Posted by: kelsijo97 | June 10, 2011

May 2011

Banerjee, SubhashAlissa HornHari Khatri, and Grigory Sereda. “A Green One-Pot Multicomponent Synthesis of 4h-Pyrans and Polysubstituted Aniline Derivatives of Biological, Pharmacological, and Optical Applications Using Silica Nanoparticles as Reusable Catalyst.” Tetrahedron Letters 52, no. 16 (2011): 1878-81.

A one-pot practical, efficient, and environmentally benign multicomponent synthesis of 4H-pyrans and polysubstituted aniline derivatives of biological, pharmacological, and optical applications has been developed using a very mild, neutral, and reusable silica nanoparticles as catalyst. The 4H-pyran derivatives were synthesized by a three component reaction of an aldehyde, malononitrile, and 5,5-dimethyl-1,3-cyclohexanedione or ethyl acetoacetate at room temperature or refluxing in ethanol. Alternatively, polysubstituted anilines were synthesized via a four component reaction of an aldehyde, a ketone, and two equivalents of malononitrile in ethanol. (C) 2011 Elsevier Ltd. All rights reserved.

Chemistry Department.

Barr, J. L., and Gina L. Forster. “Serotonergic Neurotransmission in the Ventral Hippocampus Is Enhanced by Corticosterone and Altered by Chronic Amphetamine Treatment.” Neuroscience 182 (2011): 105-14.

The ventral hippocampus modulates anxiety-like behavior in rats, and serotonergic transmission within the hippocampus facilitates adaptation to stress. Chronic amphetamine treatment results in anxiety-like behavior in rats and reduced monoamine concentrations in the ventral hippocampus. Since reduced hippocampal serotonergic transmission in response to stress is observed in rats that display high anxiety-like behavior, anxiety states in amphetamine-treated rats may be associated with reduced stress-related serotonergic transmission in the hippocampus. Therefore, using in vivo microdialysis in anesthetized rats, we investigated the effect of corticosterone infused locally into the ventral hippocampus on serotonergic transmission, and the effect of chronic amphetamine pretreatment on corticosteroid receptor protein expression and the corticosterone-induced serotonergic response. Extracellular serotonin in the ventral hippocampus was increased by corticosterone in drug naive rats, and this corticosterone-induced serotonin augmentation was blocked by the glucocorticoid receptor antagonist mifepristone. Furthermore, chronic pretreatment with amphetamine abolished the serotonin response to physiologically relevant corticosterone levels and reduced glucocorticoid receptor protein expression. Together, our results suggest that chronic amphetamine exposure reduces serotonergic neurotransmission, in part via alterations to glucocorticoid receptor-facilitation of serotonin release in the rat ventral hippocampus. Reduced serotonergic activity in the ventral hippocampus may contribute to altered stress responses and adaptive coping following repeated drug exposure. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Basic Biomedical Sciences, Vermillion Campus.

Benson, Nicholas, and Thomas Oakland. “International Classification of Functioning, Disability, and Health: Implications for School Psychologists.” Canadian Journal of School Psychology 26, no. 1 (2011): 3-17.

The International Classification of Functioning, Disability and Health (ICF) provides a framework for describing behaviors by viewing them from three broad and different perspectives: (1) physiologic, physical, and psychological functions; (2) a person’s engagement in functional life activities; and (3) their participation in social settings. The ICF Framework aligns well with current efforts in school psychology to adopt population-based models of service delivery, reflect public health models of service delivery, promote mental health, and prevent disorders or problem behaviors. Essential features of the ICF together with implications important to service delivery in general and psychoeducational assessment in particular are described. (PsycINFO Database Record (c) 2011 APA, all rights reserved) (journal abstract)

School of Education

Chaussee, Michael S.Heather R. SandbulteMargaret J. SchunemanFrank P. DePaulaLeslie A. AddengastEvelyn H. Schlenker, and Victor C. Huber. “Inactivated and Live, Attenuated Influenza Vaccines Protect Mice against Influenza:Streptococcus Pyogenes Super-Infections.” Vaccine 29, no. 21 (2011): 3773-81.

Abstract: Mortality associated with influenza virus super-infections is frequently due to secondary bacterial complications. To date, super-infections with Streptococcus pyogenes have been studied less extensively than those associated with Streptococcus pneumoniae. This is significant because a vaccine for S. pyogenes is not clinically available, leaving vaccination against influenza virus as our only means for preventing these super-infections. In this study, we directly compared immunity induced by two types of influenza vaccine, either inactivated influenza virus (IIV) or live, attenuated influenza virus (LAIV), for the ability to prevent super-infections. Our data demonstrate that both IIV and LAIV vaccines induce similar levels of serum antibodies, and that LAIV alone induces IgA expression at mucosal surfaces. Upon super-infection, both vaccines have the ability to limit the induction of pro-inflammatory cytokines within the lung, including IFN-γ which has been shown to contribute to mortality in previous models of super-infection. Limiting expression of these pro-inflammatory cytokines within the lungs subsequently limits recruitment of macrophages and neutrophils to pulmonary surfaces, and ultimately protects both IIV- and LAIV-vaccinated mice from mortality. Despite their overall survival, both IIV- and LAIV-vaccinated mice demonstrated levels of bacteria within the lung tissue that are similar to those seen in unvaccinated mice. Thus, influenza virus:bacteria super-infections can be limited by vaccine-induced immunity against influenza virus, but the ability to prevent morbidity is not complete.

Basic Biomedical Sciences, Vermillion Campus

Dong, G.J. M. FergusonA. J. DulingR. G. NicholasD. ZhangK. Rezvani, S. Fang, M. J. Monteiro, S. Li, X. J. Li, and H. Wang. “Modeling Pathogenesis of Huntington’s Disease with Inducible Neuroprogenitor Cells.”Cellular and Molecular Neurobiology 31, no. 5 (2011): 737-47.

Huntington’s disease (HD) is caused by an abnormal expansion of CAG trinucleotide repeats encoding polyglutamine (polyQ) in the first exon of the huntingtin (htt) gene. Despite considerable efforts, the pathogenesis of HD remains largely unclear due to a paucity of models that can reliably reproduce the pathological characteristics of HD. Here, we report a neuronal cell model of HD using the previously established tetracycline regulated rat neuroprogenitor cell line, HC2S2. Stable expression of enhanced green fluorescence protein tagged htt exon 1 (referred to as 28Q and 74Q, respectively) in the HC2S2 cells did not affect rapid neuronal differentiation. However, compared to the cells expressing wild type htt, the cell line expressing mutant htt showed an increase in time-dependent cell death and neuritic degeneration, and displayed increased vulnerability to oxidative stress. Increased protein aggregation during the process of neuronal aging or when the cells were exposed to oxidative stress reagents was detected in the cell line expressing 74Q but not in its counterpart. These results suggest that the neuroprogenitor cell lines mimic the major neuropathological characteristics of HD and may provide a useful tool for studying the neuropathogenesis of HD and for high throughput screening of therapeutic compounds.

Baisic Biomedical Sciences, Vermillion Campus

Finn, RozzyAttila D. Kovacs, and David A. Pearce. “Altered Sensitivity of Cerebellar Granule Cells to Glutamate Receptor Overactivation in the Cln3 Delta Ex7/8-Knock-in Mouse Model of Juvenile Neuronal Ceroid Lipofuscinosis.” Neurochemistry International 58, no. 6 (2011): 648-55.

The juvenile onset form of neuronal ceroid lipofuscinoses (JNCL) is a recessively inherited lysosomal storage disorder characterized by progressive neurodegeneration. JNCL results from mutations in the CLN3 gene that encodes a lysosomal membrane protein with unknown function.Utilizing a Cln3-knock-out mouse model of JNCL that was created on the 12956/SvEv genetic background, we have previously demonstrated that CLN3-deficient cerebellar granule cells (CGCs) have a selectively increased sensitivity to AMPA-type glutamate receptor-mediated toxicity. Our recent findings that CGCs from 129S6/SvEv and C57BL/6J wild type (WT) mice have significant differences in glutamate receptor expression and in excitotoxic vulnerability indicated that the genetic background possibly have a strong influence on how glutamate receptor function is dysregulated in CLN3-deficient neurons. Indeed, here we show that in the Cln3(Delta ex7/8)-knock-in mouse model, that is on the C57BL/6J genetic background, mimics the most frequent mutation observed in JNCL patients and considered a null mutant, the sensitivity of CGCs to both AMPA- and NMDA-type glutamate receptor overactivations is altered. Cultured wild type and Cln3(Delta ex7/8) CGC5 were equally sensitive to AMPA toxicity after 2 or 3 weeks in vitro, whereas the subunit-selective AMPA receptor agonist, CPW-399, induced significantly more cell death in mature, 3-week-old Cln3(Delta ex7/8) cultures. NMDA receptor-mediated toxicity changed during in vitro development: Cln3(Delta ex7/8) CGCs were less sensitive to high concentration of NMDA after 2 weeks in culture but became more vulnerable than their WT counterparts after 3 weeks in vitro.Abnormally altered glutamate receptor function in the cerebellum may result in motor deficits, and we confirmed that 7-week-old Cln3(Delta ex7/8) mice, similarly to Cln3-knock-out mice, have a motor coordination deficit as measured by an accelerating rotarod.Our results demonstrate altered glutamate receptor function in Cln3(Delta ex7/8) neurons and suggest that both AMPA and NMDA receptors are potential therapeutic targets in JNCL (C) 2011 Elsevier Ltd. All rights reserved.

Sanford School of Medicine, Sioux Falls Campus.

Ganze, Ronald J. “The Individual in the Afterlife: Theological and Sociopolitical Concerns in King Alfred’s Translation of Augustine’s Soliloquies.” Studia Neophilologica 83, no. 1 (2011): 21-40.

This article argues that Alfred’s translation of Augustine’s Soliloquia provides vital insight into Alfred’s own philosophical positions in areas where the Alfredian voice differs from the Augustinian: philosophical concerns, especially those surrounding the self and free will; theological arguments, particularly regarding the immortality of the soul and the survival of its individuality; and socio-political issues, specifically the relationship between the social order in Alfred’s kingdom and the order of Creation. While a number of critics have used a social constructionist approach to examine the self in Alfred’s Soliloquies, this article frames both Augustine’s and Alfred’s views from the point of view of naturalized phenomenology, concluding that Alfred’s phenomenological and epistemological desires are different from Augustine’s. These disagreements can be found in the ‘fissures’ that emerge in Alfred’s translation, places where a space is created in the Augustinian text and filled with material from other patristic sources or Alfred’s own words. In making these changes, it appears that Alfred is asserting his own self, desires, and beliefs over and above Augustine’s, emphasizing the things of this world in ways that seem to contradict Augustine’s own theory of use and enjoyment. Rather than being a minor translation to be read alongside the Boethius, Alfred’s Soliloquies are an important touchstone in the development of medieval philosophy.

English Department.

Gray, F. E., C. Ruybal, J. Totushek, Dongming M. MeiK. Thomas, and C. Zhang. “Cosmic Ray Muon Flux at the Sanford Underground Laboratory at Homestake.” Nuclear Instruments & Methods in Physics Research Section a-Accelerators Spectrometers Detectors and Associated Equipment 638, no. 1 (2011): 63-66.

Measuring the muon flux is important to the Sanford Underground Laboratory at Homestake, for which several low background experiments are being planned. The nearly vertical cosmic ray muon flux was measured in three locations at this laboratory: on the surface (1.149 +/- 0.017 x 10(-2) cm(-2) s(-1) sr(-1)), at the 800 ft (0.712 km w.e.) level (2.67 +/- 0.06 x 10(-6) cm(-2) s(-1) sr(-1)), and at the 2000 ft (1.78 km w.e.) level (2.56 +/- 0.25 x 10(-7) cm(-2) s(-1) sr(-1)). These fluxes agree well with model predictions. (C) 2011 Elsevier B.V. All rights reserved.

Physics Department.

Hulac, David M., and Nicholas Benson. “Getting Students to Work Smarter and Harder: Decreasing Off-Task Behavior through Interspersal Techniques.” School Psychology Forum 5, no. 1 (2011): 29-36.

Many school psychologists are faced with the challenge of addressing offtask behaviors. Often, manipulating instructional variables can increase on-task behavior and reduce problematic off-task behaviors. When task difficulty is found to cause off-task behavior, adjusting the ratio of mastered tasks to not yet mastered tasks included in an activity may prove beneficial. Such practices are known as interspersal techniques. This article reviews interspersal techniques and provides practical applications that school psychologists may recommend to improve student on-task behavior.

School of Education.

Husak, Jerry F., G. Ribak, G. S. Wilkinson, and John G. Swallow. “Compensation for Exaggerated Eye Stalks in Stalk-Eyed Flies (Diopsidae).” Functional Ecology 25, no. 3 (2011): 608-16.

P>1. Exaggerated male ornaments often are hypothesised to increase predation risk due to reduced locomotor performance, yet empirical evidence supporting this proposition is equivocal. In part, current costs of ornaments may be difficult to detect in nature due to the evolution of compensatory mechanisms that offset detrimental effects. 2. The exaggerated eye stalks of male stalk-eyed flies increase their moment of inertia compared with females, yet males do not suffer a flight performance decrement. We tested for evidence of compensation within seven species of stalk-eyed flies, examining eyespan and wing size in four dimorphic and three monomorphic species. 3. We found that, within species, males had larger wings than females in two species dimorphic for eyespan but not in any monomorphic species. In males of the dimorphic species, there were positive relationships between relative eyespan and relative wing area, indicating compensation, whereas there were no such relationships in females of the dimorphic species or in either males or females of the monomorphic species. 4. We propose that examining compensatory abilities relative to ornament size is a powerful way to test for costs of ornaments in correlational and experimental studies.

Biology Department.

Inoue, K., G. R. Moyer, A. Williams, Emy M. Monroe, and D. J. Berg. “Isolation and Characterization of 17 Polymorphic Microsatellite Loci in the Spectaclecase, Cumberlandia Monodonta (Bivalvia: Margaritiferidae).”Conservation Genetics Resources 3, no. 1 (2011): 57-60.

We isolated 29 microsatellite loci from Cumberlandia monodonta, a freshwater mussel species that has experienced population declines throughout its range. Seventeen loci were polymorphic, with 3-13 alleles, observed heterozygosity values of 0.375-1.00, and 38% of alleles found in more than one population. These loci should be useful for describing population genetic diversity, which will facilitate ongoing conservation efforts for C. monodonta.

Biology Department.

Johnson, P. T. J., V. J. McKenzie, A. C. Peterson, Jacob L. KerbyJennifer Brown, A. R. Blaustein, and T. Jackson. “Regional Decline of an Iconic Amphibian Associated with Elevation, Land-Use Change, and Invasive Species.” Conservation Biology 25, no. 3 (2011): 556-66.

Ecological theory predicts that species with restricted geographic ranges will have the highest probability of extinction, but species with extensive distributions and high population densities can also exhibit widespread population losses. In the western United States populations of northern leopard frogs (Lithobates pipiens)-historically one of the most widespread frogs in North America-have declined dramatically in abundance and geographic distribution. To assess the status of leopard frogs in Colorado and evaluate causes of decline, we coupled statewide surveys of 196 historically occupied sites with intensive sampling of 274 wetlands stratified by land use. We used an information-theoretic approach to evaluate the contributions of factors at multiple spatial extents in explaining the contemporary distribution of leopard frogs. Our results indicate leopard frogs have declined in Colorado, but this decline was regionally variable. The lowest proportion of occupied wetlands occurred in eastern Colorado (2-28%), coincident with urban development and colonization by non-native bullfrogs (Lithobates catesbeianus). Variables at several spatial extents explained observed leopard frog distributional patterns. In low-elevation wetlands introduced fishes, bullfrogs, and urbanization or suburbanization associated negatively with leopard frog occurrence, whereas wetland area was positively associated with occurrence. Leopard frogs were more abundant and widespread west of the Continental Divide, where urban development and bullfrog abundance were low. Although the pathogenic chytrid Batrachochytrium dendrobatidis (Bd) was not selected in our best-supported models, the nearly complete extirpation of leopard frogs from montane wetlands could reflect the individual or interactive effects of Bd and climate patterns. Our results highlight the importance of considering multiple, competing hypotheses to explain species declines, particularly when implicated factors operate at different spatial extents.

Biology Department.

Kadarkaraisamy, MariappanSoudsakhone ThammavongkeoPrem N. BasaGerald Caple, and Andrew G. Sykes. “Substitution of Thiophene Oligomers with Macrocyclic End Caps and the Colorimetric Detection of Hg(Ii).”Organic Letters 13, no. 9 (2011): 2364-67.

Alkyl substitution at the a position(s) of mono-, bi-, and terthiophenes via electrophilic addition of macrocyclic end caps combines linear, pi-conjugated aromatic compounds and annular macrocycles. Addition of the Hg(II) ion to terthiophene adducts produces intense color changes, allowing for the selective, colorimetric detection of mercury(II). Chemical oxidation of the asymmetric terthiophene adduct produces the sexithiophene oligomer.

Chemistry Department.

Kruml, Susan M., and Mark D. Yockey. “Developing the Emotionally Intelligent Leader: Instructional Issues.”Journal of Leadership & Organizational Studies (Sage Publications Inc.) 18, no. 2 (2011): 207-15.

This study generates evidence that participants who completed a specific leadership development curriculum increased their emotional intelligence (EI). This study also fills a gap in the literature by providing evidence that (a) there are no differences in the effectiveness between a face-to-face and hybrid (online and face-to-face) curriculum, or (b) between a 7-week and 16-week curriculum, and that (c) participants with initial low or average EI experience improvements in their EI, whereas those with initial high EI do not.

Beacom School of Business.

Mabee, Paula. M.Erika. A. Grey, G. Arratia, N. Bogutskaya, A. Boron, M. M. Coburn, K. W. Conway, S. P. He, A. Naseka, N. Rios, A. Simons, J. Szlachciak, and X. Z. Wang. “Gill Arch and Hyoid Arch Diversity and Cypriniform Phylogeny: Distributed Integration of Morphology and Web-Based Tools.” Zootaxa, no. 2877 (2011): 1-40.

Using the multiple tools available to support an online collaborative environment, we surveyed 62 morphological features from the hyoid arch and gill arches of 53 species of cypriniform fishes that matched those sampled in recent molecular analyses and two sets of outgroup species (‘Saitoh outgroups’ and ‘Basal outgroups’). This is a skeletal region whose variation is considered historically significant within fishes and Cypriniformes in particular, and we review previous work in light of our own. The clarity of description of characters was enhanced by the use of a community reference ontology, the Teleost Anatomy Ontology. Terms, synonyms, and definitions for skeletal features from this region were contributed to this ontology, and links to these terms and relationships are included in our character descriptions. One thousand two hundred sixty-three images of features from this region were linked to ontology terms and deposited in a community image repository, Morphbank; these are linked to the characters described herein. Character data were analyzed using parsimony and Bayesian methods for two sets of outgroups, one of which matched that used in previous molecular analyses. The parsimony results, using either outgroup set, indicated similar higher-level relationships, including a sister group relationship between cyprinids and loaches. A basal trichotomy among Gyrinocheilus, catostomids and cyprinids + loaches was the result of Saitoh outgroup analysis in contrast to a sister group relationship between Gyrinocheilus and catostomids discovered in the Basal outgroup analysis. Interestingly, analyses including basal outgroups recovered a monophyletic Cyprinidae, consistent with all previous studies. Character evolution that supports higher-level nodes of interest in the consensus tree is described. In some respects, it might be a surprise that 62 morphological characters from a small skeletal region for only 53 cypriniform species (out of over 3,200 total species) could provide as much resolution as it does. We expect, however, further phylogenetic resolution as morphological data from across skeleton regions are combined, species sampling is increased, and molecular data are added.

Biology Department.

Maher, Diane M., Brij K. GuptaSatoshi NagataMeena Jaggi, and Subhash C. Chauhan. “Mucin 13: Structure, Function, and Potential Roles in Cancer Pathogenesis.” Molecular Cancer Research 9, no. 5 (2011): 531-37.

Mucin 13 (MUC13) is a high-molecular-weight transmembrane glycoprotein that is frequently and aberrantly expressed in a variety of epithelial carcinomas, including gastric, colorectal, and ovarian cancers. On the basis of the high expression of MUC13 in cancer cells as well as recent laboratory findings suggesting a malignant phenotype of MUC13-transfected cell lines, the oncogenic potential of MUC13 has emerged. The various functional domains of MUC13 may confer oncogenic potential to MUC13. For example, the bulky extracellular domain with extensive modification with glycan chains may prevent cell-cell and cell-extracellular matrix binding whereas the cytoplasmic tail containing serine and tyrosine residues for potential phosphorylation may participate in cell signaling. MUC13 exhibits the characteristics suitable as an early marker for cancer screening and presents a promising target for antibody-guided targeted therapy. Mol Cancer Res; 9(5); 531-7. (C) 2011 AACR.

Sanford School of Medicine, Sioux Falls Campus.

McGlaughlin, M. E., Lynn Riley, L. E. Wallace, and Kaius Helenurm. “Isolation of Microsatellite Loci from Endangered Members of Lotus (Fabaceae) Subgenus Syrmatium.” Conservation Genetics Resources 3, no. 1 (2011): 117-21.

Lotus subgenus Syrmatium is a group of 11 plant species that exhibit extensive ecological and morphological diversity throughout the California floristic province. Fifteen polymorphic microsatellite loci were isolated from two taxa, Lotus argophyllus var. adsurgens and L. dendroideus var. traskiae, and were screened for variability in 15 additional taxa within Lotus subgenus Syrmatium. Moderate levels of variability were observed with mean numbers of alleles per locus ranging from 1.3 to 7.3. The mean observed and expected heterozygosities ranged from 0.09 to 0.47 and 0.10 to 0.79, respectively. These new loci will be useful in conservation genetic and evolutionary studies within Lotus subgenus Syrmatium.

Biology Department.

Myer, G. D., A. D. Faigenbaum, Michael F. Bergeron, and T. E. Hewett. “When to Initiate Integrative Neuromuscular Training to Reduce Sports-Related Injuries and Enhance Health in Youth?” Current Sports Medicine Reports10, no. 3 (2011): 157-66.

Regular participation in organized youth sports does not ensure adequate exposure to skill- and health-related fitness activities, and sport training without preparatory conditioning does not appear to reduce risk of injury in young athletes. Current trends indicate that widespread participation in organized youth sports is occurring at a younger age, especially in girls. Current public health recommendations developed to promote muscle strengthening and bone building activities for youth aged 6 yr and older, along with increased involvement in competitive sport activities at younger ages, has increased interest and concern from parents, clinicians, coaches, and teachers regarding the optimal age to encourage and integrate more specialized physical training into youth development programs. This review synthesizes the latest literature and expert opinion regarding when to initiate neuromuscular conditioning in youth and presents a how-to integrative training conceptual model that could maximize the potential health-related benefits for children by reducing sports-related injury risk and encouraging lifelong, regular physical activity.

Sanford School of Medicine, Sioux Falls Campus.

Roark, Abrea, B. P. Wilson, Kathleen M. EysterGary L. TimmermanBrandon L. Allard, and Keith A. Hansen. “Hypercalcemia: An Unusual Etiology of a Common Menopausal Symptom.” Fertility and Sterility 95, no. 7 (2011).

Objective: To describe atypical vasomotor symptoms that were secondary to primary hyperparathyroidism. Design: Case report. Setting: University medical center. Patient(s): A 57-year-old, postmenopausal woman with recalcitrant hot flushes. Intervention(s): Parathyroid adenomectomy. Main Outcome Measure(s): Vasomotor symptom relief. Result(s): Postoperative relief of atypical vasomotor symptoms. Conclusion(s): A patient 17 years postmenopause presented with atypical vasomotor symptoms that did not respond to hormone therapy and proved to be due to hypercalcemia secondary to primary hyperparathyroidism. An atypical manifestation of a common condition or an uncharacteristic therapeutic response should alert health care providers to the possibility of a different diagnosis. (Fertil Steril (R) 2011; 95: 2434.e7-e9. (C) 2011 by American Society for Reproductive Medicine.)

Sanford School of Medicine, Sioux Falls Campus.

Sergeant, S., J. A. McQuail, D. R. Riddle, F. H. Chilton, Steven B. Ortmeier, J. A. Jessup, L. Groban, and M. M. Nicolle. “Dietary Fish Oil Modestly Attenuates the Effect of Age on Diastolic Function but Has No Effect on Memory or Brain Inflammation in Aged Rats.” Journals of Gerontology Series a-Biological Sciences and Medical Sciences 66, no. 5 (2011): 521-33.

Fish oil (FO) mediates a number of cardioprotective benefits in patients with cardiovascular disease. In the absence of cardiovascular disease, however, the effects of FO on cardiac structure and function are not clear. In addition, it is not known if an effective dosing strategy for attenuating age-related cardiac dysfunction is also effective at limiting cognitive dysfunction. Therefore, we determined if 4 months of FO supplementation in aged rats would lessen age-related cardiac dysfunction while concomitantly preventing the cognitive decline that is normally observed in this population. The results indicate that FO initiated late in life modifies diastolic function in a small but positive way by attenuating the age-related increases in filling pressure, posterior wall thickness, and interstitial collagen without mitigating age-related deficits in memory or increases in brain inflammation. These data raise the possibility that FO supplementation for purposes of cardiac and brain protection may need to occur earlier in the life span.

Sanford School of Medicine, Sioux Falls Campus.

Stys, Adam T.Tomasz Stys, and P. Recki. “A Novel Method of Ultra-Low Contrast Administration for Coronarography and Percutaneous Coronary Intervention Using the Automatic Injector. The Need to Focus on Contrast Preservation Techniques.” Postepy W Kardiologii Interwencyjnej 7, no. 1 (2011): 8-14.

Background: Contrast-induced nephropathy (CIN) is becoming a more pertinent issue in coronary percutaneous procedures, as the population at risk grows. Contrast preservation is the first and probably most important step in prevention of CIN, and yet the research focus seems to be on CIN preventing drugs. Aim: We describe a novel method of contrast preservation for coronarography and percutaneous coronary intervention (PCI) based on use of the automatic contrast injector (ACI). The method also uses a standardized approach to catheterization aimed at minimizing contrast load; however, it is the programming of the ACI that allows for the ultra-low contrast dose. We present two cases to illustrate the technique. Material and methods: We have used this standardized protocol successfully for the last 4 years in our cath lab in patients with increased risk of CIN, consistently achieving 10 ml or less of contrast load per coronary case. Our ACI programming protocol is relatively easy to follow. Results and conclusions: We think that use of ACI with appropriate programming should become a preferred, if not standard approach in patients at increased CIN risk. We believe that refocusing on contrast preservation techniques and their distribution throughout the interventional community is of utmost importance for public health.

Sanford School of Medicine, Sioux Falls Campus.

Yallapu, Murali MohanMeena Jaggi, and Subhash C. Chauhan. “Design and Engineering of Nanogels for Cancer Treatment.” Drug Discovery Today 16, no. 9/10 (2011): 457-63.

Here, we provide a comprehensive insight into current advances in the use of nanogel-mediated chemotherapy for cancer treatment. Nanogels are composed of cross-linked three-dimensional polymer chain networks that are formed via covalent linkages or self-assembly processes. The porosity between the cross-linked networks of nanogels not only provides an ideal reservoir for loading drugs, oligonucleotides and imaging agents, but also protects them from environmental degradation and hazards. Here, we focus mainly on novel synthetic strategies and key considerations in the design of nanogel-based drug delivery systems for controlled and targeted cancer therapeutic applications.

Sanford School of Medicine, Sioux Falls Campus.

Yang, Da-QingMarie-Jo HalabyYan LiJody C. Hibma, and Paul Burn. “Cytoplasmic Atm Protein Kinase: An Emerging Therapeutic Target for Diabetes, Cancer and Neuronal Degeneration.” Drug Discovery Today 16, no. 7-8 (2011): 332-38.

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder characterized by cerebellar ataxia and oculocutaneous telangiectasias. The gene mutated in this disease, Atm (A-T mutated), encodes a serine/threonine protein kinase that has been traditionally considered to be a nuclear protein controlling cell-cycle progression. However, many of the growth abnormalities observed in patients with A-T, including neuronal degeneration and insulin resistance, remain difficult to explain with nuclear localization of ATM. Here, recent advances in elucidating the cytoplasmic localization and function of ATM are reviewed. Particular attention is given to the role of ATM in insulin signaling and Akt activation. The potential for cytoplasmic ATM protein kinase to be an emerging therapeutic target for treating diabetes, cancer and neuronal degeneration is discussed.

Sanford School of Medicine, Sioux Falls Campus

Zhuang, Yougxian X., and W. Keith Miskimins. “Metformin Induces Both Caspase-Dependent and Poly(Adp-Ribose) Polymerase-Dependent Cell Death in Breast Cancer Cells.” Molecular Cancer Research 9, no. 5 (2011): 603-15.

There is substantial evidence that metformin, a drug used to treat type 2 diabetics, is potentially useful as a therapeutic agent for cancer. However, a better understanding of the molecular mechanisms through which metformin promotes cell-cycle arrest and cell death of cancer cells is necessary. It will also be important to understand how the response of tumor cells differs from normal cells and why some tumor cells are resistant to the effects of metformin. We have found that exposure to metformin induces cell death in all but one line, MDA-MB-231, in a panel of breast cancer cell lines. MCF10A nontransformed breast epithelial cells were resistant to the cytotoxic effects of metformin, even after extended exposure to the drug. In sensitive lines, cell death was mediated by both apoptosis and a caspase-independent mechanism. The caspase-independent pathway involves activation of poly(ADP-ribose) polymerase (PARP) and correlates with enhanced synthesis of PARP and nuclear translocation of apoptosis-inducing factor (AIF), which plays an important role in mediating cell death. Metformin-induced, PARP-dependent cell death is associated with a striking enlargement of mitochondria. Mitochondrial enlargement was observed in all sensitive breast cancer cell lines but not in nontransformed cells or resistant MDA-MB-231. Mitochondrial enlargement was prevented by inhibiting PARP activity or expression. A caspase inhibitor blocked metformin-induced apoptosis but did not affect PARP-dependent cell death or mitochondrial enlargement. Thus, metformin has cytotoxic effects on breast cancer cells through 2 independent pathways. These findings will be pertinent to efforts directed at using metformin or related compounds for cancer therapy. Mol Cancer Res; 9(5); 603-15. (C) 2011 AACR.

Sanford School of Medicine, Sioux Falls Campus.

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