for the dragonfly. We nondestructively sampled 557 adults and larvae from 16 sites in Illinois, Michigan, and Wisconsin from 2008 through 2011 and used ten microsatellite markers to estimate levels of genetic variability, and genetic structure. Mean allelic richness across all sites and years was 5.03 (+/- 0.64) and expected heterozygosity was 0.52 (+/- 0.032). Northern and southern recovery units as designated in the original recovery plan were genetically distinct. We delineated two genetic populations in the northern unit and three within the southern including two disjunct sites.

Biology Department.

Qiu, Chao, Bao, Ying,Netzer, Nathan L., & Jiang, Chaoyang. (2014). Environment-dependent optical scattering of cuprous oxide microcrystals in liquid dispersions and Langmuir-Blodgett films. Journal of Materials Chemistry C, 2(29), 5910-5915.

Optical properties of semiconductor materials are important for their broad applications, especially when the materials are nano-and micrometer crystals. Here we show that cuprous oxide microcrystals have three extinction peaks that are environment sensitive in the visible-near infrared region. The extinction peaks show a linear blue shift with the increase in refractive index of the surrounding medium. The environment-dependent shift of extinction spectra can also be observed for cuprous oxide in cast films and Langmuir-Blodgett films. The sensitivity of environment-dependent optical behavior depends on the energy of the extinction peaks. Both experimental work and theoretical calculation on the environment-dependent spectra of cuprous oxide microcrystals provide valuable knowledge on these functional semiconductor materials for various applications.

Chemistry Department.

St. Louis, Kenneth O., Williams, Mandy J., Ware, Mercedes B., Guendouzi, Jacqueline, & Reichel, Isabella K. (2014). The Public Opinion Survey of Human Attributes-Stuttering (POSHA-S) and Bipolar Adjective Scale (BAS): Aspects of validity. Journal of Communication Disorders, 50, 36-50.

Purpose In order to estimate instrument validity, attitudes toward stuttering measured by the newly developed Public Opinion Survey of Human Attributes-Stuttering (POSHA-S) and the Woods and Williams (1976) semantic differential scale (referred to herein as the Bipolar Adjective Scale [BAS]) are compared in college students on one occasion as well as before and after coursework on fluency disorders. Method Undergraduate and graduate students (n = 321) from four universities filled out online versions of the POSHA-S and BAS. Two-thirds were speech-language pathology (SLP) majors; one-third were students in other majors. A subset of the SLP students (n = 35) filled out the two instruments again after 8-13 weeks of coursework on fluency disorders. Results Correlations between all ratings of the POSHA-S and BAS were run for the 321 students. Only 26% of the correlations were statistically significant (R ≥±0.129), and the large majority of these reflected small relationships. POSHA-S ratings were correlated with up to 77% of the items of the BAS while BAS items were correlated with up to 45% of the POSHA-S ratings. After coursework on stuttering, students’ attitudes improved on both instruments, but more on the POSHA-S than the BAS. Conclusions Greater evidence of discriminant validity than convergent validity characterized the POSHA-S and BAS. Both measures showed improved attitudes after fluency disorders coursework, but more so for the POSHA-S, confirming previous reports of construct validity. The POSHA-S taps relevant constructs not included in the BAS, which provide advantages for intracultural, international, and other comparisons of public attitudes toward stuttering. Learning outcomes: The reader will be able to: (1) describe differentiating characteristics of the POSHA-S and BAS as measures of public attitudes toward stuttering, (2) describe the overlap and lack of overlap in the constructs measured by POSHA-S and BAS, (3) describe discriminant versus convergent validity and (4) describe advantages of the POSHA-S and BAS in various types of comparative studies of stuttering attitudes.

Communications Disorders Department.

Ehsan, Md. Amimul, Khizar, M., Raja, M. Y. A., & Mei, Dongming. (2014). Numerical Analysis of a-Si/c-Si1-xGex/c-Si Heterostructures Based on Si and Ge Thin-Film Solar Cells. Arabian Journal for Science and Engineering, 39(7), 5347-5353.

The electrical transport properties of a-Si/cSi(1-x)Ge(x)/c-Si heterostructure thin-film solar cells are described. A lattice mismatch of similar to 4.17 % between Si and Ge is always challenging when considering such material system. Numerical optimization of the layer by layer structure shows that Si absorber and p Si1-xGex strained layers play a critical role to improve the light absorption properties of a-Si/c-Si1-xGex/c-Si heterostructure for their infrared detection applications. For this study, a finite element analysis technique is used to solve the fully coupled two carrier semiconductor transport equations. Obtained results show a substantial enhancement in the conversion efficiency of the newly designed a-Si/c-Si1-xGex/c-Si heterostructure thin-film solar cell. Achieved enhancement in conversion efficiency is attributed due to a noticeable improvement in the open circuit voltage (V-OC) and a corresponding increase in the optical path lengths. Comparative study of the Si-and Ge-based thin-film solar cells shows that the conversion efficiency of Si-based heterostructures is better than germanium mainly due to the low thermal and lattice mismatch of Si to the design hetero-epitaxial structure. As much as a conversion efficiency of similar to 21.19 % was calculated for a-Si/cSi(1-x)Ge(x)/c-Si heterostructure thin-film solar cell.

Physics Department.

Messier, Erick C., Quevillon, Randal P., & Simons, Jeffrey S. (2014). The Effect of Perceived Parental Approval of Drinking on Alcohol Use and Problems. Journal of Alcohol& Drug Education, 58(1), 44-59.

The relationship between perceived parental approval of drinking and alcohol use and problems was explored with undergraduate students in a small midwestern university. Participants completed a survey measuring demographic information, perceived approval of drinking, and alcohol use and problems. Results indicated perceived parental approval of drinking was significantly related to alcohol use and problems. Path analysis demonstrated perceived parental approval of drinking affected weekly drinking quantity, alcohol use frequency, and negative consequences of alcohol indirectly through perceived friends’ approval of drinking. There was also a significant direct effect from parental approval to alcohol use frequency. These findings suggest that parents may influence their children’s drinking by mechanisms such as affecting peer selection.

Psychology Department.

Simons, Jeffrey S., Wills, Thomas A., & Neal, Dan J. (2014). The Many Faces of Affect: A Multilevel Model of Drinking Frequency/Quantity and Alcohol Dependence Symptoms Among Young Adults. Journal of Abnormal Psychology, 123(3), 676-694.

This research tested a multilevel structural equation model of associations between 3 aspects of affective functioning (state affect, trait affect, and affective lability) and 3 alcohol outcomes (likelihood of drinking, quantity on drinking days, and dependence symptoms) in a sample of 263 college students. Participants provided 49 days of experience sampling data over 1.3 years in a longitudinal burst design. Within-person results: At the daily level, positive affect was directly associated with greater likelihood and quantity of alcohol consumption. Daily negative affect was directly associated with higher consumption on drinking days and with higher dependence symptoms. Between-person direct effects: Affect lability was associated with higher trait negative, but not positive, affect. Trait positive affect was inversely associated with the proportion of drinking days, whereas negative affectivity predicted a greater proportion of drinking days. Affect lability exhibited a direct association with dependence symptoms. Between-person indirect effects: Trait positive affect was associated with fewer dependence symptoms via proportion of drinking days. Trait negative affect was associated with greater dependence symptoms via proportion of drinking days. The results distinguish relations of positive and negative affect to likelihood versus amount of drinking and state versus trait drinking outcomes, and highlight the importance of affect variability for predicting alcohol dependence symptoms.

Psychology Department.

Hansen, Keith A. (2014). What Is New in Polycystic Ovary Syndrome?Obstetrics & Gynecology, 124(3), 630-632s.

Sanford School of Medicine, Sioux Falls Campus.

Harris, William S., Pottala, James V., Thiselton, D. L., Varvel, S. A., Baedke, A. M., Dayspring, T. D., Warnick, G. R., & McConnell, J. P. (2014). Does APOE Genotype Modify the Relations Between Serum Lipid and Erythrocyte Omega-3 Fatty Acid Levels? Journal of Cardiovascular Translational Research, 7(5), 526-532.

Earlier reports indicated that patients with the apolipoprotein APOE epsilon 4 allele responded to fish oil supplementation with a rise in serum low-density lipoprotein cholesterol (LDL-C) compared to epsilon 3 homozygotes. In this study, we used clinical laboratory data to test the hypothesis that the cross-sectional relation between RBC omega-3 fatty acid status (the Omega-3 Index) and LDL-C was modified by APOE genotype. Data from 136,701 patients were available to compare lipid biomarker levels across Omega-3 Index categories associated with heart disease risk in all APOE genotypes. We found no adverse interactions between APOE genotype and the Omega-3 Index for LDL-C, LDL particle number, apoB, HDL-C, or triglycerides. However, we did find evidence that epsilon 2 homozygotes lack an association between omega-3 status and LDL-C, apoB, and LDL particle number. In summary, we found no evidence for a deleterious relationship between lipid biomarkers and the Omega-3 Index by APOE genotype.

Sanford School of Medicine, Sioux Falls Campus.

Levin, S. W., Baker, E. H., Zein, W. M., Zhang, Z. J., …, Griffin, Kurt J., Bianconi, S., Chandra, G., Khan, O. I., Caruso, R. C., Liu, A. Y., & Mukherjee, A. B. (2014). Oral cysteamine bitartrate and N-acetylcysteine for patients with infantile neuronal ceroid lipofuscinosis: a pilot study.Lancet Neurology, 13(8), 777-787.

Background Infantile neuronal ceroid lipofuscinosis is a devastating neurodegenerative lysosomal storage disease caused by mutations in the gene (CLN1 or PPT1) encoding palmitoyl-protein thioesterase-1 (PPT1). We have previously reported that phosphocysteamine and N-acetylcysteine mediate ceroid depletion in culured cells from patients with this disease. We aimed to assess whether combination of oral cysteamine bitartrate and N-acetylcysteine is beneficial for patients with neuronal ceroid lipofuscinosis. Methods Children between 6 months and 3 years of age with infantile neuronal ceroid lipofuscinosis with any two of the seven most lethal PPT1 mutations were eligible for inclusion in this pilot study. All patients were recruited from physician referrals. Patients received oral cysteamine bitartrate (60 mg/kg per day) and N-acetylcysteine (60 mg/kg per day) and were assessed every 6-12 months until they had an isoelectric electroencephalogram (EEG, attesting to a vegetative state) or were too ill to travel. Patients were also assessed by electroretinography, brain MRI and magnetic resonance spectroscopy (MRS), and electron microscopic analyses of leukocytes for granular osmiophilic deposits (GRODs). Children also underwent physical and neurodevelopmental assessments on the Denver scale. Outcomes were compared with the reported natural history of infantile neuronal ceroid lipofuscinosis and that of affected older siblings. Findings Between March 14, 2001, and June 30, 2012, we recruited ten children with infantile neuronal ceroid lipofuscinosis; one child was lost to follow-up after the first visit and nine patients (five girls and four boys) were followed up for 8 to 75 months. MRI showed abnormalities similar to those in previous reports; brain volume and N-acetyl aspartic acid (NAA) decreased steadily, but no published quantitative MRI or MRS studies were available for comparison. None of the children acquired new developmental skills, and their retinal function decreased progressively. Average time to isoelectric EEG (52 months, SD 13) was longer than reported previously (36 months). At the first follow-up visit, peripheral leukocytes in all nine patients showed virtually complete depletion of GRODs. Parents and physicians reported less irritability, improved alertness, or both in seven patients. No treatment-related adverse events occurred apart from mild gastrointestinal discomfort in two patients, which disappeared when liquid cysteamine bitartrate was replaced with capsules. Interpretation Our findings suggest that combination therapy with cysteamine bitartrate and N-acetylcysteine is associated with delay of isoelectric EEG, depletion of GRODs, and subjective benefits as reported by parents and physicians. Our systematic and quantitative report of the natural history of patients with infantile neuronal ceroid lipofuscinosis provides a guide for future assessment of experimental therapies.

Sanford School of Medicine, Sioux Falls Campus.

Reindl, Bailey A., Lynch, Douglas W., & Jassim, Ali D. (2014). Aggressive Variant of a Solid Pseudopapillary Neoplasm A Case Report and Literature Review. Archives of Pathology & Laboratory Medicine, 138(7), 974-978.

Solid pseudopapillary neoplasm, a lesion of uncertain cellular differentiation, is an unusual tumor of the pancreas with an indolent clinical course that typically arises in young females. We report a case of solid pseudopapillary neoplasm arising in a 17-year-old adolescent girl who presented with progressive abdominal pain. The patient underwent surgical resection of an 18 x 14 x 8-cm pancreatic mass that displayed the usual histologic features of a solid pseudopapillary neoplasm in addition to prominent nuclear atypia, increased proliferative index, and extensive necrosis. These unusual histologic findings are rare and are of particular interest owing to the dramatically decreased survival time displayed in this case. Although precise pathologic criteria suggesting a high risk for aggressive behavior of solid pseudopapillary neoplasms are uncertain, recognition of the unusual pathologic features displayed in this case may be useful in the prediction of potentially more aggressive neoplasms that portend a poorer prognosis.

Sanford School of Medicine, Sioux Falls Campus.

Newland, Lisa A. (2014). Supportive family contexts: promoting child well-being and resilience. Early Child Development & Care, 184(9/10), 1336-1346.

Prevention and intervention programmes for children at risk aim to improve child well-being and resilience. They do so using both direct and indirect strategies, intervening with children but also considering broader contextual factors (such as family dynamics). Children’s subjective well-being comprises five main components (physical health, mental health, self-regulation, social competence, and cognitive competence) and is predicted by person, relationship, and contextual factors. Children’s resilience, or ability to beat the odds under adverse conditions, is predicted by similar protective factors. Family well-being (FWB) is one of the strongest and most consistent predictors of child well-being and resilience. Aspects of FWB (including adult health and well-being, family self-sufficiency, and family resiliency) have been shown to impact child well-being through positive parent–child interactions. However, risk factors (including poverty and living in geographic locales with limited resources or high levels of neighbourhood violence) can threaten both family and child well-being. Strategies are offered for promoting FWB as a means of supporting resilience and well-being in children at risk for violence, abuse, or neglect.

School of Education.

Biricocchi, Charlanne, Drake, JamieLynn,& Svien, Lana. (2014). Balance Outcomes Following a Tap Dance Program for a Child With Congenital Myotonic Muscular Dystrophy. Pediatric Physical Therapy, 26(3), 360-365.

Purpose: This case report describes the effects of a 6-week progressive tap dance program on static and dynamic balance for a child with type 1 congenital myotonic muscular dystrophy (congenital MMD1). Summary of Key Points: A 6-year-old girl with congenital MMD1 participated in a 1-hour progressive tap dance program. Classes were held once a week for 6 consecutive weeks and included 3 children with adaptive needs and 1 peer with typical development. The Bruininks-Oseretsky Test of Motor Proficiency, second edition (BOT-2) balance subsection and the Pediatric Balance Scale were completed at the beginning of the first class and the sixth class. The participant’s BOT-2 score improved from 3 to 14. Her Pediatric Balance Scale score did not change. Conclusion: Participation in a progressive tap dance class by a child with congenital MMD1 may facilitate improvements in static and dynamic balance.

Scnool of Health Sciences.

 

Posted by: reganenosusd | September 9, 2014

July 2014

Huber, Victor C. (2014). Influenza vaccines: from whole virus preparations to recombinant protein technology. Expert Review of Vaccines, 13(1), 31-42.

Vaccination against influenza represents our most effective form of prevention. Historical approaches toward vaccine creation and production have yielded highly effective vaccines that are safe and immunogenic. Despite their effectiveness, these historical approaches do not allow for the incorporation of changes into the vaccine in a timely manner. In 2013, a recombinant protein-based vaccine that induces immunity toward the influenza virus hemagglutinin was approved for use in the USA. This vaccine represents the first approved vaccine formulation that does not require an influenza virus intermediate for production. This review presents a brief history of influenza vaccines, with insight into the potential future application of vaccines generated using recombinant technology.

Basic Biomedical Sciences, Vermillion Campus.

Liu, N. N., Liu, C. J., Li, X. F., …., Wang, Xuejun, Dou, Q. P., & Liu, J. B. (2014). A novel proteasome inhibitor suppresses tumor growth via targeting both 19S proteasome deubiquitinases and 20S proteolytic peptidases. Scientific Reports, 4, 13.

The successful development of bortezomib-based therapy for treatment of multiple myeloma has established proteasome inhibition as an effective therapeutic strategy, and both 20S proteasome peptidases and 19S deubiquitinases (DUBs) are becoming attractive targets of cancer therapy. It has been reported that metal complexes, such as copper complexes, inhibit tumor proteasome. However, the involved mechanism of action has not been fully characterized. Here we report that (i) copper pyrithione (CuPT), an alternative to tributyltin for antifouling paint biocides, inhibits the ubiquitin-proteasome system (UPS) via targeting both 19S proteasome-specific DUBs and 20S proteolytic peptidases with a mechanism distinct from that of the FDA-approved proteasome inhibitor bortezomib; (ii) CuPT potently inhibits proteasome-specific UCHL5 and USP14 activities; (iii) CuPT inhibits tumor growth in vivo and induces cytotoxicity in vitro and ex vivo. This study uncovers a novel class of dual inhibitors of DUBs and proteasome and suggests a potential clinical strategy for cancer therapy.

Basic Biomedical Sciences, Vermillion Campus.

Ouellette, Scott P., Rueden, Kelsey J., Gauliard, E., Persons, L., de Boer, P. A., & Ladant, D. (2014). Analysis of MreB interactors in Chlamydia reveals a RodZ homolog but fails to detect an interaction with MraY. Frontiers in Microbiology, 5.

Chlamydia is an obligate intracellular bacterial pathogen that has significantly reduced its genome in adapting to the intracellular environment. One class of genes for which the bacterium has few annotated examples is cell division, and Chlamydia lacks FtsZ, a central coordinator of the division apparatus. We have previously implicated MreB as a potential substitute for FtsZ in Chlamydia (Ouellette et al., 2012). Thus, to identify new chlamydial cell division components, we searched for proteins that interacted with MreB. We performed a small-scale screen using a Gateway (R) compatible version of the Bacterial Adenylate Cyclase Two Hybrid (BACTH) system, BACTH(Gw), to detect proteins interacting with chlamydial MreB and identified a RodZ (YfgA) homolog. The chlamydial RodZ aligns well with the cytoplasmic domain of E. coli RodZ but lacks the periplasmic domain that is dispensable for rod cell shape maintenance in E. coli. The expression pattern of yfgA/rodZ was similar to that of mreB and ftsl, suggesting that these genes may operate in a common functional pathway. The chlamydial RodZ correctly localized to the membrane of E. coli but was unable to complement an E. coli rodZ mutant strain, likely because of the inability of chlamydial RodZ to interact with the native E. coli MreB. Finally, we also tested whether chlamydial MreB could interact with MraY, as suggested by Gaballah et al. (2011). However, we did not detect an interaction between these proteins even when using an implementation of the BACTH system to allow native orientation of the N- and C-termini of MraY in the periplasm. Thus, further work will be needed to establish this proposed interaction. In sum, we have added to the repertoire of potential cell division proteins of Chlamydia.

Basic Biomedical Sciences, Vermillion Campus.

Shewchuk, Richard M., Carlson, Greg L., Klosterman, Matt, Cullen, Stephen, & Qu, Haiyan. (2014). Frictions as Barriers to Perioperative Alignment: Results From a Latent Class Analysis. Quality Management in Health Care, 23(3), 188-200.

The quality of the relationship between the sterile processing department (SPD) and the operating room (OR) is an important determinant of OR safety and performance. In this article, the concept of “friction ” refers to the SPD behaviors and attributes that can negatively affect OR performance. Panels of SPD professionals initially were asked to identify and operationally define different ways in which behaviors of a hospital’s SPD could compromise OR performance. A national convenience sample of OR nurses (N = 291 ) rated 14 frictions in terms of their agreement or disagreement that each had a negative effect on OR performance in their hospital. Overall, more than 50% of the entire sample agreed that 2 frictions, “SPD does not communicate effectively with the OR” (55%) and “SPD inventories are insufficient for surgical volume” (52%), had negative effect on OR performance. However, a latent class analysis revealed 3 distinct classes of nurses who varied with respect to their level of agreement that SPD-OR frictions negatively affected OR performance. The observed heterogeneity in how different groups of nurses viewed different frictions suggests that effective efforts aimed at reducing performance-limiting frictions should be customized so that resources can be used where they are most needed. [ABSTRACT FROM AUTHOR]

Copyright of Quality Management in Health Care is the property of Lippincott Williams & Wilkins — Nursing and

Beacom School of Business.

Thiruppathi, Eagappanath, & Mani, Gopinath. (2014). Vitamin-C Delivery from CoCr Alloy Surfaces Using Polymer-Free and Polymer-Based Platforms For Cardiovascular Stent Applications. Langmuir, 30(21), 6237-6249.

Antiproliferative drugs such as paclitaxel and sirolimus are delivered from stents to inhibit the growth of smooth muscle cells (SMCs) for preventing neointimal hyperplasia. However, these drugs delay the growth of endothelial cells (ECs) as well and cause late stent thrombosis. We recently demonstrated the use of Vitamin-C (L-ascorbic acid, L-AA) over paclitaxel and sirolimus for inhibiting SMCs growth and promoting EC growth simultaneously. In this study, we have investigated the delivery of L-AA from CoCr alloy surfaces for potential use in stents. A polymer-free phosphoric acid (PA) platform and a polymer-based poly-(lactic-co-glycolic acid) (PLGA) platform were used for coating L-AA onto CoCr surfaces. For the PA platform, FTIR confirmed that the PA was coated on CoCr, while the AFM showed that the PA coating on the CoCr surface was homogeneous. The successful deposition of L-AA on PA-coated CoCr was also confirmed by FTIR. The uniform distribution of L-AA crystals on PA-coated CoCr was shown by SEM, optical profilometer, and AFM. The drug release studies showed that L-AA (276 mu g/cm(2)) was burst released from the PA platform by 1 h. For the PLGA platform, SEM showed that the L-AA incorporated polymer films were smoothly and uniformly coated on CoCr. FTIR showed that L-AA was incorporated into the bulk of the PLGA film. DSC showed that the L-AA was present in an amorphous form and formed an intermolecular bonding interaction with PLGA. The drug release studies showed that L-AA was sustained released from the PLGA coated CoCr for up to 24 h. The SEM, FTIR, and DSC characterizations of samples collected post drug release shed light on the mechanism of L-AA release from PLGA coated CoCr. Thus, this study demonstrated the delivery of L-AA from biomaterial surfaces for potential applications in stents and other implantable medical devices.

Biomedical Engineering, Sioux Falls Campus.

Dong, F., Koodali, Ranjit T., Wang, H. Q., & Ho, W. K. (2014). Nanomaterials for Environmental Applications. Journal of Nanomaterials.

Chemistry Department.

Han, Yulun, Lin, Cuikun,Meng, Qingguo, Dai, Fenggrong, Sykes, Andrew G., Berry, Mary T., & May, P. Stanley. (2014). (BMI)(3)LnCl(6) Crystals as Models for the Coordination Environment of LnCl(3) (Ln = Sm, Eu, Dy, Er, Yb) in 1-Butyl-3-methylimidazolium Chloride Ionic-Liquid Solution. Inorganic Chemistry, 53(11), 5494-5501.

A series of (BMI)(3)LnCl(6) (Ln = Sm, Eu, Dy, Er, Yb) crystals was prepared from solutions of LnCl(3) dissolved in the ionic liquid, 1-butyl-3-methylimidazolium chloride (BMICl). Crystals with Ln = 5% Sm + 95% Gd and with Ln = 5% Dy + 95% Gd were also grown to assess the importance of cross-relaxation in the Sm and Dy samples. The crystals are isostructural, with monoclinic space group P2(1)/c and four formula units per unit cell. The first coordination sphere of Ln(3+) consists of six Cl- anions forming a slightly distorted octahedral LnCl(6)(3-) center. The second coordination sphere is composed of nine BMI+ cations. The emission spectra and luminescence lifetimes of both (BMI)(3)LnCl(6) crystals and LnCl(3) in BMICl solution were measured. The spectroscopic similarities suggest that crystalline (BMI)(3)LnCl(6) provides a good model of the Ln(3+) coordination environment in BMICl solution.

Chemistry Department.

Jia, L., Hui, Y. C., Li, Z. S., Sun, H. L., & Wang, Zhenqiang. (2014). Luminescent lanthanide-2-phenylpyrimidine-carboxylate frameworks: structure and luminescence tuning. Crystengcomm, 16(28), 6483-6490.

Six novel luminescent lanthanide-2-phenylpyrimidine-carboxylate frameworks, namely, [Ln(ppmc)(3)(phen)] (Ln = Eu (1), Tb (2)), [Ln(ppmc)(2)(C2O4)(0.5)(H2O)] (Ln = Eu (3), Tb (4)), {[Eu(ppmdc)(phen)(C2O4)(0.5)]center dot 0.5H(2)O} (5) and [Tb(ppmdc)(benzoate)(phen)] (6) (Hppmc = 2- phenylpyrimidine-4-carboxylic acid, H(2)ppmdc = 2-phenylpyrimidine-4,6-dicarboxylic acid) have been synthesized. The X-ray structure analyses reveal that all of the compounds contain carboxylate-bridged dimer units; however, coordination environments of Ln(3+) ions, bridging modes of carboxylate, and the linkage between them are different. In the isostructural compounds 1 and 2, extensive pi-pi stacking exists between the anti-anti carboxylate bridged dimer. However, syn-anti carboxylate bridges are found in compounds 3 and 4 in which oxalate connects the dimers to form 1D chains. Compound 5 has a 2D structure connected by both mu 4-ppmdc(2-) and oxalate in which the carboxylates adopt both anti-anti and chelate-bridging modes. Compound 6 featuring 1D chains also contains anti-anti carboxylate-bridged dimers that are linked by the mu 3-ppmdc(2-) ligand. All six compounds show characteristic red or green emission attributed to Eu3+ and Tb3+. The luminescence lifetime and quantum yield are presented and discussed in detail. The use of different ligands and reaction conditions has led to distinct coordination environments of lanthanide ions and the aggregation of dimeric units, which are considered as the dominating factors for the resulting photoluminescence behaviour of solid samples.

Chemistry Department.

Rasalingam, Shivatharsiny, Peng, Rui, & Koodali, Ranjit T. (2014). Removal of Hazardous Pollutants from Wastewaters: Applications of TiO2-SiO2 Mixed Oxide Materials. Journal of Nanomaterials.

The direct release of untreated wastewaters from various industries and households results in the release of toxic pollutants to the aquatic environment. Advanced oxidation processes (AOP) have gained wide attention owing to the prospect of complete mineralization of nonbiodegradable organic substances to environmentally innocuous products by chemical oxidation. In particular, heterogeneous photocatalysis has been demonstrated to have tremendous promise in water purification and treatment of several pollutant materials that include naturally occurring toxins, pesticides, and other deleterious contaminants. In this work, we have reviewed the different removal techniques that have been employed for water purification. In particular, the application of TiO2-SiO2 binary mixed oxide materials for wastewater treatment is explained herein, and it is evident from the literature survey that these mixed oxide materials have enhanced abilities to remove a wide variety of pollutants.

Chemistry Department.

Suter, John D., Pekas, Nicholas J., Berry, Mary T., & May, P. Stanley. (2014). Real-Time-Monitoring of the Synthesis of beta-NaYF4:17% Yb,3% Er Nanocrystals Using NIR-to-Visible Upconversion Luminescence. Journal of Physical Chemistry C, 118(24), 13238-13247.

In situ real-time monitoring of upconversion emission is applied to study the reaction mechanism for the synthesis of beta-NaYF4:17% Yb,3% Er nanoparticles in oleic acid and octadecene via the heat-up method. Transmission electron microscopy is used to correlate the spectroscopic signature of the reaction mixture with its composition. The power of real-time spectroscopic monitoring to precisely time the duration of the various stages of the reaction, and to accurately identify the transitions between those stages, including the completion of the reaction, is demonstrated. During the heat-up stage, the initial precipitate present is transformed into small alpha-phase nanoparticles. In the second and longest stage of the reaction, a period of relative stasis is maintained, during which there is at most a slight change in the size distribution of the alpha-phase nanoparticles formed during heat-up. In the third stage, a relatively rapid conversion of small alpha-phase nanoparticles to the larger beta-phase product nanoparticles is observed. The size distribution of the beta product remains relatively constant during the phase-transition stage, indicating that, once the beta particles begin to form, they grow very rapidly to the final product size. A significant variation in the time required to complete the reaction is observed, which is due almost entirely to the variation in the duration of the second reaction stage. The time required to complete the reaction does not appear to affect the size or uniformity of the product beta-NaYF4:17% Yb,3% Er nanoparticles.

Chemistry Department.

Wang, C. Y., Lin, Cuikun, Zhang, L. H., Quan, Z. W., Sun, K., Zhao, Bo, . . . Fang, J. Y. (2014). Pt3Co Concave Nanocubes: Synthesis, Formation Understanding, and Enhanced Catalytic Activity toward Hydrogenation of Styrene. Chemistry-a European Journal, 20(6), 1753-1759.

We report a facile synthesis route to prepare high-quality Pt3Co nanocubes with a concave structure, and further demonstrate that these concave Pt3Co nanocubes are terminated with high-index crystal facets. The success of this preparation is highly dependent on an appropriate nucleation process with a successively anisotropic overgrowth and a preservation of the resultant high-index planes by control binding of oleyl-amine/oleic acid with a fine-tuned composition. Using a hydrogenation of styrene as a model reaction, these Pt3Co concave nanocubes as a new class of nanocatalysts with more open structure and active atomic sites located on their high-index crystallographic planes exhibit an enhanced catalytic activity in comparison with low-indexed surface terminated Pt3Co nanocubes in similar size.

Chemistry Department.

Yulun, Han, Cuikun, Lin,Qingguo, Meng, Dai, Fengrong, Sykes, Andrew G., Berry, Mary T., & May, P. Stanley. (2014). (BMI)3LnCl6 Crystals as Models for the Coordination Environment of LnCl3 (Ln = Sm, Eu, Dy, Er, Yb) in l-Butyl-3-methylimidazolium Chloride Ionic-Liquid Solution. Inorganic Chemistry, 53(11), 5494-5501.

A series of (BMI)3LnCl6 (Ln = Sm, Eu, Dy, Er, Yb) crystals was prepared from solutions of LnCl3 dissolved in the ionic liquid, l-butyl-3-methylimidazolium chloride (BMICl). Crystals with Ln = 5% Sm + 95% Gd and with Ln = 5% Dy + 95% Gd were also grown to assess the importance of cross-relaxation in the Sm and Dy samples. The crystals are isostructural, with monoclinic space group P2l/c and four formula units per unit cell. The first coordination sphere of Ln3+ consists of six Cl- anions forming a slightly distorted octahedral LnCl63- center. The second coordination sphere is composed of nine BMI+ cations. The emission spectra and luminescence lifetimes of both (BMI)3LnCl6 crystals and LnCl3 in BMICI solution were measured. The spectroscopic similarities suggest that crystalline (BMI)3LnCl6 provides a good model of the Ln3+ coordination environment in BMICl solution. [ABSTRACT FROM AUTHOR]

Copyright of Inorganic Chemistry is the property of American Chemical Society and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder’s express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Chemistry Department.

Roripaugh, Lee Ann. (2014). Moist Towelette. North American Review, 299(2), 14-15.

English Department.

Flores, Jose D., & Gonzalez-Olivares, E. (2014). Dynamics of a predator-prey model with Allee effect on prey and ratio-dependent functional response. Ecological Complexity, 18, 59-66.

We analyze a ratio-dependent predator-prey model with Allee effect on the prey by making a parametric analysis of the stability properties of the dynamics of the system in which the functional response is a function of the ratio of prey to predator abundance. An important mathematical feature of these type of models is that while the functional response is undefined at the origin, the origin is singular equilibrium. We present the different types of system behaviors for different parameter values, showing the existence of separatrix curves in the phase plane determining that the long-term system’s dynamic is dependent on the initial conditions. The model is studied analytically as well as numerically, including stability and bifurcation analysis. We also discuss the biological relevance of the model regarding both coexistence (conservation) and extinction (biological control) issues. (C) 2014 Elsevier B.V. All rights reserved.

Mathematics Department.

Mirabolfathi, N., Amman, M., Faiez, D., Luke, P. N., Martin, Ryan D., Rolla, J. A., . . . Vetter, K. (2014). Neganov-Luke Phonon Amplification in P-type Point Contact Detectors. Journal of Low Temperature Physics, 176(3-4), 209-215.

The Cryogenic Dark Matter Search (CDMS) detectors measure ionization and athermal phonons in high purity germanium crystals to discriminate between nuclear recoils from dark matter candidates and radioactive backgrounds. In order to reach lower energy detection thresholds, the CDMSlite experiment operates the CDMS detectors with a larger voltage bias to increase the signal-to-noise ratio using the Neganov-Luke effect. Breakdown in those detectors was observed at fields of order 30 V/cm, but the reason for the breakdown is unknown. It is unclear if the breakdowns are due to surface leakage current, impact ionization in the bulk of the crystals, or some other effect due to the very low operating temperatures of the detectors. Germanium detectors used in gamma spectroscopy at 77 K are regularly operated with fields in excess of 1,000 V/cm. In order to understand the origin of breakdown in the CDMS detectors, a P-type Point Contact detector was equipped with transition edge phonon thermistors and operated at a base temperature of 30 mK. The linearity of the Neganov-Luke phonon amplification was studied and no sign of breakdown for biases up to 400 V was observed. This excludes impact ionization on neutral impurity states as the primary cause of the breakdown observed in the CDMSLite detectors. This demonstrates that the Neganov-Luke phonon amplification is a viable method for lowering the energy threshold in germanium detectors of masses of order 1 kg.

Physics Department.

Emery, Noah N., Simons, Jeffrey S., Clarke, C. Joseph, & Gaher, Raluca M. (2014). Emotion differentiation and alcohol-related problems: The mediating role of urgency. Addictive Behaviors, 39(10), 1459-1463.

Deficits in emotional and behavioral regulation figure prominently in etiological models of alcohol-related problems. This study tests a model linking poor differentiation of emotion to alcohol-related problems via urgency. The sample consisted of 102 undergraduates between the ages 18 and 24 who reported moderate to heavy alcohol consumption. As hypothesized, negative urgency mediated the relationship between negative emotion differentiation and alcohol-related problems. However, contrary to hypothesis, positive urgency was not associated with either positive emotion differentiation or alcohol-related problems and the indirect effect of positive emotion differentiation via positive urgency was not significant. Instead, positive emotion differentiation exhibited a significant direct effect on alcohol-related problems. This study provides an initial examination of connections between specificity in labeling emotions, behavioral disinhibition, and problematic alcohol use. These findings suggest that poor differentiation of negative emotion may foster impulsive behavior when negatively aroused. Whereas, impulsive behavior when positively aroused may reflect heightened sensitivity to positive reinforcement, which may not be related to reflective processes underlying emotion differentiation.

Psychology Department.

Struckman-Johnson, Cindy, Gaster, Samuel, & Struckman-Johnson, Dave. (2014). A preliminary study of sexual activity as a distraction for young drivers. Accident Analysis& Prevention, 71, 120-128.

In what may be the first in-depth study of sexual activity as a driving distraction in the US, a sample of 195 male and 511 female college students at a Midwestern university (M age = 19.7) participated in an on-line study of sex while driving (SWD). Of these, 64 (32.8%) men and 47 (9.3%) women had engaged in sex while driving (SWD). Nine percent of men and 29% of women had engaged in SWD as a passenger. In most recent SWD incidents, respondents reported that the two most common acts were oral sex (70.3%) and genital touching (60.4%). About 11% engaged in vaginal intercourse. Sexual activity lasted from 1 to 10 min for 42.7% of the respondents. Nearly half (49.1%) were traveling 61-80 mph during sex. Considering respondents’ lifetime incidents of SWD, the most common driving errors reported were speeding (37.8%), drifting into another lane (36%), and letting go of the steering wheel (10.8%). Only 1.8% nearly had a crash, and none actually had a crash. Separate regression analyses for male and female respondents revealed that lower intentions to engage in SWD in the future were associated with higher estimates of the probability of a car crash. The authors consider SWD to be an under-reported in-vehicle distraction and encourage more research and prevention efforts.

Psychology Department.

Ahrendt, April D., Kattelmann, Kendra K., Rector, Thomas S., & Maddox, David A. (2014). The effectiveness of telemedicine for weight management in the MOVE! Program. The Journal of Rural Health, 30(1), 113-119.

Purpose: To examine the effectiveness of videoconferencing technology for delivering comprehensive weight management treatment. Methods: This retrospective cohort study was conducted by extraction of data from medical records for the years 2008‐2010. The treatment included a series of 12 weekly MOVE!® classes delivered using videoconferencing. Data were extracted from the time of baseline weight to 1 year after baseline weight for the MOVE! participants (n = 60) and from a concurrent control group (n = 60) that did not participate in MOVE! treatment. Findings: Results indicated that the MOVE! group lost weight while the control group gained weight, resulting in a mean difference between the groups of −5.5 ± 2.7 kg (95% CI = −8.0 to −3.0; P &lt; .0001). Conclusions: These results indicate that videoconferencing is an effective method to provide the MOVE! Weight Management Program to veterans. Weight loss was maintained for one year after baseline in the MOVE! group. This is very promising as weight re‐gain is a common issue and these results support using videoconferencing for a long‐term weight management treatment option. (PsycINFO Database Record (c) 2014 APA, all rights reserved). (journal abstract)

Sanford School of Medicine, Sioux Falls Campus.

Harris, William S. (2014). Achieving optimal n-3 fatty acid status: the vegetarian’s challenge … or not. American Journal of Clinical Nutrition, 100(1), 449S-452S.

The long chain n-3 (omega-3) fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), although originally synthesized by microorganisms in the oceans, are primarily obtained from the consumption of fish. Vegetarians, by definition, do not eat fish and thus consume virtually no EPA and DHA. Because conversion of the plant-derived n-3 fatty acid a-linolenic acid (ALA) to EPA and DHA is very low, n-3 tissue concentrations in vegetarians are lower than in omnivores. This review asks 2 questions: what is the evidence that increased n-3 concentrations reduce the risk of cardiovascular disease in vegetarians, and, if it does, how can vegetarians increase their blood and tissue concentrations of these animal-derived fatty acids? At present, both cardiovascular risk markers and cardiovascular events appear to be significantly reduced in vegetarians compared with those in omnivores. If so, and in the absence of data to show that risk in vegetarians could be even lower with higher n-3 concentrations, then the second question becomes moot. However, the absence of evidence is not evidence of absence; therefore, at our present state of knowledge, increasing n-3 concentrations is not an unreasonable goal for vegetarians. This can be accomplished by a variety of approaches, including increased intakes of ALA, consumption of stearidonic acid enriched soybean oil (if and when it comes to the market), and the use of supplements containing EPA, DHA, or both derived from nonanimal sources (microalgae, biotech yeast, and, in the future, biotech plant oils).

Sanford School of Medicine, Sioux Falls Campus.

Hershman, D. L., Lacchetti, C., Dworkin, R. H., Smith, E. M. L., Bleeker, Jonathan, Cavaletti, G., . . . Loprinzi, C. L. (2014). Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers: American Society of Clinical Oncology Clinical Practice Guideline. Journal of Clinical Oncology, 32(18), 1941-+.

Purpose To provide evidence-based guidance on the optimum prevention and treatment approaches in the management of chemotherapy-induced peripheral neuropathies (CIPN) in adult cancer survivors. Methods A systematic literature search identified relevant, randomized controlled trials (RCTs) for the treatment of CIPN. Primary outcomes included incidence and severity of neuropathy as measured by neurophysiologic changes, patient-reported outcomes, and quality of life. Results A total of 48 RCTs met eligibility criteria and comprise the evidentiary basis for the recommendations. Trials tended to be small and heterogeneous, many with insufficient sample sizes to detect clinically important differences in outcomes. Primary outcomes varied across the trials, and in most cases, studies were not directly comparable because of different outcomes, measurements, and instruments used at different time points. The strength of the recommendations is based on the quality, amount, and consistency of the evidence and the balance between benefits and harms. Recommendations: On the basis of the paucity of high-quality, consistent evidence, there are no agents recommended for the prevention of CIPN. With regard to the treatment of existing CIPN, the best available data support a moderate recommendation for treatment with duloxetine. Although the CIPN trials are inconclusive regarding tricyclic antidepressants (such as nortriptyline), gabapentin, and a compounded topical gel containing baclofen, amitriptyline HCL, and ketamine, these agents may be offered on the basis of data supporting their utility in other neuropathic pain conditions given the limited other CIPN treatment options. Further research on these agents is warranted. (C) 2014 by American Society of Clinical Oncology

Sanford School of Medicine, Sioux Falls Campus.

Kim, D. I., Birendra, K. C., Zhu, W. H., Motamedchaboki, K., Doye, V., & Roux, Kyle J. (2014). Probing nuclear pore complex architecture with proximity-dependent biotinylation. Proceedings of the National Academy of Sciences of the United States of America, 111(24), E2453-E2461.

Proximity-dependent biotin identification (BioID) is a method for identifying protein associations that occur in vivo. By fusing a promiscuous biotin ligase to a protein of interest expressed in living cells, BioID permits the labeling of proximate proteins during a defined labeling period. In this study we used BioID to study the human nuclear pore complex (NPC), one of the largest macromolecular assemblies in eukaryotes. Anchored within the nuclear envelope, NPCs mediate the nucleocytoplasmic trafficking of numerous cellular components. We applied BioID to constituents of the Nup107-160 complex and the Nup93 complex, two conserved NPC subcomplexes. A strikingly different set of NPC constituents was detected depending on the position of these BioID-fusion proteins within the NPC. By applying BioID to several constituents located throughout the extremely stable Nup107-160 subcomplex, we refined our understanding of this highly conserved subcomplex, in part by demonstrating a direct interaction of Nup43 with Nup85. Furthermore, by using the extremely stable Nup107-160 structure as a molecular ruler, we defined the practical labeling radius of BioID. These studies further our understanding of human NPC organization and demonstrate that BioID is a valuable tool for exploring the constituency and organization of large protein assemblies in living cells.

Sanford School of Medicine, Sioux Falls Campus.

Levin, Sondra W., Baker, Eva H., Zein, Wadih M., …., Griffin, Kurt J., Bianconi, Simona, . . . Mukherjee, Anil B. (2014). Oral cysteamine bitartrate and N-acetylcysteine for patients with infantile neuronal ceroid lipofuscinosis: a pilot study. Lancet Neurology, 13(8), 777-787.

Background: Infantile neuronal ceroid lipofuscinosis is a devastating neurodegenerative lysosomal storage disease caused by mutations in the gene (CLN1 or PPT1) encoding palmitoyl-protein thioesterase-1 (PPT1). We have previously reported that phosphocysteamine and N-acetylcysteine mediate ceroid depletion in cultured cells from patients with this disease. We aimed to assess whether combination of oral cysteamine bitartrate and N-acetylcysteine is beneficial for patients with neuronal ceroid lipofuscinosis. Methods: Children between 6 months and 3 years of age with infantile neuronal ceroid lipofuscinosis with any two of the seven most lethal PPT1 mutations were eligible for inclusion in this pilot study. All patients were recruited from physician referrals. Patients received oral cysteamine bitartrate (60 mg/kg per day) and N-acetylcysteine (60 mg/kg per day) and were assessed every 6-12 months until they had an isoelectric electroencephalogram (EEG, attesting to a vegetative state) or were too ill to travel. Patients were also assessed by electroretinography, brain MRI and magnetic resonance spectroscopy (MRS), and electron microscopic analyses of leukocytes for granular osmiophilic deposits (GRODs). Children also underwent physical and neurodevelopmental assessments on the Denver scale. Outcomes were compared with the reported natural history of infantile neuronal ceroid lipofuscinosis and that of affected older siblings. This trial is registered with ClinicalTrials.gov, number NCT00028262. Findings: Between March 14, 2001, and June 30, 2012, we recruited ten children with infantile neuronal ceroid lipofuscinosis; one child was lost to follow-up after the first visit and nine patients (five girls and four boys) were followed up for 8 to 75 months. MRI showed abnormalities similar to those in previous reports; brain volume and N-acetyl aspartic acid (NAA) decreased steadily, but no published quantitative MRI or MRS studies were available for comparison. None of the children acquired new developmental skills, and their retinal function decreased progressively. Average time to isoelectric EEG (52 months, SD 13) was longer than reported previously (36 months). At the first follow-up visit, peripheral leukocytes in all nine patients showed virtually complete depletion of GRODs. Parents and physicians reported less irritability, improved alertness, or both in seven patients. No treatment-related adverse events occurred apart from mild gastrointestinal discomfort in two patients, which disappeared when liquid cysteamine bitartrate was replaced with capsules. Interpretation: Our findings suggest that combination therapy with cysteamine bitartrate and N-acetylcysteine is associated with delay of isoelectric EEG, depletion of GRODs, and subjective benefits as reported by parents and physicians. Our systematic and quantitative report of the natural history of patients with infantile neuronal ceroid lipofuscinosis provides a guide for future assessment of experimental therapies. Funding: National Institutes of Health.

Sanford School of Medicine, Sioux Falls Campus.

May, P. A., Hamrick, K. J., Corbin, K. D., Hoyme, H. Eugene, Hasken, J. M., Marais, A. S., Brooke, L. E., . . . Gossage, J. P. (2014). Dietary intake, nutrition, and fetal alcohol spectrum disorders in the Western Cape Province of South Africa. Reproductive Toxicology, 46, 31-39.

In this study, we describe the nutritional status of women from a South African community with very high rates of fetal alcohol spectrum disorders (FASD). Nutrient intake (24-h recall) of mothers of children with FASD was compared to mothers of normal controls. Nutrient adequacy was assessed using Dietary Reference Intakes (DRIs). More than 50% of all mothers were below the Estimated Average Requirement (EAR) for vitamins A, D, E, and C, thiamin, riboflavin, vitamin B-6, folate, calcium, magnesium, iron, and zinc. Mean intakes were below the Adequate Intake (AI) for vitamin K, potassium, and choline. Mothers of children with FASD reported significantly lower intake of calcium, docosapentaenoic acid (DPA), riboflavin, and choline than controls. Lower intake of multiple key nutrients correlates significantly with heavy drinking. Poor diet quality and multiple nutritional inadequacies coupled with prenatal alcohol exposure may increase the risk for FASD in this population. (C) 2014 Elsevier Inc. All rights reserved.

Sanford School of Medicine, Sioux Falls Campus.

Persons, J. E., Robinson, J. G., Ammann, E. M., …., Harris, William S., Manson, J. E., & Fiedorowicz, J. G. (2014). Omega-3 fatty acid biomarkers and subsequent depressive symptoms. International Journal of Geriatric Psychiatry, 29(7), 747-757.

ObjectiveWe sought to determine the relationship between the omega-3 fatty acid content of red blood cell membranes (RBC), in particular docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), and baseline and new-onset depressive symptoms in post-menopausal women. We secondarily sought to characterize the association between dietary omega-3 fatty acid intake and depressive symptomatology. MethodsStudy participants included 7086 members of the Women’s Health Initiative Memory Study (aged 63-81years) who had an assessment of RBC omega-3 fatty acid concentrations at the baseline screening visit. Depressive symptoms at baseline and follow-up were characterized using the Burnam eight-item scale for depressive disorders (Center for Epidemiologic Studies Depression Scale/Diagnostic Interview Schedule short form) and secondarily additionally inferred by antidepressant medication use. ResultsIn multivariable-adjusted models, our primary exposure, RBC DHA+EPA, was not related to depressive symptoms by any measure at baseline or follow-up, nor were RBC total omega-3, DHA, or EPA (all p>0.2). In contrast, dietary intake of omega-3 was positively associated with depressive symptoms at baseline (adjusted odds ratio 1.082, 95% confidence interval 1.004-1.166; p=0.04 for dietary DHA+EPA and Burnam score 0.06), although this generally did not persist at follow-up. ConclusionNo relationship between RBC omega-3 levels and subsequent depressive symptoms was evident, and associations between dietary omega-3 and depressive symptoms were variable. Biomarkers of omega-3 status do not appear to be related to risk of new depression in post-menopausal women.

Sanford School of Medicine, Sioux Falls Campus.

Reindl, Bailey A., Lynch, Douglas W., & Jassim, Ali D. (2014). Aggressive Variant of a Solid Pseudopapillary Neoplasm: A Case Report and Literature Review. 138, 974-978.

Solid pseudopapillary neoplasm, a lesion of uncertain cellular differentiation, is an unusual tumor of the pancreas with an indolent clinical course that typically arises in young females. We report a case of solid pseudopapillary neoplasm arising in a 17-year-old adolescent girl who presented with progressive abdominal pain. The patient underwent surgical resection of an 18 × 14 × 8-cm pancreatic mass that displayed the usual histologic features of a solid pseudopapillary neoplasm in addition to prominent nuclear atypia, increased proliferative index, and extensive necrosis. These unusual histologic findings are rare and are of particular interest owing to the dramatically decreased survival time displayed in this case. Although precise pathologic criteria suggesting a high risk for aggressive behavior of solid pseudopapillary neoplasms are uncertain, recognition of the unusual pathologic features displayed in this case may be useful in the prediction of potentially more aggressive neoplasms that portend a poorer prognosis.

Sanford School of Medicine, Sioux Falls Campus.

Terrier, B., Nagata, Satashi, Ise, Tomoko, Rosenzwajg, M., Pastan, I., Klatzmann, D., . . . Cacoub, P. (2014). CD21(-/low) Marginal Zone B Cells Highly Express Fc Receptor-like 5 Protein and Are Killed by Anti-Fc Receptor-like 5 Immunotoxins in Hepatitis C Virus-Associated Mixed Cryoglobulinemia Vasculitis. Arthritis & Rheumatology, 66(2), 433-443.

Objective. Hepatitis C virus (HCV) is associated with B cell lymphoproliferative disorders, including mixed cryoglobulinemia (MC) vasculitis and B cell non-Hodgkin’s lymphoma. The expansion of clonal and autoreactive rheumatoid factor-bearing CD21(-/low) marginal zone (MZ) B cells was demonstrated in patients with HCV-associated MC vasculitis. Fc receptor-like (FCRL) proteins comprise a family of immunoregulatory proteins preferentially expressed on B lineage cells. The goal of this study was to investigate the expression of FCRL proteins 1-5 on B cells from patients with HCV-associated MC vasculitis. Methods. Expression of FCRL proteins 1-5 was assessed by flow cytometry on B cells from 15 HCV-infected patients with type II MC (7 of whom had B cell non-Hodgkin’s lymphoma), 20 HCV-infected patients without MC, and 20 healthy donors. To evaluate FCRL-5 as an immunotherapy target in HCV-associated MC vasculitis, 2 anti-FCRL-5 recombinant immunotoxins were produced using anti-FCRL-5 monoclonal antibodies and Pseudomonas exotoxin. Results. Expression of FCRLs 2, 3, and 5 was markedly increased while expression of FCRL-1 was decreased on clonal CD21(-/low) MZ B cells, as compared with other B cell subsets, from HCV-infected patients and healthy donors. However, there was no difference in the pattern of FCRL expression between HCV-MC patients with lymphoma and those without lymphoma. The anti-FCRL-5 immunotoxins showed specific cytotoxicity against FCRL-5-expressing clonal CD21(-/low) MZ B cells isolated from HCV-infected patients as well as FCRL-5-transfected cell lines. No cytotoxicity against T cells or conventional B cells was observed. Conclusion. These findings suggest that FCRL-5-targeting therapies could be a specific treatment for HCV-associated MC vasculitis and other FCRL-5-positive autoimmune B cell disorders.

Sanford School of Medicine, Sioux Falls Campus.

Talbot, Elizabeth Peffer, & McMillin, Joan A. (2014). The Social Work Reinvestment Initiative: Advocacy and Social Work Practice. Social Work, 59(3), 201-210.

In 2006, NASW launched the Social Work Reinvestment Initiative by granting each state chapter $15,000 in seed money to address the most pressing social work needs in the state. This article describes how NASW-SD, with 246 members, launched an epic campaign that resulted in the establishment of the only MSW program in South Dakota. Using historical research methods, this article demonstrates the power of social work advocacy when members unify in pursuit of a common goal and describes how the social workers rallied to educate policymakers and the public on the value of social work and its delivery of necessary social services at all levels and in all fields of practice. The research highlights an uphill battle of advocacy and the skillful planning and implementation of a campaign to secure state funding to establish the first MSW program in the state, at the beginning of the most difficult economic recession since the Great Depression.

School of Health Sciences.

 

Posted by: reganenosusd | August 27, 2014

June 2014

Eyster, Kathleen M., Appt, S., Chalpe, Abha, Mark-Kappeler, Connie J., Register, T. C., & Clarkson, T. B. (2014). Effects of estradiol on transcriptional profiles in atherosclerotic iliac arteries in ovariectomized cynomolgus macaques. Menopause-the Journal of the North American Menopause Society, 21(2), 143-152.

Objective This study aimed to assess the in vivo effects of estradiol treatment on arterial gene expression in atherosclerotic postmenopausal female monkeys. Methods Eight ovariectomized cynomolgus monkeys were fed atherogenic diets for 6.5 years. The left iliac artery was biopsied before randomization to the estradiol group (human equivalent dose of 1 mg/d, n = 4) or the vehicle group (n = 4) for 8 months. The right iliac artery was obtained at necropsy. Transcriptional profiles in pretreatment versus posttreatment iliac arteries were compared to assess the responses of atherosclerotic arteries to estradiol. Results Iliac artery plaque size did not differ between the estradiol group and the placebo group at baseline or during the treatment period. Nevertheless, estradiol treatment was associated with increased expression of 106 genes and decreased expression of 26 genes in the iliac arteries. Estradiol treatment increased the expression of extracellular matrix genes, including the 1 chain of type I collagen, the 2 chain of type VI collagen, and fibulin 2, suggestive of an increase in the proportion or phenotype of smooth muscles or fibroblasts in lesions. Also increased were components of the insulin-like growth factor pathway (insulin-like growth factor 1, insulin-like growth factor binding protein 4, and insulin-like growth factor binding protein 5) and the Wnt signaling pathway (secreted frizzled-related protein 2, secreted frizzled-related protein 4, low-density lipoprotein receptor-related protein 6, and Wnt1-inducible signaling pathway protein 2). Conclusions Estradiol treatment of monkeys with established atherosclerosis affected iliac artery gene expression, suggesting changes in the cellular composition of lesions. Moreover, it is probable that the presence of atherosclerotic plaque affected the gene expression responses of arteries to estrogen.

Basic Biomedical Sciences, Vermillion Campus.

Ouellette, Scot P.,Gauliard, Emilie, Antosova, Zuzana,& Ladant, Daniel. (2014). A Gateway((R)) -compatible bacterial adenylate cyclase-based two-hybrid system. Environmental Microbiology Reports, 6(3), 259-267.

The bacterial adenylate cyclase two-hybrid (BACTH) system has been widely used to characterize protein-protein interactions in the prokaryotic world. This system relies on the interaction-mediated reconstitution of adenylate cyclase activity in Escherichia coli by bringing together two complementary fragments of the catalytic domain of the adenylate cyclase toxin of Bordetella pertussis. A limiting factor in performing large-scale two-hybrid interaction screens with full-length open reading frames (ORFs) is the need to clone each ORF individually into the plasmids used to express the hybrid proteins. The Gateway((R)) (GW) cloning system (Life Technologies, Grand Island, NY, USA) partially circumvents this limitation, and we describe here modifications to the BACTH system for compatibility with this recombineering technology. We validated and tested the functionality of the BACTH Gateway (BACTH(GW)) system using several models of protein-protein interactions, focusing particularly on those involved in bacterial cell division. We further modified the BACTH plasmids to incorporate a transmembrane (TM) segment downstream of the cyclase fragments to permit analysis of extracytoplasmic protein interactions. This approach was also useful to identify putative TM segments and to experimentally validate bioinformatically identified TM domains. The BACTH(GW) system will prove a useful addition to the study of protein-protein interactions.

Basic Biomedical Sciences, Vermillion Campus.

Paulson, Alicia F., Prasad, M. S., Thuringer, Amanda H., & Manzerra, Pasquale. (2014). Regulation of cadherin expression in nervous system development. Cell Adhesion & Migration, 8(1), 19-28.

This review addresses our current understanding of the regulatory mechanisms for classical cadherin expression during development of the vertebrate nervous system. The complexity of the spatial and temporal expression patterns is linked to morphogenic and functional roles in the developing nervous system. While the regulatory networks controlling cadherin expression are not well understood, it is likely that the multiple signaling pathways active in the development of particular domains also regulate the specific cadherins expressed at that time and location. With the growing understanding of the broader roles of cadherins in cell-cell adhesion and non-adhesion processes, it is important to understand both the upstream regulation of cadherin expression and the downstream effects of specific cadherins within their cellular context.

Basic Biomedical Sciences, Vermillion Campus.

Zheng, Zhaoqing,& Keifer, Joyce. (2014). Sequential Delivery of Synaptic GluA1-and GluA4-containing AMPA Receptors ( AMPARs) by SAP97 Anchored Protein Complexes in Classical Conditioning. Journal of Biological Chemistry, 289(15), 10540-10550.

Background: Subunit-specific synaptic delivery of AMPARs during associative learning is not well characterized. Results: SAP97-AKAP/PKA-GluA1 followed by SAP97-KSR1/PKC-GluA4 complexes function for surface delivery of AMPARs. Conclusion: SAP97 interacts with AKAP and KSR1 proteins to coordinate the sequential synaptic delivery of AMPAR subunits during in vitro classical conditioning. Significance: A cooperative interaction of multiple scaffolding proteins selectively delivers AMPARs to synapses during conditioning. Multiple signaling pathways are involved in AMPAR trafficking to synapses during synaptic plasticity and learning. The mechanisms for how these pathways are coordinated in parallel but maintain their functional specificity involves subcellular compartmentalization of kinase function by scaffolding proteins, but how this is accomplished is not well understood. Here, we focused on characterizing the molecular machinery that functions in the sequential synaptic delivery of GluA1- and GluA4-containing AMPARs using an in vitro model of eyeblink classical conditioning. We show that conditioning induces the interaction of selective protein complexes with the key structural protein SAP97, which tightly regulates the synaptic delivery of GluA1 and GluA4 AMPAR subunits. The results demonstrate that in the early stages of conditioning the initial activation of PKA stimulates the formation of a SAP97-AKAP/PKA-GluA1 protein complex leading to synaptic delivery of GluA1-containing AMPARs through a SAP97-PSD95 interaction. This is followed shortly thereafter by generation of a SAP97-KSR1/PKC-GluA4 complex for GluA4 AMPAR subunit delivery again through a SAP97-PSD95 interaction. These data suggest that SAP97 forms the molecular backbone of a protein scaffold critical for delivery of AMPARs to the PSD during conditioning. Together, the findings reveal a cooperative interaction of multiple scaffolding proteins for appropriately timed delivery of subunit-specific AMPARs to synapses and support a sequential two-stage model of AMPAR synaptic delivery during classical conditioning.

Basic Biomedical Sciences, Vermillion Campus.

Zheng, W. H., Liu, J. S., & Swanson, David L. (2014). Seasonal Phenotypic Flexibility of Body Mass, Organ Masses, and Tissue Oxidative Capacity and Their Relationship to Resting Metabolic Rate in Chinese Bulbuls. Physiological and Biochemical Zoology, 87(3), 432-444.

Survival of small birds in fluctuating environments is facilitated by seasonal metabolic and morphological flexibility. Chinese bulbuls Pycnonotus sinensis show winter increases in resting metabolic rate (RMR), nutritional organ masses, and liver and muscle cellular aerobic capacity relative to summer. In this study, we build on these findings from previous studies by measuring seasonal adjustments in body mass (M-b), RMR, nutritional and exercise organ masses, and several physiological, biochemical, and hormonal markers over the entire annual cycle in wild-trapped Chinese bulbuls from Wenzhou, China. Furthermore, we analyzed the relationships between variation in organ masses and cellular aerobic capacity and variation in RMR in individual birds. M-b and RMR were higher in spring (March-May) and winter (December-February) than in summer (June-August). The dry masses of several nutritional organs and mitochondrial protein content, state 4 respiration, and cytochrome c oxidase (COX) activity in liver and muscle were all heightened in winter relative to other seasons. In addition, dry masses of heart and pectoral muscle, but not nutritional organs, and biochemical markers of cellular aerobic capacity in liver and muscle were positively correlated with RMR. Plasma triiodothyronine (T-3) concentration was higher in winter and spring than in summer and autumn, and it was positively correlated with RMR, mitochondrial protein content, state 4 respiration, and COX activity in liver and muscle. These results suggest that seasonal changes in nutritional and exercise organ masses and liver and muscle cellular aerobic capacity interact to promote seasonal metabolic flexibility in Chinese bulbuls. T-3 appears to promote these seasonal thermoregulatory adjustments.

Biology Department.

Dai, Feng-Rong,Sambasivam, Uma, Hammerstrom, Alex J.,& Wang, Zhenqiang. (2014). Synthetic Supercontainers Exhibit Distinct Solution versus Solid State Guest-Binding Behavior. Journal of the American Chemical Society, 136(20), 7480-7491.

The phase-dependent host-guest binding behavior of a new family of synthetic supercontainers has been probed in homogeneous solution and at liquid-liquid, solid-liquid, and solid-gas interfaces. The synthetic hosts, namely, type II metal-organic supercontainers (MOSCs), are constructed from the assembly of divalent metal ions, 1,4-benzenedicarboxylate (BDC) linker, and sulfonylcalix[4]arene-based container precursors. One member of the MOSCs, MOSC-II-tBu-Ni, which is derived from Ni(II), BDC, and p-tert-butylsulfonylcalix[4] arene (TBSC), crystallizes in the space group R (3) over bar and adopts pseudo face-centered cubic (fcc) packing, whereas other MOSCs, including TBSC analogue MOSC-II-tBu-Co, p-tert-pentylsulfonylcalix[4]arene (TPSC) analogues MOSC-II-tPen-Ni/Co, and p-tert-octylsulfonylcalix[4]arene (TOSC) analogues MOSC-II-tOc-Ni/Mg/Co, all crystallize in the space group I4/m and assume a pseudo body-centered cubic (bcc) packing mode. This solid-state structural diversity is nevertheless not reflected in their solution host-guest chemistry, as evidenced by the similar binding properties of MOSC-II-tBu-Ni and MOSC-II-tBu-Co in solution. Both MOSCs show comparable binding constants and adsorb ca. 7 equiv of methylene blue (MB) and ca. 30 equiv of aspirin in chloroform. In contrast, the guest-binding behavior of the MOSCs in solid state reveals much more variations. At the solid-liquid interface, MOSC-II-tBu-Co adsorb ca. S equiv of MB from an aqueous solution at a substantially faster rate than MOSC-II-tBu-Ni does. However, at the solid-gas interface, MOSC-II-tBu-Ni has higher gas uptake than MOSC-II-tBu-Co, contradicting their overall porosity inferred from the crystal structures. This discrepancy is attributed to the partial collapse of the solid-state packing of the MOSCs upon solvent evacuation. It is postulated that the degree of porosity collapse correlates with the molecular size of the MOSCs, i.e., the larger the MOSCs, the more severe they suffer from the loss of porosity. The same principle can rationalize the negligible N-2 and O-2 adsorption seen in the larger MOSC-II-tPen-Co and MOSC-II-tOC-Ni/Mg/Co molecules. MOSC-II-tPen-Ni features an intermediate molecular size and endures a partial structural collapse in such a way that the resulting pore dimension permits the inclusion of kinetically smaller O-2 (3.46 angstrom) but excludes larger N-2 (3.64 angstrom), explaining the observed remarkable O-2/N-2 adsorption selectivity.

Chemistry Department.

Feng-Rong, Dai,Sambasivam, Uma, Hammerstrom, Alex J.,& Zhenqiang, Wang. (2014). Synthetic Supercontainers Exhibit Distinct Solution versus Solid State Guest-Binding Behavior. Journal of the American Chemical Society, 136(20), 7480-7491.

The phase-dependent host-guest binding behavior of a new family of synthetic supercontainers has been probed in homogeneous solution and at liquid-liquid, solid-liquid, and soUd-gas interfaces. The synthetic hosts, namely, type II metalorganic supercontainers (MOSCs), are constructed from the assembly of divalent metal ions, 1,4-benzenedicarboxylate (BDC) linker, and sulfonylcalix[4]arene-based container precursors. One member of the MOSCs, MOSC-II-tBu-Ni, which is derived fi-om Ni(Il), BDC, and ]7-tert-butylsulfonylcalix[4]arene (TBSC), crystallizes in the space group R3 and adopts pseudo facecentered cubic (fee) packing, whereas other MOSCs, including TBSC analogue MOSC-II-tBu-Co, p-tert-pentylsulfonylcalix- [4]arene (TPSC) analogues MOSC-II-tPen-Ni/Co, and j)-iert-octylsulfonylcalix[4]arene (TOSC) analogues MOSC-II-tOc-Ni/ Mg/Co, all crystallize in the space group IA/m and assume a pseudo body-centered cubic (bcc) packing mode. This solid-state structural diversity is nevertheless not reflected in their solution host-guest chemistry, as evidenced by the similar binding properties of MOSC-II-tBu-Ni and MOSC-II-tBu-Co in solution. Both MOSCs show comparable binding constants and adsorb ca. 7 equiv of methylene blue (MB) and ca. 30 equiv of aspirin in chloroform. In contrast, the guest-binding behavior of the MOSCs in solid state reveals much more variations. At the solid-liquid interface, MOSC-II-tBu-Co adsorb ca. 5 equiv of MB from an aqueous solution at a substantially faster rate than MOSC-II-tBu-Ni does. However, at the solid-gas interface, MOSCII- tBu-Ni has higher gas uptake than MOSC-II-tBu-Co, contradicting their overall porosity inferred from the crystal structures. This discrepancy is attributed to the partial collapse of the solid-state packing of the MOSCs upon solvent evacuation. It is postulated that the degree of porosity collapse correlates with the molecular size of the MOSCs, i.e., the larger the MOSCs, the more severe they suffer fi-om the loss of porosity. The same principle can rationalize the negligible N2 and O2 adsorption seen in the larger MOSC-II-tPen-Co and MOSC-II-tOC-Ni/Mg/Co molecules. MOSC-II-tPen-Ni features an intermediate molecular size and endures a partial structural collapse in such a way that the resulting pore dimension permits the inclusion of kinetically smaller O2 (3.46 A) but excludes larger N2 (3.64 A), explaining the observed remarkable O2/N2 adsorption selectivity.

Chemistry Department.

Messersmith, Jessica J.,Lockie, Jill, Jorgensen, Lindsey,Bauer Vaith, Shana, & Falk, Elizabeth. (2014). Legislation Impacting Audiology and the Provision of Audiological Services: A Review of Legislation Across the United States. American Journal of Audiology, 23(1), 142-150.

Purpose: The purpose of this review was to investigate the legislation about the provision of audiology services. Specifically, the goal of the review was to investigate the similarities and differences in legislation regarding the identification of, and audiology services provided to, children with hearing loss. Method: A systematic review was conducted to collect state-specific legislation regarding the audiology licensure requirements, requirements about the identification and management of children with hearing loss, and insurance coverage regulations. Compiled data were analyzed for similarities and differences between state regulations and legislature. Results: All states require audiologists to hold licensure; however, many differences exist between the requirements of acquiring and maintaining the license. Some states regulate the identification and management of children with hearing loss, whereas others do not. Additionally, states differ in their regulation of services provided to children with hearing loss, who can provide these services, and what is covered by insurance. Conclusion: It is critical for audiologists to understand the requirements of their state in the provision of audiology services. Specifically, it is important for audiologists to understand how the laws may impact the services they provide to children with hearing loss.

Communication Disorders Department.

Ehlers, Sarah. (2014). Mourning the Modernist Undead: Robert Duncan’s Company and the Felt Silence of the Lost Generation. Contemporary Literature, 55(1), 89-117.

The article offers criticism of the poem “September 1961″ by Robert Duncan. The author discusses the development of the American Poetry and preoccupation with silence and loss of speech. It explores Duncan’s process of mourning over the death of H. D., his process for constructing his poems amid perceived loss of his mentors.

English Department.

Robles, Elias, Emery, Noah N., Vargas, Perla A., Moreno, Araceli, Marshall, Brent, Grove, Richard C., & Zhang, Huateng. (2014). Patterns of Responding on a Balloon Analogue Task Reveal Individual Differences in Overall Risk-Taking: Choice Between Guaranteed and Uncertain Cash. Journal of General Psychology, 141(3), 207-227.

ABSTRACT. We explored the utility of analyzing within- and between-balloon response patterns on a balloon analogue task (BAT) in relation to overall risk scores, and to a choice between a small guaranteed cash reward and an uncertain reward of the same expected value. Young adults (n = 61) played a BAT, and then were offered a choice between $5 in cash and betting to win $0 to $15. Between groups, pumping was differentially influenced by explosions and by the number of successive unexploded balloons, with risk takers responding increasingly on successive balloons after an explosion. Within-balloons, risk takers showed a characteristic pattern of constant high rate, while non-risk takers showed a characteristic variable lower rate. Overall, results show that the higher number of pumps and explosions that characterize risk takers at a molar level, result from particular forms of adaptation to the positive and negative outcomes of choices seen at a molecular level. Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/vgen.

Psychology Department [graduate student].

Pottala, James V., Djira, G. D., Espeland, M. A., Ye, J., Larson, M. G., & Harris, William S. (2014). Structural Equation Modeling for Analyzing Erythrocyte Fatty Acids in Framingham. Computational and Mathematical Methods in Medicine.

Research has shown that several types of erythrocyte fatty acids (i.e., omega-3, omega-6, and trans) are associated with risk for cardiovascular diseases. However, there are complex metabolic and dietary relations among fatty acids, which induce correlations that are typically ignored when using them as risk predictors. A latent variable approach could summarize these complex relations into a few latent variable scores for use in statistical models. Twenty-two red blood cell (RBC) fatty acids were measured in Framingham (N = 3196). The correlation matrix of the fatty acids was modeled using structural equation modeling; the model was tested for goodness-of-fit and gender invariance. Thirteen fatty acids were summarized by three latent variables, and gender invariance was rejected so separate models were developed for men and women. A score was developed for the polyunsaturated fatty acid (PUFA) latent variable, which explained about 30% of the variance in the data. The PUFA score included loadings in opposing directions among three omega-3 and three omega-6 fatty acids, and incorporated the biosynthetic and dietary relations among them. Whether the PUFA factor score can improve the performance of risk prediction in cardiovascular diseases remains to be tested.

Sanford School of Medicine, Sioux Falls Campus

Bledsoe, Adam,Baloun, Brett, Murray, Jeffrey,& Atiq, Muslim. (2014). Retrieval of a sharp foreign body from the stomach: a novel approach. Endoscopy, 46, E105-E106.

Sanford School of Medicine, Sioux Falls Campus.

Evans, Rick L.,Pottala, James V., & Egland, Kristi A.(2014). Classifying Patients for Breast Cancer by Detection of Autoantibodies against a Panel of Conformation-Carrying Antigens. Cancer Prevention Research, 7(5), 545-555.

Patients with breast cancer elicit an autoantibody response against cancer proteins, which reflects and amplifies the cellular changes associated with tumorigenesis. Detection of autoantibodies in plasma may provide a minimally invasive mechanism for early detection of breast cancer. To identify cancer proteins that elicit a humoral response, we generated a cDNA library enriched for breast cancer genes that encode membrane and secreted proteins, which are more likely to induce an antibody response compared with intracellular proteins. To generate conformation-carrying antigens that are efficiently recognized by patients’ antibodies, a eukaryotic expression strategy was established. Plasma from 200 patients with breast cancer and 200 age-matched healthy controls were measured for autoantibody activity against 20 different antigens designed to have conformational epitopes using ELISA. A conditional logistic regression model was used to select a combination of autoantibody responses against the 20 different antigens to classify patients with breast cancer from healthy controls. The best combination included ANGPTL4, DKK1, GAL1, MUC1, GFRA1, GRN, and LRRC15; however, autoantibody responses against GFRA1, GRN, and LRRC15 were inversely correlated with breast cancer. When the autoantibody responses against the 7 antigens were added to the base model, including age, BMI, race and current smoking status, the assay had the following diagnostic capabilities: c-stat (95% CI), 0.82 (0.78-0.86); sensitivity, 73%; specificity, 76%; and positive likelihood ratio (95% CI), 3.04 (2.34-3.94). The model was calibrated across risk deciles (HosmerLemeshow, P = 0.13) and performed well in specific subtypes of breast cancer including estrogen receptor positive, HER-2 positive, invasive, in situ and tumor sizes > 1 cm. Cancer Prev Res; 7(5); 545-55. (C) 2014 AACR.

Sanford School of Medicine, Sioux Falls Campus.

May, Philip A., Hamrick, Kari J., ….., Hoyme, H. Eugene, & Gossage, J. Phillip. (2014). Dietary intake, nutrition, and fetal alcohol spectrum disorders in the Western Cape Province of South Africa. Reproductive Toxicology, 46(x), 31-39.

Highlights: [•] Dietary intake of women in South Africa is compared to recommended intakes for specific nutrients. [•] For most nutrients, all mothers were significantly below Dietary Reference Intakes. [•] Mothers of FASD children had significantly lower intakes of calcium, DPA, riboflavin, and choline than controls. [•] Lower nutrient intake correlates with binge drinking. [•] Nutritional inadequacies with prenatal alcohol exposure increase the risk for FASD.

Sanford School of Medicine, Sioux Falls Campus.

O’Neil, Amanda,& Schumacher, Bette. (2014). Application of a Pectin Barrier for Medical Adhesive Skin Injury (Epidermal Stripping) in a Premature Infant. Journal of Wound Ostomy and Continence Nursing, 41(3), 219-221.

BACKGROUND: Premature infants require, as part of their care, devices such as monitors and temperature probes to be attached to their skin. However, because of immaturity of the skin, they are especially vulnerable to medical adhesive-related skin injury. CASE: This case discusses the application of a hydrocolloid (pectin) barrier between the adhesive surface of a silver reflective patch covering thermistor probe and the neonate’s skin resulting in medical adhesive skin injury (epidermal stripping). CONCLUSIONS: The use of this pectin barrier proved to be a suitable surface to secure the temperature probe and avoid further medical adhesive-related skin injury.

Sanford School of Medicine, Sioux Falls Campus.

Pottala, James V., Yaffe, K., Robinson, J. G., Espeland, M. A., Wallace, R., & Harris, William S. (2014). Higher RBC EPA plus DHA corresponds with larger total brain and hippocampal volumes WHIMS-MRI Study. Neurology, 82(5), 435-442.

Objective:To test whether red blood cell (RBC) levels of marine omega-3 fatty acids measured in the Women’s Health Initiative Memory Study were related to MRI brain volumes measured 8 years later.Methods:RBC eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and MRI brain volumes were assessed in 1,111 postmenopausal women from the Women’s Health Initiative Memory Study. The endpoints were total brain volume and anatomical regions. Linear mixed models included multiple imputations of fatty acids and were adjusted for hormone therapy, time since randomization, demographics, intracranial volume, and cardiovascular disease risk factors.Results:In fully adjusted models, a 1 SD greater RBC EPA + DHA (omega-3 index) level was correlated with 2.1 cm(3) larger brain volume (p = 0.048). DHA was marginally correlated (p = 0.063) with total brain volume while EPA was less so (p = 0.11). There were no correlations between ischemic lesion volumes and EPA, DHA, or EPA + DHA. A 1 SD greater omega-3 index was correlated with greater hippocampal volume (50 mm(3), p = 0.036) in fully adjusted models. Comparing the fourth quartile vs the first quartile of the omega-3 index confirmed greater hippocampal volume (159 mm(3), p = 0.034).Conclusion:A higher omega-3 index was correlated with larger total normal brain volume and hippocampal volume in postmenopausal women measured 8 years later. While normal aging results in overall brain atrophy, lower omega-3 index may signal increased risk of hippocampal atrophy. Future studies should examine whether maintaining higher RBC EPA + DHA levels slows the rate of hippocampal or overall brain atrophy.

Sanford School of Medicine, Sioux Falls Campus.

Wachira, John K., Larson, M. K., & Harris, William S. (2014). n-3 Fatty acids affect haemostasis but do not increase the risk of bleeding: clinical observations and mechanistic insights. British Journal of Nutrition, 111(9), 1652-1662.

n-3 Fatty acids (EPA and DHA, from fish oil) are essential fatty acids that are approved for the treatment of severe hypertriacylglycerolaemia and, in some countries, used for reducing the risk of CVD. Because of their inhibitory effects on platelet function, some practitioners have, perhaps unnecessarily, discontinued their use in patients undergoing invasive procedures or being treated with anti-platelet or anticoagulation drugs. Thus, the aim of the present study was to review the effects of n-3 fatty acids on bleeding complications in a wide variety of clinical settings, and to summarise their biochemical mechanism of action in platelet function and coagulation. We surveyed recent publications that either directly studied the effects of n-3 fatty acids on the risk of bleeding or focused on different end-points and also reported the effects on bleeding. n-3 Fatty acid treatment had no effect on the risk of clinically significant bleeding in either monotherapy or combination therapy settings. Although originally believed to operate primarily via the cyclo-oxygenase system, these fatty acids have been shown to affect multiple signalling pathways and thrombotic processes beyond simply affecting platelet aggregation. The present overview found no support for discontinuing the use of n-3 fatty acid treatment before invasive procedures or when given in combination with other agents that affect bleeding. On the contrary, the use of these fatty acids in several settings improved clinical outcomes.

Sanford School of Medicine, Sioux Falls Campus.

Flynn, Stephen V., Olson, Seth D., & Yellig, Adriana D. (2014). American Indian Acculturation: Tribal Lands to Predominately White Postsecondary Settings. Journal of Counseling& Development, 92(3), 280-293.

Grounded theory provided a framework for examining 25 acculturating American Indian college students, 12 relatives of acculturating American Indians, and 7 postsecondary administrators. Acculturation was defined as the transformative process resulting from the integration of tribal culture and predominately White culture. Data sources included individual interviews, focus groups, and artifact analysis. The 16 emergent themes form an acculturation theory centered on a strength-based acculturation process affecting American Indians’ transition to predominately White postsecondary settings.

School of Education. [Flynn and Yellig no longer are at USD]

 

Posted by: kelsijo97 | March 20, 2014

Welcome to our USD Fac-Pub blog

We’re Danielle Loftus, a technology/fine arts librarian, and Steve Johnson, a business and distance ed librarian at USD’s University Libraries.

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

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

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

Posted by: kelsijo97 | March 20, 2014

March 2014

Miskimins, W. Keith, H. J. Ahn, J. Y. Kim, S. Ryu, Y. S. Jung, & J. Y. Choi. (2014). Synergistic Anti-Cancer Effect of Phenformin and Oxamate. Plos One, 9(1).

Phenformin (phenethylbiguanide; an anti-diabetic agent) plus oxamate [lactate dehydrogenase (LDH) inhibitor] was tested as a potential anti-cancer therapeutic combination. In in vitro studies, phenformin was more potent than metformin, another biguanide, recently recognized to have anti-cancer effects, in promoting cancer cell death in the range of 25 times to 15 million times in various cancer cell lines. The anti-cancer effect of phenformin was related to complex I inhibition in the mitochondria and subsequent overproduction of reactive oxygen species (ROS). Addition of oxamate inhibited LDH activity and lactate production by cells, which is a major side effect of biguanides, and induced more rapid cancer cell death by decreasing ATP production and accelerating ROS production. Phenformin plus oxamate was more effective than phenformin combined with LDH knockdown. In a syngeneic mouse model, phenformin with oxamate increased tumor apoptosis, reduced tumor size and F-18-fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography compared to control. We conclude that phenformin is more cytotoxic towards cancer cells than metformin. Furthermore, phenformin and oxamate have synergistic anti-cancer effects through simultaneous inhibition of complex I in the mitochondria and LDH in the cytosol, respectively.

Basic Biomedical Sciences, Vermillion Campus.

 

Shi, X. P., X. Chen, X. F. Li, …., Xuejun Wang, Q. P. Dou, & J. B. Liu. (2014). Gambogic Acid Induces Apoptosis in Imatinib-Resistant Chronic Myeloid Leukemia Cells via Inducing Proteasome Inhibition and Caspase-Dependent Bcr-Abl Downregulation. Clinical Cancer Research, 20(1), 151-163.

Purpose: Chronic myelogenous leukemia (CML) is characterized by the constitutive activation of Bcr-Abl tyrosine kinase. Bcr-Abl-T315I is the predominant mutation that causes resistance to imatinib, cytotoxic drugs, and the second-generation tyrosine kinase inhibitors. The emergence of imatinib resistance in patients with CML leads to searching for novel approaches to the treatment of CML. Gambogic acid, a small molecule derived from Chinese herb gamboges, has been approved for phase II clinical trial for cancer therapy by the Chinese Food and Drug Administration (FDA). In this study, we investigated the effect of gambogic acid on cell survival or apoptosis in CML cells bearing Bcr-Abl-T315I or wild-type Bcr-Abl. Experimental Design: CML cell lines (KBM5, KBM5-T315I, and K562), primary cells from patients with CML with clinical resistance to imatinib, and normal monocytes from healthy volunteers were treated with gambogic acid, imatinib, or their combination, followed by measuring the effects on cell growth, apoptosis, and signal pathways. The in vivo antitumor activity of gambogic acid and its combination with imatinib was also assessed with nude xenografts. Results: Gambogic acid induced apoptosis and cell proliferation inhibition in CML cells and inhibited the growth of imatinib-resistant Bcr-Abl-T315I xenografts in nude mice. Our data suggest that GA-induced proteasome inhibition is required for caspase activation in both imatinib-resistant and -sensitive CML cells, and caspase activation is required for gambogic acid-induced Bcr-Abl downregulation and apoptotic cell death. Conclusions: These findings suggest an alternative strategy to overcome imatinib resistance by enhancing Bcr-Abl downregulation with the medicinal compound gambogic acid, which may have great clinical significance in imatinib-resistant cancer therapy. (C) 2013 AACR.

Basic Biomedical Sciences, Vermillion Campus.

 

Zhang, Y. H., E. I. Dedkov, D. Teplitsky, Nathan Y. Weltman, C. J. Pol, V. Rajagopalan, . . . A. M. Gerdes. (2013). Both Hypothyroidism and Hyperthyroidism Increase Atrial Fibrillation Inducibility in Rats. Circulation-Arrhythmia and Electrophysiology, 6(5), 952-959.

Background Evidence indicates that cardiac hypothyroidism may contribute to heart failure progression. It is also known that heart failure is associated with an increased risk of atrial fibrillation (AF). Although it is established that hyperthyroidism increases AF incidence, the effect of hypothyroidism on AF is unclear. This study investigated the effects of different thyroid hormone levels, ranging from hypothyroidism to hyperthyroidism on AF inducibility in thyroidectomized rats. Methods and Results Thyroidectomized rats with serum-confirmed hypothyroidism 1 month after surgery were randomized into hypothyroid (N=9), euthyroid (N=9), and hyperthyroid (N=9) groups. Rats received placebo, 3.3-mg l-thyroxine (T4), or 20-mg T4 pellets (60-day release form) for 2 months, respectively. At the end of treatment, hypothyroid, euthyroid, and hyperthyroid status was confirmed. Hypothyroid animals showed cardiac atrophy and reduced cardiac systolic and diastolic functions, whereas hyperthyroid rats exhibited cardiac hypertrophy and increased cardiac function. Hypothyroidism and hyperthyroidism produced opposite electrophysiological changes in heart rates and atrial effective refractory period, but both significantly increased AF susceptibility. AF incidence was 78% in hypothyroid, 67% in hyperthyroid, and the duration of induced AF was also longer, compared with 11% in the euthyroid group (all P<0.05). Hypothyroidism increased atrial interstitial fibrosis, but connexin 43 was not affected. Conclusions Both hypothyroidism and hyperthyroidism lead to increased AF vulnerability in a rat thyroidectomy model. Our results stress that normal thyroid hormone levels are required to maintain normal cardiac electrophysiology and to prevent cardiac arrhythmias and AF.

Basic Biomedical Sciences, Vermillion Campus.

 

Kats, L. B., G. Bucciarelli, T. L. Vandergon, …., Jacob L. Kerby, & R. 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(x), 109-112.

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. (C) 2013 Elsevier Ltd. All rights reserved.

Biology Department.

 

Liu, Ming, & David L. Swanson. (2014). Physiological Evidence That Anthropogenic Woodlots Can Substitute for Native Riparian Woodlands as Stopover Habitat for Migrant Birds. Physiological and Biochemical Zoology, 87(1), 183-195.

The ability to find sufficient high-quality stopover habitat is a crucial factor for successful migration for woodland migrant birds. Woodland habitats are scarce in the Northern Prairie region of North America, and natural woodlands have been greatly reduced concurrent with the appearance of small anthropogenic woodlands on the landscape. Landbird migrants use both natural and anthropogenic woodlands in this region as stopover habitats, but the relative quality of these two habitats is unknown. We assessed the relative habitat quality of the two habitats by comparing body mass (M-b) and plasma metabolites associated with fattening (triglycerides [TRIG]) or fat catabolism (-hydroxybutyrate [BUTY], glycerol [GLYC]) in individual species, taxa, and foraging guilds of migrating woodland birds during both spring and fall migrations. The only significant difference in M-b between birds in the two habitats occurred for fall yellow-rumped warblers (Setophaga coronata), where M-b was 8% greater in corridors than in woodlots. No significant between-habitat differences occurred for plasma TRIG at either season. Significant between-habitat differences for plasma BUTY occurred only for ruby-crowned kinglets (Regulus calendula; 61% higher in corridors) in fall. Plasma GLYC differed significantly between habitats for a few groups, including vireos (190% higher in woodlots), warbling vireos (Vireo gilvus; 263% higher in woodlots), and Nashville warblers (Oreothlypis ruficapilla; 226% higher in woodlots) in fall. The few significant differences and absence of a consistent direction of variation in M-b and plasma metabolites suggests similar stopover habitat quality in these two habitat types. Thus, during migration through the Northern Prairie region anthropogenic woodlots can, at least partially, substitute as stopover habitat for lost and degraded native riparian habitats for woodland birds.

Biology Department.

 

Swanson, David L., Marissa O. King, & Erin Harmon. (2014). Seasonal variation in pectoralis muscle and heart myostatin and tolloid-like proteinases in small birds: a regulatory role for seasonal phenotypic flexibility? Journal of Comparative Physiology B-Biochemical Systemic and Environmental Physiology, 184(2), 249-258.

Seasonally variable environments produce seasonal phenotypes in small birds such that winter birds have higher thermogenic capacities and pectoralis and heart masses. One potential regulator of these seasonal phenotypes is myostatin, a muscle growth inhibitor, which may be downregulated under conditions promoting increased energy demand. We examined summer-to-winter variation in skeletal muscle and heart masses and used qPCR and Western blots to measure levels of myostatin and its metalloproteinase activators TLL-1 and TLL-2 for two small temperate-zone resident birds, American goldfinches (Spinus tristis) and black-capped chickadees (Poecile atricapillus). Winter pectoralis and heart masses were significantly greater than in summer for American goldfinches. Neither myostatin expression nor protein levels differed significantly between seasons for goldfinch pectoralis. However, myostatin levels in goldfinch heart were significantly greater in summer than in winter, although heart myostatin expression was seasonally stable. In addition, expression of both metalloproteinase activators was greater in summer than in winter goldfinches for both pectoralis and heart, significantly so except for heart TLL-2 (P = 0.083). Black-capped chickadees showed no significant seasonal variation in muscle or heart masses. Seasonal patterns of pectoralis and heart expression and/or protein levels for myostatin and its metalloproteinase activators in chickadees showed no consistent seasonal trends, which may help explain the absence of significant seasonal variation in muscle or heart masses for chickadees in this study. These data are partially consistent with a regulatory role for myostatin, and especially myostatin processing capacity, in mediating seasonal metabolic phenotypes of small birds.

Biology Department.

 

Foss, Berit L., T. W. Maxwell, & Ying Deng. (2014). Chondroprotective supplementation promotes the mechanical properties of injectable scaffold for human nucleus pulposus tissue engineering. Journal of the Mechanical Behavior of Biomedical Materials, 29, 56-67.

A result of intervertebral disc (ND) degeneration, the nucleus pulposus (NP) is no longer able to withstand applied load leading to pain and disability. The objective of this study is to fabricate a tissue-engineered injectable scaffold with chondroprotective supplementation in vitro to improve the mechanical properties of a degenerative NP. Tissue-engineered scaffolds were fabricated using different concentrations of alginate and calcium chloride and mechanically evaluated. Fabrication conditions were based on structural and mechanical resemblance to the native NP. Chondroprotective supplementation, glucosamine (GCSN) and chondroitin sulfate (CS), were added to scaffolds at concentrations of 0:0 pg/mL (0:0-S), 125:100 lig/mL (125:100-S), 250:2001.tg/mL (250:200-S), and 500:400 pg/mL (500:400-5), GCSN and CS, respectively. Scaffolds were used to fabricate tissue-engineered constructs through encapsulation of human nucleus pulposus cells (HNPCs). The tissue-engineered constructs were collected at days 1, 14, and 28 for biochemical and biomechanical evaluations. Confocal microscopy showed HNPC viability and rounded morphology over the 28 day period. MIT analysis resulted in significant increases in cell proliferation for each group. Collagen type II ELISA quantification and compressive aggregate moduli (HA) showed increasing trends for both 250:200-S and the 500:400-S groups on Day 28 with significantly greater HA compared to 0:0-S group. Glycosaminoglycan and water content decreased for all groups. Results indicate the increased mechanical properties of the 250:200-S and the 500:400-S was due to production of a functional matrix. This study demonstrated potential for a chondroprotective supplemented injectable scaffold to restore biomechanical function of a degenerative disc through the production of a mechanically functional matrix. (C) 2013 Elsevier Ltd. All rights reserved.

Biomedical Engineering, Sioux Falls Campus.

 

Anderson, R. B., S. J. Smith, P. Stanley May, & Mary T. Berry. (2014). Revisiting the NIR-to-Visible Upconversion Mechanism in beta-NaYF4:Yb3+,Er3+. Journal of Physical Chemistry Letters, 5(1), 36-42.

Here, we show that the long-accepted mechanism for the production of red and blue emission through upconversion (UC) of 1 mu m excitation in Yb3+/Er3+-doped materials does not apply in the popular beta-NaYF4 host. We propose a new mechanism involving Yb3+-to-Er3+ energy-transfer UC out of thegreen-emitting H-2(11/2), S-4(3/2) states that quantitatively accounts for all of the observed optical behavior. Rate constants for the relevant radiative and nonradiative processes are reported along with a prediction of the power dependence of the pulsed and continuous-wave UC quantum efficiency.

Chemistry Department.

 

Chen, Jiangchao, Qingguo Meng, P. Stanley May, Mary T. Berry, & Dimtri S. Kilin. (2014). Time-dependent excited-state molecular dynamics of photodissociation of lanthanide complexes for laser-assisted metal-organic chemical vapour deposition. Molecular Physics, 112(3-4), 508-517.

Ab initio molecular dynamics (AIMD) algorithm was modified for treating time-dependent excited-state molecular dynamics (TDESMD). This algorithm addresses the situations when electron density and nuclear potential are being periodically driven by a strong laser field, which induces periodic population-depopulation Rabi cycles. The electron hopping between different potential energy surfaces, such as ground state and ligand-to-metal charge-transfer (LMCT) state, creates the nuclear trajectories. In the computed trajectories, the inter-atomic distances can demonstrate different regimes, from small oscillations to abrupt elongations, corresponding to fragmentation of the studied compound. This algorithm was used to explore photodissociation mechanisms for laser-assisted metal-organic chemical vapour deposition (LCVD or laser-assisted MOCVD) process using lanthanide cyclopentadienyl-type precursors. The computed fragments are compared with the ones elucidated experimentally using photoionisation time-of-flight mass spectrometry.

Chemistry Department.

 

Chu, lek-Heng, Dimitri S. Kilin, & Hai-Ping Cheng. (2013). First-Principles Studies of Photoinduced Charge Transfer in Noncovalently Functionalized Carbon Nanotubes. Journal of Physical Chemistry C, 117(35), 17909-17918.

We have studied the energetics, electronic structure, optical excitation, and electron relaxation of dinitromethane molecules (CH2N2O4) adsorbed on semi-conducting carbon nanotubes (CNTs) of chiral index (n,0) (n = 7, 10, 13, 16, 19). Using first-principles density functional theory (DFT) with generalized gradient approximations and van der Waals corrections, we have calculated adsorption energies of dinitropentylpyrene, in which the dinitromethane is linked to the pyrene via an aliphatic chain, on a CNT. A 780 meV (18.0 kcal/mol) binding energy has been found, which explains why such aliphatic chain pyrene units can be and have been used in experiments to bind functional molecules to CNTs. The calculated electronic structures. show that the dinitromethane introduces a localized state inside the band gap of CNT systems of n = 10, 13, 16. and 19; such a state can trap an electron when the CNT is photoexcited. We have therefore investigated the dynamics of intraband relaxations using the reduced density matrix formalism in conjunction with Dn. For pristine CNTs, we have found that the calculated charge relaxation constants agree well with the experimental time scales, Upon adsorption, these constants are modified, but there is not a clear trend for the direction and magnitude of the change. Nevertheless, our calculations predict that electron relaxation in the conduction band is faster than hole relaxation in the valence band for CNTs with and without molecular adsorbates.

Chemistry Department.

 

Han, Yulun, S. Tretiak, & Dmitri S. Kilin. (2014). Dynamics of charge transfer at Au/Si metal-semiconductor nano-interface. Molecular Physics, 112(3-4), 474-484.

An ab initio analysis of the periodic array of Au/Si nanostructure composed of gold clusters linked to silicon quantum dot (QD) co-doped by aluminium and phosphorus along [111] direction is presented in this paper. The density functional theory (DFT) is used to compute the electronic structure of the simulated system. Non-adiabatic coupling implemented in the form of dissipative equation of motion for reduced density matrix is used to study the phonon-induced relaxation in the simulated system. The density of states clearly shows that the formation of Au-Si bonds contributes states to the band gap of the model. Dynamics of selected photo-excitations shows that hole relaxation in energy and in space is much faster than electron relaxation, which is due to the higher density of states of the valence band.

Chemistry Department.

 

Huang, Shuping, & Dmitri S. Kilin. (2014). Electronic structure and hot carrier relaxation in (001) anatase TiO2 nanowire. Molecular Physics, 112(3-4), 539-545.

We present an electronic structure and non-adiabatic excited state dynamics study of 001 anatase TiO2 nanowire (NW) by combining density matrix formalism and ab initio electronic structure calculations. Our results show that quantum confinement increases the energy gap as the dimension of TiO2 is reduced from the bulk to a NW with a diameter of several nanometres and that the probability of electronic transitions induced by lattice vibrations for the NW follows band gap law. The electron non-radiative relaxation to the bottom of the conduction band is involving Ti 3d orbitals, while the hole non-radiative relaxation of holes to the top of the valence band occurs by subsequent occupation of O 2p orbitals.

Chemistry Department.

 

Kryjevski, Andrei, & Dmitri S. Kilin. (2014). Multiple exciton generation in silicon quantum dot arrays: density functional perturbation theory computation. Molecular Physics, 112(3-4), 430-440.

We use the density functional theory (DFT) combined with the many-body perturbation theory to derive expressions for the rates of the optical photonexciton and photonbi-exciton processes in nanoparticles, and for quantum efficiency, all to the leading order in the screened Coulomb interaction between Kohn-Sham quasiparticles. Also, we calculate excitonbi-exciton rates due to the impact ionisation (II) mechanism in Si29H36 quantum dots (QDs) with both crystalline and amorphous core structures, and in quasi-one dimensional (1-D) arrays constructed from these QDs. We observe significant dependence of the carrier multiplication rates on the structure’s morphology and structural disorder. Amorphous silicon QD arrays are predicted to have more efficient bi-exciton generation rates as a function of exciton energy compared to their crystalline counterparts, and the isolated QDs of both kinds.

Chemistry Department.

 

Mottishaw, Jeffrey D., Dimitri S. Kilin, H. P. Cheng, V. V. Karasiev, Q. H. Fan, & Haoran Sun. (2014). Elucidating the role of non-radiative processes in charge transfer of core-shell Si SiO2 nanoparticles. Molecular Physics, 112(3-4), 422-429.

Crystalline silicon is the most commonly used material in photovoltaics but has limitations due to its high cost and non-tunable band gap. A new approach of using inexpensive, non-toxic materials with layers that have different band gaps which absorb a wide range of the solar spectrum has the potential to dramatically increase the efficiencies and lower the costs. Core-shell Si-SiO2 nanoparticles are ideally suited for the photovoltaic application and have been synthesised by different groups in an array of sizes allowing for absorption in a wide spectral range. A theoretical investigation of fundamental charge transfer processes in these systems can potentially lead to improved devices. Calculations on a model core-shell interface with the formula Si264O160 which features a silicon layer sandwiched between two SiO2 layers were performed using the Vienna ab initio software package. The Perdew-Burke-Ernzerhof functional in the basis of plane waves was used along with pseudopotentials to simulate electronic structure. The nuclear motion was considered using ab initio molecular dynamics. The density of states, absorption spectrum, partial charge densities, and radiative recombination lifetimes have been calculated. This interface shows quantum confinement behaviour similar to a particle in a box. The role of non-radiative recombination was also determined by relaxation dynamics.

Chemistry Department.

 

Peng, Rui, Cuikun Lin, J. Baltrusaitis, C. M. Wu, N. M. Dimitrijevic, T. Rajh, . . . Ranjit T. Koodali. (2014). Insight into band positions and inter-particle electron transfer dynamics between CdS nanoclusters and spatially isolated TiO2 dispersed in cubic MCM-48 mesoporous materials: a highly efficient system for photocatalytic hydrogen evolution under visible light illumination. Physical Chemistry Chemical Physics, 16(5), 2048-2061.

CdS incorporated Si-MCM-48 and Ti-MCM-48 cubic phased mesoporous photocatalysts were prepared by a two-step modification synthetic approach under relatively mild conditions. A highly efficient (24.8%, apparent quantum yield (AQY)) photocatalyst for visible light (lambda > 400 nm) enabled solar hydrogen evolution can be realized by assembling CdS with Ti-MCM-48 cubic mesoporous materials in the absence of a noble metal co-catalyst. The photocatalytic mechanism was thoroughly investigated and demonstrated by conducting a wealth of characterization techniques such as powder X-ray diffraction (XRD), nitrogen adsorption isotherm, transmission electron microscopy (TEM), UV-visible diffuse reflectance spectroscopy (DRS), X-ray photoelectron spectroscopy (XPS), ultraviolet photoelectron spectroscopy (UVPS), atomic absorption spectroscopy (AAS), photoluminescence (PL) spectroscopy, time-resolved fluorescence emission decay, and electron paramagnetic resonance (EPR) spectroscopy studies. This work is the first to unambiguously identify the band positions of both CdS and TiO2 encapsulated in porous materials. The photocatalytic activity of the CdS incorporated Ti-MCM-48 mesoporous photocatalysts was found to be dependent on the content of both CdS and TiO2. A correlation between the electron injection efficiency and the photocatalytic activity was established as well in the CdS incorporated Ti-MCM-48 mesoporous photocatalysts.

Chemistry Department.

 

Putta, Anjaneyulu, Jeffrey D. Mottishaw, Zhihua H. Wang, & Haoran R. Sun. (2014). Rational Design of Lamellar pi-pi Stacked Organic Crystalline Materials with Short Interplanar Distance. Crystal Growth & Design, 14(1), 350-356.

Organic crystalline materials having a lamellar pi-pi stacked structural motif with short interplanar distance are significant for many applications. By asymmetrically introducing perfluoroalkyl substituents onto and polarizable sulfur atoms into N-containing heteroaromatics, we successfully synthesized a novel type of aromatic material that preferentially forms lamellar pi-pi stacked crystalline materials with a interplanar pi-pi distance of 3.247 angstrom, more than 0.1 angstrom shorter than that of highly oriented pyrolytic graphite (HOPG) where interplanar distance ranges from 3.35 to 3.39 angstrom.

Chemistry Department.

 

Yao, Ge, Shuping Huang, Mary T. Berry, P. Stanley May, & Dmitri S. Kilin. (2014). Non-collinear spin DFT for lanthanide ions in doped hexagonal NaYF4. Molecular Physics, 112(3-4), 546-556.

Trivalent lanthanide ions (Ln(3+)) doped in hexagonal ()-NaYF4 nanocrystals (Na(24)Y(23)Ln(1)F(96), Ln = La, Ce, Pr, Nd, Pm, Sm, Eu, Gd) were systematically studied by density functional theory (DFT) with a perturbative account for spin-orbit coupling. The simulated results, including the optimised molecular structures, electronic and magnetic properties, are compared to previous spin-polarised DFT studies in the same system. The spin-orbit coupling effects become significant with the increase in the number of unpaired 4f electrons in the doped lanthanide ions, particularly for the Sm3+-, Eu3+- and Gd3+-doped nanocrystals. Abnormal behaviour of Eu3+-doped nanocrystals was observed due to the Wybourne-Downer mechanism. A sandwich-like’ 2p-4f-4d,5d electronic structure for Na(24)Y(23)Ln(1)F(96) and the energies of the highest occupied 4f electrons from Ce3+ to Gd3+ are consistent with Dorenbos’s relationship. The energy difference between the first and second Russell-Saunders terms (L2S+1) of the lanthanide dopant is consistent with Carnall’s experimental results and with earlier spin-polarised DFT calculations.

Chemistry Department.

 

Zhang, Yuchi, Chao Qiu, & Dmitri S. Kilin. (2014). Electron dynamics in charged wet TiO2 anatase (001) surface functionalised by ruthenium ions. Molecular Physics, 112(3-4), 441-452.

The surface of charged wet TiO2 anatase (001) functionalised by ruthenium ion at ambient temperatures is studied by computational modelling. Response of this model to photoexcitations at ambient temperatures is explored with the Redfield density matrix equation of motion on the basis of Kohn-Sham orbitals. The parameters of the Redfield equation are on-the-fly non-adiabatic couplings for electronic degrees of freedom obtained along the ab initio molecular dynamics nuclear trajectories. The main results in this study are the following: (1) optical properties of the doped models such as light absorption intensity and transition energies can be tuned by modifying total charge; (2) electron and hole relaxation rates depend on the initial excitation; and (3) in the doped model, excitations of lower energy provide quicker relaxation. Results of computational modelling would benefit understanding of the mechanism of electron transfer processes on the surface of ruthenium-doped TiO2.

Chemistry Department.

 

Zhang, Z. L., M. Dubey, D. Galipeau, Q. H. Fan, James D. Hoefelmeyer, & I. Y. Al-Qaradawi. (2013). Creating textured surfaces using plasma electrolysis. Mrs Communications, 3(4), 255-258.

Plasma electrolysis (PE) is a combination of electrolysis and plasma discharge. Previous studies indicated that PE usually created porous surface with irregular morphology as a result of the plasma-cathode interaction that was dominated by physical reactions. This paper demonstrated that highly ordered textured silicon surfaces could be created using PE. This abnormal anisotropic etching phenomenon implied that the chemical reactions were decoupled from the physical processes and the physical reactions were suppressed. Raman spectra confirmed that the textured silicon surface created by PE conserved the crystalline structure. Therefore, PE may lead to new process regimes for surface engineering.

Chemistry Department.

 

May, P. A., B. G. Tabachnick, J. P. Gossage, …., H. Eugene Hoyme, & C. M. Adnams. (2013). Maternal Factors Predicting Cognitive and Behavioral Characteristics of Children with Fetal Alcohol Spectrum Disorders. Journal of Developmental and Behavioral Pediatrics, 34(5), 314-325.

Objective: To provide an analysis of multiple predictors of cognitive and behavioral traits for children with fetal alcohol spectrum disorders (FASDs). Method: Multivariate correlation techniques were used with maternal and child data from epidemiologic studies in a community in South Africa. Data on 561 first-grade children with fetal alcohol syndrome (FAS), partial FAS (PFAS), and not FASD and their mothers were analyzed by grouping 19 maternal variables into categories (physical, demographic, childbearing, and drinking) and used in structural equation models (SEMs) to assess correlates of child intelligence (verbal and nonverbal) and behavior. Results: A first SEM using only 7 maternal alcohol use variables to predict cognitive/behavioral traits was statistically significant (B = 3.10, p < .05) but explained only 17.3% of the variance. The second model incorporated multiple maternal variables and was statistically significant explaining 55.3% of the variance. Significantly correlated with low intelligence and problem behavior were demographic (B = 3.83, p < .05) (low maternal education, low socioeconomic status [SES], and rural residence) and maternal physical characteristics (B = 2.70,p < .05) (short stature, small head circumference, and low weight). Childbearing history and alcohol use composites were not statistically significant in the final complex model and were overpowered by SES and maternal physical traits. Conclusions: Although other analytic techniques have amply demonstrated the negative effects of maternal drinking on intelligence and behavior, this highly controlled analysis of multiple maternal influences reveals that maternal demographics and physical traits make a significant enabling or disabling contribution to child functioning in FASD.

May, Philip A. Tabachnick, Barbara G. Gossage, J. Phillip Kalberg, Wendy O. Marais, Anna-Susan Robinson, Luther K. Manning, Melanie A. Blankenship, Jason Buckley, David Hoyme, H. Eugene Adnams, Colleen M.

 

Bersamin, M. M., B. L. Zamboanga, S. J. Schwartz, M. B. Donnellan, …., & S. Jean Caraway. (2014). Risky Business: Is There an Association between Casual Sex and Mental Health among Emerging Adults? Journal of Sex Research, 51(1), 43-51.

A multiethnic sample of single, heterosexual, emerging-adult college students (N=3,907) ages 18 to 25, from 30 institutions across the United States, participated in a study about identity, culture, psychological well-being, and risky behaviors. Given ongoing debates about the connection between casual sex and psychological adjustment, in the current study we assessed the cross-sectional association of participation in casual sex with psychological well-being and distress. A greater proportion of men (18.6%) compared to women (7.4%) reported having had casual sex in the month prior to assessment. Structural equation modeling indicated that casual sex was negatively associated with well-being (ss=.20, p <.001) and positively associated with psychological distress (ss=.16, p <.001). Gender did not moderate these associations. For emerging-adult college students, engaging in casual sex may elevate risk for negative psychological outcomes.

Psychology Department.

 

Dezutter, J., A. S. Waterman, S. J. Schwartz, …., & S. Jean Caraway. (2014). Meaning in Life in Emerging Adulthood: A Person-Oriented Approach. Journal of Personality, 82(1), 57-68.

The present study investigated naturally occurring profiles based on two dimensions of meaning in life: Presence of Meaning and Search for Meaning. Cluster analysis was used to examine meaning-in-life profiles, and subsequent analyses identified different patterns in psychosocial functioning for each profile. A sample of 8,492 American emerging adults (72.5% women) from 30 colleges and universities completed measures on meaning in life, and positive and negative psychosocial functioning. Results provided support for five meaningful yet distinguishable profiles. A strong generalizability of the cluster solution was found across age, and partial generalizability was found across gender and ethnicity. Furthermore, the five profiles showed specific patterns in relation to positive and negative psychosocial functioning. Specifically, respondents with profiles high on Presence of Meaning showed the most adaptive psychosocial functioning, whereas respondents with profiles where meaning was largely absent showed maladaptive psychosocial functioning. The present study provided additional evidence for prior research concerning the complex relationship between Presence of Meaning and Search for Meaning, and their relation with psychosocial functioning. Our results offer a partial clarification of the nature of the Search for Meaning process by distinguishing between adaptive and maladaptive searching for meaning in life.

Psychology Department.

 

Ammann, E. M., J. V. Pottala, William S. Harris, M. A. Espeland, R. Wallace, N. L. Denburg, . . . J. G. Robinson. (2013). Omega-3 fatty acids and domain-specific cognitive aging Secondary analyses of data from WHISCA. Neurology, 81(17), 1484-1491.

Objective: To test the hypothesis that higher levels of red blood cell (RBC) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have a protective association with domain-specific cognitive function in women aged 65 years and older. Methods: A total of 2,157 women with normal cognition enrolled in a clinical trial of postmenopausal hormone therapy were followed with annual cognitive testing for a median of 5.9 years. In this retrospective cohort study, we assessed the relationship between prerandomization RBC DHA +/- EPA levels and a) cognitive measures at baseline, and b) cognitive change over time. Endpoints were composite cognitive function and performance in 7 cognitive domains: fine motor speed, verbal memory, visual memory, spatial ability, verbal knowledge, verbal fluency, and working memory. Results: After adjustment for demographic, clinical, and behavioral characteristics, no significant (p < 0.01) cross-sectional cognitive differences were found between women in the high and low DHA + EPA tertiles at the time of the first annual cognitive battery. In addition, no significant (p < 0.01) differences were found between the high and low DHA +/- EPA tertiles in the rate of cognitive change over time. Conclusions: We did not find an association between RBC DHA +/- EPA levels and age-associated cognitive decline in a cohort of older, dementia-free women.

Sanford School of Medicine, Sioux Falls Campus.

 

Martin-Montalvo, A., I. Gonzalez-Mariscal, T. Pomares-Viciana, Sergio Padilla-Lopez, M. Ballesteros, L. Vazquez-Fonseca, . . . C. Santos-Ocana. (2013). The Phosphatase Ptc7 Induces Coenzyme Q Biosynthesis by Activating the Hydroxylase Coq7 in Yeast. Journal of Biological Chemistry, 288(39), 28126-28137.

The study of the components of mitochondrial metabolism has potential benefits for health span and lifespan because the maintenance of efficient mitochondrial function and antioxidant capacity is associated with improved health and survival. In yeast, mitochondrial function requires the tight control of several metabolic processes such as coenzyme Q biosynthesis, assuring an appropriate energy supply and antioxidant functions. Many mitochondrial processes are regulated by phosphorylation cycles mediated by protein kinases and phosphatases. In this study, we determined that the mitochondrial phosphatase Ptc7p, a Ser/Thr phosphatase, was required to regulate coenzyme Q(6) biosynthesis, which in turn activated aerobic metabolism and enhanced oxidative stress resistance. We showed that Ptc7p phosphatase specifically activated coenzyme Q(6) biosynthesis through the dephosphorylation of the demethoxy-Q(6) hydroxylase Coq7p. The current findings revealed that Ptc7p is a regulator of mitochondrial metabolism that is essential to maintain proper function of the mitochondria by regulating energy metabolism and oxidative stress resistance.

Sanford School of Medicine, Sioux Falls Campus.

 

May, P. A., J. Blankenship, A. S. Marais, …., H. Eugene Hoyme, B. Tabachnick, & S. Seedat. (2013). Maternal alcohol consumption producing fetal alcohol spectrum disorders (FASD): Quantity, frequency, and timing of drinking. Drug and Alcohol Dependence, 133(2), 502-512.

Background: Concise, accurate measures of maternal prenatal alcohol use are needed to better understand fetal alcohol spectrum disorders (FASD). Methods: Measures of drinking by mothers of children with specific FASD diagnoses and mothers of randomly-selected controls are compared and also correlated with physical and cognitive/behavioral outcomes. Results: Measures of maternal alcohol use can differentiate maternal drinking associated with FASD from that of controls and some from mothers of alcohol-exposed normals. Six variables that combine quantity and frequency concepts distinguish mothers of FASD children from normal controls. Alcohol use variables, when applied to each trimester and three months prior to pregnancy, provide insight on critical timing of exposure as well. Measures of drinking, especially bingeing, correlate significantly with increased child dysmorphology and negative cognitive/behavioral outcomes in children, especially low non-verbal IQ, poor attention, and behavioral problems. Logistic regression links (p < .001) first trimester drinking (vs. no drinking) with FASD, elevating FASD likelihood 12 times; first and second trimester drinking increases FASD outcomes 61 times; and drinking in all trimesters 65 times. Conversely, a similar regression (p = .008) indicates that drinking only in the first trimester makes the birth of a child with an FASD 5 times less likely than drinking in all trimesters. Conclusions: There is significant variation in alcohol consumption both within and between diagnostic groupings of mothers bearing children diagnosed within the FASD continuum. Drinking measures are empirically identified and correlated with specific child outcomes. Alcohol use, especially heavy use, should be avoided throughout pregnancy. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

Sanford School of Medicine, Sioux Falls Campus.

 

Nagle, A. S., Matthew A. Barker, S. D. Kleeman, B. Haridas, & T. D. Mast. (2014). Passive biomechanical properties of human cadaveric levator ani muscle at low strains. Journal of Biomechanics, 47(2), 583-586.

The objective of this study was to measure and model the passive biomechanics of cadaveric levator ani muscle in the fiber direction at low strains with a moderately slow deformation rate. Nine levator ani samples, extracted from female cadavers aged 64 to 96 years, underwent preconditioning and uniaxial biomechanical analysis on a tensile testing apparatus after the original width, thickness, and length were measured. The load extension data and measured dimensions were used to calculate stress-strain curves for each sample. The resulting stress-strain curves up to 10% strain were fit to four different constitutive models to determine which model was most appropriate for the data. A power-law model with two parameters was found to fit the data most accurately. Constitutive parameters did not correlate significantly with age in this study; this may be because all of the cadavers were postmenopausal. (C) 2013 Elsevier Ltd. All rights reserved.

Sanford School of Medicine, Sioux Falls Campus.

 

Pradip, De, M. Bouzyk, Nandini Dey, & Brian Leyland-Jones. (2013). Dissecting GRB7-mediated signals for proliferation and migration in HER2 overexpressing breast tumor cells: GTP-ase rules. American Journal of Cancer Research, 3(2), 173-U126.

Amplification of human Her2 and its aberrant signaling in 20-30% of early breast cancer patients is responsible for highly aggressive tumors with poor outcome. Grb7 is reported to be co-amplified with Her2. We report a concurrent high expression of mRNA (from FFPE tumor samples; mRNA correlation, Pearson r(2)=0.806), and high levels of GRB7 protein (immunoblot) in HER2+ breast cancer cell lines. We demonstrated the signaling mechanism of HER2 and downstream effectors that contributes to proliferation and migration. Using HER2+ and trastuzumab-resistant breast cancer cell lines, we identified the interaction between GRB7 and HER2 in the control of HER2+ cell proliferation. Our co-IP data show that GRB7 recruits SHC into the HER2-GRB7 signaling complex. This complex formation leads to activation of RAS-GTP. We also observed that following integrin engagement, GRB7 is phosphorylated at tyrosine in a p-FAK (Y397) dependent manner. This FAK-GRB7 complex leads to downstream activation of RAC1-GTP (responsible for migration) probably through the recruitment of VAV2. Our CO-IP data demonstrate that GRB7 directly binds with VAV2 following fibronectin engagement in HER2+ cells. To address whether GRB7 could serve as a pathway specific therapeutic target, we used siRNA to suppress GRB7 expression. Knockdown of GRB7 expression in the HER2+ breast cancer cell lines decreases RAS activation, cell proliferation, 2D and 3D colony formation and also blocked integrin-mediated RAC1 activation along with integrin-directed cell migration. These findings dissected the HER2-mediated signaling cascade into (1) HER2+ cell proliferation (HER2-GRB7-SHC-RAS) and (2) HER2+ cell migration (alpha5 beta1/alpha4 beta1-FAK-GRB7-VAV2-RAC1). Our data clearly demonstrate that a coupling of GRB7 with HER2 is required for the proliferative and migratory signals in HER2+ breast tumor cells.

Sanford School of Medicine, Sioux Falls Campus.

 

Randall, Bradley B., D. S. Paterson, E. A. Haas, K. G. Broadbelt, J. R. Duncan, O. J. Mena, . . . H. C. Kinney. (2013). Potential Asphyxia and Brainstem Abnormalities in Sudden and Unexpected Death in Infants. Pediatrics, 132(6), E1616-E1625.

OBJECTIVE: Sudden and unexplained death is a leading cause of infant mortality. Certain characteristics of the sleep environment increase the risk for sleep-related sudden and unexplained infant death. These characteristics have the potential to generate asphyxial conditions. We tested the hypothesis that infants may be exposed to differing degrees of asphyxia in sleep environments, such that vulnerable infants with a severe underlying brainstem deficiency in serotonergic, g-aminobutyric acid-ergic, or 14-3-3 transduction proteins succumb even without asphyxial triggers (eg, supine), whereas infants with intermediate or borderline brainstem deficiencies require asphyxial stressors to precipitate death. METHODS: We classified cases of sudden infant death into categories relative to a “potential asphyxia” schema in a cohort autopsied at the San Diego County Medical Examiner’s Office. Controls were infants who died with known causes of death established at autopsy. Analysis of covariance tested for differences between groups. RESULTS: Medullary neurochemical abnormalities were present in both infants dying suddenly in circumstances consistent with asphyxia and infants dying suddenly without obvious asphyxia-generating circumstances. There were no differences in the mean neurochemical measures between these 2 groups, although mean measures were both significantly lower (P<.05) than those of controls dying of known causes. CONCLUSIONS: We found no direct relationship between the presence of potentially asphyxia conditions in the sleep environment and brainstem abnormalities in infants dying suddenly and unexpectedly. Brainstem abnormalities were associated with both asphyxia-generating and non-asphyxia generating conditions. Heeding safe sleep messages is essential for all infants, especially given our current inability to detect underlying vulnerabilities.

Sanford School of Medicine, Sioux Falls Campus.

 

Smythe, M. A., J. Fanikos, Michael P. Gulseth, A. K. Wittkowsky, S. A. Spinler, W. E. Dager, & E. A. Nutescu. (2013). Rivaroxaban: Practical Considerations for Ensuring Safety and Efficacy. Pharmacotherapy, 33(11), 1223-1245.

Rivaroxaban is the first agent available within a new class of anticoagulants called direct factor Xa inhibitors. Rivaroxaban is approved for use in the United States for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, for the prevention of deep vein thrombosis in patients undergoing total hip replacement and total knee replacement, for the treatment of deep vein thrombosis and pulmonary embolism, and for the reduction in risk of recurrence of deep vein thrombosis and pulmonary embolism (with additional indications under review). Rivaroxaban dose and frequency of administration vary depending on the indication. As of result of predictable pharmacokinetics and pharmacodynamics, a fixed dose of rivaroxaban is administered without routine coagulation testing. Rivaroxaban has a short half-life, undergoes a dual mode of elimination (hepatic and renal), and is a substrate for P-glycoprotein. Rivaroxaban has a lower potential for drug interactions compared with warfarin. Despite the advantages of a once/day fixed-dose oral agent, in many clinical situations limited evidence is available to guide optimal management of rivaroxaban therapy. In this article, we review the available evidence and provide recommendations where possible for such situations including the desire to monitor the anticoagulation intensity, use in special patient populations, managing drug interactions, and transitioning across anticoagulant agents. Potential strategies for reversing rivaroxaban’s anticoagulant effect are reviewed. Health systems will need to perform a systematic safety evaluation and ensure that numerous hospital policies related to anticoagulation are updated to include rivaroxaban. A comprehensive approach to education is needed for clinicians, patients, and technical support personnel involved in patient interactions to ensure safe use.

Sanford School of Medicine, Sioux Falls Campus.

 

Williams, Casey B., S. Kambhampati, W. Fiskus, J. Wick, C. Dutreix, S. Ganguly, . . . J. P. McGuirk. (2013). Preclinical and Phase I Results of Decitabine in Combination with Midostaurin (PKC412) for Newly Diagnosed Elderly or Relapsed/Refractory Adult Patients with Acute Myeloid Leukemia. Pharmacotherapy, 33(12), 1341-1352.

PURPOSE To determine the preclinical activity, clinical maximum tolerated dose (MTD), and recommended phase II dose of midostaurin (MS) combined either sequentially or concurrently with intravenous decitabine (DAC) in newly diagnosed patients 60 years or older or relapsed/refractory adult patients (18 years or older) with acute myeloid leukemia (AML). PATIENTS AND METHODS Cultured and primary AML cells were treated with DAC and/or MS and analyzed by flow cytometry and immunoblot analyses. In the phase I study, 16 patients were enrolled; 8 were newly diagnosed patients 60 years or older and 8 were 18 years or older with relapsed AML. Only 2 of 16 patients (13%) had FLT3-internal tandem duplication (ITD) mutations, and no patient had KIT mutations. RESULTS Compared with treatment with either agent alone, sequential treatment with DAC and MS exerted superior anti-AML activity in cultured and primary FLT3-ITD-expressing AML cells. In the subsequent phase I study, the MTD and schedule of administration of the combination was identified as DAC followed by MS. Three patients developed dose-limiting toxicities: two patients developed pulmonary edema requiring mechanical ventilation and one patient developed a prolonged QTc greater than 500 msec. Based on an intent-to-treat analysis, 57% of the patients achieved stable disease or better while enrolled in the trial; 25% had a complete hematologic response. Pharmacokinetic analysis revealed results similar to those previously reported for MS. CONCLUSION The in vitro combination of DAC and MS is synergistically active against FLT3-ITD mutations expressing AML cells. In a clinical setting, the combination of sequentially administered DAC followed by MS is possible without significant unexpected toxicity, but the concurrent administration of DAC and MS led to pulmonary toxicity after only a few doses. On the basis of these results, additional studies exploring the sequential combination of untreated AML in elderly patients are warranted to further evaluate this combination at the MTD.

Sanford School of Medicine, Sioux Falls Campus.

 

Beebe, Justin A., Roger W. Hines, Laura T. McDaniel, & Brenda L. Shelden. (2013). An Isokinetic Training Program for Reducing Falls in a Community-Dwelling Older Adult: A Case Report. Journal of Geriatric Physical Therapy, 36(3), 146-153.

Background: With the population older than 65 years, projected to double by the year 2030, falls in older adults are a substantial health concern. Muscle strength deficits are one of the multifactorial components linked to increased fall risk, and decreasing these deficits has been one of the goals of interventions designed to decrease fall risk. These interventions have traditionally focused on improving peak torque; however, recent research suggests that exercise protocols that focus on the rate of torque development (RTD) may be more effective in decreasing fall risk. Purpose: This case report examines clinical outcomes following implementation of an isokinetic strengthening protocol coupled with a balance program designed to reduce fall risk in a community-dwelling older adult. Methods: The individual was a 70-year-old woman with a history of 3 falls over the past 8 months and no related medical etiology who had self-limited her activities because of fear of another fall. She was classified as having substantial risk for future falls because of fall history, increased fear of falling, and below age norms on the Berg Balance Scale (BBS), and the Timed Up and Go (TUG). The treatment program consisted of 12 weeks of high-intensity isokinetic knee extensor training, high challenge dynamic gait and balance activities, and core strengthening. The isokinetic protocol consisted of 4 sets of 10 concentric-only repetitions at speeds of 240 degrees/sec and 300 /sec for a total of 8 work sets. Dynamic gait activities incorporating directional and obstacle drills, and rocker and balance boards were used for balance training activities. Progressive theraband exercises were used for core strengthening. As her home program, the participant was encouraged to return to line dancing twice per week. During the 12-week protocol, the participant completed two 90-minute therapy sessions and two 90-minute dance classes per week. Results: After the 12 weeks of treatment, knee extensor peak torque at 150 ms improved on the right from 67.8 N to 107.1 N (57.9% increase), and on the left from 65.1 N to 97.6 N (49.9% increase). The BBS score improved from 45 to 52; and the TUG improved from 14.0 to 8.6 seconds. Both final scores exceeded fall risk cutoffs (BBS = 48; TUG = 13.5 seconds) and the change score exceeded minimal detectable change (BBS = 7; TUG 5.4 seconds). Conclusions: The treatment program produced improvements in knee extensor peak torque and RTD, but more importantly, the final scores on the clinical outcome measures placed the participant above established fall-risk cutoff scores. Although future research with increased numbers of participants and a control group should be conducted to confirm this study’s results, these findings support the use of isokinetic training to reduce fall risk in older adults.

School of Health Sciences.


Posted by: kelsijo97 | January 24, 2014

January 2014

Bhuiyan, M. S., Pattison, J. Scott, Osinska, H., James, J., Gulick, J., McLendon, P. M., . . . Robbins, J. (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 CryAB(R120G) 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 CryAB(R120G) 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(R120G) mice and the Atg7-crossed CryAB(R120G) mice to voluntary exercise, which also upregulates autophagy. The entire exercised Atg7-crossed CryAB(R120G) 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.

Canguo, Zhao, Shouting, Liu, Changshan, Yang, Xiaofen, Li, Hongbiao, Huang, Ningning, Liu, . . . Jinbao, Liu. (2013). Gambogic acid moderates cardiac responses to chronic hypoxia likely by acting on the proteasome and NF-κB pathway. American Journal of Cardiovascular Disease, 3(3), 135-145.

Gambogic acid (GA) is the principal active ingredient of gamboges. GA was reported to exert anti-tumor and anti-inflammatory effects both in vitro and in vivo. Previously, we have shown that GA is a more tissue-specific proteasome inhibitor than bortezomib and it is less toxic to peripheral white blood cells compared to bortezomib. Ubiquitous proteasome inhibition was shown by some reports, but not by others, to prevent cardiac remodeling in response to pressure overload by blocking the NF-κB pathway; however, whether GA modulates the development of chronic hypoxia-induced right ventricular hypertrophy has not been investigated yet. Here we report that GA can significantly attenuate right ventricular hypertrophy induced by chronic hypoxia, reduce cardiac fibrosis, and remarkably block the reactivation of bona fide fetal genes in the cardiac tissue. Furthermore, we also investigated the potential molecular targets of GA on right ventricular hypertrophy. The results showed that GA could accumulate the IκB levels associated with decreased proteasomal activity, block the translocation of NF-κB from the cytoplasm to the nucleus, decrease NF-κB DNA-binding activity, and reduce IL-2 levels. In conclusion, GA is capable of preventing the development of chronic hypoxia-induced right ventricular hypertrophy. GA has great potential to be developed into an effective anti-hypertrophy agent.

Basic Biomedical Sciences, Vermillion Campus.

Novick, Andrew M., Miiller, Leah C., Forster, Gina L., & Watt, Michael J. (2013). Adolescent social defeat decreases spatial working memory performance in adulthood. Behavioral and Brain Functions, 9.

Background: Adolescent social stress is associated with increased incidence of mental illnesses in adulthood that are characterized by deficits in cognitive focus and flexibility. Such enhanced vulnerability may be due to psychosocial stress-induced disruption of the developing mesocortical dopamine system, which plays a fundamental role in facilitating complex cognitive processes such as spatial working memory. Adolescent rats exposed to repeated social defeat as a model of social stress develop dopaminergic hypofunction in the medial prefrontal cortex as adults. To evaluate a direct link between adolescent social stress and later deficits in cognitive function, the present study tested the effects of adolescent social defeat on two separate tests of spatial working memory performance. Methods: Adult rats exposed to adolescent social defeat and their controls were trained on either the delayed win-shift task or the delayed alternating T-Maze task and then challenged with various delay periods. To evaluate potential differences in motivation for the food reward used in memory tasks, consumption and conditioned place preference for sweetened condensed milk were tested in a separate cohort of previously defeated rats and controls. Results: Compared to controls, adult rats defeated in adolescence showed a delay-dependent deficit in spatial working memory performance, committing more errors at a 90 s and 5 min delay period on the T-maze and win-shift tasks, respectively. Observed memory deficits were likely independent of differences in reward motivation, as conditioned place preference for the palatable food used on both tasks was similar between the adolescent social defeat group and control. Conclusions: The results demonstrate that severe social stressors during adolescence can produce long term deficits in aspects of cognitive function. Given the dependence of spatial working memory on prefrontal dopamine, pharmacologically reversing dopaminergic deficiencies caused by adolescent social stress has the potential to treat such cognitive deficits.

Basic Biomedical Sciences, Vermillion Campus.

Rajagopalan, Viswanathan, Mingming, Zhao, Reddy, Sushma, Fajardo, Giovanni, Xuejun, Wang, Dewey, Shannamar, . . . Bernstein, Daniel. (2013). Altered ubiquitin-proteasome signaling in right ventricular hypertrophy and failure. American Journal of Physiology: Heart & Circulatory Physiology, 305(4), H551-H562.

Alterations in the ubiquitin-proteasome system (UPS) have been described in left ventricular hypertrophy and failure, although results have been inconsistent. The role of the UPS in right ventricular (RV) hypertrophy (RVH) and RV failure (RVF) is unknown. Given the greater percent increase in RV mass associated with RV afterload stress, as present in many congenital heart lesions, we hypothesized that alterations in the UPS could play an important role in RVH/RVF. UPS expression and activity were measured in the RV from mice with RVH/RVF secondary to pulmonary artery constriction (PAC). Epoxomicin and MG132 were used to inhibit the proteasome, and overexpression of the 11S PA28a subunit was used to activate the proteasome. PAC mice developed RVH (109.3% increase in RV weight to body weight), RV dilation with septal shift, RV dysfunction, and clinical RVF. Proteasomal function (26S ß5 chymotrypsin-like activity) was decreased 26% (P < 0.05). Protein expression of 19S subunit Rpt5 (P < 0.05), UCHL1 deubiquitinase (P < 0.0001), and Smurf1 E3 ubiquitin ligase (P < 0.01) were increased, as were polyubiquitinated proteins (P < 0.05) and free-ubiquitins (P = 0.05). Pro-apoptotic Bax was increased (P < 0.0001), whereas anti-apoptotic Bcl-2 decreased (P < 0.05), resulting in a sixfold increase in the Bax/Bcl-2 ratio. Proteasomal inhibition did not accelerate RVF. However, proteasome enhancement by cardiac-specific proteasome overexpression partially improved survival. Proteasome activity is decreased in RVH/RVF, associated with upregulation of key UPS regulators and pro-apoptotic signaling. Enhancement of proteasome function partially attenuates RVF, suggesting that UPS dysfunction contributes to RVF.

Basic Biomedical Sciences, Vermillion Campus.

Yuan, Sharleen, & Burrell, Brian D. (2013). Nonnociceptive afferent activity depresses nocifensive behavior and nociceptive synapses via an endocannabinoid-dependent mechanism. Journal of Neurophysiology, 110(11), 2607-2616.

Previously, low-frequency stimulation (LFS) of a nonnociceptive touch-sensitive neuron has been found to elicit endocannabinoid-dependent long-term depression (eCB-LTD) in nociceptive synapses in the leech central nervous system (CNS) that requires activation of a presynaptic transient receptor potential vanilloid (TRPV)-like receptor by postsynaptically synthesized 2-arachidonoyl glycerol (2-AG). This capacity of nonnociceptive afferent activity to reduce nociceptive signaling resembles gate control of pain, albeit longer lasting in these synaptic experiments. Since eCB-LTD has been observed at a single sensory-motor synapse, this study examines the functional relevance of this mechanism, specifically whether this form of synaptic plasticity has similar effects at the behavioral level in which additional, intersegmental neural circuits are engaged. Experiments were carried out using a semi-intact preparation that permitted both synaptic recordings and monitoring of the leech whole body shortening, a defensive withdrawal reflex that was elicited via intracellular stimulation of a single nociceptive neuron (the N cell). The same LFS of a nonnociceptive afferent that induced eCB-LTD in single synapses also produced an attenuation of the shortening reflex. Similar attenuation of behavior was also observed when 2-AG was applied. LFS-induced behavioral and synaptic depression was blocked by tetrahydrolipstatin (THL), a diacylglycerol lipase inhibitor, and by SB366791, a TRPV1 antagonist. The effects of both THL and SB366791 were observed following either bath application of the drug or intracellular injection into the presynaptic (SB366791) or postsynaptic (THL) neuron. These findings demonstrate a novel, endocannabinoid-based mechanism by which nonnociceptive afferent activity may modulate nocifensive behaviors via action on primary afferent synapses.

Basic Biomedical Sciences, Vermillion Campus.

Zou, Jianqiu, Rezvani, Khosrow, Wang, Hongmin, Lee, K. S., & Zhang, Dong. (2013). BRCA1 downregulates the kinase activity of Polo-like kinase 1 in response to replication stress. Cell Cycle, 12(14), 2255-2265.

In response to DNA damage or replication stress, proliferating cells are arrested at different cell cycle stages for DNA repair by downregulating the activity of both the cyclin-dependent kinases (CDKs) and other important cell cycle kinases, including Polo-like kinase 1 (PLK1) . The signaling pathway to inhibit CDKs is relatively well understood, and breast cancer gene 1 (BRCA1) and other DNA damage response (DDR) factors play a key role in this process. However, the DNA damage-induced inhibition of PLK1 is still largely a mystery. Here we show that DNA damage and replication stress stimulate the association between BRCA1 and PLK1. Most importantly, we demonstrate that BRCA1 downregulates the kinase activity of PLK1 by modulating the dynamic interactions of Aurora A, hBora, and PLK1. Together with previous findings, we propose that in response to replication stress and DNA damage, BRCA1 plays a critical role in downregulating the kinase activity of both CDKs and PLK1.

Basic Biomedical Sciences, Vermillion Campus.

Ghosh, Suvankar, & Li, X. L. (2013). A Real Options Model for Generalized Meta-Staged Projects-Valuing the Migration to SOA. Information Systems Research, 24(4), 1011-1027.

This paper develops an innovative real options (RO) model for valuing multistage information technology (IT) projects that can be viewed as comprising meta stages. In RO literature, multistage investment programs have been treated as either interproject or intraproject programs, with intraproject programs being evaluated using n-fold Geske compound options and interproject programs valued using the so-called “subsidy-to-exercise price” logic. Our innovative RO model integrates the Geske compound option model with the subsidy-to-exercise price approach to value sequential investment programs that are neither purely interproject nor purely intraproject in nature but are composed of meta-stages. A meta-stage as a whole can be considered an interproject stage resulting in cash flows, but internally it consists of several intraproject stages that do not result in cash flows. We show that a key problem in IT, which is migrating to a Service-Oriented Architecture (SOA) for integrating a firm’s many disparate applications, systems, data, and business processes, is best viewed as an investment program comprising meta-stages. Examining SOA migration from an RO lens is particularly apt at this time not only because of the importance of SOA but also because doubts have surfaced about the value of SOA. We illustrate our RO model by applying it to the simulated case of a firm migrating to SOA. We also develop a software tool based on the Mathematica T computational platform so that practitioners can easily apply our innovative options pricing model to determine the true value of SOA in their business contexts.

Beacom School of Business.

Brown, Jennifer, & Kerby, Jacob. (2013). Batrachochytrium dendrobatidis in South Dakota, USA Amphibians. Herpetological Review, 44(3), 457-458.

Biology Department.

Bubak, Andrew N., Renner, Kenneth J., & Swallow, John G. (2014). Heightened serotonin influences contest outcome and enhances expression of high-intensity aggressive behaviors. Behavioural Brain Research, 259, 137-142.

Highlights: [•] We pharmacologically altered brain 5-HT levels using the precursor 5-HTP. [•] We found heightened 5-HT increased the probability of winning aggressive contests. [•] High-intensity behaviors and retreat threshold are influenced by 5-HT. [•] Other biogenic amines including octopamine remained unaltered following fights.

Biology Department.

Siler, Cameron D., Welton, Luke J., Rock, Ashley A., & Brown, Rafe M. (2013). Population Genetic Structure and Revised Geographic Range for the Tridactyl Skink (Brachymeles muntingkamay) from Luzon Island, Philippines. Herpetological Review, 44(1), 30-33.

Biology Department.

Thomas, Nathan E., & Swanson, David L. (2013). PLASMA METABOLITES AND CREATINE KINASE LEVELS OF SHOREBIRDS DURING FALL MIGRATION IN THE PRAIRIE POTHOLE REGION. Auk, 130(4), 580-590.

Wetland habitats in the Prairie Pothole Region of North America have been greatly reduced since European settlement, but the availability of managed wetlands has increased. The relative efficacy of these two habitats for meeting energetic demands of migrating shorebirds is unknown. To assess the relative suitability of stopover sites, we measured plasma metabolites and creatine kinase in Least Sandpipers (Calidris minutilla), Semipalmated Sandpipers (C. pusilla), and Pectoral Sandpipers (C. melanotos) at natural and managed wetland sites during fall migration in northeastern South Dakota and west-central Minnesota. We used stepwise multiple regression to identify significant effectors of plasma metabolite levels, followed by analysis of covariance to compare metabolite values between birds in the two habitat types. Plasma metabolite levels generally did not differ significantly between birds in the two habitat types, with two exceptions. Plasma triglycerides of Pectoral Sandpipers were 2.6x higher at managed than at natural wetlands, suggesting higher rates of fattening at managed sites, but this was not supported by plasma glycerol levels, which did not differ significantly between birds in the two habitat types, or by body mass, which was greater for adult males in natural wetlands. Plasma creatine kinase levels of Least Sandpipers were 75% higher at managed than at natural wetlands, which suggests that repair of flight-induced muscle damage may be slower for this species at managed wetlands. The general absence of significant differences in plasma metabolites among shorebirds in the two wetland types suggests that natural and managed wetlands serve as similarly effective stopover habitat for fall-migrating shorebirds in the Prairie Pothole Region.

Biology Department.

Wu, Chia-Ming, Peng, Rui, Dimitrijevic, Nada M., Rajh, Tijana, & Koodali, Ranjit T. (2014). Preparation of TiO2–SiO2 aperiodic mesoporous materials with controllable formation of tetrahedrally coordinated Ti4+ ions and their performance for photocatalytic hydrogen production. International Journal of Hydrogen Energy, 39(1), 127-136.

Abstract: The efficiency of photocatalytic water splitting for TiO2 dispersed on four SiO2 aperiodic porous supports is discussed in this work. The four TiO2–SiO2 composite materials were prepared via a sol–gel method and then subjected to supercritical drying, natural drying, rotatory vapor drying, or hydrothermal synthesis and the materials were subsequently calcined under identical conditions. These synthetic strategies result in differences in textural properties (specific surface area, pore diameter etc.) and in the amount of tetrahedrally coordinated Ti4+ ions. The TiO2–SiO2 materials were thoroughly characterized by powder X-ray diffraction (XRD), UV–Vis diffuse reflectance spectra (DRS), nitrogen adsorption studies, FT-IR spectroscopy, transmission electron microscopic (TEM) studies, and electron paramagnetic resonance (EPR) studies. The photocatalytic activity for hydrogen production is maximum when the amount of tetrahedrally coordinated Ti4+ ions is high. Thus, this work provides guidance towards the preparation of photoactive materials for generating hydrogen from water.

Chemistry Department.

Bersamin, Melina M., Zamboanga, Byron L., Schwartz, Seth J., ….., & Caraway, S. Jean. (2014). Risky Business: Is There an Association between Casual Sex and Mental Health among Emerging Adults? Journal of Sex Research, 51(1), 43-51.

A multiethnic sample of single, heterosexual, emerging-adult college students (N = 3,907) ages 18 to 25, from 30 institutions across the United States, participated in a study about identity, culture, psychological well-being, and risky behaviors. Given ongoing debates about the connection between casual sex and psychological adjustment, in the current study we assessed the cross-sectional association of participation in casual sex with psychological well-being and distress. A greater proportion of men (18.6%) compared to women (7.4%) reported having had casual sex in the month prior to assessment. Structural equation modeling indicated that casual sex was negatively associated with well-being (ß = .20,p < .001) and positively associated with psychological distress (ß = .16,p < .001). Gender did not moderate these associations. For emerging-adult college students, engaging in casual sex may elevate risk for negative psychological outcomes.

Psychology Department.

Contractor, A. A., Elhai, J. D., Ractliffe, Kendra C., & Forbes, D. (2013). PTSD’s underlying symptom dimensions and relations with behavioral inhibition and activation. Journal of Anxiety Disorders, 27(7), 645-651.

Reinforcement sensitivity theory (RST) stipulates that individuals have a behavioral activation system (BAS) guiding approach (rewarding) behaviors (Gray, 1971, 1981), and behavioral inhibition system (BIS) guiding conflict resolution between approach and avoidance (punishment) behaviors (Gray & McNaughton, 2000). Posttraumatic stress disorder (PTSD) severity overall relates to both BIS (e.g., Myers, VanMeenen, & Servatius, 2012; Pickett, Bardeen, & Orcutt, 2011) and BAS (Pickett et al., 2011). Using a more refined approach, we assessed specific relations between PTSD’s latent factors (Simms, Watson, & Doebbeling, 2002) and observed variables measuring BIS and BAS using 308 adult, trauma-exposed primary care patients. Confirmatory factor analysis and Wald chi-square tests demonstrated a significantly greater association with BIS severity compared to BAS severity for PTSD’s dysphoria, avoidance, and re-experiencing factors. Further, PTSD’s avoidance factor significantly mediated relations between BIS/BAS severity and PTSD’s dysphoria factor. (C) 2013 Elsevier Ltd. All rights reserved.

Psychology Department.

Berdahl, John P., & Jensen, M. P. (2014). The business of refractive laser assisted cataract surgery (ReLACS). Current Opinion in Ophthalmology, 25(1), 62-70.

Purpose of reviewRefractive Laser Assisted Cataract Surgery (ReLACS) combines the femtosecond laser with other noncovered tests and services in an attempt to reduce spectacle dependence in combination with cataract surgery. Significant interest is present among ophthalmologists who are considering adopting this technology, however significant capital outlays and continuing expenses can make the decision to adopt ReLACS foreboding. We review the financial considerations of ReLACS and review the trends seen in early adopters of this technology.Recent findingsRecent findings have shown that ReLACS is a growing segment of cataract surgery. Most practices who have implemented the technology have broken even and have a positive outlook on the financial return of implementing the ReLACS program. The average break-even analysis point for practices is around 230 cases a year.SummaryReLACS is growing and appears to be a financial viable approach for many practices.

Sanford School of Medicine, Sioux Falls Campus.

Doorn, Joshua M., & Kruer, Michael C. (2013). Newly Characterized Forms of Neurodegeneration with Brain Iron Accumulation. Current Neurology and Neuroscience Reports, 13(12).

Neurodegeneration with brain iron accumulation (NBIA) comprises a group of brain iron deposition syndromes that lead to mixed extrapyramidal features and progressive dementia. Historically, there has not been a clearly identifiable molecular cause for many patients with clinical and radiologic features of NBIA. Recent discoveries have shown that mutations in C19orf12 or WDR45 can lead to NBIA. C19orf12 mutations are inherited in an autosomal recessive manner, and lead to a syndrome similar to that caused by mutations in PANK2 or PLA2G6. In contrast, WDR45 mutations lead to a distinct form of NBIA characterized by spasticity and intellectual disability in childhood followed by the subacute onset of dystonia-parkinsonism in adulthood. WDR45 mutations act in an X-linked dominant manner. Although the function of C19orf12 is largely unknown, WDR45 plays a key role in autophagy. Each of these new forms of NBIA thus leads to a distinct clinical syndrome, and together they implicate new cellular pathways in the pathogenesis of these disorders.

Sanford School of Medicine, Sioux Falls Campus.

Hellwig, Thaddaus, & Gulseth, Michael. (2013). Pharmacokinetic and Pharmacodynamic Drug Interactions With New Oral Anticoagulants: What Do They Mean for Patients With Atrial Fibrillation? Annals of Pharmacotherapy, 47(11), 1478-1487.

Objective: To review pharmacokinetic and pharmacodynamic drug-drug interactions (DDIs) involving new oral anticoagulants for atrial fibrillation. Data Sources: A literature search was conducted via PubMed and the Cochrane database to identify DDI studies using the terms drug interactions, dabigatran, rivaroxaban, and apixaban. Prescribing information and Food and Drug Administration briefing documents were used to supplement published data. Study Selection and Data Extraction: English publications identified on Medline from 2005 up to August 2013 and US prescribing information for approved oral anticoagulants. Data Synthesis: Articles reviewed focused on drugs affecting the permeability glycoprotein (P-gp) efflux transporter protein and/or cytochrome P (CYP) 450 3A4 enzymes, and pharmacodynamic DDIs when drugs are administered concomitantly. Phase I DDI studies have reported pharmacokinetic DDIs mediated by P-gp alone (dabigatran etexilate) or in combination with CYP3A4 enzymes (rivaroxaban and apixaban). Dabigatran etexilate should not be administered with any P-gp inhibitor in patients with severe renal impairment. Briefing documents indicate that rivaroxaban and apixaban should not be used with drugs that are strong inhibitors of both P-gp and CYP3A4. DDI studies involving rifampicin suggest that rivaroxaban and apixaban should be avoided when strong inducers of P-gp and CYP3A4 are used concurrently. Concomitant use of apixaban and strong dual inhibitors of P-gp and CYP3A4 should be avoided or the dose reduced. Five randomized clinical trials report additive effects with rivaroxaban, dabigatran, and apixaban when used concomitantly with antiplatelet agents; bleeding rates have been found to be higher, especially with dual antiplatelet therapy. Conclusions: Awareness of drugs that alter the function of the P-gp efflux transporter protein and CYP3A4 enzymes and provide additive effects should enable prescribers to anticipate and avoid potential DDIs involving the new oral anticoagulants. To this end, briefing documents and prescribing information have applied cautionary measures for individuals treated with these newer anticoagulants.

Sanford SChool of Medicine, Sioux Falls Campus.

Stys, Adam T., Stys, Tomasz P., Rajpurohit, Naveen, & Khan, Muhammed A. (2013). A Novel Application of Guide Liner Catheter for Thrombectomy in Acute Myocardial Infarction: A Case Series. Journal of Invasive Cardiology, 25(11), 620-624.

Angiographically visible thrombus and distal embolization are relatively common during percutaneous coronary intervention (PCI) in myocardial infarction (MI) and correspond to worse outcomes. Several aspiration and thrombectomy devices have been shown to be effective for prevention of distal embolization. We present a technique with successful use of the GuideLiner catheter (Vascular Solutions) for thrombus aspiration after dedicated manual aspiration thrombectomy devices have failed. Our case series includes large thrombus burden in clinical scenarios of ST-elevation MI in a native vessel, non-ST elevation MI in a vein graft, and ST-elevation MI due to native vessel in stent thrombosis.

Sanford School of Medicine, Sioux Falls Campus.

Wysocka, M., Kossenkov, A. V., Benoit, B. M., TroxeI, A. B., ….., Nagata, Satoshi, . . . Rook, A. H. (2014). CD164 and FCRL3 Are Highly Expressed on CD4+CD26-T Cells in Sezary Syndrome Patients. Journal of Investigative Dermatology, 134(1), 229-236.

Sezary syndrome (SS) cells express cell surface molecules also found on normal activated CD4 T cells. In an effort to find a more specific surface marker for malignant SS cells, a nnicroarray analysis of gene expression was performed. Results showed significantly increased levels of mRNA for CD164, a sialomucin found on human CD34+ hematopoietic stem cells, and FCRL3, a molecule present on a subset of human natural T regulatory cells. Both markers were increased in CD4 T cells from SS patients compared with healthy donors (HD). Flow cytometry studies confirmed the increased expression of CD164 and FCRL3 primarily on CD4 + CD26 – T cells of SS patients. Importantly, a statistically significant correlation was found between an elevated percentage of CD4 + CD164+ T cells and an elevated percentage of CD4 + CD26 T cells in all tested SS patients but not in patients with mycosis fungoides and atopic dermatitis or HD. FCRL3 expression was significantly increased only in patients with high tumor burden. CD4 + CD164 + cells displayed cerebriform morphology and their loss correlated with clinical improvement in treated patients. Our results suggest that CD164 can serve as a marker for diagnosis and for monitoring progression of cutaneous T-cell lymphoma (CTCL)/SS and that FCRL3 expression correlates with a high circulating tumor burden.

Sanford School of Medicine, Sioux Falls Campus.

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.
Posted by: kelsijo97 | November 12, 2013

Welcome to our USD Fac-Pub blog

We’re Danielle Loftus, a technology/fine arts librarian, and Steve Johnson, a business and distance ed librarian at USD’s University Libraries.

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

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

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

Posted by: kelsijo97 | November 12, 2013

November 2013

Doorn, Joshua M., & Michael C. Kruer. (2013). Newly characterized forms of neurodegeneration with brain iron accumulation. Current neurology and neuroscience reports, 13(12), 413.
 
Neurodegeneration with brain iron accumulation (NBIA) comprises a group of brain iron deposition syndromes that lead to mixed extrapyramidal features and progressive dementia. Historically, there has not been a clearly identifiable molecular cause for many patients with clinical and radiologic features of NBIA. Recent discoveries have shown that mutations in C19orf12 or WDR45 can lead to NBIA. C19orf12 mutations are inherited in an autosomal recessive manner, and lead to a syndrome similar to that caused by mutations in PANK2 or PLA2G6. In contrast, WDR45 mutations lead to a distinct form of NBIA characterized by spasticity and intellectual disability in childhood followed by the subacute onset of dystonia-parkinsonism in adulthood. WDR45 mutations act in an X-linked dominant manner. Although the function of C19orf12 is largely unknown, WDR45 plays a key role in autophagy. Each of these new forms of NBIA thus leads to a distinct clinical syndrome, and together they implicate new cellular pathways in the pathogenesis of these disorders.
 
Basic Biomedical Sciences, Vermillion Campus.
 
 
Morecraft, Robert J., Jizhi Ge, Kimberly S. Stilwell-Morecraft, David W. McNeal, Marc A. Pizzimenti, & Warren G. Darling. (2013). Terminal distribution of the corticospinal projection from the hand/arm region of the primary motor cortex to the cervical enlargement in rhesus monkey. The Journal of comparative neurology, 521(18), 4205-4235.
 
To further our understanding of the corticospinal projection (CSP) from the hand/arm representation of the primary motor cortex (M1), high-resolution anterograde tracing methodology and stereology were used to investigate the terminal distribution of this connection at spinal levels C5 to T1. The highest number of labeled terminal boutons occurred contralaterally (98%) with few ipsilaterally (2%). Contralaterally, labeled boutons were located within laminae I-X, with the densest distribution found in lamina VII and, to a lesser extent, laminae IX and VI. Fewer terminals were found in other contralateral laminae. Within lamina VII, terminal boutons were most prominent in the dorsomedial, dorsolateral, and ventrolateral subsectors. Within lamina IX, the heaviest terminal labeling was distributed dorsally. Ipsilaterally, boutons were found in laminae V-X. The most pronounced distribution occurred in the dorsomedial and ventromedial sectors of lamina VII and fewer labeled boutons were located in other ipsilateral laminae. Segmentally, contralateral lamina VII labeling was highest at levels C5-C7. In contrast, lamina IX labeling was highest at C7-T1 and more widely dispersed among the quadrants at C8-T1. Our findings suggest dominant contralateral influence of the M1 hand/arm CSP, a contralateral innervation pattern in lamina VII supporting Kuypers (1982) conceptual framework of a “lateral motor system,” and a projection to lamina IX indicating significant influence on motoneurons innervating flexors acting on the shoulder and elbow rostrally (C5-C7), along with flexors, extensors, abductors and adductors acting on the digits, hand and wrist caudally (C8-T1). J. Comp. Neurol. 521:4205-4235, 2013. 2013 Wiley Periodicals, Inc. Copyright 2013 Wiley Periodicals, Inc.
 
Basic Biomedical Sciences, Vermillion Campus.
 
 
Dececchi, T. Alexander, & H. C. E. Larsson. (2013). BODY AND LIMB SIZE DISSOCIATION AT THE ORIGIN OF BIRDS: UNCOUPLING ALLOMETRIC CONSTRAINTS ACROSS A MACROEVOLUTIONARY TRANSITION. Evolution, 67(9), 2741-2752.
 
The origin of birds and powered flight is a classic major evolutionary transition. Research on their origin often focuses on the evolution of the wing with trends of forelimb elongation traced back through many nonavian maniraptoran dinosaurs. We present evidence that the relative forelimb elongation within avian antecedents is primarily due to allometry and is instead driven by a reduction in body size. Once body size is factored out, there is no trend of increasing forelimb length until the origin of birds. We report that early birds and nonavian theropods have significantly different scaling relationships within the forelimb and hindlimb skeleton. Ancestral forelimb and hindlimb allometric scaling to body size is rapidly decoupled at the origin of birds, when wings significantly elongate, by evolving a positive allometric relationship with body size from an ancestrally negative allometric pattern and legs significantly shorten by keeping a similar, near isometric relationship but with a reduced intercept. These results have implications for the evolution of powered flight and early diversification of birds. They suggest that their limb lengths first had to be dissociated from general body size scaling before expanding to the wide range of fore and hindlimb shapes and sizes present in today’s birds.
 
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.
 
 
Scott, M. L., G. T. Auble, Mark D. Dixon, W. C. Johnson, & L. A. Rabbe. (2013). LONG-TERM COTTONWOOD FOREST DYNAMICS ALONG THE UPPER MISSOURI RIVER, USA. River Research and Applications, 29(8), 1016-1029.
 
The upper Missouri River bottomland in north-central Montana, USA, retains much of the physical character it had when traversed by Lewis and Clark around 1805. We used geospatial data to quantify long-term changes in the distribution of bottomland vegetation, land use patterns and channel planform for a 257-rkm segment of the Missouri River above Fort Peck Reservoir. This segment is less ecologically altered than downstream segments, but two dams completed in the mid-1950s have decreased the frequency and magnitude of floods. The area of forest is sparse because of geomorphic setting but, contrary to public perception, has remained relatively constant during the past century. However, the stability of forest area obscures its spatial and temporal dynamics. We used state and transition models to quantify fates and sources of forest during two periods: 1890s-1950s and 1950s-2006. Total forest area was 6% greater in 2006 than it was in the 1890s, largely due to reduced forest loss to erosional processes and gains related to progressive channel narrowing. Channel narrowing resulted in part from human-caused peak flow attenuation. A modified transition matrix, used to examine future steady-state conditions, projected little change in forest area; however, these projections are likely an overestimate. The extent to which 2006 forest area represents a transient adjustment to a new flow regime versus a dynamic, quasi-steady state will be determined by the long-term interplay among hydrologic factors, channel processes, water management and land use practices. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.
 
Biology Department.
 
 
Kibombo, Harrison S., A. S. Weber, Chia-Ming Wu, K. R. Raghupathi, & Ranjit T. Koodali. (2013). Effectively dispersed europium oxide dopants in TiO2 aerogel supports for enhanced photocatalytic pollutant degradation. Journal of Photochemistry and Photobiology a-Chemistry, 269, 49-58.
 
The influence of supercritical drying and the europium oxide content on the physicochemical properties and the resultant photocatalytic activity of Eu-TiO2 aerogels for the degradation of salicylic acid were explored for the first time. It was demonstrated that the efficiencies might be influenced by a combination of factors such as enhanced adsorption, presence of trap states, and/or suppression of rutile phase formation. The well dispersed europium oxide dopants may act as trap states. A subsequent enhancement of charge separation avails electrons for oxygen attack to form superoxide ions, from which (OH)-O-center dot radicals can be generated, and are postulated to be primary contributors toward the degradation efficiencies in this study. (C) 2013 Elsevier B.V. All rights reserved.
 
Chemistry Department
 
 
Kone, K. Y., C. Druon, Etienne Z. Gnimpieba, M. Delmotte, A. Duquenoy, & J. C. Laguerre. (2013). Power density control in microwave assisted air drying to improve quality of food. Journal of Food Engineering, 119(4), 750-757.
 
Currently, the new trend is the development of microwave hot air drying control in order to solve the problem of hot spots on the product. So in this study, a microwave/hot air drying system with the ability of automatic power density control was developed for tomato drying. Three power densities (3, 5 and 7 W/g) at 40 degrees C air temperature were applied and the output, reflected microwave power and the mass of the sample were registered online. Two different drying strategies were implemented. The first consisted of a microwave drying without specific power control. The second one introduced power control. A feedback control based on specific power related to the actual sample mass resulted in the best power control and the improvement of product quality compared to the dry sample without power control. (C) 2013 Elsevier Ltd. All rights reserved.
 
Computer Science Department.
 
 
Dutkay, D. E., Gabriel Picioroaga, & M. S. Song. (2014). Orthonormal bases generated by Cuntz algebras. Journal of Mathematical Analysis and Applications, 409(2), 1128-1139.
 
We show how some orthonormal bases can be generated by representations of the Cuntz algebra; these include Fourier bases on fractal measures, generalized Walsh bases on the unit interval and piecewise exponential bases on the middle third Cantor set. (C) 2013 Published by Elsevier Inc.
 
Mathematics Department.
 
 
Lio, Y. L., T. R. Tsai, M. Aslam, & Nan Jiang. (2014). Control Charts for Monitoring Burr Type-X Percentiles. Communications in Statistics-Simulation and Computation, 43(4), 761-776.
 
When the sampling distribution of a parameter estimator is unknown, using normality asymptotically, the Shewhart-type chart may provide improper control limits. To monitor Burr type-X percentiles, two parametric bootstrap charts (PBCs) are proposed and compared with the Shewhart-type chart via a Monte Carlo simulation. Simulation results exhibit that the proposed PBCs perform well with a short average run length to signal out-of-control when the process is out-of-control, and have more adequate control limits than the Shewhart-type chart in view of in-control false alarm rate. An example regarding single fiber strength is presented for illustrating the proposed PBCs.
 
Mathematics Department.
 
 
Barker, D., W. Z. Wei, D. M. Mei, & C. Zhang. (2013). Ionization efficiency study for low energy nuclear recoils in germanium. Astroparticle Physics, 48, 8-15.
 
We used the internal conversion (E-0 transition) of germanium-72 to indirectly measure the low energy nuclear recoils of germanium. Together with a reliable Monte Carlo package, in which we implement the internal conversion process, the data was compared to the Lindhard (k = 0.159) and Barker-Mei models. A shape analysis indicates that both models agree well with data in the region of interest within 4%. The most probable value (MPV) of the nuclear recoils obtained from the shape analysis is 17.5 +/- 0.12 (sys) +/- 0.035 (stat) keV with an average path-length of 0.014 mu m. Published by Elsevier B.V.
 
Physics Department.
 
 
Wang, Guojian, Xifa Long, Lizhen Zhang, Zhoubin Lin, & Guofu Wang. (2013). Growth and spectral properties of Nd3+:Ba2LiNb5O15 crystal. Optical Materials, 35(12), 2703-2706.
 
Highlights: [•] Nd3+:Ba2LiNb5O15 crystal was obtained by Czochralski method. [•] The refractive index was measured by the minimum deviation method. [•] The polarized absorption and luminescence spectra were investigated. [•] The spectral parameters were calculated according to Judd–Ofelt theory.
 
Physics Department.
 
 
Dvorak, R. D., Tyler B. Wray, Nicholas J. Kuvaas, & Tess M. Kilwein. (2013). Mania and sexual risk: Associations with behavioral self-regulation. Journal of Affective Disorders, 150(3), 1076-1081.
 
Introduction: Risky sexual behavior among young adults is a central public health concern. Hallmark cognitive effects of mania involve grandiose extrinsic goal-setting, which may be part of a tendency to approach rewarding cues while understanding potential negative consequences. Poor impulse control also reflects a tendency to seek reward and rely on emotional decision-making. In contrast, effortful control is associated with adaptive decision making. Methods: Participants (n=595) completed measures of impulsivity, risk for mania, and risky sexual behavior. Relationships between risk for mania, behavioral self-regulation, and risky sexual behavior were examined in a negative binomial hurdle model. Results: For the hurdle portion, sensation-seeking was positively associated with the likelihood of engaging in risky sexual behavior. Effortful control was inversely associated with the likelihood of engaging in risky sexual behavior, but only among those high in risk for mania. Among those endorsing engagement in risky sex, urgency was positively, and effortful control negatively, associated with frequency of risky sex. Risk for mania was positively associated with frequency of risky sex, but only for those low in effortful control. Limitations: Findings were among a homogeneous, young adult, nonclinical population, limiting generalizability. Examining these associations among a clinical population in an active manic episodic is warranted. Conclusion: Results suggest high levels of effortful control may diminish the hallmark effects of mania on cognition thereby reducing engagement in risky sexual behavior. Treatments targeting emotion-based rash action and effortful decision making may be particularly important for those experiencing manic symptoms. (C) 2013 Elsevier B.V. All rights reserved.
 
Psychology Department.
 
 
Ammann, Eric M., James V. Pottala, William S. Harris, Mark A. Espeland, Robert Wallace, Natalie L. Denburg, . . . Jennifer G. Robinson. (2013). Omega-3 fatty acids and domain-specific cognitive aging: Secondary analyses of data from WHISCA. Neurology, 81(17), 1484-1491.
 
OBJECTIVE: To test the hypothesis that higher levels of red blood cell (RBC) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have a protective association with domain-specific cognitive function in women aged 65 years and older.; METHODS: A total of 2,157 women with normal cognition enrolled in a clinical trial of postmenopausal hormone therapy were followed with annual cognitive testing for a median of 5.9 years. In this retrospective cohort study, we assessed the relationship between prerandomization RBC DHA + EPA levels and a) cognitive measures at baseline, and b) cognitive change over time. Endpoints were composite cognitive function and performance in 7 cognitive domains: fine motor speed, verbal memory, visual memory, spatial ability, verbal knowledge, verbal fluency, and working memory.; RESULTS: After adjustment for demographic, clinical, and behavioral characteristics, no significant (p < 0.01) cross-sectional cognitive differences were found between women in the high and low DHA + EPA tertiles at the time of the first annual cognitive battery. In addition, no significant (p < 0.01) differences were found between the high and low DHA + EPA tertiles in the rate of cognitive change over time.; CONCLUSIONS: We did not find an association between RBC DHA + EPA levels and age-associated cognitive decline in a cohort of older, dementia-free women.
 
Sanford School of Medicine, Sioux Falls Campus.
 
 
De, Pradip, M. Hasmann, & Brian Leyland-Jones. (2013). Molecular determinants of trastuzumab efficacy: What is their clinical relevance? Cancer Treatment Reviews, 39(8), 925-934.
 
Trastuzumab-containing therapy is a standard of care for human epidermal growth factor receptor-2 (HER2)-positive breast cancer. In pre-clinical models, a wide range of molecular mechanisms have been associated with reduced sensitivity to trastuzumab in vitro. These include expression of the truncated HER2 receptor fragment p95(HER2), activating mutation of the gene encoding the class 1A catalytic subunit of phosphatidylinositol 3-kinase (PIK3CA), loss of phosphatase and tensin homolog (PTEN), activation of other downstream signal transducers, prevention of cell cycle arrest, increased signaling through alternative (HER or non-HER) tyrosine kinase receptors, and resistance to antibody-dependent cellular cytotoxicity. However, the clinical significance of these mechanisms as determinants of trastuzumab efficacy in vivo has been unclear. Here, we review clinical studies of potential predictive biomarkers of trastuzumab efficacy in HER2-positive breast cancer and consider whether evaluation of such markers might inform patient selection for therapy. We find that clinical evidence relating to potential predictive biomarkers is mostly limited to small, retrospective studies, many of which have yielded conflicting findings. Some trends are evident in the retrospective data and in biomarker analyses from randomized clinical trials, particularly relating to activation of the phosphatidylinositol 3-kinase pathway, but none is sufficiently strong to form a basis for patient selection. This may be explained by the fact that multiple mechanisms of action determine the clinical efficacy of trastuzumab. In the absence of novel, validated biomarkers of efficacy, trastuzumab eligibility should continue to be based on evaluation of HER2 status according to standard methods. (C) 2013 Elsevier Ltd. All rights reserved.
 
Sanford School of Medicine, Sioux Falls Campus.
 
 
Dey, Nandini, Brandon Young, Mark Abramovitz, Mark Bouzyk, Benjamin 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), e77425.
 
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.
 
 
Flock, Michael R., William S. Harris, & Penny M. Kris-Etherton. (2013). Long-chain omega-3 fatty acids: time to establish a dietary reference intake. Nutrition Reviews, 71(10), 692-707.
 
The beneficial effects of consuming omega-3 polyunsaturated fatty acids (n-3 PUFAs), specifically eicosapentaenoic acid ( EPA) and docosahexaenoic acid ( DHA), on cardiovascular health have been studied extensively. To date, there is no dietary reference intake ( DRI) for EPA and DHA, although many international authorities and expert groups have issued dietary recommendations for them. Given the substantial new evidence published since the last Institute of Medicine ( IOM) report on energy and macronutrients, released in 2002, there is a pressing need to establish a DRI for EPA and DHA. In order to set a DRI, however, more information is needed to define the intakes of EPA and DHA required to reduce the burden of chronic disease. Information about potential gender- or race-based differences in requirements is also needed. Given the many health benefits of EPA and DHA that have been described since the 2002 IOM report, there is now a strong justification for establishing a DRI for these fatty acids.
 
Sanford School of Medicine, Sioux Falls Campus.
 
 
Gara, Rishi Kumar, Vasudha Sundram, Subhash C. Chauhan, & Meena Jaggi. (2013). Anti-Cancer Potential of a Novel SERM Ormeloxifene. Current Medicinal Chemistry, 20(33), 4177-4184.
 
Ormeloxifene is a non-steroidal Selective Estrogen Receptor Modulator (SERM) that is used as an oral contraceptive. Recent studies have shown its potent anti-cancer activities in breast, head and neck, and chronic myeloid leukemia cells. Several in vivo and clinical studies have reported that ormeloxifene possesses an excellent therapeutic index and has been well-tolerated, without any haematological, biochemical or histopathological toxicity, even with chronic administration. A reasonably long period of time and an enormous financial commitment are required to develop a lead compound into a clinically approved anti-cancer drug. For these reasons and to circumvent these obstacles, ormeloxifene is a promising candidate on a fast track for the development or repurposing established drugs as anti-cancer agents for cancer treatment. The current review summarizes recent findings on ormeloxifene as an anti-cancer agent and future prospects of this clinically safe pharmacophore.
 
Sanford School of Medicine, Sioux Falls Campus.
 
 
Grenon, S. Marlene, Christopher D. Owens, Hugh Alley, ….., William Harris, Millie Hughes-Fulford, & Michael S. Conte. (2013). n-3 Polyunsaturated fatty acids supplementation in peripheral artery disease: the OMEGA-PAD trial. Vascular Medicine, 18(5), 263-274.
 
Despite current consensus guidelines recommending intensive cardiovascular risk factor management for peripheral artery disease (PAD), patients suffering from PAD continue to experience significant morbidity and mortality. This excess morbid burden is at least partially related to impaired vascular function and systemic inflammation. Interventions bridging this gap are critical. Dietary supplementation of n-3 polyunsaturated fatty acids (n-3 PUFA) has been shown to improve endothelial function and reduce inflammation in different cohorts, as well as to decrease cardiovascular events in secondary prevention trials in patients with coronary artery disease. Their effects in the PAD population are, however, less well understood. The OMEGA-PAD trial is a double-blinded, randomized, placebo-controlled trial that examines the impact of a high-dose, short-duration dietary oral supplementation of n-3 PUFA on vascular function and inflammation in patients with established PAD. The purpose of this article is to provide a detailed description of the design and methods of the OMEGA-PAD trial, and a summary of baseline characteristics of the cohort.
 
Sanford School of Medicine, Sioux Falls Campus.
 
 
Harris, William S., S. A. Varvel, J. V. Pottala, G. R. Warnick, & J. P. McConnell. (2013). Comparative effects of an acute dose of fish oil on omega-3 fatty acid levels in red blood cells versus plasma: Implications for clinical utility. Journal of Clinical Lipidology, 7(5), 433-440.
 
BACKGROUND: Omega-3 fatty acid (n-3 FA) biostatus can be estimated with red blood cell (RBC) membranes or plasma. The matrix that exhibits the lower within-person variability and is less affected by an acute dose of n-3 FA is preferred in clinical practice. OBJECTIVE: We compared the acute effects of a large dose of n-3 FA on RBC and plasma levels of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA). METHODS: Healthy volunteers (n = 20) were given 4 capsules containing 3.6 g of n-3 FA with a standardized breakfast. Blood samples were drawn at 0, 2, 4, 6, 8, and 24 hours. The EPA + DHA content of RBC membranes and plasma (the latter expressed as a percentage of total FA and as a concentration) were determined. General linear mixed models were used to analyze the mean response profiles in FA changes over time for plasma and RBCs. RESULTS: At 6 hours after load, the plasma concentration of EPA + DHA had increased by 47% (95% confidence interval [CI], 24% to 73%) and the plasma EPA + DHA percentage of total FA by 19% (95% CI, 4.7% to 36%). The RBC EPA + DHA percentage of composition was unchanged [-0.6% (95% CI, -2.6% to 1.5%)]. At 24 hours, the change in both of the plasma EPA + DHA markers was 10-fold greater than that in RBCs. CONCLUSIONS: An acute dose of n-3 FA (eg, a meal of oily fish or fish oil supplements) taken within a day before a doctor’s visit can elevate levels of EPA + DHA in plasma, whether expressed as a percentage or a concentration, but not in RBC membranes. Similar to hemoglobin A(1c), which is not affected by an acute glycemic deviation, RBCs provide a more reliable estimate of a patient’s chronic EPA + DHA status than does plasma. (c) 2013 National Lipid Association. All rights reserved.
 
Sanford School of Medicine, Sioux Falls Campus.
 
 
Horn, H. F., D. I. Kim, G. D. Wright, ….., & Kyle J. Roux. (2013). A mammalian KASH domain protein coupling meiotic chromosomes to the cytoskeleton. Journal of Cell Biology, 202(7), 1023-1039.
 
Chromosome pairing is an essential meiotic event that ensures faithful haploidization and recombination of the genome. Pairing of homologous chromosomes is facilitated by telomere-led chromosome movements and formation of a meiotic bouquet, where telomeres cluster to one pole of the nucleus. In metazoans, telomere clustering is dynein and microtubule dependent and requires Sun1, an inner nuclear membrane protein. Here we provide a functional analysis of KASH5, a mammalian dynein-binding protein of the outer nuclear membrane that forms a meiotic complex with Sun1. This protein is related to zebrafish futile cycle (Fue), a nuclear envelope (NE) constituent required for pronuclear migration. Mice deficient in this Fue homologue are infertile. Males display meiotic arrest in which pairing of homologous chromosomes fails. These findings demonstrate that telomere attachment to the NE is insufficient to promote pairing and that telomere attachment sites must be coupled to cytoplasmic dynein and the microtubule system to ensure meiotic progression.
 
Sanford School of Medicine, Sioux Falls Campus.
 
 
Judd, Kyle T., Sean Burns, & Karen Hand. (2013). Finding a job in an overcrowded market: getting what you want. Journal of orthopaedic trauma, 27 Suppl 1, S2-4.
 
As the number of fellowship-trained orthopaedic trauma surgeons entering the workforce increases, so does the competition for available practice opportunities. The process of finding employment has seemingly become more involved as the relative availability of positions has declined over recent years. To manage this new environment, new graduates need to become much more proactive in the process of seeking and obtaining orthopaedic trauma positions.
 
Sanford School of Medicine, Sioux Falls Campus.
 
 
May, Philip A., Jason Blankenship, Anna-Susan Marais, ….., H. Eugene Hoyme, Barbara Tabachnick, & Soraya Seedat. (2013). Maternal alcohol consumption producing fetal alcohol spectrum disorders (FASD): Quantity, frequency, and timing of drinking. Drug & Alcohol Dependence, 133(2), 502-512.
 
Abstract: Background: Concise, accurate measures of maternal prenatal alcohol use are needed to better understand fetal alcohol spectrum disorders (FASD). Methods: Measures of drinking by mothers of children with specific FASD diagnoses and mothers of randomly-selected controls are compared and also correlated with physical and cognitive/behavioral outcomes. Results: Measures of maternal alcohol use can differentiate maternal drinking associated with FASD from that of controls and some from mothers of alcohol-exposed normals. Six variables that combine quantity and frequency concepts distinguish mothers of FASD children from normal controls. Alcohol use variables, when applied to each trimester and three months prior to pregnancy, provide insight on critical timing of exposure as well. Measures of drinking, especially bingeing, correlate significantly with increased child dysmorphology and negative cognitive/behavioral outcomes in children, especially low non-verbal IQ, poor attention, and behavioral problems. Logistic regression links (p <.001) first trimester drinking (vs. no drinking) with FASD, elevating FASD likelihood 12 times; first and second trimester drinking increases FASD outcomes 61 times; and drinking in all trimesters 65 times. Conversely, a similar regression (p =.008) indicates that drinking only in the first trimester makes the birth of a child with an FASD 5 times less likely than drinking in all trimesters. Conclusions: There is significant variation in alcohol consumption both within and between diagnostic groupings of mothers bearing children diagnosed within the FASD continuum. Drinking measures are empirically identified and correlated with specific child outcomes. Alcohol use, especially heavy use, should be avoided throughout pregnancy.
 
Sanford School of Medicine, Sioux Falls Campus.
 
 
Pothula, S., H. E. P. Bazan, & Gudiseva Chandrasekher. (2013). Regulation of Cdc42 Expression and Signaling Is Critical for Promoting Corneal Epithelial Wound Healing. Investigative Ophthalmology & Visual Science, 54(8), 5343-5352.
 
PURPOSE. Cdc42, a member of Rho GTPases (guanosine triphosphatases), participates in cytokine-and growth factor-controlled biological functions in mammalian tissues. Here, we examined Cdc42 role in corneal epithelial wound healing and the influence of hepatocyte, keratinocyte, and epidermal growth factor (HGF, KGF, and EGF)-mediated signaling on Cdc42. METHODS. Epithelial wounds were created on the corneas of live rabbits by complete debridement and in rabbit corneal epithelial primary cultures through scratch injury. Cdc42 expression in cultures was suppressed using Cdc42 siRNA. Cdc42 activation was determined by pull-down assays with PAK-agarose beads. Cdc42 expression was analyzed by immunoblotting and immunofluorescence. Association of Cdc42 with cell-cycle proteins was identified by immunoprecipitation. RESULTS. In rabbit corneas, significant increase in Cdc42 expression that occurred 2 to 4 days after the injury coincided with wound closure, and by 8 days the expression reached near basal levels. Silencing of Cdc42 expression in cultures caused inhibition of wound closure as a result of 60% to 75% decrease in epithelial migration and growth. HGF, KGF, and EGF increased Cdc2 expression, activation, and its phosphorylation on ser71. Inhibition of growth factor-mediated PI-3K signaling resulted in the downregulation of Cdc42 expression and its phosphorylation. Increased association of cell-cycle proteins p27(kip) and cyclin-dependent kinase 4 (CDK4) with Cdc42; and phosphorylated Cdc42 with plasma membrane leading edges was also observed in the presence of growth factors. CONCLUSIONS. Cdc42 is an important regulator of corneal epithelial wound repair. To promote healing, Cdc42 may interact with receptor tyrosine kinase-activated signaling cascades that participate in cell migration and cell-cycle progression.
 
Sanford School of Medicine, Sioux Falls Campus.
 
 
Sharma, Jitendra, A. Nanda, R. S. Jung, S. Mehta, J. Pooria, & D. P. Hsu. (2013). Risk of contrast-induced nephropathy in patients undergoing endovascular treatment of acute ischemic stroke. Journal of Neurointerventional Surgery, 5(6), 543-545.
 
Background and purpose We report the incidence and risk factors for contrast-induced nephropathy after the use of iodinated contrast for endovascular treatment of acute ischemic stroke. Methods A retrospective chart review was performed in 194 consecutive patients who underwent endovascular treatment for acute ischemic stroke between January 2006 and January 2011. No patients were excluded from treatment for elevated creatinine (Cr). Each patient received approximately 150ml intra-arterial non-ionic low-osmolar contrast agent (Optiray 320) during the endovascular procedure. Contrast-induced nephropathy (CIN) was defined according to the Acute Kidney Injury Network criteria as a relative increase of serum Cr 50% above the baseline or an absolute increase of 0.3mg/dl at 48h following the endovascular procedure. Results Of 194 patients (mean age 6514years), 52% were women (n=100) and 25% (n=48) were diabetic. Baseline Cr levels for 191 patients ranged between 0.4 and 2.7mg/dl. Three patients on chronic hemodialysis had baseline Cr levels ranging between 5.3 and 6.1mg/dl. Cr was 1.5mg/dl in 163 patients (84%) and 1.5mg/dl in 31 (16%). Three of the 191 patients (1.5%) developed CIN as noted from Cr measurements between baseline and within 48h. One patient who developed an elevated Cr level had a known history of chronic renal insufficiency (Cr >1.5mg/dl) and two had baseline Cr levels within the normal range. An additional CT angiogram was obtained in 44 patients, none of which developed CIN. Female gender and diabetes were not associated with a higher risk of developing CIN. Conclusions The risk of developing CIN is low among patients with acute stroke who undergo emergency endovascular treatment. Treatment of acute stroke should be performed irrespective of Cr levels.
 
Sanford School of Medicine, Sioux Falls Campus.
 
 
Smythe, Maureen A., John Fanikos, Michael P. Gulseth, Ann K. Wittkowsky, Sarah A. Spinler, William E. Dager, & Edith A. Nutescu. (2013). Rivaroxaban: Practical Considerations for Ensuring Safety and Efficacy. Pharmacotherapy, 33(11), 1223-1245.
 
Rivaroxaban is the first agent available within a new class of anticoagulants called direct factor Xa inhibitors. Rivaroxaban is approved for use in the United States for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, for the prevention of deep vein thrombosis in patients undergoing total hip replacement and total knee replacement, for the treatment of deep vein thrombosis and pulmonary embolism, and for the reduction in risk of recurrence of deep vein thrombosis and pulmonary embolism (with additional indications under review). Rivaroxaban dose and frequency of administration vary depending on the indication. As of result of predictable pharmacokinetics and pharmacodynamics, a fixed dose of rivaroxaban is administered without routine coagulation testing. Rivaroxaban has a short half-life, undergoes a dual mode of elimination (hepatic and renal), and is a substrate for P-glycoprotein. Rivaroxaban has a lower potential for drug interactions compared with warfarin. Despite the advantages of a once/day fixed-dose oral agent, in many clinical situations limited evidence is available to guide optimal management of rivaroxaban therapy. In this article, we review the available evidence and provide recommendations where possible for such situations including the desire to monitor the anticoagulation intensity, use in special patient populations, managing drug interactions, and transitioning across anticoagulant agents. Potential strategies for reversing rivaroxaban’s anticoagulant effect are reviewed. Health systems will need to perform a systematic safety evaluation and ensure that numerous hospital policies related to anticoagulation are updated to include rivaroxaban. A comprehensive approach to education is needed for clinicians, patients, and technical support personnel involved in patient interactions to ensure safe use.
 
Sanford School of Medicine, Sioux Falls Campus.
 
 
Sun, Yuliang, Nandini Dey, M. Brammer, Pradip De, & Brian Leyland-Jones. (2013). Bevacizumab confers additional advantage to the combination of trastuzumab plus pertuzumab in trastuzumab-refractory breast cancer model. Cancer Chemotherapy and Pharmacology, 72(4), 733-745.
 
We investigated antitumor activity of trastuzumab (T)/T-DM1 + pertuzumab (P) + bevacizumab (B) in T-sensitive (BT474) and T-resistant (BT474HerR) BC models in order to test whether or not the addition of an anti-angiogenic drug can provide a supplementary advantage to the antitumor activity of double HER2-mAB combination. In addition to the antitumor activity (xenograft model), we tested antiproliferative effect, and HER2-mediated signals of different antibodies (T or P or T-DM1) in HER2-amplified T-sensitive, T-resistant and HER2-amplified/PIK3CA mutated (HCC1954) BT cell lines by 3D ON-TOP clonogenic growth assay and Western blots. Data show (1) T, T-DM1 or P blocked p-AKT (> 60 %), p-ERK (> 50 %) following heregulin in only T-sensitive cells, (2) T/T-DM1 + P, T/T-DM1 + B, and P + B reduced tumor growth as compared to any single-agent treatment, (3) T + P + B achieved almost complete regression of tumor growth, decreased cell proliferation, and inhibited tumor-induced angiogenesis, in both models, (4) antitumor activity of T + P + B was associated with the pharmacodynamic knockdown of p-AKT, and (5) T-DM1 + P caused complete regression of tumor volume in both models. Our data demonstrate that B imparts a significant advantage when combined with T + P in the resistant model, in contrast to T-DM1 + P, as the triple combination of T-DM1 + P + B and the double combination of T-DM1 + P showed a comparable antitumor activity. Our study reveals the preclinical evidence in favor of the inclusion of B when combined with T + P in T-resistant BC patients.
 
Sanford School of Medicine, Sioux Falls Campus.
 
 
Ikiugu, Moses N. (2013). The validity of occupational performance assessments: a validity generalization meta-analysis. Occupational therapy in health care, 27(4), 372-391.
 
ABSTRACT The purpose of this meta-analysis was to determine sample weighted mean validity effect sizes for occupational performance assessments, and their generalizability from research to clinical settings. The bare-bones Validity Generalization (VG) guidelines developed by Hunter and Schmidt ( 2004 ) augmented by Maximum Likelihood (ML) procedures were used to complete the meta-analysis. The sample consisted of 27 studies in which convergent, divergent, and predictive validity estimates of occupational performance assessments were investigated. The mean coefficients of assessments validated in the studies constituting the sample for this meta-analysis ranged from medium to large. Further meta-analysis with complete dis-attenuation of observed mean validity coefficients is indicated.
 
School of Health Sciences.
 
 
Nick, Jan M., Nancy C. Sharts-Hopko, & Debra Woodard Leners. (2013). From Committee to Commission: The History of the NLN’s Academic Certified Nurse Educator Program. Nursing Education Perspectives, 34(5), 298-302.
 
AIM: To describe the historical events surrounding the development of the National League for Nursing (NLN) Academic Nurse Educator Certification Program (ANECP) and document its transition from a committee to a commission. BACKGROUND: During the latter half of the 20th century, certification became a demonstrated standard of excellence in nursing. A few visionaries suggested that nursing education itself was a specialty, but the timing for certification was not right. METHOD: The events have been studied through three primary sources: archived minutes, oral interviews, and the authors’ eyewitness accounts. RESULTS: Growing pains, personnel changes and the rapid growth from committee to commission occurred during a few short years. While the NLN made sound decisions during the change process by seeking evidence and the guidance of experts and consultants, unexpected challenges occurred. CONCLUSION: The tremendous growth of the ANECP in its first years demonstrated that change was clearly desired so long as it was anchored in an evidence-based process focused on quality.
 
School of Health Sciences.

 

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