Posted by: reganenosusd | February 4, 2015

January 2015

Davis, Drew R., Kathryn D. Feller, Rafe M. Brown, & Cameron D. Siler. (2014). Evaluating the Diversity of Philippine Slender Skinks of the Brachymeles bonitae Complex (Reptilia: Squamata: Scincidae): Redescription of B. tridactylus and Descriptions of Two New Species. Journal of Herpetology, 48(4), 480-494.

We review the species of the Brachymeles bonitae Complex ( B. bonitae and B. tridactylus) and describe an additional two new species in this highly specialized, limb-reduced, endemic Philippine clade of fossorial lizards. For more than 4 decades, B. bonitae has been recognized as a single ‘widespread’ species, a perception that has persisted as a result of limited sampling and similar overall morphology (body sizes, scale pigmentation) among populations. However, on the basis of new collections we note consistent morphological differences between populations, and our new data build on previous observations, allowing us to utilize newly defined character state differences for the purpose of delimiting unambiguous boundaries between species. Here, we use morphological and molecular data to define species limits in B. bonitae and its close relatives. Our data indicate that the ‘widespread’ species B. bonitae is actually a complex of four distinct evolutionary lineages, several of which are not each others’ closest relatives. The taxa we define possess allopatric geographic ranges (biogeographically supporting our taxonomic conclusions) and differ from their congeners by several diagnostic characters of external morphology. We conclude that each, therefore, should be recognized as full species in accordance with lineage-based species concepts. Species diversity in the genus has doubled in the last 4 yr, with newly described taxa increasing the total number of species of Brachymeles to 38.

Biology Department.

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

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

Biology Department.

Balasanthiran, Choumini, & James D. Hoefelmeyer. (2014). Facile method to attach transition metal ions to the surface of anatase TiO2 nanorods. Chemical Communications, 50(43), 5721-5724.

We report a robust, low-cost method to attach transition metal ions directly to the surface of anatase TiO2 rod-shaped nanocrystals with preservation of the host nanocrystal morphology and phase. The procedure has been optimized to achieve quantitative control of metal ion loading on the surface of the nanorods. The metal ion can be attached to the nanocrystal surface up to full monolayer coverage, after which the surface becomes saturated and there is no further addition.

Chemistry Department.

Feng-Rong, Dai, Dustin C. Becht, & Zhenqiang Wang. (2014). Modulating guest binding in sulfonylcalixarene-based metal-organic supercontainers. Chemical Communications, 50(40), 5385-5387.

Metal-organic supercontainers (MOSCs) represent a new family of synthetic receptors derived from container precursors and featuring both endo and exo cavities. A neutral MOSC has been functionalized into an anionic container by incorporating sulfo groups. The anionic MOSC exhibits cavity-specific binding properties in both solid state and solution.

Chemistry Department.

Summers, Torrie, Sara Holec, & Brian D. Burrell. (2014). Physiological and behavioral evidence of a capsaicin-sensitive TRPV-like channel in the medicinal leech. Journal of Experimental Biology, 217(23), 4167-4173.

Transient receptor potential vanilloid (TRPV) channels are found throughout the animal kingdom, where they play an important role in sensory transduction. In this study, we combined physiological studies with in vivo behavioral experiments to examine the presence of a putative TRPV-like receptor in the medicinal leech, building upon earlier studies in this lophotrochozoan invertebrate. The leech polymodal nociceptive neuron was activated by both peripheral and central application of the TRPV1-activator capsaicin in a concentration-dependent manner, with 100 mu moll(-1) being the lowest effective concentration. Responses to capsaicin were inhibited by the selective TRPV1 antagonist SB366791. The polymodal nociceptive neuron also responded to noxious thermal stimuli (>40 degrees C), and this response was also blocked by SB366791. Capsaicin sensitivity was selective to the polymodal nociceptor with no direct response being elicited in the mechanical nociceptive neuron or in the non-nociceptive touch-or pressure-sensitive neurons. Capsaicin also elicited nocifensive behavioral responses (withdrawals and locomotion) in a concentration-dependent manner, and these behavioral responses were significantly attenuated with SB366791. These results suggest the presence of a capsaicin-sensitive TRPV-like channel in the medicinal leech central nervous system and are relevant to the evolution of nociceptive signaling.

Basic Biomedical Science, Vermillion Campus.

Killian, J. K., M. Miettinen, R. L. Walker, …., M. Scott Killian, C. C. Lau, . . . P. S. Meltzer. (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, Jamie L. Scholl, Wenyu Tu, James E. Hassell, Michael J. Watt, Gina L. Forster, & Kenneth J. Renner. (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.

Wang, Changhua, & Xuejun Wang. (2015). The interplay between autophagy and the ubiquitin–proteasome system in cardiac proteotoxicity. BBA – Molecular Basis of Disease, 1852(2), 188-194.

Proteotoxicity refers to the detrimental effects of damaged/misfolded proteins on the cell. Cardiac muscle is particularly susceptible to proteotoxicity because sustained and severe proteotoxic stress leads to cell death and the cardiac muscle has very limited self-renewal capacity. The ubiquitin–proteasome system (UPS) and the autophagic-lysosomal pathway (ALP) are two major pathways responsible for degradation of most cellular proteins. Alterations of UPS and ALP functions are associated with the accumulation of proteotoxic species in the heart, a key pathological feature of common forms of heart disease including idiopathic, ischemic, and pressure-overloaded cardiomyopathies and a large subset of congestive heart failure. Emerging evidence suggests that proteasome inhibition or impairment activates autophagy and conversely, acute ALP inhibition may sometimes increase intrinsic proteasome peptidase activities but chronic ALP inhibition hinders UPS performance in ubiquitinated protein degradation. The exact molecular basis on which the two degradative pathways interact remains largely undefined. Here we review current understanding of the roles of the UPS and autophagy in the control of cardiac proteotoxicity, with a specific focus on the crosstalk between the two pathways. This article is part of a Special Issue entitled: Autophagy and protein quality control in cardiometabolic diseases.

Basic Biomedical Sciences, Vermillion Campus.

Kerby, Jacob, & Andrew Sih. (2015). Effects of carbaryl on species interactions of the foothill yellow legged frog ( Rana boylii) and the Pacific treefrog ( Pseudacris regilla). Hydrobiologia, 746(1), 255-269.

Amphibian species worldwide are being confronted with novel anthropogenic stressors such as contaminants and invasive species. While much work has been done to examine these factors individually, less is known about how these stressors might interact. No studies to this point have examined the potentially synergistic impacts between these two stressors on a threatened amphibian species. We present the results from three separate laboratory studies focusing on two species of frogs, the Pacific tree frog ( Pseudacris regilla) and a federal species of concern, the foothill yellow legged frog ( Rana boylii). These experiments examine the toxicity of an insecticide, carbaryl, on each species, on their competitive interactions, and on their interaction with a non-native crayfish predator ( Pacifastacus leniusculus). R. boylii were more susceptible to pesticide exposure than P. regilla and exposure reduced their ability to compete. This differential effect of the pesticide resulted in a remarkable increase in mortality (50%) for R. boylii with an invasive crayfish predator present while P. regilla exhibited no change. These results add to concerns over the utility of single species toxicity tests in determining safe levels for environmental exposure and advocate for the use of multiple species tests that focus on key species interactions.

Biology Department.

Nguyen, Huu Tam, Hyunwoo Park, Karen L. Koster, Rebecca E. Cahoon, Hanh T. M. Nguyen, John Shanklin, . . . Edgar 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 (16:1∆9) and cis-vaccenic acid (18:1∆11), 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 ~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 ~5% of the seed oil versus ~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.

Thiruppathi, Eagappanath, Mark K. Larson, & Gopinath Mani. (2015). Surface Modification of CoCr Alloy Using Varying Concentrationsof 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 variouscardiovascular medical devices for its excellent physical and mechanicalproperties. However, the formation of blood clots on the alloy surfacesis a serious concern. This research is focused on the surface modificationof CoCr alloy using varying concentrations (1, 25, 50, 75, and 100mM) of phosphoric acid (PA) and phosphonoacetic acid (PAA) to generatevarious surfaces with different wettability, chemistry, and roughness.Then, the adsorption of blood plasma proteins such as albumin andfibrinogen and the adhesion, activation, and aggregation of plateletswith the various surfaces generated were investigated. Contact angleanalysis showed PA and PAA coatings on CoCr provided a gradient ofhydrophilic surfaces. FTIR showed PA and PAA were covalently boundto CoCr surface and formed different bonding configurations dependingon the concentrations of coating solutions used. AFM showed the formationof homogeneous PA and PAA coatings on CoCr. The single and dual proteinadsorption studies showed that the amount of albumin and fibrinogenadsorbed on the alloy surfaces strongly depend on the type of PA andPAA coatings prepared by different concentrations of coating solutions.All PA coated CoCr showed reduced platelet adhesion and activationwhen compared to control CoCr. Also, 75 and 100 mM PA-CoCr showedreduced platelet aggregation. For PAA coated CoCr, no significantdifference in platelet adhesion and activation was observed betweenPAA coated CoCr and control CoCr. Thus, this study demonstrated thatCoCr can be surface modified using PA for potentially reducing theformation of blood clots and improving the blood compatibility ofthe alloy.

Biomedical Engineering, Sioux Falls Campus.

Rashwan, Khaled, Erik Brakke, & Grigoriy Sereda. (2014). Fluorescent labeling of materials using silica nanoparticles. Nanotechnology Reviews, 3(6), 591-596.

The article is focused on the implementation of fluorescent silica nanoparticles in the laboratory curriculum. Along with a brief overview of experimental procedures appropriate for teaching in the laboratory and scarce examples of utilization of silica nanoparticles in the laboratory instruction, a new mini-laboratory course is described in detail. The series of the developed experiments allow the students to synthesize silica nanoparticles, place organic functionalities on their surface, and explore nanoparticles as labels and building blocks for nanoassemblies. Introduction of students to the art of using the most popular specific interaction in nanomedicine (avidin-biotin), along with synthesis and manipulation of nanoparticles, will help them bridge their existing or future knowledge of organic chemistry, materials science, and nanomedicine. The experiment is beneficial for students’ understanding of the relationship between organic chemistry, materials science, and nanomedicine, regardless of their level of expertise in those fields.

Chemistry Department.

Ladegaard, Hans J., & Christopher J. Jenks. (2015). Language and intercultural communication in the workplace: critical approaches to theory and practice. Language & Intercultural Communication, 15(1), 1-12.

An introduction is presented in which the authors discuss topics within the issue, including intercultural communication (ICC) in the workplace, the professional experiences within multicultural and multilingual workplaces, and language behaviour in Malaysian workplaces.

English Department.

Jastram, A., H. R. Harris, R. Mahapatra, …., Joel Sander, & S. Upadhyayula. (2015). Cryogenic Dark Matter Search detector fabrication process and recent improvements. Nuclear Instruments & Methods in Physics Research Section a-Accelerators Spectrometers Detectors and Associated Equipment, 772, 14-25.

A dedicated facility has been commissioned for Cryogenic Dark Matter Search (CDMS) detector fabrication at Texas A&M University (TAMU) The fabrication process has been carefully tuned using this facility and its equipment. Production of successfully tested detectors has been demonstrated. Significant improvements in detector performance have been made using new fabrication methods/equipment and tuning of process parameters. (C) 2014 Elsevier B.V. All rights reserved.

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.

Dvorak, R. D., & Jeffrey S. Simons. (2014). Daily Associations Between Anxiety and Alcohol Use: Variation by Sustained Attention, Set Shifting, and Gender. Psychology of Addictive Behaviors, 28(4), 969-979.

Many theories of emotion regulation and alcohol use posit that alcohol is consumed as a way to regulate negative mood. However, the literature has conflicting evidence on mood – alcohol use associations. Understanding how individual differences affect mood – alcohol use associations remains an important area of study. Previous research has suggested that cognitive abilities may affect the relationship between mood and alcohol. The current ecological momentary study examined associations between daytime anxious and positive mood and both (a) the likelihood of alcohol use and (b) the intensity of use on drinking nights as a function of sustained attention, set shifting, and gender. Participants (n = 100) completed assessments of sustained attention and set shifting, then carried palmtop computers for 21 days, reporting mood and alcohol use up to 8 times per day. Results showed that positive mood was consistently associated with both likelihood and intensity of alcohol use, but the association between positive mood and alcohol outcomes was not affected by cognitive abilities. Anxious mood was positively associated with the likelihood of drinking for men with high cognitive abilities. Anxious mood was positively associated with intoxication on drinking nights for men with high sustained attention, but inversely associated with intoxication on drinking nights for women with high sustained attention. Results suggest that variation in mood, executive functioning, and gender interact to contribute to observed differences in drinking behavior. These differences may be the result of gender-specific coping strategies in response to negative emotion.

Psychology Department.

Gaher, Raluca M., Austin M. Hahn, Hanako Shishido, Jeffrey S. Simons, & Sam Gaster. (2015). Associations between sensitivity to punishment, sensitivity to reward, and gambling. Addictive Behaviors, 42, 180-184.

The majority of individuals gamble during their lifetime; however only a subset of these individuals develops problematic gambling. Gray’s Reinforcement Sensitivity Theory may be relevant to understanding gambling problems. Differences in sensitivity to punishments and rewards can influence an individual’s behavior and may be pertinent to the development of gambling problems. This study examined the functional associations between sensitivity to punishment (SP), sensitivity to reward (SR), and gambling problems in a sample of 2254 college students. Zero-inflated negative binomial regression was used to predict gambling problems as well as the absence of gambling problems. Gambling problems were hypothesized to be positively associated with SR and inversely associated with SP. In addition, SP was hypothesized to moderate the association between SR and gambling problems, attenuating the strength of the association. As hypothesized, SR was positively associated with gambling problems. However, SP did not moderate the relationship between SR and gambling problems. SP did, however, moderate the relationship between SR and the likelihood of never experiencing gambling problems. The results demonstrate that individual differences in SP and SR are functionally associated with gambling problems. (PsycINFO Database Record (c) 2015 APA, all rights reserved). (journal abstract)

Psychology Department.

Gaher, Raluca M., Jeffrey S. Simons, Austin M. Hahn, Nicole L. Hofman, Jamie Hansen, & J. Buchkoski. (2014). An Experience Sampling Study of PTSD and Alcohol-Related Problems. Psychology of Addictive Behaviors, 28(4), 1013-1025.

Posttraumatic stress disorder (PTSD) represents a debilitating psychiatric condition that is affecting the lives of many returning veterans. PTSD and alcohol use and dependence are highly comorbid. The purpose of this study was to understand the functional mechanisms between PTSD and alcohol use and problems. Specifically, the role of negative urgency and emotional intelligence were investigated as vulnerability and resiliency factors, respectively. This study utilized experience sampling to test associations between PTSD symptoms and alcohol use and related problems in a sample of 90 OIF/OEF veterans. Participants completed 8 brief questionnaires daily for 2 weeks on palmtop computers. Elevations in PTSD symptoms during the day were associated with subsequent increases in alcohol use and associated problems that night. PTSD symptoms were associated with greater problems above and beyond the effect of drinking level at both the within-and between-person level. Emotional intelligence was associated with lower negative urgency, fewer PTSD symptoms, and less alcohol use and associated problems. The effects of emotional intelligence were primarily indirect via negative urgency and the effects of negative urgency on alcohol use and problems were indirect via its positive association with PTSD symptoms. Hypothesized cross-level effects of emotional intelligence and negative urgency were not supported. The findings suggest a functional association between PTSD symptoms and alcohol consumption. The association between PTSD symptoms and alcohol consumption is consistent with a self-medication model. However, the significant associations between PTSD symptoms and alcohol problems, after controlling for use level, suggest a broader role of dysregulation.

Psychology Department.

Messler, Erick C., Noah N. Emery, & Randy P. Quevillon. (2015). Does relationship quality matter? Perceived mutual reciprocity as a moderator between perceived parental approval of drinking and college alcohol use. Journal of Substance Use, 20(1), 44-49.

Alcohol misuse among young adult college students remains a major public health problem in USA. Although much effort has been made to identify factors associated with problem drinking among college students, there is a lack of research investigating the role parents may have on college student drinking. Recent evidence indicates that parents matter when it comes to adolescent drinking, both before and after their children go to college. In this study, the authors examined mutual reciprocity as a moderator variable between perceived parental approval of drinking and negative consequences of alcohol use. Contrary to the hypothesized results, our findings indicate that mutual reciprocity does not moderate the relationship between perceived parental approval and negative alcohol-related consequences.

Psychology Department.

Oliver-Rodríguez, Juan C., & X. T. Wang. (2015). Non-parametric three-way mixed ANOVA with aligned rank tests. British Journal of Mathematical & Statistical Psychology, 68(1), 23-42.

Research problems that require a non-parametric analysis of multifactor designs with repeated measures arise in the behavioural sciences. There is, however, a lack of available procedures in commonly used statistical packages. In the present study, a generalization of the aligned rank test for the two-way interaction is proposed for the analysis of the typical sources of variation in a three-way analysis of variance (ANOVA) with repeated measures. It can be implemented in the usual statistical packages. Its statistical properties are tested by using simulation methods with two sample sizes ( n = 30 and n = 10) and three distributions (normal, exponential and double exponential). Results indicate substantial increases in power for non-normal distributions in comparison with the usual parametric tests. Similar levels of Type I error for both parametric and aligned rank ANOVA were obtained with non-normal distributions and large sample sizes. Degrees-of-freedom adjustments for Type I error control in small samples are proposed. The procedure is applied to a case study with 30 participants per group where it detects gender differences in linguistic abilities in blind children not shown previously by other methods.

Psychology Department.

Wray, Tyler B., Jeffrey S. Simons, & Stephen A. Maisto. (2015). Effects of alcohol intoxication and autonomic arousal on delay discounting and risky sex in young adult heterosexual men. Addictive Behaviors, 42, 9-13.

Objectives: The relationship between alcohol use and risky sexual behavior is complex and depends on psychological and environmental factors. The alcohol myopia model predicts that, due to alcohol’s impact on attention, the behavior of intoxicated individuals will become increasingly directed by salient cues. Autonomic arousal (AA) may have a similar effect on attention. Experiential delay discounting (DD) may be increased by both alcohol consumption and AA due to their common effects and may mediate the relationship between these conditions and risky sex. Methods: This study employed a 3 (alcohol, placebo, control)×2 (high, low arousal) experimental design to examine the effects of acute alcohol intoxication and AA on experiential delay discounting, subjective sexual arousal, and risky sex. Results: Path models revealed complex results that only partially supported study hypotheses. Ratings of subjective sexual arousal did not differ across either beverage or arousal conditions. DD was also unrelated to any study variable. However, subjective sexual arousal was positively related to risky sexual intentions. Alcohol intoxication was also positively associated with increased unprotected sex intentions, consistent with past studies. Conclusions: These results affirm the role of subjective sexual arousal and alcohol intoxication in risky sexual decision-making, yielding effect sizes similar to comparable past studies. The lack of differences across autonomic arousal groups also suggests that effects of attentional myopia may be behavior-specific. Failure to replicate effects of alcohol intoxication on DD also suggests reservation regarding its involvement in alcohol-involved risky sex.

Psychology Department.

Ceccanti, Mauro, Daniela Fiorentino, Giovanna Coriale, …., H. Eugene Hoyme, J. Phillip Gossage, . . . Philip A. May. (2014). Maternal risk factors for fetal alcohol spectrum disorders in a province in Italy. Drug and Alcohol Dependence, 145, 201-208.

Background: Maternal risk factors for fetal alcohol spectrum disorders (FASD) in Italy and Mediterranean cultures need clarification, as there are few studies and most are plagued by inaccurate reporting of antenatal alcohol use. Methods: Maternal interviews (n = 905) were carried out in a population-based study of the prevalence and characteristics of FASD in the Lazio region of Italy which provided data for multivariate case control comparisons and multiple correlation models. Results: Case control findings from interviews seven years post-partum indicate that mothers of children with FASD are significantly more likely than randomly-selected controls or community mothers to: be shorter; have higher body mass indexes (BMI); be married to a man with legal problems; report more drinking three months pre-pregnancy; engage in more current drinking and drinking alone; and have alcohol problems in her family. Logistic regression analysis of multiple candidate predictors of a FASD diagnosis indicates that alcohol problems in the child’s family is the most significant risk factor, making a diagnosis within the continuum of FASD 9 times more likely (95% C.I. = 1.6 to 50.7). Sequential multiple regression analysis of the child’s neuropsychological performance also identifies alcohol problems in the child’s family as the only significant maternal risk variable (p &lt; .001) when controlling for other potential risk factors. Conclusions: Underreporting of prenatal alcohol use has been demonstrated among Italian and other Mediterranean antenatal samples, and it was suspected in this sample. Nevertheless, several significant maternal risk factors for FASD have been identified. (PsycINFO Database Record (c) 2015 APA, all rights reserved). (journal abstract)

Sanford School of Medicine, Sioux Falls Campus.

Harris, William S., & Michelle L. Baack. (2015). Beyond building better brains: bridging the docosahexaenoic acid (DHA) gap of prematurity. Journal of Perinatology, 35(1), 1-7.

Long-chain polyunsaturated fatty acids (LCPUFA) including docosahexaenoic acid (DHA) are essential for normal vision and neurodevelopment. DHA accretion in utero occurs primarily in the last trimester of pregnancy to support rapid growth and brain development. Premature infants, born before this process is complete, are relatively deficient in this essential fatty acid. Very low birth weight (VLBW) infants remain deficient for a long period of time due to ineffective conversion from precursor fatty acids, lower fat stores and a limited nutritional provision of DHA after birth. In addition to long-term visual and neurodevelopmental risks, VLBW infants have significant morbidity and mortality from diseases specific to premature birth, including bronchopulmonary dysplasia, necrotizing enterocolitis, and retinopathy of prematurity. There is increasing evidence that DHA has protective benefits against these disease states. The aim of this article is to identify the unique needs of premature infants, review the current recommendations for LCPUFA provision in infants and discuss the caveats and innovative new ways to overcome the DHA deficiency through postnatal supplementation, with the long-term goal of improving morbidity and mortality in this at-risk population.

Sanford School of Medicine, Sioux Falls Campus.

Liaw, W., S. Coleman, A. Bazemore, & Mark K. Huntington. (2014). Another risk to US travelers-malaria. Journal of Family Practice, 63(11), E1-E7.

Sanford School of Medicine, Sioux Falls Campus.

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

Sanford School of Medicine, Sioux Falls Campus.

Bjornestad, A. G., Amy Schweinle, & J. D. Elhai. (2014). Measuring Secondary Traumatic Stress Symptoms in Military Spouses With the Posttraumatic Stress Disorder Checklist Military Version. Journal of Nervous and Mental Disease, 202(12), 864-869.

Little research to date has examined secondary traumatic stress symptoms in spouses of military veterans. This study investigated the presence and severity of posttraumatic stress symptoms in a sample of 227 Army National Guard veterans and secondary traumatic stress symptoms among their spouses. The veterans completed the posttraumatic stress disorder (PTSD) Checklist Military Version (PCL-M) (Weathers et al., 1993) to determine the probable prevalence rate of posttraumatic stress symptoms. A modified version of the PCL-M was used to assess secondary traumatic stress symptoms in the spouses. A confirmatory factor analysis showed that the modified version of the PCL-M used to assess secondary traumatic stress symptoms in spouses fits using the same four-factor PTSD structure as the PCL-M for veterans. This study provides initial evidence on the underlying symptom structure of secondary traumatic stress symptoms among spouses of traumatic event victims.

School of Education.

Newland, Lisa A., Jarod T. Giger, Michael J. Lawler, Eliann R. Carr, Emily A. Dykstra, & Soonhee Roh. (2014). Subjective well-being for children in a rural community. Journal of Social Service Research, 40(5), 642-661.

This study examined indicators of rural children’s subjective well-being and the prediction of well-being indicators from person variables as well as home, life, neighborhood, school, and peer-group contexts. Seventh-grade children (Mage = 13 years, age range = 12–14 years) in a rural Midwestern U.S. community (N = 149) completed an adapted version of an international survey measuring children’s subjective well-being and ecological contexts in childhood and adolescence. Indicators of children’s subjective well-being (including life satisfaction, mental health, and self-image) were significantly correlated with all home, life, neighborhood, school, and peer contexts except life stress. Regression and bootstrap analyses suggest that the strongest predictors of both life satisfaction and mental health were school satisfaction and family, teacher, and peer relationships. The strongest predictors of self-image were gender, number of residences, school satisfaction, and teacher and peer relationships. Findings suggest that a model of subjective well-being that accounts for relational factors, as well as person and other environmental factors, is potentially useful for understanding children’s subjective well-being. Results are discussed in the context of ecological, relationship-based interventions from early childhood through school-age years. Future studies should test this model with samples diverse in child age, culture, and geographical locations. (PsycINFO Database Record (c) 2014 APA, all rights reserved). (journal abstract)

School of Education.

Shim, Andrew L., & Shannon Norman. (2015). Incorporating Pedal-less Bicycles into a Pre-K through Third-grade Curriculum to Improve Stability in Children. JOPERD: The Journal of Physical Education, Recreation & Dance, 86(1), 50-51.

Physical educators are expected to develop activities that promote psychological and physiological benefits for children during their pre-adolescent years, especially in pre-K through third grade. One of these skill components is the development and acquisition of stability or balance. This article describes how to use pedal-less bicycles to teach balance and stability to pre-K through third-grade children.

School of Education.

Cho, Sunhee, So-Young Park, Kunsook S. Bernstein, Soonhee Roh, & Gyeong-Suk Jeon. (2014). Socio-demographic and health behavioral correlates of depressive symptoms among korean americans. Community Mental Health Journal, 50(9), x.

This study identifies the associations between socio-demographic characteristics and help seeking behaviors for depressive symptoms among adult Korean Americans (KAs). Using survey data from 230 residents of the New York City, Teaneck, New Jersey, and Philadelphia areas, simple and multiple logistic regression analyses were performed to assess the association between depressive symptoms and the covariates. Women were at much lower risk of depressive symptoms than were men, even after adjusting other covariates (OR 0.45, 95 % CI 0.21–0.96). Having no health insurance (OR 4.02, 95 % CI 1.28–12.61) and having experience in seeking professional help for mental health problems during the last year were significantly associated with depressive symptoms (OR 2.96, 95 % CI 1.29–6.80). The findings suggest more attention to the risk of depression of KA men and further efforts on understanding the unique contribution of socio-demographic factors and health-related behaviors on depressive symptoms among KAs.

School of Health Sciences.

Giger, Jarod T., Natalie D. Pope, H. Bruce Vogt, Cassity Gutierrez, Lisa A. Newland, Jason Lemke, & Michael J. Lawler. (2015). Remote patient monitoring acceptance trends among older adults residing in a frontier state. Computers in Human Behavior, 44, 174-182.

This pilot study aims to present a methodological approach for investigating remote patient monitoring system acceptance trends for older adults residing in a frontier state. For this purpose, extended Technology Acceptance Model (TAM) variables, which included subjective norm , perceived usefulness , perceived ease of use , and behavioral intention were investigated using growth curve methods and modern resampling techniques. Results revealed our methodological and analytical approach shows promise for investigating technology acceptance over time on subjects where little literature exists and where recruiting adequate sample sizes for statistical power purposes may be challenging. Results of the data analysis showed there was a significant and reliable linear trend on subjective norm. Time did not predict perceived usefulness, perceived ease of use, or behavioral intention, indicating the levels of these factors were high and stable over the course of the study. Older adults accepted remote patient monitoring, and family and friends may influence technology acceptance promoting behaviors. The longer participants used the technology, the more they perceived those important to them would want them to use it. Attention to social influence to optimize the implementation of in-home health monitoring among this population is warranted. Recommendations for future research are provided.

School of Health Sciences.

Roh, Soonhee, Catherine E. Burnette, Kyoung Hag Lee, Yeon-Shim Lee, Scott D. Easton, & Michael J. Lawler. (2015). Risk and protective factors for depressive symptoms among American Indian older adults: Adverse childhood experiences and social support. Aging & Mental Health, 19(4), 371-380.

Objectives:Despite efforts to promote health equity, many American Indian and Alaska Native (AI/AN) populations, including older adults, experience elevated levels of depression. Although adverse childhood experiences (ACE) and social support are well-documented risk and protective factors for depression in the general population, little is known about AI/AN populations, especially older adults. The purpose of this study was to examine factors related to depression among a sample of AI older adults in the midwest. Method:Data were collected using a self-administered survey completed by 233 AIs over the age of 50. The survey included standardized measures such as the Geriatric Depression Scale-Short Form, ACE Questionnaire, and the Multidimensional Scale of Perceived Social Support. Hierarchical multivariate regression analyses were conducted to evaluate the main hypotheses of the study. Results:Two dimensions of ACE (i.e., childhood neglect, household dysfunction) were positively associated with depressive symptoms; social support was negatively associated with depressive symptoms. Perceived health and living alone were also significant predictors. Conclusion: ACE may play a significant role in depression among AI/AN across the life course and into old age. Social support offers a promising mechanism to bolster resilience among AI/AN older adults.

School of Health Sciences.

Porter, Megan L., Kingston, A. C. N., McCready, R., Cameron, E. G., Hofmann, C. M., Suarez, L., Olsen, G. H., Cronin, T. W., & Robinson, P. R. (2014). Characterization of visual pigments, oil droplets, lens and cornea in the whooping crane Grus americana. Journal of Experimental Biology, 217(21), 3883-3890.

Vision has been investigated in many species of birds, but few studies have considered the visual systems of large birds and the particular implications of large eyes and long-life spans on visual system capabilities. To address these issues we investigated the visual system of the whooping crane Grus americana (Gruiformes, Gruidae), which is one of only two North American crane species. It is a large, long-lived bird in which UV sensitivity might be reduced by chromatic aberration and entrance of UV radiation into the eye could be detrimental to retinal tissues. To investigate the whooping crane visual system we used microspectrophotometry to determine the absorbance spectra of retinal oil droplets and to investigate whether the ocular media (i.e. the lens and cornea) absorb UV radiation. In vitro expression and reconstitution was used to determine the absorbance spectra of rod and cone visual pigments. The rod visual pigments had wavelengths of peak absorbance (lambda(max)) at 500 nm, whereas the cone visual pigment lambda(max) values were determined to be 404 nm (SWS1), 450 nm (SWS2), 499 nm (RH2) and 561 nm (LWS), similar to other characterized bird visual pigment absorbance values. The oil droplet cut-off wavelength (lambda(cut)) values similarly fell within ranges recorded in other avian species: 576 nm (R-type), 522 nm (Y-type), 506 nm (P-type) and 448 nm (C-type). We confirm that G. americana has a violet-sensitive visual system; however, as a consequence of the lambda(max) of the SWS1 visual pigment (404 nm), it might also have some UV sensitivity.

Biology Department.

Roberts, N. W., How, M. J., Porter, Megan L., Temple, S. E., Caldwell, R. L., Powell, S. B., Gruev, V., Marshall, N. J., & Cronin, T. W. (2014). Animal Polarization Imaging and Implications for Optical Processing. Proceedings of the Ieee, 102(10), 1427-1434.

Biologically inspired solutions for modern-day sensory systems promise to deliver both higher capacity and faster, more efficient processing of information than current computational approaches. Many animals are able to perform remarkable sensing tasks despite only being able to process what would be considered modest data rates and bandwidths. The key biological innovations revolve around dedicated filter designs. By sacrificing some flexibility, specifically matched and hard-wired sensory systems, designed primarily for single roles, provide a blueprint for data and task-specific efficiency. In this paper, we examine several animal visual systems designed to use the polarization of light in spatial imaging. We investigate some implications for artificial optical processing based on models of polarization image processing in fiddler crabs, cuttlefish, octopus, and mantis shrimp.

Biology Department.

Netzer, Nathan L., Dai, Feng-Rong, Wang, Zhenqiang, & Jiang, Chaoyang. (2014). pH-Modulated Molecular Assemblies and Surface Properties of Metal-Organic Supercontainers at the Air-Water Interface. Angewandte Chemie-International Edition, 53(41), 10965-10969.

The orientation of metal-organic supercontainer (MOSC) molecules in Langmuir films was systematically studied at the air-water interface. The acidity of the aqueous subphases plays a significant role in tuning the orientation of MOSC molecules in the Langmuir films. Furthermore, Langmuir-Blodgett films of MOSCs were prepared and the uniform multilayer structures demonstrated various surface properties, depending on their conditions of fabrication. Our use of Langmuir films provides a novel approach to access tunable assemblies of MOSC molecules in two-dimensional thin films.

Chemistry Department.

Thiel, C. W., Macfarlane, R. M., Sun, Yongchen, Bottger, T., Sinclair, N., Tittel, W., & Cone, R. L. (2014). Measuring and analyzing excitation-induced decoherence in rare-earth-doped optical materials. Laser Physics, 24(10).

A method is introduced for quantitatively analyzing photon echo decay measurements to characterize excitation-induced decoherence resulting from the phenomenon of instantaneous spectral diffusion. Detailed analysis is presented that allows fundamental material properties to be extracted that predict and describe excitation-induced decoherence for a broad range of measurements, applications and experimental conditions. Motivated by the need for a method that enables systematic studies of ultra-low decoherence systems and direct comparison of properties between optical materials, this approach employs simple techniques and analytical expressions that avoid the need for difficult to measure and often unknown material parameters or numerical simulations. This measurement and analysis approach is demonstrated for the H-3(6) to H-3(4) optical transition of three thulium-doped crystals, Tm3+:YAG, Tm3+:LiNbO3 and Tm3+:YGG, that are currently employed in quantum information and classical signal processing demonstrations where minimizing decoherence is essential to achieve high efficiencies and large signal bandwidths. These new results reveal more than two orders of magnitude variation in sensitivity to excitation-induced decoherence among the materials studied and establish that the Tm3+:YGG system offers the longest optical coherence lifetimes and the lowest levels of excitation-induced decoherence yet observed for any known thulium-doped material.

Physics Department.

Struckman-Johnson, Cindy, Gaster, Samuel, Struckman-Johnson, Dave, Johnson, Melissa, & May-Shinagle, Gabby. (2015). Gender differences in psychosocial predictors of texting while driving. Accident Analysis & Prevention, 74, 218-228.

A sample of 158 male and 357 female college students at a midwestern university participated in an on-line study of psychosocial motives for texting while driving. Men and women did not differ in self-reported ratings of how often they texted while driving. However, more women sent texts of less than a sentence while more men sent texts of 1–5 sentences. More women than men said they would quit texting while driving due to police warnings, receiving information about texting dangers, being shown graphic pictures of texting accidents, and being in a car accident. A hierarchical regression for men’s data revealed that lower levels of feeling distracted by texting while driving (20% of the variance), higher levels of cell phone dependence (11.5% of the variance), risky behavioral tendencies (6.5% of the variance) and impulsivity (2.3%) of the variance) were significantly associated with more texting while driving (total model variance = 42%). A separate regression for women revealed that higher levels of cell phone dependence (10.4% of the variance), risky behavioral tendencies (9.9% of the variance), texting distractibility (6.2%), crash risk estimates (2.2% of the variance) and driving confidence (1.3% of the variance) were significantly associated with more texting while driving (total model variance = 31%.) Friendship potential and need for intimacy were not related to men’s or women’s texting while driving. Implications of the results for gender-specific prevention strategies are discussed.

Psychology Department.

Anderson, Joe, Nykamp, M., Danielson, Laura, Remund, T., & Kelly, P. W. (2014). A novel endovascular debranching technique using physician-assembled endografts for repair of thoracoabdominal aneurysms. Journal of Vascular Surgery, 60(5), 1177-1184.

Objective: The objective of this study was to demonstrate a technique that uses physician-assembled endografts to make use of the benefits of parallel grafts while also providing for circumferential seal and fixation in repair of thoracoabdominal aneurysms in inoperable patients. Methods: A single-center all-comers retrospective analysis of 14 patients was performed that looked at the early outcomes of patients treated for thoracoabdominal aneurysms. Three Crawford type II, four type III, four type IV, and three type V thoracoabdominal aneurysms were treated. Contrast material, fluoroscopy time, length of stay, clinical success, and technical success were measured. Results: There was no in-hospital, 30-day, or 6-month mortality. We found two type III endoleaks in the early design. One required coil embolization. Average volume of contrast material and average fluoroscopy time were 76.9 mL and 119.1 minutes, respectively. Average length of stay was 10.5 days, and average procedure time was 251.2 minutes. Clinical success was observed in 78.6% of patients to date, and technical success was observed in 85.7% of patients. Conclusions: Short-term results show that this approach is safe. The device can be safely implanted, is off-the-shelf, and can treat each of the Crawford thoracoabdominal aneurysm types. Finally, the assembly of off-the-shelf components may shorten the regulatory path for this physician-assembled endograft.

Sanford School of Medicine, Sioux Falls Campus.

May, Phiip A., Baete, Amy, Russo, Jaymi, Elliott, Amy J., Blankenship, J., …., & Hoyme, H. Eugene. (2014). Prevalence and Characteristics of Fetal Alcohol Spectrum Disorders. Pediatrics, 134(5), 855-866.

OBJECTIVES: To determine the prevalence and characteristics of fetal alcohol spectrum disorders (FASD) among first grade students (6- to 7-year-olds) in a representative Midwestern US community. METHODS: From a consented sample of 70.5% of all first graders enrolled in public and private schools, an oversample of small children (<= 25th percentile on height, weight, and head circumference) and randomly selected control candidates were examined for physical growth, development, dysmorphology, cognition, and behavior. The children’s mothers were interviewed for maternal risk. RESULTS: Total dysmorphology scores differentiate significantly fetal alcohol syndrome (FAS) and partial FAS (PFAS) from one another and from unexposed controls. Alcohol-related neuro developmental disorder (ARND) is not as clearly differentiated from controls. Children who had FASD performed, on average, significantly worse on 7 cognitive and behavioral tests and measures. The most predictive maternal risk variables in this community are late recognition of pregnancy, quantity of alcoholic drinks consumed 3 months before pregnancy, and quantity of drinking reported for the index child’s father. From the final multidisciplinary case findings, 3 techniques were used to estimate prevalence. FAS in this community likely ranges from 6 to 9 per 1000 children (midpoint, 7.5), PFAS from 11 to 17 per 1000 children (midpoint, 14), and the total rate of FASD is estimated at 24 to 48 per 1000 children, or 2.4% to 4.8% (midpoint, 3.6%). CONCLUSIONS: Children who have FASD are more prevalent among first graders in this Midwestern city than predicted by previous, popular estimates.

Sanford School of Medicine, Sioux Falls Campus.

Nosova, E. V., Chong, K. C., Alley, H. F., Harris, William S., Boscardin, W. J., Conte, M. S., Owens, C. D., & Grenon, S. M. (2014). Clinical correlates of red blood cell omega-3 fatty acid content in male veterans with peripheral arterial disease. Journal of Vascular Surgery, 60(5), 1325-1331.

Objective: Despite available medical therapies, patients with peripheral arterial disease (PAD) remain at high risk for cardiovascular events. The n-3 polyunsaturated fatty acids (PUFA), derived from marine sources, have been shown to improve cardiovascular mortality. The Omega-3 Index (O3I), a proportion of the n-3 PUFA eicosapentaenoic acid and docosahexaenoic acid in the red blood cell membrane, correlates with cardiovascular risk. Previous investigations have found that n-3 PUFA supplementation, fish consumption, older age, and smoking history affect the O3I in different patient populations, although similar correlations have never been explored in PAD. We hypothesized that in our PAD cohort, blood content of omega-3 fatty acids would directly and positively correlate with a history of fish oil supplementation and older age and inversely correlate with a smoking history and obesity. Methods: This cross-sectional study included 111 patients who had an ankle-brachial index of <0.9 associated with claudication symptoms. We used linear regression to determine the association between clinical factors and the O3I. Results: The mean age of the cohort was 69 +/- 8 years; 37% had diabetes mellitus (hemoglobin A(1c), 7% +/- 1%), and 94% reported current smoking or a history of smoking. The mean O3I was 5% +/- 2%. In multivariate linear regression analysis, the O3I was associated with older age, increasing body mass index, and a history of smoking and fish oil intake. Conclusions: This is the first report of the relation between blood content of omega-3 fatty acids and clinical factors in a PAD population. In patients with PAD, older age, elevated body mass index, and prior fish oil supplementation predicted a higher O3I. A history of smoking correlated with a lower O3I. These results demonstrate that the O3I is a reliable measure of dietary n-3 PUFA intake and that clinical factors related to the O3I in PAD are similar to those observed in other populations.

Sanford School of Medicine, Sioux Falls Campus.

Surendran, Kameswaran, Vitiello, S. P., & Pearce, David A. (2014). Lysosome dysfunction in the pathogenesis of kidney diseases. Pediatric Nephrology, 29(12), 2253-2261.

The lysosome, an organelle central to macromolecule degradation and recycling, plays a pivotal role in normal cell processes, ranging from autophagy to redox regulation. Not surprisingly, lysosomes are an integral part of the renal epithelial molecular machinery that facilitates normal renal physiology. Two inherited diseases that manifest as kidney dysfunction are Fabry’s disease and cystinosis, each of which is caused by a primary biochemical defect at the lysosome resulting from loss-of-function mutations in genes that encode lysosomal proteins. The functions of the lysosomes in the kidney and how lysosomal dysfunction might contribute to Fabry’s disease and cystinosis are discussed. Unlike most other pediatric renal diseases, therapies are available for Fabry’s disease and cystinosis, but require early diagnosis. Recent analysis of ceroid neuronal lipofuscinosis type 3 (Cln3) null mice, a mouse model of lysosomal disease that is primarily associated with neurological deficits, revealed renal functional abnormalities. As current and future therapeutics increase the life-span of those suffering from diseases like neuronal ceroid lipofuscinosis, it remains a distinct possibility that many more lysosomal disorders that primarily manifest as infant and juvenile neurodegenerative diseases may also include renal disease phenotypes.

Sanford School of Medicine, Sioux Falls Campus.

Zhuang, Yongxian, Chan, Daniel K., Haugrud, Allison B., & Miskimins, W. Keith. (2014). Mechanisms by Which Low Glucose Enhances the Cytotoxicity of Metformin to Cancer Cells Both In Vitro and In Vivo. Plos One, 9(9).

Different cancer cells exhibit altered sensitivity to metformin treatment. Recent studies suggest these findings may be due in part to the common cell culture practice of utilizing high glucose, and when glucose is lowered, metformin becomes increasingly cytotoxic to cancer cells. In low glucose conditions ranging from 0 to 5 mM, metformin was cytotoxic to breast cancer cell lines MCF7, MDAMB231 and SKBR3, and ovarian cancer cell lines OVCAR3, and PA-1. MDAMB231 and SKBR3 were previously shown to be resistant to metformin in normal high glucose medium. When glucose was increased to 10 mM or above, all of these cell lines become less responsive to metformin treatment. Metformin treatment significantly reduced ATP levels in cells incubated in media with low glucose (2.5 mM), high fructose (25 mM) or galactose (25 mM). Reductions in ATP levels were not observed with high glucose (25 mM). This was compensated by enhanced glycolysis through activation of AMPK when oxidative phosphorylation was inhibited by metformin. However, enhanced glycolysis was either diminished or abolished by replacing 25 mM glucose with 2.5 mM glucose, 25 mM fructose or 25 mM galactose. These findings suggest that lowering glucose potentiates metformin induced cell death by reducing metformin stimulated glycolysis. Additionally, under low glucose conditions metformin significantly decreased phosphorylation of AKT and various targets of mTOR, while phospho-AMPK was not significantly altered. Thus inhibition of mTOR signaling appears to be independent of AMPK activation. Further in vivo studies using the 4T1 breast cancer mouse model confirmed that metformin inhibition of tumor growth was enhanced when serum glucose levels were reduced via low carbohydrate ketogenic diets. The data support a model in which metformin treatment of cancer cells in low glucose medium leads to cell death by decreasing ATP production and inhibition of survival signaling pathways. The enhanced cytotoxicity of metformin against cancer cells was observed both in vitro and in vivo.

Sanford School of Medicine, Sioux Falls Campus.

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