Posted by: kelsijo97 | July 31, 2011

August 2011

Bouhlal, Yosr, Amouri, R., El Euch-Fayeche, G., and Hentati, F. “Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay: An Overview.” Parkinsonism & Related Disorders 17, no. 6 (2011).

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a distinct form of hereditary early-onset spastic ataxia related to progressive degeneration of the cerebellum and spinal cord. Following the description of the first patients in 1978, the gene responsible has been mapped and identified. It was also shown that the disease occurred worldwide with more than 70 mutations and diverse phenotypes. Because of the random partition of these mutations in the SACS gene particularly on the largest exon nine, and due to the significant clinical variability between patients described in different countries, it has been difficult to establish a genotype phenotype correlation for the disease. This paper reviews the broad clinical features and the various molecular aspects of ARSACS, reported over the last 30 years highlighting the difficulty of finding correlations. (C) 2011 Elsevier Ltd. All rights reserved.

Basic Biomedical Sciences, Vermillion Campus.

Keifer, Joyce, and Houk, James C. “Modeling Signal Transduction in Classical Conditioning with Network Motifs.” Frontiers in molecular neuroscience 4, no. x (2011).

Biological networks are constructed of repeated simplified patterns, or modules, called network motifs. Network motifs can be found in a variety of organisms including bacteria, plants, and animals, as well as intracellular transcription networks for gene expression and signal transduction processes in neuronal circuits. Standard models of signal transduction events for synaptic plasticity and learning often fail to capture the complexity and cooperativity of the molecular interactions underlying these processes. Here, we apply network motifs to a model for signal transduction during an in vitro form of eyeblink classical conditioning that reveals an underlying organization of these molecular pathways. Experimental evidence suggests there are two stages of synaptic AMPA receptor (AMPAR) trafficking during conditioning. Synaptic incorporation of GluR1-containing AMPARs occurs early to activate silent synapses conveying the auditory conditioned stimulus and this initial step is followed by delivery of GluR4 subunits that supports acquisition of learned conditioned responses (CRs). Overall, the network design of the two stages of synaptic AMPAR delivery during conditioning describes a coherent feed-forward loop (C1-FFL) with AND logic. The combined inputs of GluR1 synaptic delivery AND the sustained activation of 3-phosphoinositide-dependent protein-kinase-1 (PDK-1) results in synaptic incorporation of GluR4-containing AMPARs and the gradual acquisition of CRs. The network architecture described here for conditioning is postulated to act generally as a sign-sensitive delay element that is consistent with the non-linearity of the conditioning process. Interestingly, this FFL structure also performs coincidence detection. A motif-based approach to modeling signal transduction can be used as a new tool for understanding molecular mechanisms underlying synaptic plasticity and learning and for comparing findings across forms of learning and model systems.

Basic Biomedical Sciences, Vermillion Campus.

Tieszen, Chelsea R., Goyeneche, Alicia A., Brandhagen, BreeAnn N., Ortbahn, Casey T., and Telleria, Carlos M. “Antiprogestin Mifepristone Inhibits the Growth of Cancer Cells of Reproductive and Non-Reproductive Origin Regardless of Progesterone Receptor Expression.” BMC Cancer 11, no. 1 (2011).

Background: Mifepristone (MF) has been largely used in reproductive medicine due to its capacity to modulate the progesterone receptor (PR). The study of MF has been expanded to the field of oncology; yet it remains unclear whether the expression of PR is required for MF to act as an anti-cancer agent. Our laboratory has shown that MF is a potent inhibitor of ovarian cancer cell growth. In this study we questioned whether the growth inhibitory properties of MF observed in ovarian cancer cells would translate to other cancers of reproductive and non-reproductive origin and, importantly, whether its efficacy is related to the expression of cognate PR. Methods: Dose-response experiments were conducted with cancer cell lines of the nervous system, breast, prostate, ovary, and bone. Cultures were exposed to vehicle or increasing concentrations of MF for 72 h and analysed for cell number and cell cycle traverse, and hypodiploid DNA content characteristic of apoptotic cell death. For all cell lines, expression of steroid hormone receptors upon treatment with vehicle or cytostatic doses of MF for 24 h was studied by Western blot, whereas the activity of the G1/S regulatory protein Cdk2 in both treatment groups was monitored in vitro by the capacity of Cdk2 to phosphorylate histone H1. Results: MF growth inhibited all cancer cell lines regardless of tissue of origin and hormone responsiveness, and reduced the activity of Cdk2. Cancer cells in which MF induced G1 growth arrest were less susceptible to lethality in the presence of high concentrations of MF, when compared to cancer cells that did not accumulate in G1. While all cancer cell lines were growth inhibited by MF, only the breast cancer MCF-7 cells expressed cognate PR. Conclusions: Antiprogestin MF inhibits the growth of different cancer cell lines with a cytostatic effect at lower concentrations in association with a decline in the activity of the cell cycle regulatory protein Cdk2, and apoptotic lethality at higher doses in association with increased hypodiploid DNA content. Contrary to common opinion, growth inhibition of cancer cells by antiprogestin MF is not dependent upon expression of classical, nuclear PR. [ABSTRACT FROM AUTHOR]
Copyright of BMC Cancer is the property of BioMed Central and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder’s express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Basic Biomedical Sciences, Vermillion Campus.

Wei, Li, Zhaoqing, Zheng, and Keifer, Joyce. “Transsynaptic Ephb/Ephrin-B Signaling Regulates Growth of Presynaptic Boutons Required for Classical Conditioning.” Journal of Neuroscience 31, no. 23 (2011).

Learning-related presynaptic remodeling has been documented in only a few systems, and its molecular mechanisms are largely unknown. Here we describe a role for the bidirectional EphB/ephrin-B signaling system in structural plasticity of presynaptic nerve terminals using an in vitro model of classical conditioning. Conditioning or BDNF application induced significant growth of auditory nerve presynaptic boutons that convey the conditioned stimulus to abducens motor neurons. Interestingly, bouton enlargement occurred only for those synapses apposed to motor neuron dendrites rather than to somata. Phosphorylation of ephrin-B1, but not EphB2, was induced by both conditioning and BDNF application and was inhibited by postsynaptic injections of ephrin-B antibody. Finally, suppression of postsynaptic ephrin-B function inhibited presynaptic bouton enlargement that was rescued by activation of EphB2 by ephrin-B1-Fc. These data provide evidence for ephrin-B-induced EphB2 forward signaling in presynaptic structural plasticity during classical conditioning. They also reveal a functional interaction between BDNF/TrkB and the Eph/ephrin signaling systems in the coordination of presynaptic and postsynaptic modifications during conditioning.

Basic Biomedical Sciences, Vermillion Campus.

Zheng, Quingwen W., Su, Huabo B., Ranek, Mark J., and Wang, Xuejin J. “Autophagy and P62 in Cardiac Proteinopathy.” Circulation Research 109, no. 3 (2011).

Rationale: Recent studies suggest an important role of autophagy in protection against alpha B-crystallin-based (CryAB(R120G)) desmin-related cardiomyopathies (DRC), but this has not been demonstrated in a different model of cardiac proteinopathy. Mechanisms underlying the response of cardiomyocytes to proteotoxic stress remain incompletely understood. Objective: Our first objective was to determine whether and how the autophagic activity is changed in a mouse model of desminopathy. We also investigated the role of p62 in the protein quality control of cardiomyocytes. Methods and Results: Using an autophagosome reporter and determining changes in LC3-II protein levels in response to lysosomal inhibition, we found significantly increased autophagic flux in mouse hearts with transgenic overexpression of a DRC-linked mutant desmin. Similarly, autophagic flux was increased in cultured neonatal rat ventricular myocytes (NRVMs) expressing a mutant desmin. Suppression of autophagy by 3-methyladenine increased, whereas enhancement of autophagy by rapamycin reduced the ability of a comparable level of mutant desmin overexpression to accumulate ubiquitinated proteins in NRVMs. Furthermore, p62 mRNA and protein expression was significantly up-regulated in cardiomyocytes by transgenic overexpression of the mutant desmin or CryAB(R120G) both in intact mice and in vitro. The p62 depletion impaired aggresome and autophagosome formation, exacerbated cell injury, and decreased cell viability in cultured NRVMs expressing the misfolded proteins. Conclusions: Autophagic flux is increased in desminopathic hearts, and as previously suggested in CryAB(R120G)-based DRC, this increased autophagic flux serves as an adaptive response to overexpression of misfolded proteins. The p62 is up-regulated in mouse proteinopathic hearts. The p62 promotes aggresome formation and autophagy activation and protects cardiomyocytes against proteotoxic stress. (Circ Res. 2011; 109: 296-308.)

Basic Biomedical Sciences, Vermillion Campus.

Darling, Warren G., Pizzimenti, Marc A., Hynes, Stephanie M., Ge, Jizhi, Stilwell-Morecraft, Kimberly S., McNeal, David W., Solon-Cline, Kathryn M., and Morecraft, Robert J. “Volumetric Effects of Motor Cortex Injury on Recovery of Ipsilesional Dexterous Movements.” Experimental Neurology 231, no. 1 (2011).

Abstract: Damage to the motor cortex of one hemisphere has classically been associated with contralateral upper limb paresis, but recent patient studies have identified deficits in both upper limbs. In non-human primates, we tested the hypothesis that the severity of ipsilesional upper limb motor impairment in the early post-injury phase depends on the volume of gray and white matter damage of the motor areas of the frontal lobe. We also postulated that substantial recovery would accompany minimal task practice and that ipsilesional limb recovery would be correlated with recovery of the contralesional limb. Gross (reaching) and fine hand motor functions were assessed for 3–12months post-injury using two motor tests. Volumes of white and gray matter lesions were assessed using quantitative histology. Early changes in post-lesion motor performance were inversely correlated with white matter lesion volume indicating that larger lesions produced greater decreases in ipsilesional hand movement control. All monkeys showed improvements in ipsilesional hand motor skill during the post-lesion period, with reaching skill improvements being positively correlated with total lesion volume indicating that larger lesions were associated with greater ipsilesional motor skill recovery. We suggest that reduced trans-callosal inhibition from the lesioned hemisphere may play a role in the observed skill improvements. Our findings show that significant ipsilesional hand motor recovery is likely to accompany injury limited to frontal motor areas. In humans, more pronounced ipsilesional motor deficits that invariably develop after stroke may, in part, be a consequence of more extensive subcortical white and gray matter damage.

Basic Niomedical Sciences, Vermillion Campus.

Haukenes, A. H., Barton, Bruce A., and Renner, Kenneth J. “Plasma Cortisol and Hypothalamic Monoamine Responses in Yellow Perch Perca Flavescens after Intraperitoneal Injection of Lipopolysaccharide.” Fish Physiology and Biochemistry 37, no. 3 (2011).

The concentrations of monoamines in the hypothalamus were determined in yellow perch Perca flavescens before and after injection with lipopolysaccharide (LPS; 3 mg kg(-1) fish weight) or saline to test for the presence of neurochemical changes potentially associated with changes in plasma cortisol characteristic of intraperitoneal (ip) challenge with LPS. In the first experiment, yellow perch were injected with saline or LPS and the hypothalamus removed and plasma sampled before and at 0.5, 1.5, 3.0, and 6 h after injection. Plasma cortisol was elevated in both saline- and LPS-injected fish through 1.5 h after injection and returned to levels resembling pre-injection by 3 h after injection. Significantly higher amounts of cortisol in plasma from LPS-injected relative to saline-injected fish were observed 6 h following injection. A significant decrease relative to levels observed 0.5-3 h after handling was observed in serotonin concentrations at 6 h following LPS and saline injection with a concomitant increase in the ratio of 5-hydroxyindoleacetic acid:serotonin. In the second experiment, hypothalamic monoamines were sampled before and at 3, 6, 9, 12, and 24 h after injection with LPS or saline. Significant increases from pre-injection levels were observed in the ratio 5-hydroxyindoleacetic acid:serotonin at 9, 12, and 24 h after injection, but no differences were detected between LPS- and saline-injected fish. These results support a model linking serotonergic system activation following handling stress, but no correlations with the sustained elevations of plasma cortisol associated with inflammatory challenge were observed.

Biology Department.

Mani, Gopinath, Torres, N., and Oh, S. “Paclitaxel Delivery from Cobalt-Chromium Alloy Surfaces Using Self-Assembled Monolayers.” Biointerphases 6, no. 2 (2011).

Polymer-based platforms in drug-eluting stents (DESs) can cause adverse reactions in patients. Hence, the development of a polymer-free drug delivery platform may reduce adverse reactions to DES. In this study, the use of a polymer-free platform, self-assembled monolayers (SAMs), is explored for delivering an antiproliferative drug [paclitaxel (PAT)] from a stent material [cobalt-chromium ((Co – Cr) alloy]. Initially, carboxylic acid terminated phosphonic acid SAMs were coated on Co – Cr alloy. Two different doses (25 and 100 mu g/cm(2)) of PAT were coated on SAM coated Co – Cr surfaces using a microdrop deposition method. Also, control experiments were carried out to coat PAT directly on Co – Cr surfaces with no SAM modification. The PAT coated specimens were characterized using the Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and atomic force microscopy (AFM). FTIR spectra showed the successful deposition of PAT on SAM coated and control-Co – Cr surfaces. SEM images showed islands of high density PAT crystals on SAM coated surfaces, while low density PAT crystals were observed on control-Co – Cr alloy. AFM images showed molecular distribution of PAT on SAM coated as well as control-Co – Cr alloy surfaces. In vitro drug release studies showed that PAT was released from SAM coated Co – Cr surfaces in a biphasic manner (an initial burst release in first 7 days was followed by a slow release for up to 35 days), while the PAT was burst released from control-Co – Cr surfaces within 1-3 days. Thus, this study demonstrated the use of SAMs for delivering PAT from Co – Cr alloy surfaces for potential use in drug-eluting stents.

Biomedical Engineering, Sioux Falls.

Sereda, Grigoriy, Kim, Taejin, Jones, Aubrey, Khatri, Hari, Marshall, Christopher, Subramanian, H., and Koodali, Ranjit. “Phthalocyanine- and Calixarene-Templating Effect on the Catalytic Performance of Solid Supported Vanadates.” Catalysis Letters 141, no. 8 (2011).

Catalytic performance of solid supported monovanadate catalysts toward oxidation of propane is significantly affected by the templating effect of: (1) pretreatment of the solid support with calixarene derivatives before deposition of ammonium vanadate, (2) direct deposition of vanadyl phthalocyanine as the vanadate precursor. This effect is believed to be linked to the accessibility of the active sites, and was studied in comparison with a reference mesoporous support.

Chemistry Department.

Becker, John, Raghupathi, Krishna R., St Pierre, Jordan., Zhao, D., and Koodali, Ranjit T. “Tuning of the Crystallite and Particle Sizes of Zno Nanocrystalline Materials in Solvothermal Synthesis and Their Photocatalytic Activity for Dye Degradation.” Journal of Physical Chemistry C 115, no. 28 (2011).

ZnO nanocrystalline materials with different crystallite and particle sizes were synthesized by the solvothermal approach. The structure and optical properties were investigated using powder X-ray diffraction (XRD), nitrogen adsorption isotherms, UV-vis diffuse reflectance spectroscopy (DRS), transmission and scanning electron microscopy (TEM), and room temperature photoluminescence. It was found that the crystallite and particle sizes of ZnO nanocrystalline could be controlled by changing the solvent during the solvothermal synthesis. The photocatalytic activity was evaluated by the degradation of dye Rhodamine B (RhB) under visible irradiation. The individual effect of crystallite size and particle size on the photocatalytic activity of ZnO was studied using the ZnO nanocrystallites prepared in this work.

Chemistry Department.

Del Gaizo, Ariel L., Elhai, Jon D., and Weaver, Terri L. “Posttraumatic Stress Disorder, Poor Physical Health and Substance Use Behaviors in a National Trauma-Exposed Sample.” Psychiatry research 188, no. 3 (2011).

Both experiencing a traumatic event and PTSD are related to physical health problems (e.g., Schnurr and Jankowski, 1999) and health-risk behavior (e.g., Stewart, 1996). Using structural equation modeling analyses, we examined the interrelationships among number of distinct traumatic event exposures, PTSD diagnosis, physical health, and substance use behavior using epidemiological data from the National Comorbidity Survey Replication (NCS-R; Kessler et al., 2004). Results provide some evidence that PTSD mediates the relationship between: (a) number of distinct traumatic event exposures and poor physical health defined by clusters of difficulties with gastrointestinal, musculoskeletal, and/or cardiovascular health, and (b) number of distinct traumatic event exposures and substance use behaviors. However, substance use behaviors did not significantly mediate the relationship between PTSD and poor physical health. Copyright 2011 Elsevier Ltd. All rights reserved.

Psychology Department.

Sala-Vila, A., Harris, William S., Cofan, M., Perez-Heras, A. M., Pinto, X., Lamuela-Raventos, R. M., Covas, M. I., Estruch, R., and Ros, E. “Determinants of the Omega-3 Index in a Mediterranean Population at Increased Risk for Chd.” British Journal of Nutrition 106, no. 3 (2011).

The omega-3 index, defined as the sum of EPA and DHA in erythrocyte membranes expressed as a percentage of total fatty acids, has been proposed as both a risk marker and risk factor for CHD death. A major determinant of the omega-3 index is EPA + DHA intake, but the impact of other dietary fatty acids has not been investigated. In a cross-sectional study on 198 subjects (102 men and 96 women, mean age 66 years) at high cardiovascular risk living in Spain, the country with low rates of cardiac death despite a high prevalence of cardiovascular risk factors, dietary data were acquired from FFQ and blood cell membrane fatty acid composition was measured by GC. The average consumption of EPA + DHA was 0.9 g/d and the mean omega-3 index was 7.1%. In multivariate models, EPA + DHA intake was the main predictor of the omega-3 index but explained only 12% of its variability (P<0.001). No associations with other dietary fatty acids were observed, Although the single most influential determinant of the omega-3 index measured here was the intake of EPA + DHA, it explained little of the former’s variability; hence, the effects of other factors (genetic, dietary and lifestyle) remain to be determined. Nevertheless, the high omega-3 index could at least partially explain the paradox of low rates of fatal CHD in Spain despite a high background prevalence of cardiovascular risk factors.

Sanford School of Medicine, Sioux Falls Campus.

Shinozaki, Gen. “Research Highlights: Continuous Un-Sert-Ainty of 5-Httlpr.” Pharmacogenomics 12, no. 7 (2011).

Sanford School of Medicine, Sioux Falls Campus.

Nelson, Trudi J. “Assessing Internal Group Processes in Collaborative Assignments.” English Journal 100, no. 6 (2011).

The article focuses on the assessment of group activities in a learner-centered classroom environment in the U.S. It outlines the role of teachers as facilitators which is essential in setting up successful group processes. It states that group work stimulates higher-order thinking since it encourages students to collaborate with one another in solving problems.

School of Education.

Richardson, Maurine, Richardson, James, and Sacks, Mary Kathleen. “Literacy Teachers: How the Physical Education Teachers/Coaches Can Help You Encourage Students to Read.” Reading Improvement 48, no. 2 (2011).

When motivating students to read so often the literacy teacher will ask for assistance from the language arts, social studies, mathematics, and science teachers to develop literacy and content specific activities. It is important to consider other teachers in the school that are often not asked to participate in reading activities. The physical education/coach is usually not considered. This article provided several ways to include possibly the most visible faculty member and as a role model encouraging students to read. Also, included are literacy related activities and literary works that would be appropriate for each.

School of Education.

Curry, Dale, Lawler, Michael J., Schneider-Muñoz, Andrew J., and Fox, Lorraine. “A Child and Youth Care Approach to Professional Development and Training.” Relational Child & Youth Care Practice 24, no. 1/2 (2011).

Building upon the work of child and youth care leaders who have identified common themes involved in professional child and youth care practice, this article articulates a child and youth care approach to professional development and training including the importance of relationships, a develop mental/ecological approach, therapeutic activities, and an emphasis on practical applications. Recent developments in the child and youth care field and in the area of professional development and training are high lighted. These developments elevate the importance of the role of professional development and training, challenging the field to increasingly promote professional standards and facilitate knowledge transfer from research to practice.

School of Health Sciences.

Grey, Kathryn B., and Burrell, Brian D. “Seasonal Variation of Long-Term Potentiation at a Central Synapse in the Medicinal Leech.” Journal of Experimental Biology 214, no. 15 (2011).

Long-term potentiation (LTP) is a persistent increase in synaptic transmission that is thought to contribute to a variety of adaptive processes including learning and memory. Although learning is known to undergo circannual variations, it is not known whether LTP undergoes similar changes despite the importance of LTP in learning and memory. Here we report that synapses in the CNS of the medicinal leech demonstrate seasonal variation in the capacity to undergo LTP following paired presynaptic and postsynaptic stimulation. LTP was observed during the April-October period, but no LTP was observed during the November-March period. Application of forskolin, a technique often used to produce chemical LTP, failed to elicit potentiation during the November-March period. Implementing stimulation patterns that normally result in long term depression (LTD) also failed to elicit any change in synaptic strength during the November-March period. These experiments indicate that LTP and LTD can be influenced by circannual rhythms and also suggest a seasonal influence on learning and memory.

Basic Biomedical Sciences, Vermillion Campus.

Li, WeiZheng, Zhaoqing Q., and Keifer, Joyce. “Transsynaptic Ephb/Ephrin-B Signaling Regulates Growth of Presynaptic Boutons Required for Classical Conditioning.” Journal of Neuroscience 31, no. 23 (2011).

Learning-related presynaptic remodeling has been documented in only a few systems, and its molecular mechanisms are largely unknown. Here we describe a role for the bidirectional EphB/ephrin-B signaling system in structural plasticity of presynaptic nerve terminals using an in vitro model of classical conditioning. Conditioning or BDNF application induced significant growth of auditory nerve presynaptic boutons that convey the conditioned stimulus to abducens motor neurons. Interestingly, bouton enlargement occurred only for those synapses apposed to motor neuron dendrites rather than to somata. Phosphorylation of ephrin-B1, but not EphB2, was induced by both conditioning and BDNF application and was inhibited by postsynaptic injections of ephrin-B antibody. Finally, suppression of postsynaptic ephrin-B function inhibited presynaptic bouton enlargement that was rescued by activation of EphB2 by ephrin-B1-Fc. These data provide evidence for ephrin-B-induced EphB2 forward signaling in presynaptic structural plasticity during classical conditioning. They also reveal a functional interaction between BDNF/TrkB and the Eph/ephrin signaling systems in the coordination of presynaptic and postsynaptic modifications during conditioning.

Basic Biomedical Sciences, Vermillion Campus.

Schlenker, Evelyn H., and Schultz, Harold D. “Hypothyroidism Attenuates Sch 23390-Mediated Depression of Breathing and Decreases D1 Receptor Expression in Carotid Bodies, Pvn and Striatum of Hamsters.” Brain Research 1401 (2011).

Abstract: Hypothyroidism can lead to depressed breathing. We determined if propylthiouracil (PTU)-induced hypothyroidismin hamsters (HH) altered dopamine D1 receptor expression, D1 receptor-modulated ventilation, and ventilatory chemoreflex activation by hypoxia or hypercapnia. Hypothyroidism was induced by administering 0.04% PTU in drinking water for 3months. Ventilation was evaluated following saline or 0.25mg/kg SCH 23390,a D1 receptor antagonist, while awake hamsters breathed normoxic (21% O<sub>2</sub> in N<sub>2</sub>), hypoxic (10% O<sub>2</sub>in N<sub>2</sub>) and hypercapnic (5% CO<sub>2</sub> in O<sub>2</sub>)air. Relative to euthyroid hamsters (EH), HH exhibited decreased D1 receptor protein levels in carotid bodies, striatum, and hypothalamic paraventricular nucleus, but not in the nucleus tractus solitarius. Relative to EH, HH exhibited lower ventilation during exposure to normoxia, hypoxia, or hypercapnia, but comparable ventilatory responsiveness to chemoreflex activation. SCH23390 decreased ventilation of EH hamsters exposed to normoxia, hypoxia, and hypercapnia. In HH SCH23390 increased ventilation during baseline normoxia and did not affect ventilation during exposure to hypoxia and hypercapnia, resulting in reduced ventilatory responsivess to chemoreflex activation by hypoxia and hypercapnia. Furthermore, in HH D1 receptor protein levels are decreased in several brain regions and within the carotid bodies. Moreover, D1 receptor-modulation of breathing at rest and during gas exposures were depressed in EH but not HH.

Basic Biomedical Sciences, Vermillion Campus.

Telleria, Carlos M.Tieszen, Chelsea R.Goyeneche, Alicia A.Brandhagen, BreeAnn N., and Ortbahn, C. T. “Antiprogestin Mifepristone Inhibits the Growth of Cancer Cells of Reproductive and Non-Reproductive Origin Regardless of Progesterone Receptor Expression.” Bmc Cancer 11 (2011).

Background: Mifepristone (MF) has been largely used in reproductive medicine due to its capacity to modulate the progesterone receptor (PR). The study of MF has been expanded to the field of oncology; yet it remains unclear whether the expression of PR is required for MF to act as an anti-cancer agent. Our laboratory has shown that MF is a potent inhibitor of ovarian cancer cell growth. In this study we questioned whether the growth inhibitory properties of MF observed in ovarian cancer cells would translate to other cancers of reproductive and non-reproductive origin and, importantly, whether its efficacy is related to the expression of cognate PR.

Methods: Dose-response experiments were conducted with cancer cell lines of the nervous system, breast, prostate, ovary, and bone. Cultures were exposed to vehicle or increasing concentrations of MF for 72 h and analysed for cell number and cell cycle traverse, and hypodiploid DNA content characteristic of apoptotic cell death. For all cell lines, expression of steroid hormone receptors upon treatment with vehicle or cytostatic doses of MF for 24 h was studied by Western blot, whereas the activity of the G1/S regulatory protein Cdk2 in both treatment groups was monitored in vitro by the capacity of Cdk2 to phosphorylate histone H1.

Results: MF growth inhibited all cancer cell lines regardless of tissue of origin and hormone responsiveness, and reduced the activity of Cdk2. Cancer cells in which MF induced G1 growth arrest were less susceptible to lethality in the presence of high concentrations of MF, when compared to cancer cells that did not accumulate in G1. While all cancer cell lines were growth inhibited by MF, only the breast cancer MCF-7 cells expressed cognate PR.

Conclusions: Antiprogestin MF inhibits the growth of different cancer cell lines with a cytostatic effect at lower concentrations in association with a decline in the activity of the cell cycle regulatory protein Cdk2, and apoptotic lethality at higher doses in association with increased hypodiploid DNA content. Contrary to common opinion, growth inhibition of cancer cells by antiprogestin MF is not dependent upon expression of classical, nuclear PR.

Basic Biomedical Sciences, Vermillion Campus.

Bouhlal, Yosr, Amouri, Rim, El Euch-Fayeche, Ghada, and Hentati, Fayçal. “Autosomal Recessive Spastic Ataxia of Charlevoix–Saguenay: An Overview.” Parkinsonism & Related Disorders 17, no. 6 (2011).

Abstract: Autosomal recessive spastic ataxia of Charlevoix–Saguenay (ARSACS) is a distinct form of hereditary early-onset spastic ataxia related to progressive degeneration of the cerebellum and spinal cord. Following the description of the first patients in 1978, the gene responsible has been mapped and identified. It was also shown that the disease occurred worldwide with more than 70 mutations and diverse phenotypes. Because of the random partition of these mutations in the SACS gene particularly on the largest exon nine, and due to the significant clinical variability between patients described in different countries, it has been difficult to establish a genotype–phenotype correlation for the disease. This paper reviews the broad clinical features and the various molecular aspects of ARSACS, reported over the last 30 years highlighting the difficulty of finding correlations.

Basic Biomedical Sciences, Vermillion.

Worthington, A. M., Soluk, Daniel A., and Zercher, D. S. “Influence of Roadways on Patterns of Mortality and Flight Behavior of Adult Dragonflies near Wetland Areas.” Biological Conservation 144, no. 5 (2011).

The relatively low population size and long adult lifespan of dragonflies (Odonata, Anisoptera) makes them one of the few non-vertebrate groups likely to be impacted by direct roadway mortality. We studied adult dragonfly mortality and behavior associated with roadways for a number of species. Daily mortality rates for dragonflies were estimated from standardized surveys along predetermined lengths of roads. Relative abundance and flight behavior around and across roadways, a potentially important mortality factor, was determined from timed roadside observations. Observed flight behavior provided no evidence that roads act as significant barriers to dispersal for adult dragonflies. Estimated mean number killed ranged from 2 to 35 dragonflies/km/day. Species varied greatly in their susceptibility to motor vehicles. Two species (Plathemis lydia and Libellula luctuosa) made up more than 70% of the dead dragonflies collected, but only represented 14% and 31% of live dragonflies observed, respectively. The relatively low flight heights of these two species over roads (typically under 2 m) may explain their susceptibility; however, another common species (Tramea lacerata) also exhibited low flight height but did not experience high mortality, possibly because of its increased flight agility. Large numbers of adult dragonflies were killed over the entire flight season by motor vehicle collisions, exhibiting the need for assessing the long-term impact of roadway mortality on dragonfly population dynamics. (C) 2011 Elsevier Ltd. All rights reserved.

Biology Department.

Tian, L., Gao, J., Weng, G. B., Yi, H. M., Tian, B. L., O’Brien, T. D., and Guo, Zhiguang G. “Comparison of Exendin-4 on Beta-Cell Replication in Mouse and Human Islet Grafts.” Transplant International 24, no. 8 (2011).

Exendin-4 can stimulate beta-cell replication in mice. Whether it can stimulate beta-cell replication in human islet grafts remains unknown. Therefore, we compared the effects of exendin-4 on beta-cell replication in mouse and human islet grafts. Islets, isolated from mouse and human donors at different ages, were transplanted into diabetic mice and/or diabetic nude mice that were given bromodeoxyuridine ( BrdU) with or without exendin-4. At 4 weeks post-transplantation, islet grafts were removed for insulin and BrdU staining and quantification of insulin(+)/BrdU(+) cells. Although diabetes was reversed in all mice transplanting syngeneic mouse islets from young or old donors, normoglycemia was achieved significantly faster in exendin-4 treated mice. Mouse islet grafts in exendin-4 treated mice had significantly more insulin (+)/BrdU(+) beta cells than in untreated mice (P < 0.01). Human islet grafts from <= 22-year-old donors had more insulin (+)/BrdU(+) beta cells in exendin-4 treated mice than that in untreated mice (P < 0.01). However, human islet grafts from >= 35-year-old donors contained few insulin (+)/BrdU(+) beta cells in exendin-4 treated or untreated mice. Our data demonstrated that the capacity for beta-cell replication in mouse and human islet grafts is different with and without exendin-4 treatment and indicated that GLP-1 agonists can stimulate beta-cell replication in human islets from young donors.

Biomedical Engineering, Sioux Falls Campus.

Mani, Gopinath, Torres, N., and Oh, S. “Paclitaxel Delivery from Cobalt-Chromium Alloy Surfaces Using Self-Assembled Monolayers.” Biointerphases 6, no. 2 (2011).

Polymer-based platforms in drug-eluting stents (DESs) can cause adverse reactions in patients. Hence, the development of a polymer-free drug delivery platform may reduce adverse reactions to DES. In this study, the use of a polymer-free platform, self-assembled monolayers (SAMs), is explored for delivering an antiproliferative drug [paclitaxel (PAT)] from a stent material [cobalt-chromium ((Co – Cr) alloy]. Initially, carboxylic acid terminated phosphonic acid SAMs were coated on Co – Cr alloy. Two different doses (25 and 100 mu g/cm(2)) of PAT were coated on SAM coated Co – Cr surfaces using a microdrop deposition method. Also, control experiments were carried out to coat PAT directly on Co – Cr surfaces with no SAM modification. The PAT coated specimens were characterized using the Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and atomic force microscopy (AFM). FTIR spectra showed the successful deposition of PAT on SAM coated and control-Co – Cr surfaces. SEM images showed islands of high density PAT crystals on SAM coated surfaces, while low density PAT crystals were observed on control-Co – Cr alloy. AFM images showed molecular distribution of PAT on SAM coated as well as control-Co – Cr alloy surfaces. In vitro drug release studies showed that PAT was released from SAM coated Co – Cr surfaces in a biphasic manner (an initial burst release in first 7 days was followed by a slow release for up to 35 days), while the PAT was burst released from control-Co – Cr surfaces within 1-3 days. Thus, this study demonstrated the use of SAMs for delivering PAT from Co – Cr alloy surfaces for potential use in drug-eluting stents.

Biomedical Engineering, Sioux Falls.

Banerjee, SubhashKhatri, HariBalasanthiran, VagulejanKoodali, Ranjit T., and Sereda, Grigoriy. “Synthesis of Substituted Acetylenes, Aryl–Alkyl Ethers, 2-Alkene-4-Ynoates and Nitriles Using Heterogeneous Mesoporous Pd-Mcm-48 as Reusable Catalyst.” Tetrahedron 67, no. 32 (2011).

Abstract: Pd-MCM-48 has been employed as a heterogeneous catalyst for the synthesis of substituted acetylenes via Sonogashira reactions under copper and amine-free reaction conditions. In addition, the catalyst exhibited excellent regioselectivity for primary alcohols towards C–O coupling leading to formation of alkyl–aryl ethers in high yields. A green procedure for the stereoselective synthesis of 2-alkene-4-ynoates and nitriles from the reactions of vic-(E)-diiodoalkenes with activated alkenes has also been demonstrated using Pd-MCM-48 catalyst. The catalyst was easily recovered from the reaction mixture by filtration and reused for at least six times with minimal loss of activity.

Chemistry Department.

Biffinger, J. C., Uppaluri, S., Sun, Haoran R., and DiMagno, S. G. “Ligand Fluorination to Optimize Preferential Oxidation of Carbon Monoxide by Water-Soluble Rhodium Porphyrins.” Acs Catalysis 1, no. 7 (2011).

Catalytic, low temperature preferential oxidation (PROX) of carbon monoxide by aqueous [5,10,15,20-tetrakis-(4-sulfonatopheny)-2,3,7,8,12,13,17,18-octafluoropo rphyrinato]-rhodium(III) tetrasodium salt, (1[Rh(III)]) and [5,10,15, 20-tetrakis(3-sulfonato-2,6-difluorophenyl)-2,3,7,8,12,13,17,18-octafluo roporphyrinato]rhodium(III) tetrasodium salt, (2[Rh(III)]) is reported. The PROX reaction occurs at ambient temperature in buffered (4 <= pH <= 13) aqueous solutions. Fluorination on the porphyrin periphery is shown to increase the CO PROX reaction rate, shift the metal centered redox potentials, and acidify ligated water molecules. Most importantly, beta-fluorination increases the acidity of the rhodium hydride complex (pK(a) = 2.2 +/- 0.2 for 2[Rh-D]); the dramatically increased acidity of the Rh(III) hydride complex precludes proton reduction and hydrogen activation near neutral pH, thereby permitting oxidation of CO to be unaffected by the presence of H(2). This new fluorinated water-soluble rhodium porphyrin-based homogeneous catalyst system permits preferential oxidation of Carbon monoxide in hydrogen gas streams at 308 K using dioxygen or a sacrificial electron acceptor (indigo carmine) as the terminal oxidant.

Chemistry Department.

Brandner, AmberKitahara, TaizoBeare, NickLin, Cuikun. K.Berry, Mary T., and May, P. Stanley. “Luminescence Properties and Quenching Mechanisms of Ln(Tf(2)N)(3) Complexes in the Ionic Liquid Bmpyr Tf(2)N.”Inorganic Chemistry 50, no. 14 (2011).

The emission properties, including luminescence lifetimes, of the lanthanide complexes Ln(Tf(2)N)(3) (Tf(2)N = bis-(trifluoromethanesulfonyl)amide); Ln(3+) = Eu(3+), Tm(3+), Dy(3+), Sm(3+), Pr(3+), Nd(3+), Er(3+)) in the ionic liquid bmpyr Tf(2)N (bmpyr = 1-n-butyl-1-methylpyrrolidinium) are presented. The luminescence quantum efficiencies, eta, and radiative lifetimes, tau(R), are determined for Eu(3+)((5)D(0)), Tm(3+)((1)D(2)), Dy(3+)((4)F(9/2)), Sm(3+)((4)G(5/2)), and Pr(3+)((3)P(0)) emission. The luminescence lifetimes in these systems are remarkably long compared to values typically reported for Ln(3+) complexes in solution, reflecting weak vibrational quenching. The 1.5 mu m emission corresponding to the Er(3+) ((4)I(13/2)->(4)I(15/2)) transition, for example, exhibits a lifetime of 77 mu s. The multiphonon relaxation rate constants are determined for 10 different Ln(3+) emitting states, and the trend in multiphonon relaxation is analyzed in terms of the energy gap law. The energy gap law does describe the general trend in multiphonon relaxation, but deviations from the trend are much larger than those normally observed for crystal systems. The parameters determined from the energy gap law analysis are consistent with those reported for crystalline hosts. Because Ln(3+) emission is known to be particularly sensitive to quenching by water in bmpyr Tf(2)N, the binding properties of water to Eu(3+) in solutions of Eu(Tf(2)N)(3) in bmpyr Tf(2)N have been quantified. It is observed that water introduced into these systems binds quantitatively to Ln(3+). It is demonstrated that Eu(Tf(2)N)(3) can be used as a reasonable internal standard, both for monitoring the dryness of the solutions and for estimating the quantum efficiencies and radiative lifetimes for visible-emitting [Ln(Tf(2)N)(x)](3-x) complexes in bmpyr Tf(2)N.

Chemistry Department.

Budhi, S.Kibombo, H. S.Zhao, D.Gonshorowski, A., and Koodali, R. T. “Synthesis of Titania-Silica Xerogels by Co-Solvent Induced Gelation at Ambient Temperature.” Materials Letters 65, no. 14 (2011).

A series of binary titania-silica mixed oxides was prepared by sol-gel synthesis at room temperature. The hydrolysis of titanium isopropoxide (Ti((i)OPr)(4)) and tetraethylorthosilicate (TEOS) was facilitated by co-solvent induced gelation in acidic media. The resulting gels were dried, calcined, and then characterized by powder X-ray diffraction analysis, nitrogen sorption studies (at 77 K), diffuse reflectance spectroscopy, Raman microscopy, and transmission electron microscopy. The nitrogen sorption studies indicate that the porosities could be tuned when simple aromatic solvents such as toluene, p-xylene, or mesitylene were added as a co-solvent to the synthesis gel. The binary mixed metal oxide materials obtained in this study showed high activity towards the degradation of phenol, and possessed high surface areas, and large pore volumes with narrow pore size distribution without the need for additional hydrothermal synthesis or supercritical drying. (C) 2011 Elsevier B.V. All rights reserved.

Chemistry Department.

Prasad, Maneeshi S., and Paulson, Alicia F. “A Combination of Enhancer/Silencer Modules Regulates Spatially Restricted Expression of Cadherin-7 in Neural Epithelium.” Developmental Dynamics 240, no. 7 (2011).

The spatially restricted expression of cadherin-7 to the intermediate domain of the neural epithelium and in migrating neural crest cells during early neural development is potentially regulated by multiple signaling inputs. To identify the regulatory modules involved in regulation of cadherin-7, evolutionary conserved non-coding sequences in the cadherin-7 locus were analyzed. This led to the identification of an evolutionary conserved region of 606 bp (ECR1) that together with the cadherin-7 promoter recapitulates endogenous cadherin-7 expression in intermediate neural tube, spinal motor neurons, interneurons, and dorsal root ganglia. Deletion analysis of ECR1 revealed a 19-bp block that is essential for ECR1 enhancer activity, while two separate blocks of 10 and 12 bp were found to be essential for ECR1 silencer activity in the dorsal and ventral neural epithelium, respectively. Together, these data provide an insight into tissue-specific regulatory regions that might be involved in regulation of cadherin-7 gene expression. Developmental Dynamics 240:1756-1768, 2011. (C) 2011 Wiley-Liss, Inc.

Biology Department.

Lushbough, Carol M., Jennewein, D. M., and Brendel, V. P. “The Bioextract Server: A Web-Based Bioinformatic Workflow Platform.” Nucleic Acids Research 39 (2011).

The BioExtract Server (bioextract.org) is an open, web-based system designed to aid researchers in the analysis of genomic data by providing a platform for the creation of bioinformatic workflows. Scientific workflows are created within the system by recording tasks performed by the user. These tasks may include querying multiple, distributed data sources, saving query results as searchable data extracts, and executing local and web-accessible analytic tools. The series of recorded tasks can then be saved as a reproducible, sharable workflow available for subsequent execution with the original or modified inputs and parameter settings. Integrated data resources include interfaces to the National Center for Biotechnology Information (NCBI) nucleotide and protein databases, the European Molecular Biology Laboratory (EMBL-Bank) non-redundant nucleotide database, the Universal Protein Resource (UniProt), and the UniProt Reference Clusters (UniRef) database. The system offers access to numerous preinstalled, curated analytic tools and also provides researchers with the option of selecting computational tools from a large list of web services including the European Molecular Biology Open Software Suite (EMBOSS), BioMoby, and the Kyoto Encyclopedia of Genes and Genomes (KEGG). The system further allows users to integrate local command line tools residing on their own computers through a client-side Java applet.

Computer Science Department.

Sellin Jeffries, Marlo K., Conoan, Nicholas H., Cox, Marc B., Cowman, Tim, Knight, Lindsey A., Bartelt-Hunt, Shannon L., and Kolok, Alan S. “The Anti-Estrogenic Activity of Sediments from Agriculturally Intense Watersheds: Assessment Using in Vivo and in Vitro Assays.” Aquatic Toxicology 105, no. 1/2 (2011).

Abstract: The goal of the current study was to determine whether sediments from agriculturally intense watersheds can act as a potential source of anti-estrogenic endocrine-disrupting compounds. The specific objectives of the current study were to determine (1) whether female fathead minnows (Pimephales promelas) experience alterations in endocrine function when exposed to sediments collected from agriculturally intense watersheds and (2) if these sediments display anti-estrogenic activity in an in vitro assay. In addition, sediment samples were analyzed for the presence of steroid hormones and pesticides associated with local agricultural practices. To accomplish this, sediments and water were collected from three sites within two agriculturally intense Nebraska watersheds (Bow Creek and the Elkhorn River). In 2009, minnows were exposed to sediment and/or water collected from the two Bow Creek sites (East Bow Creek and the Confluence) in the laboratory, while in 2010, minnows were exposed to sediment and/or water from East Bow Creek, the Confluence and the Elkhorn River. Following the 7-day exposure period, the hepatic mRNA expression of two-estrogen responsive genes, estrogen receptor α (ERα) and vitellogenin (Vtg) was determined. In 2009, females exposed to Confluence sediments, in the presence of laboratory water or Confluence water, experienced significant reductions in ERα expression relative to unexposed and Confluence water-exposed females. The defeminization of these females suggests the presence of a biologically available anti-estrogenic compound in sediments collected from this site. In 2010, sediments were assessed for anti-estrogenic activity on days 0 and 7 of the exposure period using a 4-h yeast estrogen screen. Lipophilic extracts (LEs) of day 0 sediments collected from the Confluence and the Elkhorn River induced significant reductions in the estrogenic reporter activity of treated yeast cultures suggesting the presence of a lipophilic anti-estrogenic compound in these extracts. Chemical analysis revealed the presence of a variety of steroid hormones, including those associated with the production of beef cattle (i.e. β-trenbolone, α-zearalanol and α-zearalenol), in sediments indicating that compounds utilized by local beef cattle operations are capable of entering nearby watersheds. Overall, the results of this study indicate that an environmentally relevant anti-estrogenic compound is present in sediments from agriculturally intense watersheds and that this compound is bioavailable to fish. Furthermore, the presence of steroid hormones in sediments from these watersheds provides evidence indicating that steroids are capable of sorbing to sediments.

Missouri River Institute

Koster, John. “A Spanish Harpsichord from Domenico Scarlatti’s Environs.” Early Music 39, no. 2 (2011).

An instrument in the collection of the Smithsonian Institution, Washington, DC, is identified as a unique example of a Spanish harpsichord in a style influenced by the Florentine school of Bartolomeo Cristofori. This influence was strong in circles of patronage associated with Domenico Scarlatti, and the Smithsonian harpsichord can be attributed to Diego Fernández, maker to the Spanish royal family. It has two 8′ registers, both permanently engaged, and a compass of G’ to g”’

National Music Museum.

Dvorak, Robert D.Simons, Jeffrey S., and Wray, Tyler B. “Alcohol Use and Problem Severity: Associations with Dual Systems of Self-Control.” Journal of Studies on Alcohol & Drugs 72, no. 4 (2011).

Objective: The current study tested the associations between a dual-systems model of self-control and alcohol use and problem severity. Method: The sample consisted of 491 college students (77.0% women) from a rural state university. Participants completed a series of online surveys that assessed aspects of self-control, alcohol consumption, and alcohol-related problems. Results: A confirmatory factor analysis model indicated two moderately correlated factors of poor control and good self-control. Poor control was positively associated with both alcohol use and problem severity. Good self-control had a negative association with problem severity. Good self-control moderated the association between poor control and alcohol use as well as between poor control and problem severity. The association between poor control and alcohol use was stronger at low levels of good self-control, whereas at high levels of good self-control, the effect of poor control was weaker and not significant. The interaction predicting problem severity was different: There was a negative association between good self-control and problem severity at low levels of poor control, and this effect diminished as poor control increased. Conclusions: The results suggest that multidimensional models of self-control may be useful in understanding problematic alcohol use and may be beneficial for prevention and intervention efforts.

Psychology Department.

Bade, Priscilla. “Improving Communication When Hearing Loss Is Present #241.” Journal of Palliative Medicine 14, no. 7 (2011).

The article discusses ways on how to communicate patients with hearing loss. It states that hearing can loss can have emotional impact including social isolation and loss of self-esteem due to communication mistakes. It highlights various techniques to improve communication with deaf patients including the reduction of background noise and distractions, using technology and to speak distinctly and clearly.

Sanford School of Medicine, Sioux Falls Campus.

Boyle, JeffreyEerden, Peter Van, and McNamara, Michael. “Second-Trimester Abortion for Fetal Anomalies or Fetal Death: Labor Induction Compared with Dilation and Evacuation.” Obstetrics and gynecology 118, no. 2 Pt 1 (2011).

Sanford School of Medicine, Sioux Falls Campus.

Chen, KaiXu, Xanmin M.Kobayashi, SatoruTimm, DerekJepperson, Tyler, and Liang, Qiangrong R. “Caloric Restriction Mimetic 2-Deoxyglucose Antagonizes Doxorubicin-Induced Cardiomyocyte Death by Multiple Mechanisms.” Journal of Biological Chemistry 286, no. 25 (2011).

Caloric restriction (CR) is a dietary intervention known to enhance cardiovascular health. The glucose analog 2-deoxy-D-glucose (2-DG) mimics CR effects in several animal models. However, whether 2-DG is beneficial to the heart remains obscure. Here, we tested the ability of 2-DG to reduce cardiomyocyte death triggered by doxorubicin (DOX, 1 mu M), an antitumor drug that can cause heart failure. Treatment of neonatal rat cardiomyocytes with 0.5 mM 2-DG dramatically suppressed DOX cytotoxicity as indicated by a decreased number of cells that stained positive for propidium iodide and reduced apoptotic markers. 2-DG decreased intracellular ATP levels by 17.9%, but it prevented DOX-induced severe depletion of ATP, which may contribute to 2-DG-mediated cytoprotection. Also, 2-DG increased the activity of AMP-activated protein kinase (AMPK). Blocking AMPK signaling with compound C or small interfering RNA-mediated knockdown of the catalytic subunit markedly attenuated the protective effects of 2-DG. Conversely, AMPK activation by pharmacological or genetic approach reduced DOX cardiotoxicity but did not produce additive effects when used together with 2-DG. In addition, 2-DG induced autophagy, a cellular degradation pathway whose activation could be either protective or detrimental depending on the context. Paradoxically, despite its ability to activate autophagy, 2-DG prevented DOX-induced detrimental autophagy. Together, these results suggest that the CR mimetic 2-DG can antagonize DOX-induced cardiomyocyte death, which is mediated through multiple mechanisms, including the preservation of ATP content, the activation of AMPK, and the inhibition of autophagy.

Sanford School of Medicine, Sioux Falls Campus.

Eid, Wael E. “Obesity and Type 2 Diabetes Mellitus in South Dakota: Focused Insight into Prevalence, Physiology and Treatment.” South Dakota Medicine: The Journal Of The South Dakota State Medical Association Spec No (2011).

Type 2 diabetes mellitus is one of the significant comorbidities of obesity. This review addresses the prevalence of obesity and diabetes mellitus nationally and in South Dakota. It elaborates on some of the mechanisms of association of obesity with diabetes mellitus, including effects related to adipokines, lipotoxicity, vitamin D deficiency and apolipoprotein C1. This review addresses the prevention and treatment of diabetes mellitus in the obese population through life style changes, medications and/or surgery. Future directions in the management of diabetes are explored in the obese population.

Sanford School of Medicine, Sioux Falls Campus.

Kai, ChenXianmin, XuKobayashi, SatoruTimm, DerekJepperson, Tyler, and Qiangrong, Liang. “Caloric Restriction Mimetic 2-Deoxyglucose Antagonizes Doxorubicin-Induced Cardiomyocyte Death by Multiple Mechanisms.” Journal of Biological Chemistry 286, no. 25 (2011).

Caloric restriction (CR) is a dietary intervention known to enhance cardiovascular health. The glucose analog 2-deoxy-D-glucose (2-DG) mimics CR effects in several animal models. However, whether 2-DG is beneficial to the heart remains obscure. Here, we tested the ability of 2-DG to reduce cardiomyocyte death triggered by doxorubicin (DOX, 1 μM), an antitumor drug that can cause heart failure. Treatment of neonatal rat cardiomyocytes with 0.5 mM 2-DG dramatically suppressed DOX cytotoxicity as indicated by a decreased number of cells that stained positive for propidium iodide and reduced apoptotic markers. 2 -DG decreased intracellular ATP levels by 17.9%, but it prevented DOX-induced severe depletion of ATP, which may contribute to 2-DG-mediated cytoprotection. Also, 2-DG increased the activity of AMP-activated protein kinase (AMPK). Blocking AMPK signaling with compound C or small interfering RNA-mediated knockdown of the catalytic subunit markedly attenuated the protective effects of 2-DG. Conversely, AMPK activation by pharmacological or genetic approach reduced DOX cardiotoxicity but did not produce additive effects when used together with 2-DG. In addition, 2-DG induced autophagy, a cellular degradation pathway whose activation could be either protective or detrimental depending on the context. Paradoxically, despite its ability to activate autophagy, 2-DG prevented DOX-induced detrimental autophagy. Together, these results suggest that the CR mimetic 2-DG can antagonize DOX-induced cardiomyocyte death, which is mediated through multiple mechanisms, including the preservation of ATP content, the activation of AMPK, and the inhibition of autophagy.

Sanford School of Medicine, Sioux Falls Campus.

Luke, A., Lazaro, R. M., Bergeron, Michael F., Keyser, L., Benjamin, H., Brenner, J., d’Hemecourt, P., Grady, M., Philpott, J., and Smith, A. “Sports-Related Injuries in Youth Athletes: Is Overscheduling a Risk Factor?”Clinical Journal of Sport Medicine 21, no. 4 (2011).

Objective: To examine the association between “overscheduling” and sports-related overuse and acute injuries in young athletes and to identify other potential contributing factors to create a working definition for “overscheduling injury.” Design: Survey. Setting: Six university-based sports medicine clinics in North America. Participants: Athletes aged 6 to 18 years (13.8 +/- 2.6) and their parents and pediatric sports medicine-trained physicians. Interventions: Questionnaires developed from literature review and expert consensus to investigate overscheduling and sports-related injuries were completed over a 3-month period. Main Outcome Measures: Physician’s clinical diagnosis and injury categorization: acute not fatigue related (AI), overuse not fatigue related (OI), acute fatigue related (AFI), or overuse fatigue related (OFI). Results: Overall, 360 questionnaires were completed (84% response rate). Overuse not fatigue-related injuries were encountered most often (44.7%), compared with AI (41.9%) and OFI (9.7%). Number of practices within 48 hours before injury was higher (1.7 +/- 1.5) for athletes with OI versus those with AI (1.3 +/- 1.4; P = 0.025). Athlete or parent perception of excessive play/training without adequate rest in the days before the injury was related to overuse (P = 0.016) and fatigue-related injuries (P = 0.010). Fatigue-related injuries were related to sleeping <= 6 hours the night before the injury (P = 0.028). Conclusions: When scheduling youth sporting events, potential activity volume and intensity over any 48-hour period, recovery time between all training and competition bouts, and potential between-day sleep time (>= 7 hours) should be considered to optimize safety. An overscheduling injury can be defined as an injury related to excessive planned physical activity without adequate time for rest and recovery, including between training sessions/competitions and consecutive days.

Sanford School of Medicine, Sioux Falls Campus.

May, P. A., Fiorentino, D., Coriale, G., Kalberg, W. O., Hoyme, H. Eugene, Aragon, A. S., Buckley, D., Stellavato, C., Gossage, J. P., Robinson, L. K., Jones, K. L., Manning, M., and Ceccanti, M. “Prevalence of Children with Severe Fetal Alcohol Spectrum Disorders in Communities near Rome, Italy: New Estimated Rates Are Higher Than Previous Estimates.” International Journal of Environmental Research and Public Health 8, no. 6 (2011).

Objective: To determine the population-based epidemiology of fetal alcohol syndrome (FAS) and other fetal alcohol spectrum disorders (FASD) in towns representative of the general population of central Italy. Methods: Slightly revised U. S. Institute of Medicine diagnostic methods were used among children in randomly-selected schools near Rome. Consented first grade children (n = 976) were screened in Tier I for height, weight, or head circumference and all children <= 10th centile on one of these measurements were included in the study. Also, teachers referred children for learning or behavioral problems. Children meeting either of these two criteria, along with randomly-selected controls, advanced to Tier II which began with a dysmorphology examination. Children with a possible FASD, and controls, advanced to Tier III for neurobehavioral testing, and their mothers were interviewed for maternal risks. Final diagnoses using indicators of dysmorphology, neurobehavior, and maternal risk were made in formally-structured, interdisciplinary case conferences. Results: Case control comparisons of physical, neurobehavioral, and maternal risk variables are presented for 46 children with an FASD and 116 randomly-selected controls without a diagnosis on the FASD continuum. Rates of diagnoses within the FASD continuum are then estimated from these in-school data via three different methods. The range of rates of FAS produced by these methods is between 4.0 to 12.0 per 1,000; Partial FAS ranges from 18.1 to 46.3 per 1,000; and an FASD was found in 2.3% to 6.3% of the children. Conclusions: These rates are substantially higher than previous estimates of FAS and overall FASD for the general populations of Western Europe and the U. S., and raise questions as to the total impact of FASD on mental deficit in mainstream populations of Western Europe and the United States where the majority are middle class and are not believed to be characterized by heavy episodic drinking.

Sanford School of Medicine, Sioux Falls Campus.

Salisbury, Adam C., Amin, Amit P., Harris, William S., Chan, Paul S., Gosch, Kensey L., Rich, Michael W., O’Keefe Jr, James H., and Spertus, John A. “Predictors of Omega-3 Index in Patients with Acute Myocardial Infarction.”Mayo Clinic Proceedings 86, no. 7 (2011).

OBJECTIVE: To identify the patient and dietary characteristics associated with low omega-3 levels in patients with acute myocardial infarction (AMI) and determine whether these characteristics are useful to identify patients who may benefit from omega-3 testing and treatment. PATIENTS AND METHODS: Dietary habits of 1487 patients in the 24-center Translational Research Investigating Underlying disparities in acute Myocardial infarction Patients’ Health status (TRIUMPH) registry between April 11, 2005, and September 28, 2007, were assessed by asking about the frequency of fast food and nonfried fish consumption. All patients had erythrocyte omega-3 index measured at the time of hospital admission for AMI. We used multivariable linear regression to Identify independent correlates of the omega-3 index and modified Poisson regression to predict risk of a low omega-3 index (<4%). RESULTS: The proportion of patients with a low omega-3 index increased with more frequent fast food intake (18.9% for <1 time monthly, 28.6% for 1-3 times monthly, 28.8% for 1-2 times weekly, and 37.6% for ≥3 times weekly; P<.001). In contrast, a low omega-3 index was less common among patients with more frequent fish intake (35.1% for <1 time monthly, 24.9% for 1-3 times monthly, 16.1% for 1-2 times weekly, and 21.1% for ≥3 times weekly; Pc.001). Fish intake, older age, race other than white, and omega-3 supplementation were independently associated with a higher omega-3 index, whereas frequent fast food intake, smoking, and diabetes mellitus were associated with a lower omega-3 index. CONCLUSION: Potentially modifiable factors, such as patient-reported fast food intake, fish intake, and smoking, are independently associated with the omega-3 index in patients with AMI. These characteristics may be useful to identify patients who would benefit most from omega-3 supplementation and lifestyle modification.

Sanford School of Medicine, Sioux Falls Campus.

Yu, John C., and Berger, Paul, 3rd. “Sleep Apnea and Obesity.” South Dakota Medicine: The Journal Of The South Dakota State Medical Association Spec No (2011).

The dramatic increase in the worldwide prevalence of obesity has paralleled the increase in the prevalence of obstructive sleep apnea (OSA). Even with heightened awareness by the lay and medical communities, OSA is still markedly under-diagnosed, as evidenced by the persistent presentation of late-stage cardiovascular complications in obese individuals newly diagnosed with sleep apnea. The clinical sequela of untreated and poorly-treated sleep apnea include conditions that are considered components of the metabolic syndrome for which central obesity is one of the major case-defining features. Hence, in this review of obesity and sleep apnea, it is unavoidable to include discussion of sleep apnea and other components of the metabolic syndrome. Proponents of this clinical perspective suggest that there are mutual genetic determinants that give rise to common phenotypic features and allow clustering of sleep apnea with the other components of the metabolic syndrome. Perhaps, the strongest observational evidence to support a link between sleep apnea and obesity is the similarity in age distribution of symptomatic sleep apnea and metabolic syndrome. The putative causal links between sleep apnea and each individual component of the metabolic syndrome have been extensively evaluated and have implicated bidirectional causality in certain metabolic conditions, such as obesity and sleep apnea, sleep apnea and diabetes mellitus, and obesity and diabetes mellitus. These studies collectively suggest that even modest weight loss improves OSA, and positively affects both metabolic and cardiovascular risk profiles.

Sanford School of Medicine, Sioux Falls Campus.

Zheng, Yongxian H., and Miskimins, W. Keith. “Cug-Binding Protein Represses Translation of P27(Kip1) Mrna through Its Internal Ribosomal Entry Site.” Rna Biology 8, no. 3 (2011).

The cyclin dependent kinase inhibitor p27(Kip1) plays an important role in controlling the eukaryotic cell cycle. The 5 ‘-untranslated region of the p27 mRNA harbors an internal ribosome entry site (IRES) which may facilitate synthesis of p27 in certain conditions. In this study, the RNA-associated protein CU GBP1 was shown to interact with the human p27 5 ‘-untranslated region. Overexpression of CU GBP1 inhibited endogenous p27 expression and reduced translation initiation through the p27 IRES. In contrast, repression of CU GBP1 by siRNA transfection enhanced p27 protein levels and stimulated p27 IRES activity. Addition of recombinant CU GBP1 repressed p27 IRES reporter mRNA translation in vitro. At last, our finding showed that cytosolic form of CU GBP1 binds efficiently to the p27 5 ‘-untranslated region.

Sanford School of Medicine, Sioux Falls Campus.

Hazlett, Lisa A.Sweeney, William J., and Reins, Kevin J. “Using Young Adult Literature Featuring Lgbtq Adolescents with Intellectual and/or Physical Disabilities to Strengthen Classroom Inclusion.” Theory Into Practice 50, no. 3 (2011).

Adolescence is chaotic for all individuals, but LGBTQ adolescents with intellectual and/or physical disabilities struggle with what it means to be furthest from the majority. These teens experience varying exclusions and harassments from peers, educators, and family members. Contemporary young adult literature can assist these adolescents through novels positively reflecting themselves and their situations and issues. Such literature also affords greater majority awareness, understanding, and acceptance of these minority individuals within schools and society.

School of Education.


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