Posted by: reganenosusd | April 20, 2015

February – April 2015

Moran III, James D., Marilyn J. Wells, & Angela Smith-Aumen. (2015). Making Undergraduate Research a Central Strategy in High-Impact Practice Reform: The PASSHE Journey. New Directions for Higher Education, 2015(169), 61-71.

This chapter describes undergraduate research expansion in the Pennsylvania State System of Higher Education (PASSHE) in the context of both fiscal and student enrollment challenges.

Academic Affairs.

King, Marisa, Yufeng Zhang, Travis Carter, Jake Johnson, Erin Harmon, & David Swanson. (2015). Phenotypic flexibility of skeletal muscle and heart masses and expression of myostatin and tolloid-like proteinases in migrating passerine birds. Journal of Comparative Physiology B: Biochemical, Systemic & Environmental Physiology, 185(3), 333-342.

Migrant birds require large flight muscles and hearts to enhance aerobic capacity and support sustained flight. A potential mechanism for increasing muscle and heart masses during migration in birds is the muscle growth inhibitor myostatin and its metalloproteinase activators, tolloid-like proteinases (TLL-1 and TLL-2). We hypothesized that myostatin, TLL-1 and TLL-2 are downregulated during migration in pectoralis and hearts of migratory passerines to promote hypertrophy. We measured seasonal variation of tissue masses, mRNA expression of myostatin, TLL- 1, and TLL- 2, and myostatin protein levels in pectoralis muscle and heart for yellow warblers ( Setophaga petechia), warbling vireos ( Vireo gilvus), and yellow-rumped warblers ( Setophaga coronata). Pectoralis mass was greatest in spring for warbling vireos and yellow warblers, but was stable between spring and fall for yellow-rumped warblers. Heart mass was higher in spring than in fall for yellow-rumped warblers, lowest in fall for warbling vireos, and seasonally stable for yellow warblers. Pectoralis and heart mRNA expression of myostatin and the TLLs did not differ significantly for any of the three species, offering little support for our hypothesis for a prominent role for myostatin in regulating migration-induced variation in pectoralis and heart masses. In contrast, pectoralis myostatin protein levels were lowest in spring for all three species, consistent with our hypothesis. Myostatin protein levels in heart, however, were seasonally stable for warbling vireos and yellow warblers, and increased in spring relative to fall for yellow-rumped warblers. These data offer mixed support for our hypothesis for the pectoralis, but suggest that myostatin is not a prominent regulator of migration-induced heart hypertrophy. Moreover, the different seasonal patterns for pectoralis mRNA and protein expression suggest that post-transcriptional modification of myostatin may contribute to pectoralis mass regulation during migration.

Biology Department.

Kim, Dae In, K.C. Birendra, & Kyle J. Roux. (2015). Making the LINC: SUN and KASH protein interactions. Biological Chemistry, 396(4), 295-310.

Cell nuclei are physically integrated with the cytoskeleton through the linker of nucleoskeleton and cytoskeleton (LINC) complex, a structure that spans the nuclear envelope to link the nucleoskeleton and cytoskeleton. Outer nuclear membrane KASH domain proteins and inner nuclear membrane SUN domain proteins interact to form the core of the LINC complex. In this review, we provide a comprehensive analysis of the reported protein-protein interactions for KASH and SUN domain proteins. This critical structure, directly connecting the genome with the rest of the cell, contributes to a myriad of cellular functions and, when perturbed, is associated with human disease.

Sanford School of Medicine, Sioux Falls Campus.

Jorgensen, Maribeth F., & Kelly Duncan. (2015). A Grounded Theory of Master’s-Level Counselor Research Identity. Counselor Education & Supervision, 54(1), 17-31.

A grounded theory approach was used to examine the research identity of 17 master’s-level counseling trainees and practitioners. The emergent theory gave an understanding to sources of variation in the process and outcome of research identity. The authors provide recommendations for counselor educators to use with current and former students.

School of Education.

Kindle, Peter A., & Mary A. Caplan. (2015). Understanding Fringe Economic Behavior: A Bourdieusian-informed Meta-ethnography. Journal of Sociology & Social Welfare, 42(1), 49-71.

This paper is a meta-ethnography of four low-income communities in order to explore fringe economic behaviors. Rejecting the interpretation of fringe economic behaviors as irrational, we affirm these behaviors as viable alternatives for people marginalized in the mainstream economy. Using a meta-ethnographic method and employing the concepts of sociologist Pierre Bourdieu, we identify the habitus and social capital values of each community as distinct Bourdieusian fields and conclude that an awareness of the localized development of a fringe economic cluster with distinct goals and rules undermines one-size-its-all social welfare programs.

School of Health Sciences.

Jehl, J. R., A. E. Henry, & David L. Swanson. (2015). Ratios, adaptations, and the differential metabolic capability of avian flight muscles. Journal of Avian Biology, 46(2), 119-124.

The eared grebe Podiceps nigricollis shows seasonal variation in the relative size of the major flight muscles that lift and lower the wing: respectively, supracoracoideus (s) and pectoralis (p). S/p ratios are low (approximate to 0.07-0.12) when grebes are in flying condition, higher (approximate to 0.11-0.15) when staging and flightless, and extreme (to 0.29) when starving. Shifts were driven by changes in the protein content in the pectoralis; intramuscular fat had little effect. S/p ratios also vary seasonally in the red knot Calidris canutus and are higher in birds newly arrived in breeding areas than at other times. If that increase was an adaptive response to promote wing-lifting in association with various breeding behaviors as suggested, one would expect it to result from an absolute increase in the post-arrival size of the supracoracoideus, which was not observed. Instead, we propose that it is unrelated to enhancing the upstroke but results from a decrease in the size of the pectoralis, which is a consequence of the greater rate at which this muscle is catabolized in times of exertion and stress, as at the end of a long migration or during starvation. Fuller data on the size, morphology and physiology of individual muscles at various stages of the annual cycle and migration will help to clarify how ratio changes are achieved, and evaluate potential adaptive significance.

Biology Department.

King, Marrisa O., Yufeng Zhang, Travis Carter, Jake Johnson, Erin Harmon, & David L. Swanson. (2015). Phenotypic flexibility of skeletal muscle and heart masses and expression of myostatin and tolloid-like proteinases in migrating passerine birds. Journal of Comparative Physiology B-Biochemical Systemic and Environmental Physiology, 185(3), 333-342.

Migrant birds require large flight muscles and hearts to enhance aerobic capacity and support sustained flight. A potential mechanism for increasing muscle and heart masses during migration in birds is the muscle growth inhibitor myostatin and its metalloproteinase activators, tolloid-like proteinases (TLL-1 and TLL-2). We hypothesized that myostatin, TLL-1 and TLL-2 are downregulated during migration in pectoralis and hearts of migratory passerines to promote hypertrophy. We measured seasonal variation of tissue masses, mRNA expression of myostatin, TLL-1, and TLL-2, and myostatin protein levels in pectoralis muscle and heart for yellow warblers (Setophaga petechia), warbling vireos (Vireo gilvus), and yellow-rumped warblers (Setophaga coronata). Pectoralis mass was greatest in spring for warbling vireos and yellow warblers, but was stable between spring and fall for yellow-rumped warblers. Heart mass was higher in spring than in fall for yellow-rumped warblers, lowest in fall for warbling vireos, and seasonally stable for yellow warblers. Pectoralis and heart mRNA expression of myostatin and the TLLs did not differ significantly for any of the three species, offering little support for our hypothesis for a prominent role for myostatin in regulating migration-induced variation in pectoralis and heart masses. In contrast, pectoralis myostatin protein levels were lowest in spring for all three species, consistent with our hypothesis. Myostatin protein levels in heart, however, were seasonally stable for warbling vireos and yellow warblers, and increased in spring relative to fall for yellow-rumped warblers. These data offer mixed support for our hypothesis for the pectoralis, but suggest that myostatin is not a prominent regulator of migration-induced heart hypertrophy. Moreover, the different seasonal patterns for pectoralis mRNA and protein expression suggest that post-transcriptional modification of myostatin may contribute to pectoralis mass regulation during migration.

Biology Department.

Wesner, Jeff S., & M. C. Belk. (2015). Variation in the trophic position of common stream fishes and its relationship to the presence of a rare fish, northern leatherside chub (Lepidomeda copei). Ecology of Freshwater Fish, 24(2), 234-241.

Variation in trophic position can be caused by structural changes in food webs that may affect the presence of, or be affected by the presence of, individual species. We examined variation in the trophic position of fishes across 14 stream sites in the Bear River drainage, WY, USA. This drainage is the focus of ongoing conservation of northern leatherside chub (Lepidomeda copei). Our goals were (i) to describe variation in trophic position of individual species and (ii) to determine whether these measures differed between sites with and without northern leatherside chub. Mean trophic position of individual fish species varied between 0 and 3 trophic positions across sites. For two of these species, trophic position declined at sites without northern leatherside chub. Importantly, habitat surveys from a previous study at 10 of these sites revealed no differences in habitat suitability for northern leatherside chub. This suggests that trophic position revealed systematic differences among sites that were not apparent based on traditional species-habitat modelling. We outline possible mechanisms behind these patterns and argue that monitoring variation in trophic position can complement traditional, habitat-based methods for understanding species distributions.

Biology Department.

Jensen, Stephanie, & Dmitri S. Kilin. (2015). Electronic properties of nickel-doped TiO2 anatase. Journal of Physics-Condensed Matter, 27(13), 14.

Atomistic details of electron transfer in semiconductor materials are characterized for TiO2 thin film surfaces doped with nickel. A periodic slab model of eight atomic layers exposes the (1 0 0) crystallographic surface and is covered with a monolayer of water. The density of states, absorption spectra, partial charge densities, molecular dynamics, and non-adiabatic couplings are compared between doped and undoped models. Our results show that Ni doping improves several electronic properties including lowering the band gap, increasing visible light absorption, and shortening the relaxation time of holes rather than electrons, which maximizes charge separation. The different mechanisms of electron and hole dynamics are discussed. The computed characteristics of a doped semiconductor material have practical potential for increasing efficiency of a photo-electrochemical cells.

Chemistry Department.

Vazhappilly, Tijo, Dmitri S. Kilin, & David A. Micha. (2015). Modeling the surface photovoltage of silicon slabs with varying thickness. Journal of Physics-Condensed Matter, 27(13), 9.

The variation with thickness of the energy band gap and photovoltage at the surface of a thin semiconductor film are of great interest in connection with their surface electronic structure and optical properties. In this work, the change of a surface photovoltage (SPV) with the number of layers of a crystalline silicon slab is extracted from models based on their atomic structure. Electronic properties of photoexcited slabs are investigated using generalized gradient and hybrid density functionals, and plane wave basis sets. Si(1 1 1) surfaces have been terminated by hydrogen atoms to compensate for dangling bonds and have been described by large supercells with periodic boundary conditions. Calculations of the SPV of the Si slabs have been done in terms of the reduced density matrix of the photoactive electrons including dissipative effects due to their interaction with medium phonons and excitons. Surface photovoltages have been calculated for model Si slabs with 4-12, and 16 layers, to determine convergence trends versus slab thickness. Band gaps and the inverse of the SPVs have been found to scale nearly linearly with the inverse thickness of the slab, while the electronic density of states increases quadratically with thickness. Our calculations show the same trends as experimental values indicating band gap reduction and absorption enhancement for Si films of increasing thickness. Simple arguments on confined electronic structures have been used to explain the main effects of changes with slab thickness. A procedure involving shifted electron excitation energies is described to improve results from generalized gradient functionals so they can be in better agreement with the more accurate but also more computer intensive values from screened exchange hybrid functionals.

Chemistry Department.

Jimenez, E. Y., C. Mangani, R. Ashorn, William S. Harris, K. Maleta, & K. G. Dewey. (2015). Breast milk from women living near Lake Malawi is high in docosahexaenoic acid and arachidonic acid. Prostaglandins Leukotrienes and Essential Fatty Acids, 95, 71-78.

Adequate long-chain polyunsaturated fatty acid (LCPUFA) intake is critical during the fetal and infant periods. We quantified fatty acid content of breast milk (n=718) and plasma from six month old infants (n=412) in southern Malawi, and in usipa (n=3), a small dried fish from Lake Malawi. Compared to global norms, Malawian breast milk fatty acid content (% of total fatty acids) was well above average levels of arachidonic acid [ARA] (0.69% vs. 0.47%) and docosahexaenoic acid [DHA] (0.73% vs. 0.32%). Average Malawian infant plasma ARA (7.5%) and DHA (3.8%) levels were comparable to those reported in infants consuming breast milk with similar fatty acid content. The amounts (mg) of DHA, EPA and ARA provided by a 3 oz (85 g) portion of dried usipa (1439, 659 and 360, respectively) are considerably higher than those for dried salmon. Usipa may be an important source of LCPUFA for populations in this region. (C) 2014 Elsevier Ltd. All rights reserved.

Sanford School of Medicine, Sioux Falls Campus.

Pickens, C. A., L. M. Sordillo, S. S. Comstock, William S. Harris, K. Hortos, B. Kovan, & J. I. Fenton. (2015). Plasma phospholipids, non-esterified plasma polyunsaturated fatty acids and oxylipids are associated with BMI. Prostaglandins Leukotrienes and Essential Fatty Acids, 95, 31-40.

The obese lipid profile is associated with increased free fatty acids and triacylglycerides. Currently, little is known about the plasma lipid species associated with obesity. In this study, we compared plasma lipid fatty acid (FA) profiles as a function of BMI. Profiling phospholipid (PL) FAs and their respective oxylipids could predict which obese individuals are more likely to suffer from diseases associated with chronic inflammation or oxidative stress. We investigated the relationship between BMI and plasma PL (PPL) FA composition in 126 men using a quantitative gas chromatography analysis. BMI was inversely associated with both PPL nervonic and linoleic acid (LA) but was positively associated with both dihomo-gamma-linolenic and palmitoleic acid. Compared to lean individuals, obese participants were more likely to have omega-6 FAs, except arachidonic acid and LA, incorporated into PPLs. Obese participants were less likely to have EPA and DHA incorporated into PPLs compared to lean participants. Non-esterified plasma PUFA and oxylipid analysis showed omega-6 oxylipids were more abundant in the obese plasma pool. These omega-6 oxylipids are associated with increased angiogenesis (i.e. epoxyeicosatrienoates), reactive oxygen species (i.e. 9-hydroxyeicosatetraenoate), and inflammation resolution (i.e. Lipoxin A4). In summary, BMI is directly associated with specific PPL FA and increased omega-6 oxylipids. (C) 2014 Elsevier Ltd. All rights reserved.

Sanford School of Medicine, Sioux Falls Campus.

 

Miller, Jake N., Attila D. Kovacs, & David A. Pearce. (2015). The novel Cln1(R151X) mouse model of infantile neuronal ceroid lipofuscinosis (INCL) for testing nonsense suppression therapy. Human Molecular Genetics, 24(1), 185-196.

The neuronal ceroid lipofuscinoses (NCLs), also known as Batten disease, are a group of autosomal recessive neurodegenerative disorders in children characterized by the progressive onset of seizures, blindness, motor and cognitive decline and premature death. Patients with mutations in CLN1 primarily manifest with infantile NCL (INCL or Haltia-Santavuori disease), which is second only to congenital NCL for its age of onset and devastating progression. CLN1 encodes a lysosomal enzyme, palmitoyl-protein thioesterase 1 (PPT1). Nonsense mutations in CLN1 account for 52.3% of all disease causing alleles in infantile NCL, the most common of which worldwide is the p.R151X mutation. Previously, we have shown how nonsense-mediated decay is involved in the degradation of CLN1 mRNA transcripts containing the p. R151X mutation in human lymphoblast cell lines. We have also shown how the read-through drugs gentamicin and ataluren (PTC124) increase CLN1 (PPT1) enzyme activity. Here, we provide the initial characterization of the novel Cln1(R151X) mouse model of infantile neuronal ceroid lipofuscinosis that we have generated. This nonsense mutation model recapitulates the molecular, histological and behavioral phenotypes of the human disease. Cln1(R151X) mice showed a significant decrease in Cln1 mRNA level and PPT1 enzyme activity, accumulation of autofluorescent storage material, astrocytosis and microglial activation in the brain. Behavioral characterization of Cln1(R151X) mice at 3 and 5 months of age revealed significant motor deficits as measured by the vertical pole and rotarod tests. We also show how the read-through compound ataluren (PTC124) increases PPT1 enzyme activity and protein level in Cln1(R151X) mice in a proof-of-principle study.

Basic Biomedical Sciences, Vermillion Campus.

Morecraft, Robert J., Jizhi Ge, Kimberly S. Stilwell-Morecraft, D. W. McNeal, S. M. Hynes, M. A. Pizzimenti, . . . W. G. Darling. (2015). Vulnerability of the Medial Frontal Corticospinal Projection Accompanies Combined Lateral Frontal and Parietal Cortex Injury in Rhesus Monkey. Journal of Comparative Neurology, 523(4), 669-697.

Concurrent damage to the lateral frontal and parietal cortex is common following middle cerebral artery infarction, leading to upper extremity paresis, paresthesia, and sensory loss. Motor recovery is often poor, and the mechanisms that support or impede this process are unclear. Since the medial wall of the cerebral hemisphere is commonly spared following stroke, we investigated the spontaneous long-term (6 and 12 month) effects of lateral frontoparietal injury (F2P2 lesion) on the terminal distribution of the corticospinal projection (CSP) from intact, ipsilesional supplementary motor cortex (M2) at spinal levels C5 to T1. Isolated injury to the frontoparietal arm/hand region resulted in a significant loss of contralateral corticospinal boutons from M2 compared with controls. Specifically, reductions occurred in the medial and lateral parts of lamina VII and the dorsal quadrants of lamina IX. There were no statistical differences in the ipsilateral CSP. Contrary to isolated lateral frontal motor injury (F2 lesion), which results in substantial increases in contralateral M2 labeling in laminae VII and IX (McNeal et al. [2010] J. Comp. Neurol. 518:586-621), the added effect of adjacent parietal cortex injury to the frontal motor lesion (F2P2 lesion) not only impedes a favorable compensatory neuroplastic response but results in a substantial loss of M2 CSP terminals. This dramatic reversal of the CSP response suggests a critical trophic role for cortical somatosensory influence on spared ipsilesional frontal corticospinal projections, and that restoration of a favorable compensatory response will require therapeutic intervention. J. Comp. Neurol. 523:669-697, 2015. (c) 2014 Wiley Periodicals, Inc.

Basic Biomedical Sciences, Vermillion Campus.

Reinbold, Emily D., Jamie L. Scholl, Kathryn M. Oliver, Michael J. Watt, & Gina L. Forster. (2014). Central CRF2 receptor antagonism reduces anxiety states during amphetamine withdrawal. Neuroscience Research, 89, 37-43.

Increased depressive and anxiety-like behaviors are exhibited by rats and humans during withdrawal from psychostimulants. Anxiety-like behaviors observed during amphetamine withdrawal are mediated by increased expression and activity of corticotropin releasing factor type 2 (CRF2) receptors in the dorsal raphe nucleus (dRN). Anxiety-like behavior of rats during withdrawal can be reversed by CRF2 receptor antagonism in the dRN, but the efficacy of global central CRF2 receptor antagonism is unknown. Rats were treated with amphetamine (2.5 mg/kg, ip.) or saline daily for 2 weeks, and were tested for anxiety-like behaviors during withdrawal. Rats undergoing withdrawal showed increased anxiety-like behavior, which was reduced by ventricular infusion of the CRF2 antagonist antisauvagine-30 (ASV 2 mu g/2 mu I). Surprisingly, ventricular ASV increased anxiety-like behavior in rats pre-treated with saline, but had an anxiolytic effect in un-treated rats. Western blots were performed to determine whether differences in CRF receptor densities could explain ASV-induced behavioral results. Saline pre-treated rats showed reduced CRF1 receptor expression in the lateral septum compared to amphetamine pre-treated and untreated rats. Overall, these results suggest that central CRF2 antagonism reduces anxiety states during amphetamine withdrawal, and that behavioral effects may be dependent upon the balance of CRF1 and CRF2 receptor activity in anxiety-related regions. (C) 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Basic Biomedical Sciences, Vermillion Campus.

Zutkis, A. A., Srivishnupriya Anbalagan, Michael S. Chaussee, & A. V. Dmitriev. (2014). Inactivation of the Rgg2 Transcriptional Regulator Ablates the Virulence of Streptococcus pyogenes. Plos One, 9(12), 21.

Streptococcus pyogenes adapts to different niches encountered in the human host via the activity of numerous regulatory proteins including the Rgg family of transcriptional regulators. The S. pyogenes chromosome encodes four Rgg paralogues designated Rgg1 (RopB), Rgg2 (MutR), Rgg3, and Rgg4 (ComR). In order to understand the role of the Rgg2 protein in the regulation of metabolic and virulence-associated properties of S. pyogenes, the rgg2 gene was inactivated in the M1 serotype strain SF370. Inactivation of rgg2 increased the growth yield of S. pyogenes in THY broth, increased biofilm formation, and increased production of SIC, which is an important virulence factor that inhibits complement mediated lysis. To identify Rgg2-regulated genes, the transcriptomes of SF370 and the rgg2 mutant strains were compared in the middle-exponential and post-exponential phases of growth. Rgg2 was found to control the expression of dozens of genes primarily in the exponential phase of growth, including genes associated with virulence (sse, scpA, slo, nga, mf-3), DNA transformation, and nucleotide metabolism. Inactivation of rgg2 decreased the ability of S. pyogenes to adhere to epithelial cells. In addition, the mutant strain was more sensitive to killing when incubated with human blood and avirulent in a murine bacteremia model. Finally, inoculation of mice with the avirulent rgg2 mutant of S. pyogenes SF370 conferred complete protection to mice subsequently challenged with the wild-type strain. Restoration of an intact rgg2 gene in mutant strain restored the wild-type phenotypes. Overall, the results demonstrate that Rgg2 is an important regulatory protein in S. pyogenes involved in controlling genes associated with both metabolism and virulence.

Basic Biomedical Sciences, Vermillion Campus.

Shewchuk, R. M., Greg L. Carlson, M. Klosterman, S. Cullen, & H. Y. Qu. (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.

Beacom School of Business.

Nguyen, H. T., H. Park, Karen L. Koster, R. E. Cahoon, H. T. M. Nguyen, J. Shanklin, . . . E. B. Cahoon. (2015). Redirection of metabolic flux for high levels of omega-7 monounsaturated fatty acid accumulation in camelina seeds. Plant Biotechnology Journal, 13(1), 38-50.

Seed oils enriched in omega-7 monounsaturated fatty acids, including palmitoleic acid (16:19) and cis-vaccenic acid (18:111), have nutraceutical and industrial value for polyethylene production and biofuels. Existing oilseed crops accumulate only small amounts (<2%) of these novel fatty acids in their seed oils. We demonstrate a strategy for enhanced production of omega-7 monounsaturated fatty acids in camelina (Camelina sativa) and soybean (Glycine max) that is dependent on redirection of metabolic flux from the typical 9 desaturation of stearoyl (18:0)-acyl carrier protein (ACP) to 9 desaturation of palmitoyl (16:0)-acyl carrier protein (ACP) and coenzyme A (CoA). This was achieved by seed-specific co-expression of a mutant 9-acyl-ACP and an acyl-CoA desaturase with high specificity for 16:0-ACP and CoA substrates, respectively. This strategy was most effective in camelina where seed oils with similar to 17% omega-7 monounsaturated fatty acids were obtained. Further increases in omega-7 fatty acid accumulation to 60-65% of the total fatty acids in camelina seeds were achieved by inclusion of seed-specific suppression of 3-keto-acyl-ACP synthase II and the FatB 16:0-ACP thioesterase genes to increase substrate pool sizes of 16:0-ACP for the 9-acyl-ACP desaturase and by blocking C18 fatty acid elongation. Seeds from these lines also had total saturated fatty acids reduced to similar to 5% of the seed oil versus similar to 12% in seeds of nontransformed plants. Consistent with accumulation of triacylglycerol species with shorter fatty acid chain lengths and increased monounsaturation, seed oils from engineered lines had marked shifts in thermotropic properties that may be of value for biofuel applications.

Biology Department.

Siler, C. D., L. J. Welton, Drew R. Davis, J. L. Watters, C. S. Davey, A. C. Diesmos, . . . R. M. Brown. (2014). TAXONOMIC REVISION OF THE PSEUDOGEKKO COMPRESICORPUS COMPLEX (REPTILIA: SQUAMATA: GEKKONIDAE), WITH DESCRIPTIONS OF THREE NEW SPECIES. Herpetological Monographs, 28, 110-139.

Recent phylogenetic analysis of false geckos, genus Pseudogekko, revealed unrecognized diversity within these exceedingly rare and enigmatic Philippine forest geckos. Newly available genetic datasets revealed that two of the four currently recognized species are complexes of multiple, deeply divergent evolutionary lineages. In this paper we evaluate species diversity in the Pseudogekko compresicorpus Complex and describe three new species in this unique clade of endemic Philippine geckos. For nearly a century, P. compresicorpus has been recognized as a single, “widespread” species with a geographic range spanning three major faunal regions and several isolated islands. This perception of the species’ wide geographic range has persisted due to the rarity of this species. We evaluate morphological data, in light of a recent phylogenetic study on the genus, to define species limits in P. compresicorpus, finding character-based evidence that unambiguously supports the recognition of four unique evolutionary lineages within the complex, three of which we describe as new species. These evolutionary species correspond to monophyletic lineages supported in recent molecular studies. We also address the historically controversial generic affiliation of Pseudogekko labialis and conclude that this poorly known species is a member of the genus Lepidodactylus. All species recognized in this study possess allopatric geographic ranges and differ from congeners by numerous diagnostic characters of external morphology and, therefore, should be recognized as full species in accordance with any lineage-based species concept. This study nearly doubles the known diversity of Philippine false geckos.

Biology Department.

Stager, M., David L. Swanson, & Z. A. Cheviron. (2015). Regulatory mechanisms of metabolic flexibility in the dark-eyed junco (Junco hyemalis). Journal of Experimental Biology, 218(5), 767-+.

Small temperate birds reversibly modify their aerobic performance to maintain thermoregulatory homeostasis under seasonally changing environmental conditions and these physiological adjustments may be attributable to changes in the expression of genes in the underlying regulatory networks. Here, we report the results of an experimental procedure designed to gain insight into the fundamental mechanisms of metabolic flexibility in the dark-eyed junco (Junco hyemalis). We combined genomic transcriptional profiles with measures of metabolic enzyme activities and whole-animal thermogenic performance from juncos exposed to four 6-week acclimation treatments that varied in temperature (cold, 3 degrees C; warm, 24 degrees C) and photoperiod (short day, 8 h light: 16 h dark; long day, 16 h light: 8 h dark). Cold-acclimated birds increased thermogenic capacity compared with warm-acclimated birds, and this enhanced performance was associated with upregulation of genes involved in muscle hypertrophy, angiogenesis, and lipid transport and oxidation, as well as with catabolic enzyme activities. These physiological changes occurred over ecologically relevant timescales, suggesting that birds make regulatory adjustments to interacting, hierarchical pathways in order to seasonally enhance thermogenic capacity.

Biology Department.

Wesner, Jeff S., P. Meyers, E. J. Billman, & M. C. Belk. (2015). Habitat selection and consumption across a landscape of multiple predators. Ecology and Evolution, 5(1), 121-129.

Predator community composition can alter habitat quality for prey by changing the strength and direction of consumptive effects. Whether predator community composition also alters prey density via nonconsumptive effects during habitat selection is not well known, but is important for understanding how changes to predator communities will alter prey populations. We tested the hypothesis that predator community composition (presence of caged trout, caged dragonflies, or caged trout+dragonflies) alters colonization of aquatic mesocosms by ovipositing aquatic insects. In a previous experiment in this system, we found a spatial contagion effect, in which insects avoided pools with predators, but only when predator-free pools were isolated (similar to 5m away from predator pools). Here, we removed the isolated predator-free pools, allowing us to test whether insects would make fine-scale (similar to 1m) oviposition decisions in the absence of preferred isolated pools. We also estimated consumptive effects by allowing predators to feed on colonists for 5days following colonization. All insects collected after 21days were dipterans, dominated by Chironomidae. Total colonization, measured as the number of developing larvae after 21days, was not affected by either predator presence or composition. Consumption was significant in the trout only treatment, reducing larval insect density by 46 +/- 37% (mean +/- SE). No other predator treatment significantly reduced prey density, although the proportion of chironomid larvae in protective cases increased in response to direct predation from dragonflies, indicating an antipredatory behavioral response. Taken together, these results reveal that predator community composition altered larval survival and behavior, but colonizing females either did not or could not assess these risks across small scales during oviposition.

Biology Department.

Thiruppathi, Eagappanath, M. K. Larson, & Gapinath Mani. (2015). Surface Modification of CoCr Alloy Using Varying Concentrations of Phosphoric and Phosphonoacetic Acids: Albumin and Fibrinogen Adsorption, Platelet Adhesion, Activation, and Aggregation Studies. Langmuir, 31(1), 358-370.

CoCr alloy is commonly used in various cardiovascular medical devices for its excellent physical and mechanical properties. However, the formation of blood clots on the alloy surfaces is a serious concern. This research is focused on the surface modification of CoCr alloy using varying concentrations (1, 25, 50, 75, and 100 mM) of phosphoric acid (PA) and phosphonoacetic acid (PAA) to generate various surfaces with different wettability, chemistry, and roughness. Then, the adsorption of blood plasma proteins such as albumin and fibrinogen and the adhesion, activation, and aggregation of platelets with the various surfaces generated were investigated. Contact angle analysis showed PA and PAA coatings on CoCr provided a gradient of hydrophilic surfaces. FTIR showed PA and PAA were covalently bound to CoCr surface and formed different bonding configurations depending on the concentrations of coating solutions used. AFM showed the formation of homogeneous PA and PAA coatings on CoCr. The single and dual protein adsorption studies showed that the amount of albumin and fibrinogen adsorbed on the alloy surfaces strongly depend on the type of PA and PAA coatings prepared by different concentrations of coating solutions. All PA coated CoCr showed reduced platelet adhesion and activation when compared to control CoCr. Also, 75 and 100 mM PA-CoCr showed reduced platelet aggregation. For PAA coated CoCr, no significant difference in platelet adhesion and activation was observed between PAA coated CoCr and control CoCr. Thus, this study demonstrated that CoCr can be surface modified using PA for potentially reducing the formation of blood clots and improving the blood compatibility of the alloy.

Biomedical Engineering, Sioux Falls Campus.

Mariappan, Kadarkaraisamy, Janani Sindhu Ragothaman, Vinothini Balasubramanian, Mariah Hoffman, Madhubabu Alaparthi, & Andrew G. Sykes. (2015). Palladium(II) complexes of anthraquinone-based As-O-As type and Se-O-Se type bipodands. Synthesis, X-ray crystallography and catalytic properties. Inorganica Chimica Acta, 429, 46-50.

The reaction of the Ph2As anion with 1,8-bis(2-bromoethoxy) anthracene-9,10-dione in 2: 1 ratio generates 1,8-bis(2-diphenylarsinoethoxy) anthracene-9,10-dione (L1). L1 and 1,8-bis(2-phenylselenoethoxy) anthraquinone (L2) reacted with bis(benzonitrile) palladium(II) chloride in 1: 1 ratio yielding Pd(L1)Cl-2 (1) and Pd(L2)Cl-2 (2). X-ray structures of 1 and 2 revealed that L1 and L2 chelate with Pd(II) and form a convex square planar geometry. The catalytic properties of both Pd(II) complexes in the Heck reaction was investigated, and the results show that compound 2 acts as a better catalyst than 1. The redox behavior of L1, 1 and 2 versus Ag/AgCl are also explored. (C) 2015 Elsevier B.V. All rights reserved.

Chemistry Department.

Meng, Qingguo, Jiangchao Chen, & Dmitri S. Kilin. (2015). Proton reduction at surface of transition metal nanocatalysts. Molecular Simulation, 41(1-3), 134-145.

Catalytic activities of neutral and charged palladium (Pd) nanoparticles are compared for hydrogen reduction half-reaction. In this work the sequential H-2 dissociation from the surface of a Pd13H24 cluster is systematically studied by ab initio molecular dynamics (AIMD) at the density functional theory level. AIMD simulation is launched by preparing initial values of momenta of all nuclei in the model corresponding to a temperature range of 0-1700K. AIMD simulation provides the trajectories of all the atoms in the cluster. A sequential H-2 desorption up to seven molecules is observed from the cluster surface due to thermal motion of nuclei. Modifications of total charge on the neutral Pd13H24 cluster model are found to affect surface H-2 desorption behaviour. A desorption rate of H-2 molecule on both neutral and charged Pd13H24 clusters is compared to the data of Pt13H24 cluster reported previously. The H-2 desorption energy on all the investigated clusters is also determined. The results reveal that Pd-13 cluster presents a higher catalytic activity than Pt-13 cluster.

Chemistry Department.

Peng, Rui, J. Baltrusaitis, Chia-Ming Wu, & Ranjit T. Koodali. (2015). Pd-Ti-MCM-48 cubic mesoporous materials for solar simulated hydrogen evolution. International Journal of Hydrogen Energy, 40(2), 905-918.

A facile synthetic method (in as little as four hours) for simultaneously loading high amounts of titania (Si/Ti = 3) and Pd-0 co-catalyst (0.1 wt.% per gram of total catalyst) in cubic mesoporous MCM-48 material was developed at room temperature. The solar simulated photocatalytic hydrogen evolution from photocatalysts containing Pd and TiO2 nanoclusters in periodic cubic MCM-48 and aperiodic mesoporous silica was compared. The results indicate that the periodicity of the mesoporous silica support, the oxidation state of Pd, the location and dispersion of Pd have a significant impact on the photocatalytic activity. Periodic cubic MCM-48 mesoporous silica containing Pd in close contact with titania exhibit superior hydrogen evolution rates, compared to Pd-0-TiO2 containing aperiodic mesoporous silica. The highly ordered and open three-dimensional mesoporous cubic MCM-48 support has high surface area and facilitate good dispersion and close contact of titania and Pd. At very low loadings of 0.1 wt.% of Pd, hydrogen yield was found to be 560 mu mol h(-1), which is among the highest reported in the literature for Pd containing TiO2 based materials under solar simulated conditions. The results suggest that the pore architecture of the support is also an important parameter that governs the photocatalytic activity. In addition, the Pd-0-mesoporous materials in general possess higher activity than Pd2+ containing mesoporous materials. The photocatalysts were extensively characterized by a variety of techniques such as powder X-ray diffraction (XRD), nitrogen sorption analysis, transmission and scanning electron microscopic studies, photoluminescence, diffuse reflectance spectroscopy (DRS), CO Chemisorption, and X-ray photoelectron spectroscopy (XPS). Copyright (C) 2014, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved.

Chemistry Department.

Rasalingam, Shivatharsiny, Chia-Ming Wu, & Ranjit T. Koodali. (2015). Modulation of Pore Sizes of Titanium Dioxide Photocatalysts by a Facile Template Free Hydrothermal Synthesis Method: Implications for Photocatalytic Degradation of Rhodamine B. Acs Applied Materials & Interfaces, 7(7), 4368-4380.

Mesoporous TiO2 photocatalysts were prepared in ethanol media by using relatively green, template free sol-gel technique. A mild hydrothermal treatment procedure was employed to tune the pore sizes of the materials. Comprehensive techniques that include powder X-ray diffraction, diffuse reflectance spectroscopy, specific surface area analysis, electron microscopy, FT-IR, TGA, and xi-potential measurements were used to characterize the titania materials. Porosity (pore size and pore volume) of the materials were found to be key factors for the variation in the rate of photocatalytic degradation of rhodamine B; in addition to specific surface area, and surface hydroxyl groups. An increase in porosity permits effective transport of the dye molecules resulting in an increase in the rate of the degradation in materials having larger pores. A detailed electrospray ionization-mass spectrometric (ESI-MS) study was carried out for selected materials to identify photodegraded intermediates and products formed during the degradation of rhodamine B. In addition, experiments were also carried out to understand the role of reactive oxygen species (ROS). In summary, this work provides a simple way to tune pore sizes without the use of any template and an insight into the influence of pore size for the photocatalytic degradation of rhodamine B.

Chemistry Department.

Vazhappilly, T., Dmitri S. Kilin, & D. A. Micha. (2015). Modeling the surface photovoltage of silicon slabs with varying thickness. Journal of Physics-Condensed Matter, 27(13), 9.

The variation with thickness of the energy band gap and photovoltage at the surface of a thin semiconductor film are of great interest in connection with their surface electronic structure and optical properties. In this work, the change of a surface photovoltage (SPV) with the number of layers of a crystalline silicon slab is extracted from models based on their atomic structure. Electronic properties of photoexcited slabs are investigated using generalized gradient and hybrid density functionals, and plane wave basis sets. Si(1 1 1) surfaces have been terminated by hydrogen atoms to compensate for dangling bonds and have been described by large supercells with periodic boundary conditions. Calculations of the SPV of the Si slabs have been done in terms of the reduced density matrix of the photoactive electrons including dissipative effects due to their interaction with medium phonons and excitons. Surface photovoltages have been calculated for model Si slabs with 4-12, and 16 layers, to determine convergence trends versus slab thickness. Band gaps and the inverse of the SPVs have been found to scale nearly linearly with the inverse thickness of the slab, while the electronic density of states increases quadratically with thickness. Our calculations show the same trends as experimental values indicating band gap reduction and absorption enhancement for Si films of increasing thickness. Simple arguments on confined electronic structures have been used to explain the main effects of changes with slab thickness. A procedure involving shifted electron excitation energies is described to improve results from generalized gradient functionals so they can be in better agreement with the more accurate but also more computer intensive values from screened exchange hybrid functionals.

Chemistry Department.

Yao, Ge, Cuikun Lin, Qingguo Meng, P. Stanley May, & Mary T. Berry. (2015). Calculation of Judd-Ofelt parameters for Er3+ in beta-NaYF4: Yb3+, Er3+ from emission intensity ratios and diffuse reflectance spectra. Journal of Luminescence, 160, 276-281.

We report the calculation of Er3+ Judd-Ofelt (JO) parameters for beta-phase NaYF4:Yb3+, Er3+. The parameters were extracted from measured emission intensity ratios and the diffuse reflectance spectrum, augmented by a single radiative rate constant The derived parameters were used to calculate the entire suite of radiative rate constants for the f-f transitions of Er3+ in the visible and near infrared (NIR) range and to calculate the absorbance spectrum. Two sets of JO parameter values, in units of pm(2), were calculated using two available sets of reduced matrix elements (Omega(2)=236, Omega(4)=-022, Omega(6)=1.24) and (Omega(2)=2.43, Omega(4)=0.21, Omega(6) = 122). (C) 2014 Elsevier B.V. All rights reserved.

Chemistry Department.

Yao, Ge, Qingguo Meng, Mary T. Berry, P. Stanley May, & Dimitri S. Kilin. (2015). Molecular dynamics in finding nonadiabatic coupling for beta-NaYF4: Ce3+ nanocrystals. Molecular Physics, 113(3-4), 385-391.

Optical and electronic properties of cerium ions doped into solid host matrices are explored by density functional theory (DFT). A spin-polarised (unrestricted) DFT + U approach is applied to beta-NaYF4: Ce3+ nanocrystals, in which the Hubbard U – J value is determined through experimental fitting to be 8.5 eV for yttrium, and 2.9 eV for cerium. Molecular dynamics simulations indicate that the energies of the localised f-like orbitals of the Ce3+ dopant exhibit strong thermal fluctuations compared to that of the p- and d-shaped orbitals due to charge-density localisation. Our observation of mixing between the d and f orbitals of Ce3+ ion is consistent with experimental results. Combining time-dependent density matrix methodology, ab initio molecular dynamics, and on-the-fly nonadiabatic couplings simulates nonradiative transitions between electronic states at ambient temperature. Transition rates between individual orbitals decrease with their energy difference, which is similar to the format of the energy gap law. These transitions contribute to integrated rates of nonradiative thermalisation of different electronic excitations to the lowest excited state through multiple pathways. The integrated rates of thermalisation decrease with energy difference of the initial photoexcitation and the final excitation.

Chemistry Department.

Lushbough, Carol M., Etienne Z. Gnimpieba, & R. Dooley. (2015). Life science data analysis workflow development using the bioextract server leveraging the iPlant collaborative cyberinfrastructure. Concurrency and Computation-Practice & Experience, 27(2), 408-419.

In order to handle the vast quantities of biological data gener6ated by high-throughput experimental technologies, the BioExtract Server (bioextract.org) has leveraged iPlant Collaborative () functionality to help address big data storage and analysis issues in the bioinformatics field. The BioExtract Server is a Web-based, workflow-enabling system that offers researchers a flexible environment for analyzing genomic data. It provides researchers with the ability to save a series of BioExtract Server tasks (e.g., query a data source, save a data extract, and execute an analytic tool) as a workflow and the opportunity for researchers to share their data extracts, analytic tools, and workflows with collaborators. The iPlant Collaborative is a community of researchers, educators, and students working to enrich science through the development of cyberinfrastructurethe physical computing resources, collaborative environment, virtual machine resources, and interoperable analysis software and data servicesthat are essential components of modern biology. The iPlant AGAVE Advanced Programming Interface, developed through the iPlant Collaborative, is a hosted, Software-as-a-Service resource providing access to a collection of high performance computing and cloud resources. Leveraging AGAVE, the BioExtract Server gives researchers easy access to multiple high performance computers and delivers computation and storage as dynamically allocated resources via the Internet. (c) 2014 The Authors. Concurrency and Computation: Practice and Experience published by John Wiley & Sons Ltd.

Computer Science Department.

Wang, L. Y., D. Ware, Carol M. Lushbough, N. Merchant, & L. Stein. (2015). A genome-wide association study platform built on iPlant cyber-infrastructure. Concurrency and Computation-Practice & Experience, 27(2), 420-432.

We demonstrate a flexible genome-wide association study platform built upon the iPlant Collaborative Cyber-infrastructure. The platform supports big data management, sharing, and large-scale study of both genotype and phenotype data on clusters. End users can add their own analysis tools and create customized analysis workflows through the graphical user interfaces in both iPlant Discovery Environment and BioExtract server. Copyright (c) 2014 John Wiley & Sons, Ltd.

Computer Science Department.

Meng, Qingguo, P. Stanley May, Mary T. Berry, & Dmitri S. Kilin. (2015). Time-resolved electronic and optical properties of a thiolate-protected Au-38 nanocluster. Molecular Physics, 113(3-4), 408-417.

Density functional theory and density matrix theory are employed to investigate the time-dependent optical and electronic properties of an Au-14 nanocluster protected by six cyclic thiolate ligands, Au-4(SCH3)(4). The Au-14[Au-4(SCH3)(4)](6) nanocluster, i.e. Au-38(SCH3)(24), is equivalent to a truncated-octahedral face-centred cubic Au-38 core coated by a monolayer of 24 methylthiol molecules. The electronic and optical properties, such as density of states, linear absorption spectra, nonradiative nonadiabatic dissipative electronic dynamics and radiative emission spectra were calculated and compared for the core Au-14 and thiolate-protected Au-38(SCH3)(24) nanocluster. The main observation from computed photoluminescence for both models is a mechanism of radiative emission. Specifically, a strong contribution to light emission intensity originates from intraband transitions inside the conduction band (CB) in addition to interband LUMO -> HOMO transition (HOMO: highest occupied molecular orbital and LUMO: lowest unoccupied molecular orbital). Such comparison clarifies the contributions from Au core and methylthiol ligands to the electronic and optical properties of the Au-38(SCH3)(24) nanocluster.

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Meng, Qingguo May, Stanley P. Berry, Mary T. Kilin, Dmitri S.

South Dakota Governor’s Office of Economic Development, NSF [EPS-0903804]; DOE, BES – Chemical Sciences, NERSC [DE-AC02-05CH11231, 86898]

This work was supported financially by the South Dakota Governor’s Office of Economic Development, NSF award EPS-0903804, DOE, BES – Chemical Sciences, NERSC Contract No. DE-AC02-05CH11231, allocation Award 86898, ‘Computational Modeling of Photo-catalysis and Photoinduced Charge Transfer Dynamics on Surfaces’. Computational resources of USD High Performance Computing facilities operated by Douglas Jennewein, the Dean’s Opportunity Fund of the College of Arts and Sciences, University of South Dakota.

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Masotti, A., P. Uva, Laura Davis-Keppen, L. Basel-Vanagaite, L. Cohen, E. Pisaneschi, . . . B. Dallapiccola. (2015). Keppen-Lubinsky Syndrome Is Caused by Mutations in the Inwardly Rectifying K+ Channel Encoded by KCNJ6. American Journal of Human Genetics, 96(2), 295-300.

Keppen-Lubinsky syndrome (KPLBS) is a rare disease mainly characterized by severe developmental delay and intellectual disability, microcephaly, large prominent eyes, a narrow nasal bridge, a tented upper lip, a high palate, an open mouth, tightly adherent skin, an aged appearance, and severe generalized lipodystrophy. We sequenced the exomes of three unrelated individuals affected by KPLBS and found de novo heterozygous mutations in KCNJ6 (GIRK2), which encodes an inwardly rectifying potassium channel and maps to the Down syndrome critical region between DIRK1A and DSCR4. In particular, two individuals shared an in-frame heterozygous deletion of three nucleotides (c.455_457del) leading to the loss of one amino acid (p.Thr152del). The third individual was heterozygous for a missense mutation (c.460G>A) which introduces an amino acid change from glycine to serine (p.Gly154Ser). In agreement with animal models, the present data suggest that these mutations severely impair the correct functioning of this potassium channel. Overall, these results establish KPLBS as a channelopathy and suggest that KCNJ6 (GIRK2) could also be a candidate gene for other lipodystrophies. We hope that these results will prompt investigations in this unexplored class of inwardly rectifying K+ channels.

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Masotti, Andrea Uva, Paolo Davis-Keppen, Laura Basel-Vanagaite, Lina Cohen, Lior Pisaneschi, Elisa Celluzzi, Antonella Bencivenga, Paola Fang, Mingyan Tian, Mingyu Xu, Xun Cappa, Marco Dallapiccola, Bruno

Italian Ministry of Health; company BVLGARI

The authors are indebted to the families who contributed to this study. The financial support of the Italian Ministry of Health and the company BVLGARI is fully acknowledged.

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Tinguely, Joseph. (2015). The Implicit Affection Between Kantian Judgment and Aristotelian Rhetoric. Philosophy and Rhetoric, 48(1), 1-25.

Recent scholarship on Kant and rhetoric suggests an inclusive relation between affectivity and cognitive judgment, but that position runs counter to a traditional philosophical opposition between sensibility and rationality. A way to overcome this opposition comes into view in the overlap in three significant areas between Kantian judgment and Aristotelian rhetoric. First, each allows that communicative capacities operate within the way a perceptual object or scene appears in the first place. Secondly, each significantly broadens such communicative capacities so as to include the entire conceptual form of one’s disposition or orientation to the world as a whole. Thirdly, each links those broad mental dispositions to specifically affective states of mind. Taken together, the areas of overlap between Kantian judgment and Aristotelian rhetoric adumbrate an integrated picture of the affective sensibilities and cognitive capacities largely missing from the contemporary landscape.

Languages, Linguistics & Philosophy Department.

Mertens, S., K. Dolde, M. Korzeczek, F. Glueck, S. Groh, Ryan D. Martin, . . . M. Steidl. (2015). Wavelet approach to search for sterile neutrinos in tritium beta-decay spectra. Physical Review D, 91(4), 10.

Sterile neutrinos in the mass range of a few keV are candidates for both cold and warm dark matter. An admixture of a heavy neutrino mass eigenstate to the electron neutrino would result in a minuscule distortion-a kink-in a beta-decay spectrum. In this paper we show that a wavelet transform is a very powerful shape analysis method to detect this signature. For a tritium source strength, similar to what is expected from the KATRIN experiment, a statistical sensitivity to active-to-sterile neutrino mixing down to sin(2)theta = 10(-6) (90% C. L.) can be obtained after three years of measurement time. It is demonstrated that the wavelet approach is largely insensitive to systematic effects that result in smooth spectral modifications. To make full use of this analysis technique a high- resolution measurement (FWHM of similar to 100 eV) of the tritium beta-decay spectrum is required.

Physics Department.

Zhang, C., & D. M. Mei. (2014). Measuring muon-induced neutrons with liquid scintillation detector at Soudan mine. Physical Review D, 90(12), 13.

We report a direct detection of muon-induced high-energy neutrons with a 12-liter neutron detector fabricated with EJ-301 liquid scintillator operating at Soudan mine for about two years. The detector response to energy from a few MeV up to similar to 20 MeV has been calibrated using radioactive sources and cosmic-ray muons. Subsequently, we have calculated the scintillation efficiency for nuclear recoils, up to a few hundred MeV, using Birks’ law in the Monte Carlo simulation. Data from an exposure of 655.1 days were analyzed and neutron-induced recoil events were observed in the energy region from 4 to 50 MeV, corresponding to fast neutrons with kinetic energy up to a few hundred MeV, depending on the scattering angle. Combining with the Monte Carlo simulation, the measured muon-induced fast neutron flux is determined to be (2.23 +/- 0.52(sta) +/- 0.99(sys) x 10(-9) cm(-2) s(-1) (E-n > 20 MeV), in a reasonable agreement with the model prediction. The muon flux is found to be (1.65 +/- 0.02(sta) +/- 0.1(sys)) x 10(-7) cm(-2) s(-1) (E-mu > 1 GeV), consistent with other measurements. As a result, the muon-induced high-energy gamma-ray flux is simulated to be 7.08 x 10(-7) cm(-2) s(-1) (E-gamma > 1 MeV) for the depth of Soudan.

Physics Department.

Newswander, Chad B. (2015). Guerrilla Statesmanship: Constitutionalizing an Ethic of Dissent. Public Administration Review, 75(1), 126-134.

According to judicial precedents, administrators informed by their expertise can speak on issues of public concern under First Amendment protections. In one sense, they could dissent by working against their employers in an attempt to direct issues of public concern through an educational function. The power to act like a statesman in raising such issues allows administrators to lead from behind and in front, as long as certain judicial thresholds are met. However, the U.S. Supreme Court recently moved to tighten the scope of such activity. This article assesses how an ethic of dissent has been translated into a constitutional perspective that at first was moderately constrained and later became very restricted. While the move to limit an ethic of dissent provides necessary constraints, it also may have weakened administrators’ ability to perform necessary statesmanship acts rooted in guerrilla government to achieve the common good.

Political Science Department.

Newswander, Chad B., & Lynita K. Newswander. (2015). Metis: Using Wile and Wisdom to Inform Administrative Discretion. American Review of Public Administration, 45(2), 153-166.

When seeking to accomplish public ends in a prudent manner, administrators are occasionally put in precarious situations that require a degree of metis. Metis is a distinct form of knowledge characterized by a mixture of wile and wisdom and is valuable because it can offer viable alternatives for solving complex problems in contingent situations. Individualized problems often require administrators to forego routinized recommendations and pursue a path to prudence through shrewd thinking and action. However, if metis is not properly contained, it runs the risk of sinking under the weight of unscrupulous motivation and of negatively affecting the legitimacy of administrative action. What is important is that a crafty ethos is bound within a proper sphere. This is why a bounded metis informed by a modified version of intermediate scrutiny may provide a meaningful guide that legitimizes the ability of administrators to handle ambiguous situations in a prudent manner.

Political Science Department.

Rao, L. L., X. T. Wang, & S. Li. (2015). Investment choice and perceived mating intentions regulated by external resource cues and internal fluctuation in blood glucose levels. Frontiers in Psychology, 5, 7.

We examined resource allocation priorities in the framework of an updated Maslow hierarchy of fundamental human needs. In Experiment 1, the participants in the food abundance priming condition viewing photos of high-calorie food allocated more money to savings than to spending. However, the participants preferred spending to savings under the condition of mating availability priming with romantic photographs. In Experiment 2, before and after drinking either water or a sugary beverage, fasting participants rated photos of a conversation between a man and a woman. Water drinking lowered the rating scores of mating intentions as well as blood glucose (BG) levels. The sugary drink buffered this decline in sexual perceptivity. Overall, the change in BG levels was positively associated with changes in the ratings of mating intentions but was not associated with other likelihood ratings. These results suggest that both external cues of food and mating resources and internal BG fluctuation regulate the cognitive priority of physiological needs vs. mate acquisition and retention.

Psychology Department.

Milanovich, Samuel, J. Peterson, J. Allred, C. Stelloh, K. Rajasekaran, J. Fisher, . . . S. Rao. (2015). Sall4 overexpression blocks murine hematopoiesis in a dose-dependent manner. Experimental Hematology, 43(1), 53-64.

Sal-like protein 4 (SALL4) is a transcription factor that exists in two splice isoforms, SALL4a and SALL4b, and regulates transcription in embryonic stem cells, hematopoiesis, and acute myeloid leukemia. Constitutive overexpression of SALL4 in mice induces acute myeloid leukemia. Interestingly, a potential benefit of using SALL4 to facilitate ex vivo hematopoietic stem cell expansion has been proposed. However, distinct roles for how SALL4 contributes to normal versus malignant processes remain undefined. Here we show that SALL4b is the predominant isoform in murine hematopoietic stem cells and progenitors. Overexpression of either SALL4 isoform in hematopoietic stem cells or progenitors impairs hematopoietic colony formation and expansion in vitro. Lineage-negative bone marrow overexpressing SALL4b fails to engraft and reconstitute hematopoiesis when transplanted. We found that both SALL4a and SALL4b overexpression impair hematopoiesis, in part through dose-dependent repression of BMI1. Additionally, we have identified the following potential novel SALL4 target genes in hematopoiesis: ARID5B (SALL4a and SALL4b), EZH2, and KLF2 (SALL4a). Lastly, we found that SALL4 expression is variable in acute myeloid leukemia, ranging from no expression to levels comparable to embryonic stem cells. These results show that SALL4 isoforms contribute to only a subset of acute myeloid leukemia and that overexpression of SALL4 isoforms impairs hematopoiesis through repression of BMI1. Together these data demonstrate the sensitivity of hematopoiesis to appropriately balanced SALL4 expression, highlighting the importance of regulating this dynamic in potential therapeutic applications such as ex vivo stem cell expansion. Copyright (C) 2015 ISEH – International Society for Experimental Hematology. Published by Elsevier Inc.

Sanford School of Medicine, Sioux Falls Campus.

Naesgaard, P. A., V. Ponitz, H. Aarsetoey, …., William S. Harris, H. Staines, & D. T. Nilsen. (2015). Prognostic Utility of Vitamin D in Acute Coronary Syndrome Patients in Coastal Norway. Disease Markers, 11.

Background. An inverse relationship between cardiovascular risk and levels of vitamin D and omega-3 index may exist. Objectives. To evaluate the prognostic utility of serum 25-hydroxyvitamin D [25(OH)D] in 871 patients with suspected acute coronary syndrome (ACS) and to assess the seasonal correlation between 25(OH)D and the omega-3 index in 456 ACS patients from southwestern Norway. Results. In the univariate analysis the hazard ratio (HR) at 2-year follow-up for all-cause mortality in the highest as compared to the lowest quartile of 25(OH)D in the total population was 0.61 (95% confidence interval (CI), 0.37-1.00), P = 0.050. At 7-year follow-up, the corresponding HR for all-cause mortality was 0.66 (95% CI, 0.49-0.90), P = 0.008, and for females alone 0.51 (95% CI, 0.32-0.83), P = 0.006. Quartile survival did not differ in the multivariable analysis, whereas 25(OH) D < 40nM (< 16 ng/mL) was found to be independently related to mortality. Seasonal differences in 25(OH)D, but not for the omega-3 index, were noted, and the two biomarkers were positively correlated, especially during winter-spring; Pearson’s correlation coefficient was 0.358, P < 0.001. Conclusion. Vitamin D levels are related to survival, especially in females, and correlate with the omega-3 index.

Sanford School of Medicine, Sioux Falls Campus.

Newman, J. W., T. L. Pedersen, Verdayne R. Brandenburg, William S. Harris, & Gregory C. Shearer. (2014). Effect of Omega-3 Fatty Acid Ethyl Esters on the Oxylipin Composition of Lipoproteins in Hypertriglyceridemic, Statin-Treated Subjects. Plos One, 9(11), 12.

Background: Oxylipins mediate inflammation, vascular tension, and more. Their presence in lipoproteins could explain why lipoproteins mediate nearly identical activities. Methods: To determine how oxylipins are distributed in the lipoproteins of hypertriglyceridemic subjects, and whether omega-3 fatty acids alter them in a manner consistent with improved cardiovascular health, we recruited 15 dyslipidemic subjects whose levels of low density lipoprotein cholesterol (LDL-C) were at goal but who remained hypertriglyceridemic (200-499 mg/dL). They were treated them with the indicated dose of 4 g/d omega-3 acid ethyl esters (P-OM3) for 8 weeks. Measured oxylipins included mid-chain alcohols (HETEs, HEPEs and HDoHEs), ketones (KETEs), epoxides (as EpETrEs, EpETEs, and EpDPEs). Results: At baseline, arachidonate-oxylipins (HETEs, KETEs, and EpETrEs) were most abundant in plasma with the greatest fraction of total abundance (mean vertical bar 95% CI vertical bar) being carried in high density lipoproteins (HDL); 42% vertical bar 31, 57 vertical bar followed by very low density lipoproteins (VLDL); 27% vertical bar 20, 36 vertical bar; and LDL 21% vertical bar 16, 28 vertical bar. EPA- and DHA-derived oxylipins constituted less than 11% of total. HDL carried alcohols and epoxides but VLDL was also rich in ketones. Treatment decreased AA-derived oxylipins across lipoprotein classes (-23% vertical bar-33, -12 vertical bar, p = 0.0003), and expanded EPA-(322% vertical bar 241, 422 vertical bar, p<0.0001) and DHA-derived oxylipins (123% vertical bar 80, 176 vertical bar, p<0.0001). Conclusions: Each lipoprotein class carries a unique oxylipin complement. P-OM3 treatment alters the oxylipin content of all classes, reducing pro-inflammatory and increasing anti-inflammatory species, consistent with the improved inflammatory and vascular status associated with the treatment.

Sanford School of Medicine, Sioux Falls Campus.

Roohani, P., T. Emiru, A. Carpenter, C. Luzzio, Jerome Freeman, S. Scarberry, . . . G. Parry. (2014). Late onset multiple sclerosis: Is it really late onset? Multiple Sclerosis and Related Disorders, 3(4), 444-449.

Background: Multiple sclerosis (MS) is the most common demyelinating disease, and onset over the age of 50 years is referred to as late onset MS (LOMS). It has been thought that LOMS patients will be more likely to exhibit a primary progressive (PPMS) clinical course. Objective: To identify the clinical characteristics of demyelinating disease in patients over the age of 50 years from four different MS centers in the Northern Midwest USA. Methods: We reviewed medical records of all patients seen at the MS centers and identified those who were 50 years of age or more at the time of first spontaneously reported symptoms. We included those who were diagnosed with MS or clinically isolated syndrome (CIS) and excluded MS mimickers. Demographics, initial clinical course diagnosis, clinical characteristics, and any available five-year follow up data were collected. The clinical course was reevaluated in each patient with careful questioning regarding any prior focal neurological symptoms that had persisted for at least 48 h, not otherwise explained. Those with a prior event who were initially diagnosed with PPMS or CIS were reclassified as secondary-progressive MS (SPMS) and relapsing-remitting MS (RRMS) respectively. Results: We identified 124 patients from a total of 3700 patients, making LOMS 3.4% MS in our population. The initial clinical course was RRMS in 50 (40%), PPMS in 44 (36%), SPMS in 15 (12%), and CIS in 15 (12%) patients. After reclassification the clinical course was RRMS in 55 (44%), PPMS in 25 (20%), SPMS in 34 (28%), and CIS in 10 (8%) patients. The clinical syndrome was identified as acute for 77 patients (62%) with transverse myelitis (N=25, 32%) as the most common type. The clinical syndrome was chronic for 47 patients (37%) and again transverse myelitis (N=24, 51%) was the most common type. Five-year follow up data was available for 44% of these patients. Discussion: LOMS is rare and RRMS is the most common clinical course. Reclassification of the clinical course, not done before in any other LOMS study, with careful questioning regarding a prior neurological event reveals that SPMS is the most common type of progressive MS and PPMS may be less common than previously thought. Transverse myelitis is the most common clinical presentation. (C) 2014 Elsevier B.V. All rights reserved.

Sanford School of Medicine, Sioux Falls Campus.

Sundram, Vasudha, A. Ganju, Joshua E. Hughes, S. Khan, S. C. Chauhan, & M. Jaggi. (2014). Protein Kinase D1 attenuates tumorigenesis in colon cancer by modulating beta-catenin/T cell factor activity. Oncotarget, 5(16), 6867-6884.

Over 80% of colon cancer development and progression is a result of the dysregulation of beta-catenin signaling pathway. Herein, for the first time, we demonstrate that a serine-threonine kinase, Protein Kinase D1 (PKD1), modulates the functions of beta-catenin to suppress colon cancer growth. Analysis of normal and colon cancer tissues reveals downregulation of PKD1 expression in advanced stages of colon cancer and its co-localization with beta-catenin in the colon crypts. This PKD1 downregulation corresponds with the aberrant expression and nuclear localization of beta-catenin. In-vitro investigation of the PKD1-beta-catenin interaction in colon cancer cells reveal that PKD1 overexpression suppresses cell proliferation and clonogenic potential and enhances cell-cell aggregation. We demonstrate that PKD1 directly interacts with beta-catenin and attenuates beta-catenin transcriptional activity by decreasing nuclear beta-catenin levels. Additionally, we show that inhibition of nuclear beta-catenin transcriptional activity is predominantly influenced by nucleus targeted PKD1. This subcellular modulation of beta-catenin results in enhanced membrane localization of beta-catenin and thereby increases cell-cell adhesion. Studies in a xenograft mouse model indicate that PKD1 overexpression delayed tumor appearance, enhanced necrosis and lowered tumor hypoxia. Overall, our results demonstrate a putative tumor-suppressor function of PKD1 in colon tumorigenesis via modulation of beta-catenin functions in cells.

Sanford School of Medicine, Sioux Falls Campus.

Tintle, N. L., J. V. Pottala, S. Lacey, V. Ramachandran, J. Westra, A. Rogers, . . . G. C. Shearer. (2015). A genome-wide association study of saturated, mono- and polyunsaturated red blood cell fatty acids in the Framingham Heart Offspring Study. Prostaglandins Leukotrienes and Essential Fatty Acids, 94, 65-72.

Most genome-wide association studies have explored relationships between genetic variants and plasma phospholipid fatty acid proportions, but few have examined apparent genetic influences on the membrane fatty acid profile of red blood cells (RBC). Using RBC fatty acid data from the Framingham Offspring Study, we analyzed over 2.5 million single nucleotide polymorphisms (SNPs) for association with 14 RBC fatty acids identifying 191 different SNPs associated with at least 1 fatty acid. Significant associations (p < 1 x 10(-8)) were located within five distinct 1 MB regions. Of particular interest were novel associations between (1) arachidonic acid and PCOLCE2 (regulates apoA-I maturation and modulates apoA-I levels), and (2) oleic and linoleic acid and LPCAT3 (mediates the transfer of fatty acids between glycerolipids). We also replicated previously identified strong associations between SNPs in the FADS (chromosome 11) and ELOVL (chromosome 6) regions. Multiple SNPs explained 8-14% of the variation in 3 high abundance ( > 11%) fatty acids, but only 1-3% in 4 low abundance ( < 3%) fatty acids, with the notable exception of dihomo-gamma linolenic acid with 53% of variance explained by SNPs. Further studies are needed to determine the extent to which variations in these genes influence tissue fatty acid content and pathways modulated by fatty acids. (C) 2014 Elsevier Ltd. All rights reserved.

Sanford School of Medicine, Sioux Falls Campus.

van Dongen, J., Erik A. Ehli, R. C. Slieker, M. Bartels, Z. M. Weber, Gareth E. Davies, . . . D. I. Boomsma. (2014). Epigenetic Variation in Monozygotic Twins: A Genome-Wide Analysis of DNA Methylation in Buccal Cells. Genes, 5(2), 347-365.

DNA methylation is one of the most extensively studied epigenetic marks in humans. Yet, it is largely unknown what causes variation in DNA methylation between individuals. The comparison of DNA methylation profiles of monozygotic (MZ) twins offers a unique experimental design to examine the extent to which such variation is related to individual-specific environmental influences and stochastic events or to familial factors (DNA sequence and shared environment). We measured genome-wide DNA methylation in buccal samples from ten MZ pairs (age 8-19) using the Illumina 450k array and examined twin correlations for methylation level at 420,921 CpGs after QC. After selecting CpGs showing the most variation in the methylation level between subjects, the mean genome-wide correlation (rho) was 0.54. The correlation was higher, on average, for CpGs within CpG islands (CGIs), compared to CGI shores, shelves and non-CGI regions, particularly at hypomethylated CpGs. This finding suggests that individual-specific environmental and stochastic influences account for more variation in DNA methylation in CpG-poor regions. Our findings also indicate that it is worthwhile to examine heritable and shared environmental influences on buccal DNA methylation in larger studies that also include dizygotic twins.

Sanford School of Medicine, Sioux Falls Campus.

Newland, Lisa A. (2015). Family well-being, parenting, and child well-being: Pathways to healthy adjustment. Clinical Psychologist, 19(1), 3-14.

Family well-being provides a foundation for positive parenting and child well-being. Many previous studies have outlined the possible connections between family well-being, parenting, and child well-being, yet translating research into practice continues to be problematic. The purpose of this article is to review the current literature (from 2000 to 2014) on family and child well-being in order to create a model of well-being that is useful for both researchers and practitioners. The model builds upon Bronfenbrenner’s Ecological Systems Theory, and is differentiated from other prominent models of family functioning by focusing on bolstering family strengths and well-being (as opposed to ameliorating family stress, risk, or deficits) and on supporting child well-being (as opposed to treating maladjustment). The model addresses family well-being (parental well-being, family self-sufficiency, and family resiliency), developmental parenting (affection, responsiveness, encouragement, teaching, engagement, positive discipline, and co-parenting), and child well-being (physical and mental health, self-regulation, social and cognitive competence). Direct and indirect connections between model components and possible moderating factors are discussed. A theory of change model is proposed as a tool for practitioners from a variety of disciplines and fields to guide their work with families. Recommendations for clinicians, limitations of the model, and future directions are discussed.

School of Education.

Newland, Lisa A., Michael J. Lawler, Jarod T. Giger, Soonhee Roh, & Eliann R. Carr. (2015). Predictors of Children’s Subjective Well-Being in Rural Communities of the United States. Child Indicators Research, 8(1), 177-198.

This study examined children’s subjective well-being in a rural Midwestern United States sample of children (N = 1,286). Fifth grade (M (age) = 10.66, SD = .55, range 10-12 years) and 7th grade (M (age) = 12.63, SD = .55, range 12-14 years) children completed an adapted version of the previously tested Children’s Worlds survey, measuring children’s subjective well-being. Surveys included individual factors (age, gender, number of residences), contextual factors of home and family (home environment, family relationships, parent involvement), life and neighborhood (financial resources, life stress, neighborhood quality), school (teacher relationships, school climate, school satisfaction), and peers (peer relationships), and subjective well-being measures for life satisfaction, mental health, and self-image. Though children’s subjective well-being was predicted by a number of individual, home and family, life and neighborhood, school, and peer variables, the strongest predictors of child well-being were relationships, school, and gender (males had higher scores). The reliability of the regression models were assessed by bootstrap resampling. Results are discussed in the context of an ecological, relationship-based framework of child well-being.

School of Health Sciences

School of Education

Sarriera, J. C., F. Casas, L. Bedin, D. Abs, M. R. Strelhow, D. Gross-Manos, & Jarod T. Giger. (2015). Material Resources and Children’s Subjective Well-Being in Eight Countries. Child Indicators Research, 8(1), 199-209.

The objective of this research is to examine the relationship between children’s perception of their available material resources and their subjective well-being. Participants (n = 13,953) resided in eight countries and were largely female (57 %), between the ages of 10-14 (M = 12.05; SD = 0.59). Each child completed a culturally appropriate country-survey that included demographic information and validated measures from the International Survey of Children’s Well-Being project (ISCIWeB), which included the Student’s Life Satisfaction Scale (SLSS) and material resources items. We tested a relational model for predicting subjective well-being and applied structural equation modelling (SEM) to the data. Results indicated that children in Uganda had limited access to material resources and the lowest average of well-being. Together with Algeria and South Africa, Uganda also had the strongest associations between the access to material resources and the SLSS. Even with access to all material resources evaluated, well-being scores are also lower in the case of South Korea, probably due to the so-called “Asian bias”. Children from Israel, Brazil, Spain, and England were similar in their levels of satisfaction and well-being. Our model fit the data well and revealed significant relationships between material resources and child subjective well-being in each country. Preliminary results underscore the importance of assessing material well-being in children and highlight the role material resources have in influencing children’s subjective well-being, especially in cases of children experiencing severe resource deprivation. Our model warrants further testing to replicate and extend our findings. Recommendations for future research are provided.

School of Health Sciences.

Bollinger, Stephen S., Weltman, Nathan Y., Gerdes, A. M., & Schlenker, Evelyn H. (2015). T-3 supplementation affects ventilatory timing & glucose levels in type 2 diabetes mellitus model. Respiratory Physiology & Neurobiology, 205, 92-98.

Type II diabetes mellitus (T2DM) can affect ventilation, metabolism, and fasting blood glucose levels. Hypothyroidism may be a comorbidity of T2DM. In this study T2DM was induced in 20 female Sprague Dawley rats using Streptozotocin (STZ) and Nicotinamide (N). One of experimental STZ/N groups (N=10 per group) was treated with a low dose of triiodothyronine (T-3). Blood glucose levels, metabolism and ventilation (in air and in response to hypoxia) were measured in the 3 groups. STZ/N-treated rats increased fasting blood glucose compared to control rats eight days and 2 months post-STZ/N injections indicating stable induction of T2DM state. Treatments had no effects on ventilation, metabolism or body weight. After one month of T-3 supplementation, there were no physiological indications of hyperthyroidism, but T-3 supplementation altered ventilatory timing and decreased blood glucose levels compared to STZ/N rats. These results suggest that low levels of T-3 supplementation could offer modest effects on blood glucose and ventilatory timing in this T2M model. (C) 2014 Elsevier B.V. All rights reserved.

Basic Biomedical Sciences, Vermillion Campus.

Chen, X., Shi, X. P., Zhao, C., …., Wang, Xuejun, & Liu, J. B. (2014). Anti-rheumatic agent auranofin induced apoptosis in chronic myeloid leukemia cells resistant to imatinib through both Bcr/Abl-dependent and -independent mechanisms. Oncotarget, 5(19), 9118-9132.

Resistance to Imatinib mesylate (IM) is an emerging problem for patients with chronic myelogenous leukemia (CML). T315I mutation in the Bcr-Abl is the predominant mechanism of the acquired resistance to IM and second generation tyrosine kinase inhibitors (TKI). Therefore it is urgent to search for new measures to overcome TKI-resistance. Auranofin (AF), clinically used to treat rheumatic arthritis, was recently approved by US Food and Drug Administration for Phase II clinical trial to treat cancer. In contrast to the reports that AF induces apoptosis by increasing intracellular reactive oxygen species (ROS) levels via inhibiting thioredoxin reductase, our recent study revealed that AF-induced apoptosis depends on inhibition of proteasomal deubiquitinases (UCHL5 and USP14). Here we report that (i) AF induces apoptosis in both Bcr-Abl wild-type cells and Bcr-Abl-T315I mutation cells and inhibits the growth of IM-resistant Bcr-Abl-T315I xenografts in vivo; (ii) AF inhibits Bcr-Abl through both downregulation of Bcr-Abl gene expression and Bcr-Abl cleavage mediated by proteasome inhibition-induced caspase activation; (iii) proteasome inhibition but not ROS is required for AF-induced caspase activation and apoptosis. These findings support that AF overcomes IM resistance through both Bcr/Abl-dependent and -independent mechanisms, providing great clinical significance for cancer treatment.

Basic Biomedical Sciences, Vermillion Campus.

Gauliard, E., Ouellette, Scot P., Rueden, Kelsey J., & Ladant, D. (2015). Characterization of interactions between inclusion membrane proteins from Chlamydia trachomatis. Frontiers in Cellular and Infection Microbiology, 5.

Chlamydiae are obligate intracellular pathogens of eukaryotes. The bacteria grow in an intracellular vesicle called an inclusion, the membrane of which is heavily modified by chlamydial proteins called lncs (Inclusion membrane proteins). lncs represent 7-10% of the genomes of Chlamydia and, given their localization at the interface between the host and the pathogen, likely play a key role in the development and pathogenesis of the bacterium. However, their functions remain largely unknown. Here, we characterized the interaction properties between various Inc proteins of C. trachomatis, using a bacterial two-hybrid (BACTH) method suitable for detecting interactions between integral membrane proteins. To validate this approach, we first examined the oligomerization properties of the well-characterized IncA protein and showed that both the cytoplasmic domain and the transmembrane region independently contribute to IncA oligomerization. We then analyzed a set of Inc proteins and identified novel interactions between these components. Two small lncs, IncF, and Ct222, were found here to interact with many other Inc proteins and may thus represent interaction nodes within the inclusion membrane. Our data suggest that the Inc proteins may assemble in the membrane of the inclusion to form specific multi-molecular complexes in an hierarchical and temporal manner. These studies will help to better define the putative functions of the Inc proteins in the infectious process of Chlamydia.

Basic Biomedical Sciences, Vermillion Campus.

Killian, J. K., Miettinen, M., Walker, R. L., …., Killian, M. Scott, Lau, C. C., Pineda, M., Walling, J., Stevenson, H., Smith, C., Wang, Z. F., Lasota, J., Kim, S. Y., Boikos, S. A., Helman, L. J., & Meltzer, P. S. (2014). Recurrent epimutation of SDHC in gastrointestinal stromal tumors. Science Translational Medicine, 6(268).

Succinate dehydrogenase (SDH) is a conserved effector of cellular metabolism and energy production, and loss of SDH function is a driver mechanism in several cancers. SDH-deficient gastrointestinal stromal tumors (dSDH GISTs) collectively manifest similar phenotypes, including hypermethylated epigenomic signatures, tendency to occur in pediatric patients, and lack of KIT/PDGFRA mutations. dSDH GISTs often harbor deleterious mutations in SDH subunit genes (SDHA, SDHB, SDHC, and SDHD, termed SDHx), but some are SDHx wild type (WT). To further elucidate mechanisms of SDH deactivation in SDHx-WT GIST, we performed targeted exome sequencing on 59 dSDH GISTs to identify 43 SDHx-mutant and 16 SDHx-WT cases. Genome-wide DNA methylation and expression profiling exposed SDHC promoter-specific CpG island hypermethylation and gene silencing in SDHx-WT dSDH GISTs [ 15 of 16 cases (94%)]. Six of 15 SDHC-epimutant GISTs occurred in the setting of the multitumor syndrome Carney triad. We observed neither SDHB promoter hypermethylation nor large deletions on chromosome 1q in any SDHx-WT cases. Deep genome sequencing of a 130-kbp (kilo-base pair) window around SDHC revealed no recognizable sequence anomalies in SDHC-epimutant tumors. More than 2000 benign and tumor reference tissues, including stem cells and malignancies with a hypermethylator epigenotype, exhibit solely a non-epimutant SDHC promoter. Mosaic constitutional SDHC promoter hypermethylation in blood and saliva from patients with SDHC-epimutant GIST implicates a postzygotic mechanism in the establishment and maintenance of SDHC epimutation. The discovery of SDHC epimutation provides a unifying explanation for the pathogenesis of dSDH GIST, whereby loss of SDH function stems from either SDHx mutation or SDHC epimutation.

Basic Biomedical Sciences, Vermillion Campus.

Li, Hao, Scholl, Jamie L., Tu, Wenyu, Hassell, James E., Watt, Michael J., Forster, Gina L., & Renner, Kenneth J. (2014). Serotonergic responses to stress are enhanced in the central amygdala and inhibited in the ventral hippocampus during amphetamine withdrawal. European Journal of Neuroscience, 40(11), 3684-3692.

Withdrawal from amphetamine increases anxiety and reduces the ability to cope with stress, which are factors that are believed to contribute to drug relapse. Stress-induced serotonergic transmission in the central nucleus of the amygdala is associated with anxiety states and fear. Conversely, stress-induced increases in ventral hippocampal serotonin (5-HT) levels have been linked to coping mechanisms. The goal of this study was to investigate the neurobiological changes induced by amphetamine that contribute to stress sensitivity during withdrawal. We tested the hypothesis that limbic serotonergic responses to restraint stress would be altered in male Sprague-Dawley rats chronically pretreated with amphetamine (2.5mg/kg, intraperitoneal) and then subjected to 2weeks of withdrawal. Amphetamine withdrawal resulted in increased stress-induced behavioral arousal relative to control treatment, suggesting that drug withdrawal induced greater sensitivity to the stressor. When microdialysis was used to determine the effects of restraint on extracellular 5-HT, stress-induced increases in 5-HT levels were abolished in the ventral hippocampus and augmented in the central amygdala during amphetamine withdrawal. Reverse dialysis of the glucocorticoid receptor antagonist mifepristone into the ventral hippocampus blocked the stress-induced increase in 5-HT levels in saline-pretreated rats, suggesting that glucocorticoid receptors mediate stress-induced increases in 5-HT levels in the ventral hippocampus. However, mifepristone had no effect on stress-induced increases in 5-HT levels in the central amygdala, indicating that stress increases 5-HT levels in this region independently of glucocorticoid receptors. During amphetamine withdrawal, the absence of stress-induced increases in ventral hippocampal 5-HT levels combined with enhanced stress-induced serotonergic responses in the central amygdala may contribute to drug relapse by decreasing stress-coping ability and heightening stress responsiveness.

Basic Biomedical Sciences, Vermillion Campus.

Liu, N. N., Li, X. F., Huang, H. B., …., Wang, Xuejun, & Liu, J. B. (2014). Clinically used antirheumatic agent auranofin is a proteasomal deubiquitinase inhibitor and inhibits tumor growth. Oncotarget, 5(14), 5453-5471.

Proteasomes are attractive emerging targets for anti-cancer therapies. Auranofin (Aur), a gold-containing compound clinically used to treat rheumatic arthritis, was recently approved by US Food and Drug Administration for Phase II clinical trial to treat cancer but its anti-cancer mechanism is poorly understood. Here we report that (i) Aur shows proteasome-inhibitory effect that is comparable to that of bortezomib/Velcade (Vel); (ii) different from bortezomib, Aur inhibits proteasome-associated deubiquitinases (DUBs) UCHL5 and USP14 rather than the 20S proteasome; (iii) inhibition of the proteasome-associated DUBs is required for Aur-induced cytotoxicity; and (iv) Aur selectively inhibits tumor growth in vivo and induces cytotoxicity in cancer cells from acute myeloid leukemia patients. This study provides important novel insight into understanding the proteasome-inhibiting property of metal-containing compounds. Although several DUB inhibitors were reported, this study uncovers the first drug already used in clinic that can inhibit proteasome-associated DUBs with promising anti-tumor effects.

Basic Biomedical Sciences, Vermillion Campus.

Butler, Stephen A., & Ghosh, D. (2015). Individual differences in managerial accounting judgments and decision making. British Accounting Review, 47(1), 33-45.

Managers are influenced in their decisions by the information provided by managerial accountants. Two typical examples from textbooks are the irrelevance of sunk costs and, more recently, the affect of knowing the outcome of a decision or revised budget forecast. Individual differences in the cognitive ability of decision makers to use information can lead to systematic differences in judgments. We identify and label one of these individual cognitive differences comprehensive thinking ability: the ability to think about multiple paths, branches or alternatives. Significant comprehensive thinking ability is likely to mitigate systematic differences in judgment in many contexts. We report the results of a series of studies using a variation on the investment trap (sunk cost or irrelevant cost) problem and a probability revision task. The findings suggest that comprehensive thinking ability may also explain other common systematic differences in judgment. (C) 2014 Elsevier Ltd. All rights reserved.

Beacom School of Business.

Balhoff, J. P., Dahdul, Wasila M., Dececchi, T. Alexander, Lapp, H., Mabee, Paula M., & Vision, T. J. (2014). Annotation of phenotypic diversity: decoupling data curation and ontology curation using Phenex. Journal of Biomedical Semantics, 5.

Background: Phenex (http://phenex.phenoscape.org/) is a desktop application for semantically annotating the phenotypic character matrix datasets common in evolutionary biology. Since its initial publication, we have added new features that address several major bottlenecks in the efficiency of the phenotype curation process: allowing curators during the data curation phase to provisionally request terms that are not yet available from a relevant ontology; supporting quality control against annotation guidelines to reduce later manual review and revision; and enabling the sharing of files for collaboration among curators. Results: We decoupled data annotation from ontology development by creating an Ontology Request Broker (ORB) within Phenex. Curators can use the ORB to request a provisional term for use in data annotation; the provisional term can be automatically replaced with a permanent identifier once the term is added to an ontology. We added a set of annotation consistency checks to prevent common curation errors, reducing the need for later correction. We facilitated collaborative editing by improving the reliability of Phenex when used with online folder sharing services, via file change monitoring and continual autosave. Conclusions: With the addition of these new features, and in particular the Ontology Request Broker, Phenex users have been able to focus more effectively on data annotation. Phenoscape curators using Phenex have reported a smoother annotation workflow, with much reduced interruptions from ontology maintenance and file management issues.

Biology Department.

Bubak, A. N., Grace, J. L., Watt, Michael J., Renner, Kenneth J., & Swallow, J. G. (2014). Neurochemistry as a bridge between morphology and behavior: Perspectives on aggression in insects. Current Zoology, 60(6), 778-790.

Aggression is a common behavioral trait shared in many animals, including both vertebrates and invertebrates. However, the type and intensity of agonistic encounters and displays can vary widely both across and within species, resulting in complicated or subjective interpretations that create difficulties in developing theoretical models that can be widely applied. The need to easily and objectively identify quantifiable behaviors and their associated morphologies becomes especially important when attempting to decipher the neurological mechanisms underlying this complex behavior. Monoamines, neuropeptides, and pheromones have been implicated as important neuromodulators for agonistic displays in both invertebrates and vertebrates. Additionally, recent breakthroughs in insect research have revealed exciting proximate mechanisms important in aggression that may be broadly relevant, due to the relatively high conservation of these neurochemical systems across animal taxa. In this review, we present the latest research demonstrating the importance of monoamines, neuropeptides, and pheromones as neuromodulators for aggression across a variety of insect species. Additionally, we describe the stalk-eyed fly as a model system for studying aggression, which integrates physiological, morphological, and neurochemical approaches in exploring detailed mechanisms responsible for this common yet complex behavior. We conclude with our perspective on the most promising lines of future research aimed at understanding the proximate and ultimate mechanisms underlying aggressive behaviors.

Biology Department.

Davis, Drew R., & Gabor, Caitlin R. (2015). Behavioral and physiological antipredator responses of the San Marcos salamander, Eurycea nana. Physiology & Behavior, 139, 145-149.

Exposure to predatory stimuli typically results in the elevation of circulating glucocorticoid levels and a behavioral response of freezing or escape behavior in many prey species. Corticosterone (CORT) is the main glucocorticoid in amphibians and is known to be important in modulating many behaviors and developmental functions. The federally threatened San Marcos salamander, Eurycea nana, decreases activity in response to both native and introduced predatory fish, however, experience may further influence these interactions. To better understand the indirect effects of fish predators on this salamander, we examined both the antipredator behavior and water-borne CORT release rates in response to chemical cues (kairomones) from two fish species that varied in temporal risk of predation: (1) a low encounter frequency predator (largemouth bass, Micropterus salmoides), (2) a high encounter frequency predator (redbreast sunfish, Lepomis auritus), and (3) a blank water control. Salamanders reduced activity (antipredator response) after exposure to both predator treatments, but not to the blank water control, and the response to M. salmoides was significantly stronger than that to L. auritus. The CORT response (post-stimulus/pre-stimulus release rates) did not differ between the blank water control and L. auritus treatments, and both were significantly less than the CORT response to M. salmoides. Overall, E. nana showed a decreased antipredator response and no CORT response towards the high encounter frequency L. auritus as compared to the low encounter frequency M. salmoides. Eurycea nana may mute antipredator and CORT responses to high temporal frequency predators. There was, however, no correlation between CORT release rates and antipredator behavior, which suggests that the presence of predators may be affecting CORT response and behavior independently. (c) 2014 Elsevier Inc. All rights reserved.

Biology Department.

Jarchow, Meghann E., Liebman, M., Dhungel, S., Dietzel, R., Sundberg, D., Anex, R. P., Thompson, M. L., & Chua, T. (2015). Trade-offs among agronomic, energetic, and environmental performance characteristics of corn and prairie bioenergy cropping systems. Global Change Biology Bioenergy, 7(1), 57-71.

Cellulosic bioenergy production provides opportunities to utilize a range of cropping systems that can enhance the multifunctionality of agricultural landscapes. In a 9-ha field experiment located on fertile land in Boone County, IA, USA, we directly compared a corn-soybean rotation harvested for grain, continuous corn harvested for grain and stover, continuous corn harvested for grain and stover with a rye cover crop, newly reconstructed prairie harvested for biomass and fertilized with nitrogen, and unfertilized newly reconstructed prairie harvested for biomass. Comparisons were made using four performance indicators: harvestable yield, net energy balance (NEB), root production, and nutrient balances. We found trade-offs among systems in terms of the measured performance indicators. Continuous corn systems were the highest yielding, averaging 13Mgha(-1) of harvested biomass (grain plus stover), whereas fertilized and unfertilized prairies produced the least harvested biomass at 8.8 and 6.5Mgha(-1), respectively. Mean NEBs were highest in continuous corn systems at 45.1GJha(-1), intermediate in the corn-soybean rotation at 28.6GJha(-1), and lowest in fertilized and unfertilized prairies at 11.4 and 10.5GJha(-1), respectively. Concomitant with the high yields of the continuous corn systems were the large nutrient requirements of these systems compared to the prairie systems. Continuous corn with rye required three times more nitrogen inputs than fertilized prairie. Root production, on the other hand, was on average seven times greater in the prairie systems than the annual crop systems. On highly fertile soils, corn-based cropping systems are likely to play an important role in maintaining the high productivity of agricultural landscapes, but alternative cropping systems, such as prairies used for bioenergy production, can produce substantial yield, require minimal externally derived inputs, and can be incorporated into the landscape at strategic locations to maximize the production of other ecosystem services.

Biology Department.

Nguyen, H. T., Park, H., Koster, Karen L., Cahoon, R. E., Nguyen, H. T. M., Shanklin, J., Clemente, T. E., & Cahoon, E. B. (2015). Redirection of metabolic flux for high levels of omega-7 monounsaturated fatty acid accumulation in camelina seeds. Plant Biotechnology Journal, 13(1), 38-50.

Seed oils enriched in omega-7 monounsaturated fatty acids, including palmitoleic acid (16:19) and cis-vaccenic acid (18:111), have nutraceutical and industrial value for polyethylene production and biofuels. Existing oilseed crops accumulate only small amounts (<2%) of these novel fatty acids in their seed oils. We demonstrate a strategy for enhanced production of omega-7 monounsaturated fatty acids in camelina (Camelina sativa) and soybean (Glycine max) that is dependent on redirection of metabolic flux from the typical 9 desaturation of stearoyl (18:0)-acyl carrier protein (ACP) to 9 desaturation of palmitoyl (16:0)-acyl carrier protein (ACP) and coenzyme A (CoA). This was achieved by seed-specific co-expression of a mutant 9-acyl-ACP and an acyl-CoA desaturase with high specificity for 16:0-ACP and CoA substrates, respectively. This strategy was most effective in camelina where seed oils with similar to 17% omega-7 monounsaturated fatty acids were obtained. Further increases in omega-7 fatty acid accumulation to 60-65% of the total fatty acids in camelina seeds were achieved by inclusion of seed-specific suppression of 3-keto-acyl-ACP synthase II and the FatB 16:0-ACP thioesterase genes to increase substrate pool sizes of 16:0-ACP for the 9-acyl-ACP desaturase and by blocking C18 fatty acid elongation. Seeds from these lines also had total saturated fatty acids reduced to similar to 5% of the seed oil versus similar to 12% in seeds of nontransformed plants. Consistent with accumulation of triacylglycerol species with shorter fatty acid chain lengths and increased monounsaturation, seed oils from engineered lines had marked shifts in thermotropic properties that may be of value for biofuel applications.

Biology Department.

Han, Yulun, Micha, D. A., & Kilin, Dmitri S. (2015). Ab initio study of the photocurrent at the Au/Si metal-semiconductor nanointerface. Molecular Physics, 113(3-4), 327-335.

Photo-induced charge transfer at the interface of two materials is a fundamental process in photovoltaic applications. In this study, we have considered a model of a simplified photovoltaic cell composed of a Si nanocrystal co-doped with Al and P, interfacing with Au electrodes. The photo-induced time-dependent electric currents were computed from a combination of ab initio electronic structure and time-dependent density matrix methodology, and using the continuity equation for electronic currents. A dissipative equation of motion for the reduced density matrix for electronic degrees of freedom is used to study the phonon-induced relaxation of hot electrons in the simulated system. Equations are solved in a basis set of orbitals generated ab initio from a density functional. Non-adiabatic couplings between electronic orbitals are computed on-the-fly along nuclear trajectories. Charge carrier dynamics induced by selected photoexcitations show that hole relaxation in energy and in space is much faster than electron relaxation. The overall net charge transfer across the slab is small; however, local currents at the Si/Au interfaces are substantial. It is also shown that the relaxation of the induced current can be used to parameterise the dynamical conductivity by means of a fluctuation-dissipation relation.

Chemistry Department.

Ho, W. K., Zhang, Z. Z., Lin, W., Huang, Shuping, Zhang, X. W., Wang, X. X., & Huang, Y. (2015). Copolymerization with 2,4,6-Triaminopyrimidine for the Rolling-up the Layer Structure, Tunable Electronic Properties, and Photocatalysis of g-C3N4. Acs Applied Materials & Interfaces, 7(9), 5497-5505.

Copolymerization with 2,4,6-triaminopyrimidine (TAP) is developed for precise substitution of one nitrogen with carbon atom in the triazine ring of polymeric g-C3N4. Direct incorporation of C4N2 ring from TAP into the network retains the structural features of g-C3N4, but induces the rolling-up of g-C3N4 sheets into tubular configuration. The band gap energy is narrowed from 2.7 to 2.4 eV by a negative shift of valence band of the g-C3N4 photocatalyst, which enhances charge-carrier migration and separation, leading to higher photocatalytic activity for NO gas pollutant removal. It is attributed to the decrease of the pi-deficiency and the generation of imbalanced electron density in pi-electron conjugated units of g-C3N4 by TAP incorporation. This work provides a significant technique for precise control of heteroatom in the framework of g-C3N4 to finely adjust its intrinsic electronic properties and its photocatalytic properties.

Chemistry Department.

Clark, Prentiss. (2014). Pulse for Pulse in Harmony with the Universal Whole: Hearing “Self-Reliance” Anew. Nineteenth-Century Literature, 69(3), 319-341.

This essay recounts how Ralph Waldo Emerson, the nineteenth-century thinker perhaps most associated with individualism, is equally, and perhaps necessarily, a student of the intimacies in which we exist. More specifically, the essay contests the explanatory power criticism generally attributes to what Emerson called “self-reliance” by delineating how “self-reliance” (the idea and the 1841 essay by this name) participates in Emerson’s broad work of investigating what he termed “man’s true position in the universe” and its implications for one’s conduct of life. In this reading, which draws from Emerson’s neglected as well as canonical essays, lectures, and sermons, “the infinitude of the private man”-the “one doctrine” Emerson says he teaches in all his lectures-has less to do with the singular human self as such than with our standing ever amid innumerable and consequential relations and accountable for all it entails. Ultimately, this essay hopes to demonstrate how Emerson speaks, from the first, to the ethical potential of rediscovering our connections-connections to ourselves, fellow persons, nature, and beyond (even when at the distances to which our differences can put us).

English Department.

De, Pradip, Carlson, J., Leyland-Jones, Brian, & Dey, Nawdini. (2014). Oncogenic nexus of cancerous inhibitor of protein phosphatase 2A (CIP2A): an oncoprotein with many hands. Oncotarget, 5(13), 4581-4602.

Oncoprotein CIP2A a Cancerous Inhibitor of PP2A forms an “oncogenic nexus” by virtue of its control on PP2A and MYC stabilization in cancer cells. The expression and prognostic function of CIP2A in different solid tumors including colorectal carcinoma, head & neck cancers, gastric cancers, lung carcinoma, cholangiocarcinoma, esophageal cancers, pancreatic carcinoma, brain cancers, breast carcinoma, bladder cancers, ovarian carcinoma, renal cell carcinomas, tongue cancers, cervical carcinoma, prostate cancers, and oral carcinoma as well as a number of hematological malignancies are just beginning to emerge. Herein, we reviewed the recent progress in our understanding of (1) how an ” oncogenic nexus” of CIP2A participates in the tumorigenic transformation of cells and (2) how we can prospect/view the clinical relevance of CIP2A in the context of cancer therapy. The review will try to understand the role of CIP2A (a) as a biomarker in cancers and evaluate the prognostic value of CIP2A in different cancers (b) as a therapeutic target in cancers and (c) in drug response and developing chemo-resistance in cancers.

ISI Document Delivery No.: AZ0EG

Times Cited: 2

Cited Reference Count: 127

De, Pradip Carlson, Jennifer Leyland-Jones, Brian Dey, Nandini

Impact journals llc

Albany

Hanlon, S. M., Lynch, K. J., Kerby, Jacob, & Parris, M. J. (2015). Batrachochytrium dendrobatidis exposure effects on foraging efficiencies and body size in anuran tadpoles. Diseases of Aquatic Organisms, 112(3), 237-242.

Chytridiomycosis, the amphibian disease caused by the pathogenic fungus Batrachochytrium dendrobatidis (Bd), is fatal to adults of many species. Bd is largely sublethal to amphibian larvae; however, it is known to reduce larval (i.e. tadpole) growth rates, with possible long-term effects on population dynamics and fitness. We conducted an experiment to test how Bd altered southern leopard frog Lithobates sphenocephalus tadpole mouthpart damage, percentage of food ingested, and subsequent body size. We examined our results using path analyses. We hypothesized that Bd would increase mouthpart damage, causing less food to be ingested, and ultimately reduce body size. In our model, both Bd exposure and increased mouthpart damage significantly reduced food ingested and subsequent body size. However, our study provides evidence against the long-standing hypothesis of mouthpart damage as a pathway for Bd-induced reductions in larval group. Here we provide evidence for reduced foraging efficiency (percentage of food ingested) as a mechanism for Bd-induced reductions in body size. This work highlights the importance of studying the sublethal effects of Bd on larval amphibians.

ISI Document Delivery No.: AZ2EZ

Times Cited: 0

Cited Reference Count: 31

Hanlon, Shane M. Lynch, Kyle J. Kerby, Jake Parris, Matthew J.

Inter-research

Oldendorf luhe

Balakrishnan, N., Jiang, Nan, Tsai, T. R., Lio, Y. L., & Chen, D. G. (2015). Reliability Inference on Composite Dynamic Systems Based on Burr Type-XII Distribution. IEEE Transactions on Reliability, 64(1), 144-153.

Failure of a component in a composite dynamic system often induces a higher load on surviving components, and increases the hazard rate. Statistical inferential procedures on composite dynamic systems are developed here based on a Burr type-XII distribution with a power-trend hazard rate function. Point estimates of the Burr type-XII parameters, and interval estimates of the baseline survival function are obtained based on the maximum-likelihood estimates, and the Fisher information matrix. A test procedure is presented for examining the relationship between the hazard rate function and the number of failed components. The performance of the proposed method is then evaluated by means of an extensive Monte Carlo simulation study. An example is finally presented for illustrative purpose.

Mathematics Department.

Hecock, R. D., & Jepsen, Eric M. (2014). The Political Economy of FDI in Latin America 1986-2006: A Sector-Specific Approach. Studies in Comparative International Development, 49(4), 426-447.

This study examines the political determinants of foreign direct investment (FDI) across 15 Latin American countries from 1986 to 2006. In contrast to existing scholarship, we focus on the causes of investment by economic sector-primary resources, manufacturing, and services. Additionally, a regional focus on Latin America helps to control for omitted variables by comparing relatively similar countries. We find substantial variation in the causes and characteristics of FDI across sector. Specifically, manufacturing investment is volatile and attracted to less democratic regimes. In contrast, investment in primary resources privileges greater democracy and property rights protection, while FDI in services is associated with public fiscal responsibility. These results yield important theoretical and practical implications for scholars and policymakers throughout the region.

Political Science Department.

Brennan, M. L., Adam, M. P., Seaver, L. H., Myers, Angela, Schelley, S., Zadeh, N., Hudgins, L., & Bernstein, J. A. (2015). Increased Body Mass in Infancy and Early Toddlerhood in Angelman Syndrome Patients with Uniparental Disomy and Imprinting Center Defects. American Journal of Medical Genetics Part A, 167A(1), 142-146.

The diagnosis of Angelman syndrome (AS) is based on clinical features and genetic testing. Developmental delay, severe speech impairment, ataxia, atypical behavior and microcephaly by two years of age are typical. Feeding difficulties in young infants and obesity in late childhood can also be seen. The NIH Angelman-Rett-Prader-Willi Consortium and others have documented genotype-phenotype associations including an increased body mass index in children with uniparental disomy (UPD) or imprinting center (IC) defects. We recently encountered four cases of infantile obesity in non-deletion AS cases, and therefore examined body mass measures in a cohort of non-deletion AS cases. We report on 16 infants and toddlers (ages 6 to 44 months; 6 female, and 10 male) with severe developmental delay. Birth weights were appropriate for gestational age in most cases, >97th% in one case and not available in four cases. The molecular subclass case distribution consisted of: UPD (n = 2), IC defect (n = 3), UPD or IC defect (n = 3), and UBE3A mutation (n = 8). Almost all (7 out of 8) UPD, IC and UPD/IC cases went on to exhibit >90th% age-and gender-appropriate weight for height or BMI within the first 44 months. In contrast, no UBE3A mutation cases exhibited obesity or pre-obesity measures (percentiles ranged from <3% to 55%). These findings demonstrate that increased body mass may be evident as early as the first year of life and highlight the utility of considering the diagnosis of AS in the obese infant or toddler with developmental delay, especially when severe. Although a mechanism explaining the association of UPD, and IC defects with obesity has not been identified, recognition of this correlation may inform investigation of imprinting at the PWS/AS locus and obesity. (C) 2014 Wiley Periodicals, Inc.

Sanford School of Medicine, Sioux Falls Campus.

Dorman, Jason C., Valentine, Verle D., Munce, Thayne A., Tjarks, B. Joel, Thompson, Paul A., & Bergeron, Michael F. (2015). Tracking postural stability of young concussion patients using dual-task interference. Journal of Science and Medicine in Sport, 18(1), 2-7.

Objectives: This study examined the diagnostic benefit of using dual-task interference balance testing in young concussion patients and the longitudinal changes in postural stability that occur relative to other standard clinical assessments of concussion injury. Design: Longitudinal, case-control. Methods: Eighteen patients (16.6 (1.6)y) diagnosed with a concussion provided 22 separate ratings to characterize the severity of their current concussion-related symptoms and were evaluated for postural stability at each of four clinical visits. Twenty-six injury-free adolescents (17 (2.8) y) performed balance testing on two occasions, separated by 1 week. Results: There was a progressive decrease in self-reported symptoms from visit 1 to visit 4 (P<0.0001-0.001). A similar improvement occurred in postural stability, indicated by 95% ellipse area and velocity. However, the differences in ellipse area and velocity were significant only between visit 1 and the rest of the visits as a whole (P<0.0001-0.05). There was a significant difference between concussion patients and healthy, injury-free participants in ellipse area and velocity during visit 1. A group difference was also observed in ellipse area on visit 2, but only during the two balance tests that involved a concomitant secondary cognitive task. Conclusions: Improvements in postural stability coincide with reductions in reported symptoms, though apparent recovery of these selected measures of postural stability seemingly occurs sooner. Because of the distinguishing time course of recovery indicated by dual-task interference balance testing, this type of balance testing assessment may be particularly valuable in evaluating integrated functional impairment and recovery in young concussion patients. (C) 2013 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Sanford School of Medicine, Sioux Falls Campus.

Guo, Q. S., Wang, Y. Q., Tripathi, P., Manda, K. R., Mukherjee, Malay, Chaklader, M., Austin, P. F., Surendran, Kameswaran, & Chen, F. (2015). Adam10 Mediates the Choice between Principal Cells and Intercalated Cells in the Kidney. Journal of the American Society of Nephrology, 26(1), 149-159.

A disintegrin and metalloproteinase domain 10 (Adam10), a member of the ADAM family of cell membrane-anchored proteins, has been linked to the regulation of the Notch, EGF, E-cadherin, and other signaling pathways. However, it is unclear what role Adam10 has in the kidney in vivo. In this study, we showed that Adam10 deficiency in ureteric bud (UB) derivatives leads to a decrease in urinary concentrating ability, polyuria, and hydronephrosis in mice. Furthermore, Adam10 deficiency led to a reduction in the percentage of aquaporin 2 (Aqp2)(+) principal cells (PCs) in the collecting ducts that was accompanied by a proportional increase in the percentage of intercalated cells (ICs). This increase was more prominent in type A ICs than in type B ICs. Foxi1, a transcription factor important for the differentiation of ICs, was upregulated in the Adam10 mutants. The observed reduction of Notch activity in Adam10 mutant collecting duct epithelium and the similar reduction of PC/IC ratios in the collecting ducts in mice deficient for mindbomb E3 ubiquitin protein ligase 1, a key regulator of the Notch and Wnt/receptor-like tyrosine kinase signaling pathways, suggest that Adam10 regulates cell fate determination through the activation of Notch signaling, probably through the regulation of Foxi1 expression. However, phenotypic differences between the Adam10 mutants, the Mib1 mutants, and the Foxi1 mutants suggest that the functions of Adam10 in determining the fate of collecting duct cells are more complex than those of a simple upstream factor in a linear pathway involving Notch and Foxi1.

Sanford School of Medicine, Sioux Falls Campus.

Jung, Y. S., Vermeer, Paola D., Vermeer, Daniel W., Lee, S. J., Goh, A. R., Ahn, H. J., & Lee, John H. (2015). CD200: Association with cancer stem cell features and response to chemoradiation in head and neck squamous cell carcinoma. Head and Neck-Journal for the Sciences and Specialties of the Head and Neck, 37(3), 327-335.

BackgroundThe purpose of this study was to characterize the expression of CD200, a membrane protein that functions in immune evasion, to examine its correlations with cancer stem cell (CSC)-like features and analyze its response to chemotherapy and radiation in human papillomavirus (HPV)-positive (+) and negative (-) head and neck squamous cell carcinomas (HNSCCs). MethodsCD200 expression was analyzed in several HNSCC cell lines. CD200 was overexpressed in HPV(+) murine tonsil epithelial cells, its effects on Shh and Bmi-1 were examined in vitro, and tumor growth and response to chemoradiation were analyzed in vitro and in vivo. ResultsCD200 was diversely expressed and consistently associated with expression of Bmi-1 and Shh. Overexpression of CD200 induced Bmi-1 and Shh. Tumors grew similarly between C57BL/6 and Rag1(-/-) C57BL/6 mice. CD200 expression enhanced the resistance to chemoradiation only in vivo. ConclusionCD200 was related to CSC features and modulates response to chemoradiation in vivo. Attenuating this might be a potential therapeutic strategy. (c) 2014 Wiley Periodicals, Inc. Head Neck, 37: 327-335, 2015

Sanford School of Medicine, Sioux Falls Campus.

Kaess, B. M., Harris, William S., Lacey, S., Larson, M. G., Hamburg, N. M., Vita, J. A., Robins, S. J., Benjamin, E. J., Mitchell, G. F., & Vasan, R. S. (2015). The relation of red blood cell fatty acids with vascular stiffness, cardiac structure and left ventricular function: The Framingham Heart Study. Vascular Medicine, 20(1), 5-13.

Polyunsaturated fatty acids have been associated with beneficial influences on cardiovascular health. However, the underlying mechanisms are not clear, and data on the relations of polyunsaturated fatty acids to subclinical disease measures such as vascular stiffness and cardiac function are sparse and inconclusive. In a large community-based cohort, we examined the relations of omega-3 and other fatty acids to a comprehensive panel of vascular function measures (assessing microvascular function and large artery stiffness), cardiac structure and left ventricular function. Red blood cell (RBC) membrane fatty acid composition, a measure of long-term fatty acid intake, was assessed in participants of the Framingham Offspring Study and Omni cohorts and related to tonometry-derived measures of vascular stiffness and to a panel of echocardiographic traits using partial correlations. Up to n=3055 individuals (56% women, mean age 66 years) were available for analyses. In age- and sex-adjusted models, higher RBC omega-3 content was moderately associated (p0.002) with several measures of vascular stiffness and function in a protective direction. However, after multivariable adjustment, only an association of higher RBC omega-3 content with lower carotid-femoral pulse wave velocity (a measure of aortic stiffness) remained significant (r = -0.06, p=0.002). In secondary analyses, higher linoleic acid, the major nutritional omega-6 fatty acid, was associated with smaller left atrial size, even after multivariable adjustment (r = -0.064, p<0.001). In conclusion, in our cross-sectional community-based study, we found several associations consistent with the notion of protective effects of omega-3 and linoleic acid. The clinical significance of these modest associations remains to be elucidated.

Sanford School of Medicine, Sioux Falls Campus.

Khan, S., Ebeling, Mara C., Zaman, M. S., Sikander, M., …., Thompson, Paul A., Jaggi, M., & Chauhan, S. C. (2014). MicroRNA-145 targets MUC13 and suppresses growth and invasion of pancreatic cancer. Oncotarget, 5(17), 7599-7609.

Pancreatic cancer has a poor prognosis due to late diagnosis and ineffective therapeutic multimodality. MUC13, a transmembrane mucin is highly involved in pancreatic cancer progression. Thus, understanding its regulatory molecular mechanisms may offer new avenue of therapy for prevention/treatment of pancreatic cancer. Herein, we report a novel microRNA (miR-145)-mediated mechanism regulating aberrant MUC13 expression in pancreatic cancer. We report that miR-145 expression inversely correlates with MUC13 expression in pancreatic cancer cells and human tumor tissues. miR-145 is predominantly present in normal pancreatic tissues and early Pancreatic Ductal Adenocarcinoma (PDAC) precursor lesions (PanIN I) and is progressively suppressed over the course of development from PanIN II/III to late stage poorly differentiated PDAC. We demonstrate that miR-145 targets 3′ untranslated region of MUC13 and thus downregulates MUC13 protein expression in cells. Interestingly, transfection of miR-145 inhibits cell proliferation, invasion and enhances gemcitabine sensitivity. It causes reduction of HER2, P-AKT, PAK1 and an increase in p53. Similar results were found when MUC13 was specifically inhibited by shRNA directed at MUC13. Additionally, intratumoral injections of miR-145 in xenograft mice inhibited tumor growth via suppression of MUC13 and its downstream target, HER2. These results suggest miR-145 as a novel regulator of MUC13 in pancreatic cancer.

Sanford School of Medicine, Sioux Falls Campus.

Kuppast, B., Spyridaki, K., Lynch, C., Hu, Yuehan, Liapakis, G., Davies, Gareth E., & Fahmy, H. (2015). Synthesis of New Thiazolo 4,5-d pyrimidines as Corticotropin Releasing Factor Modulators. Medicinal Chemistry, 11(1), 50-59.

Corticotropin-releasing factor (CRF) is a neurohormone that plays a crucial role in integrating the body’s overall response to stress. It appears necessary and sufficient for the organism to mount functional, physiological and endocrine responses to stressors. CRF is released in response to various triggers such as chronic stress. The role of CRF and its involvement in these neurological disorders suggest that new drugs that can target the CRF function or bind to its receptors may represent a new development of neuropsychiatric medicines to treat various stress-related disorders including depression, anxiety and addictive disorders. Based on pharmacophore of the CRF1 receptor antagonists, a new series of thiazolo[4,5-d] pyrimidines were synthesized as Corticotropin-releasing factor (CRF) receptor modulators and the prepared compounds carry groups shown to produce optimum binding affinity to CRF receptors. Twenty two compounds were evaluated for their CRF1 receptor binding affinity in HEK 293 cell lines and two compounds 5o and 5s showed approximately 25% binding affinity to CRF1 receptors. Selected compounds (5c and 5f) were also evaluated for their effect on expression of genes associated with depression and anxiety disorders such as CRF1, CREB1, MAO-A, SERT, NPY, DatSLC6a3, and DBH and significant upregulation of CRF1 mRNA has been observed with compound 5c.

Sanford School of Medicine, Sioux Falls Campus.

Hooper, D. R., Cook, B. M., Comstock, Brent A., Szivak, T. K., Flanagan, S. D., Looney, D. P., DuPont, W. H., & Kraemer, W. J. (2015). SYNTHETIC GARMENTS ENHANCE COMFORT, THERMOREGULATORY RESPONSE, AND ATHLETIC PERFORMANCE COMPARED WITH TRADITIONAL COTTON GARMENTS. Journal of Strength and Conditioning Research, 29(3), 700-707.

The ability of a fabric to transfer moisture is referred to as “wicking,” and an increase in this property may have benefits in terms of comfort and thermoregulation. However, this phenomenon has not been studied in the context of sporting-type activities. Therefore, the purpose of this study is to assess whether comfort, thermal physiological parameters, and physical performance can be affected by the garment that is used. Ten men (age: 27.5 +/- 4.4 years; height: 169.3 +/- 14.2 cm; weight: 80.05 +/- 10.87 kg) and 10 women (age: 26.8 +/- 3.7 years; height: 166.6 +/- 4.46 cm; weight: 64.63 +/- 4.49 kg) volunteered to participate in the study. A within-group crossover counterbalanced design was used that included the Illinois Agility Run (IAR) and the Multistage Fitness Test (MSFT). The IAR was also performed while wearing protective padding. The protocol was completed on 2 occasions, once while wearing a cotton garment (C) and again while wearing a polyester (P) garment. Questionnaires referring to sensations of various components of comfort were completed after each test. The P garment provided significantly (p <= 0.05) greater comfort in men and women after both the IAR and the MSFT. The P garment led to significantly (p <= 0.05) improved performance during the IAR in women. The P garment also provided significantly (p <= 0.05) greater body mass loss during the protocol in women. This study demonstrated dramatic increases in the comfort of P garments, including while using protective equipment. This study also discovered the influence of P garments on anaerobic tasks and also revealed dramatic sex differences, where women seem to be much more sensitive to the benefits of P garments. Strength and conditioning coaches should be aware of the dramatic impact of garment choice, in aerobic and anaerobic tasks, particularly in women.

School of Education.

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