Posted by: kelsijo97 | January 2, 2013

January 2013

Huang, H. B., N. N. Liu, H. P. Guo, Xuejun Wang, Q. P. Dou, and  J. B. Liu. (2012). L-Carnitine Is an Endogenous HDAC Inhibitor Selectively Inhibiting Cancer Cell Growth In Vivo and In Vitro. [Article]. Plos One, 7(11).
L-carnitine (LC) is generally believed to transport long-chain acyl groups from fatty acids into the mitochondrial matrix for ATP generation via the citric acid cycle. Based on Warburg’s theory that most cancer cells mainly depend on glycolysis for ATP generation, we hypothesize that, LC treatment would lead to disturbance of cellular metabolism and cytotoxicity in cancer cells. In this study, Human hepatoma HepG2, SMMC-7721 cell lines, primary cultured thymocytes and mice bearing HepG2 tumor were used. ATP content was detected by HPLC assay. Cell cycle, cell death and cell viability were assayed by flow cytometry and MTS respectively. Gene, mRNA expression and protein level were detected by gene microarray, Real-time PCR and Western blot respectively. HDAC activities and histone acetylation were detected both in test tube and in cultured cells. A molecular docking study was carried out with CDOCKER protocol of Discovery Studio 2.0 to predict the molecular interaction between L-carnitine and HDAC. Here we found that (1) LC treatment selectively inhibited cancer cell growth in vivo and in vitro; (2) LC treatment selectively induces the expression of p21(cip1) gene, mRNA and protein in cancer cells but not p27(kip1); (4) LC increases histone acetylation and induces accumulation of acetylated histones both in normal thymocytes and cancer cells; (5) LC directly inhibits HDAC I/II activities via binding to the active sites of HDAC and induces histone acetylation and lysine-acetylation accumulation in vitro; (6) LC treatment induces accumulation of acetylated histones in chromatin associated with the p21(cip1) gene but not p27(kip1) detected by ChIP assay. These data support that LC, besides transporting acyl group, works as an endogenous HDAC inhibitor in the cell, which would be of physiological and pathological importance.
Basic Biomedical Sciences, Vermillion Campus.
Huber, Victor C. (2012). Can surveillance of the influenza virus PB1-F2 gene be used to predict the severity of secondary bacterial infections? Virulence, 3(6), 523-524.
Basic Biomedical Sciences, Vermillion Campus.
Moore, Elizabeth R. (2012). Sphingolipid Trafficking and Purification in Chlamydia trachomatis-Infected Cells. Current protocols in microbiology, Chapter 11, Unit11A.12.
Chlamydia trachomatis is an obligate intracellular human pathogen, which lacks a system that allows genetic manipulation. Therefore, chlamydial researchers must manipulate the host cell to better understand chlamydial biology. Host-derived lipid acquisition is critical for chlamydial survival within the host. Hence, the ability to track and purify sphingolipids in/from chlamydial infected cells has become an integral part of pivotal studies in chlamydial biology. This unit outlines protocols that provide details about labeling eukaryotic cells with exogenous lipids to examine Golgi-derived lipid trafficking to the chlamydial inclusion and then performing imaging studies or lipid extractions for quantification. Details are provided to allow these protocols to be applied to subconfluent, polarized, or siRNA knockdown cells. In addition, one will find important experimental design considerations and techniques. These methods are powerful tools to aid in the understanding of mechanisms, which allow C. trachomatis to manipulate and usurp host cell trafficking pathways. Curr. Protoc. Microbiol. 27:11A.2.1-11A.2.19. 2012 by John Wiley & Sons, Inc.
Basic Biomedical Sciences, Vermillion Campus.
An, Heng, Zhaodan Huang, and  Ting Zhang. (2013). What determines corporate pension fund risk-taking strategy? [Article]. Journal of Banking & Finance, 37(2), 597-613.
Abstract: Corporate sponsors of defined benefit pension plans generally assume low investment risk when they have low funding ratios and high default risk, consistent with the risk management hypothesis. However, for financially distressed sponsors and sponsors that freeze, terminate, or convert defined benefit to defined contribution plans, the risk-shifting incentive (moral hazard) dominates. Pension fund risk-taking is also affected by labor unionization and sponsor incentives to maximize tax benefits, restore financial slack, and justify the accounting choices of pension assumptions. Sponsors shift toward an aggressive risk strategy when their pension plans emerge from underfunding, bankruptcy risk is reduced, or marginal tax rate decreases. Overall, we show that corporate sponsors adopt a dynamic risk-taking strategy in their pension fund investments.
Beacom School of Business.
Arendt, David H., Justin P. Smith, Christel C. Bastida, Maneeshi S. Prasad, Kevin D. Oliver, Kathleen M. Eyster, Tangi R. Summers, Yvon Delville, and  Cliff H. Summers. (2012). Contrasting hippocampal and amygdalar expression of genes related to neural plasticity during escape from social aggression. [Article]. Physiology & Behavior, 107(5), 670-679.
Abstract: Social subjugation has widespread consequences affecting behavior and underlying neural systems. We hypothesized that individual differences in stress responsiveness were associated with differential expression of neurotrophin associated genes within the hippocampus and amygdala. To do this we examined the brains of hamsters placed in resident/intruder interactions, modified by the opportunity to escape from aggression. In the amygdala, aggressive social interaction stimulated increased BDNF receptor TrKB mRNA levels regardless of the ability to escape the aggressor. In contrast, the availability of escape limited the elevation of GluR1 AMPA subunit mRNA. In the hippocampal CA1, the glucocorticoid stress hormone, cortisol, was negatively correlated with BDNF and TrKB gene expression, but showed a positive correlation with BDNF expression in the DG. Latency to escape the aggressor was also negatively correlated with CA1 BDNF expression. In contrast, the relationship between amygdalar TrKB and GluR1 was positive with respect to escape latency. These results suggest that an interplay of stress and neurotrophic systems influences learned escape behavior. Animals which escape faster seem to have a more robust neurotrophic profile in the hippocampus, with the opposite of this pattern in the amygdala. We propose that changes in the equilibrium of hippocampal and amygdalar learning result in differing behavioral stress coping choices.
Biology Department.
Whitfield, Steven M., Maureen A. Donnelly, Erica Geerdes, and  Jacob Kerby. (2012). Ranavirus Infection in Native Amphibians at La Selva Biological Station, Costa Rica: First Report of Ranavirus in Central America. [Article]. Herpetological Review, 43(3), 425-427.
Biology Department.
Whitfield, Steven M., Jacob Kerby, L. R. Gentry, and  M. A. Donnelly. (2012). Temporal Variation in Infection Prevalence by the Amphibian Chytrid Fungus in Three Species of Frogs at La Selva, Costa Rica. [Article]. Biotropica, 44(6), 779-784.
The emerging infectious disease chytridiomycosis, caused by the amphibian chytrid fungus, Batrachochytrium dendrobatidis (Bd), is implicated in widespread population declines, extirpations, and extinctions of amphibians throughout the world. In the Neotropics, most amphibian declines have occurred in cool mid- to high-elevation sites (> 400 m asl), and it is hypothesized that high temperatures limit the growth of Bd in lowland tropical sites, despite few data available on the distribution of Bd in lowland forests. Here, we report the results of a 12-mo pathogen surveillance program for three common species of frogs at a warm lowland site in northeastern Costa Rica. We combine standard non-invasive skin swabbing techniques with a quantitative polymerase chain reaction assay to analyze the infection prevalence and Bd load across a 1-yr period. Our data indicate an overall Bd infection rate of 6.1 percent, but prevalence varies from < 5 percent in warmer months to a peak of 34.7 percent in the coolest months of the year. Despite very little seasonal variation in temperature (< 4 degrees C), our data indicate strong seasonal variation in the prevalence of Bd, with highest prevalence of infection in months with coolest air temperatures. While it has been suggested that Bd is primarily a riparian fungus, we find no difference in prevalence of infection among our species despite considerable differences in affiliation of these species with water. Our study provides further evidence that infection by Bd is regulated by temperature and shows that warm temperatures in lowland forests may restrict, but not prevent, infection by Bd.
Biology Department.
Bao, Ying, Quoc An N. Luu, Y. Zhao, H. Fong, P. Stanley May, and  Chaoyang Jiang. (2012). Upconversion polymeric nanofibers containing lanthanide-doped nanoparticles via electrospinning. [Article]. Nanoscale, 4(23), 7369-7375.
Flexible and freestanding poly(methyl methacrylate) nanofibers containing the upconversion nanoparticles (UCNPs) of lanthanide-doped sodium yttrium fluoride have been successfully fabricated via an electrospinning process. The UCNPs in nanofibers commonly formed chain-like aggregates aligned along the fiber axes. The effect of the electrospinning process on the upconversion properties of the embedded UCNPs was explored by characterizing the time evolution of the upconversion emission following pulsed near-infrared excitation. Our study revealed that there is only a slight reduction of upconversion efficiency for the UCNPs in electrospun nanofibers, indicating that upconversion properties of the UCNPs are largely preserved in the nanofibrous films. The prepared upconversion nanocomposites (in the form of nanofibrous films) with controlled morphologies, structures, and properties could be useful for broad photonic applications.
Chemistry Department.
Chen, Jiangchao, Andrew Schmitz, and  Dmitri S. Kilin. (2012). Computational simulation of the p-n doped silicon quantum dot. [Article]. International Journal of Quantum Chemistry, 112(24), 3879-3888.
Elongated crystalline silicon quantum dot (QD) codoped with aluminum and phosphorous together has been modeled with a formula of Si36Al1P1H42. The calculations of electronic structure are done by VASP software in the basis of plane waves, and valent electrons are treated explicitly while core electrons are described with pseudopotentials. Compared with undoped model, Si38H42, the results show the features in the electronic structure of the codoped QD of lowest unoccupied molecular orbital and highest occupied molecular orbital contributed by dopants, and transitions between those bands make contributions to many properties different from undoped model. The role of thermal motion of ions was also explored at (i) high and (ii) ambient temperatures. (i) At high temperature, the thermal motion of ions leads to the break of crystal structure. (ii) At ambient temperatures, the motion of ions facilitates the nonadiabatic couplings between electronic states. The relevant electronic dynamics also calculated with computed nonadiabatic couplings. This simulation predicts the charge transfer across p-n junction on atomistic scale.
Chemistry Department.
Jensen, Stephanie, and  Dmitri Kilin. (2012). Anatase (100) thin film surface computational model for photoelectrochemical cell. [Article]. International Journal of Quantum Chemistry, 112(24), 3874-3878.
Using computational approaches, one is able to better understand electron transfer and specific atomistic behaviors in semiconductor materials; it is also more cost and time effective than experimental methods. If computed semiconductor characteristics show promise, experimentalists can synthesize and further examine the structure. Specifically, doping TiO2 thin film surfaces with platinum and ruthenium have shown great promise for efficient H2 production and is beneficial in comparison to other materials such as the pure silicon used for most of today’s solar cells. In computational studies, TiO2 anatase thin film (100) surfaces are doped with platinum and ruthenium. The formulas used are Pt2Ti32O72H16 or Ru2Ti32O72H16 with the (100) crystallographic surface exposed and covered with a monolayer of water. Optimization is completed by density functional theory and Perdue Burke Ernzerhof, (PBE) in Vienna Ab-initio simulation package (VASP) software. The density of states, absorption spectra, and partial charge densities are compared between slabs doped by the two elements as well as Ti32 O72H16 with no dopant as a standard for reference. The information can be used to show the mechanism of how doping the titanium dioxide nanocrystals facilitates photoinduced charge transfer at the surfaces, which is useful in understanding photoelectrochemical water splitting.
Chemistry Department.
Meng, Qingguo, P. Stanley May, Mary T. Berry, and  Dmitri Kilin. (2012). Sequential hydrogen dissociation from a charged Pt13H24 cluster modeled by ab initio molecular dynamics. [Article]. International Journal of Quantum Chemistry, 112(24), 3896-3903.
Platinum is one of the most valuable catalysts that have been used in the catalytic fields of hydrogenation, fuel-cell technologies, and photocatalytic water splitting. In this work, the dissociative chemisorption of hydrogen in a molecular form on a Pt13H24 cluster with cuboctahedral symmetry ( Oh), which has one center Pt atom and side 12 Pt atoms (each bonded by two hydrogen), is investigated by using first-principles density functional theory calculation. After computing geometry optimization on the Pt13H24 cluster, the equilibrium distances of PtPt and PtH are inspected. Two nonequilibrium modifications, for example, addition of electrons and heat treatment were applied on the cluster, with the aim to simulate the experimental reaction of hydrogen on the Pt13 H24 cluster. An ab initio molecular dynamics (MD) is simulated after the cluster is charged and heat treated at high temperature to compute the trajectory for the positions of all the atoms. The computation results reveal that H2 desorption is observed during the MD simulation, and higher temperature is beneficial to the H2 desorption. An elementary hydrogen evolution mechanism on the charged Pt cluster can be established as 2Hads+ + 2e− + Ptads→ [PtadsHadsHads] → H2↑ + Pt. A rate (fs1) of hydrogen desorption from different cluster models is determined, together with the hydrogen dissociative activation energy as a function of total charge.
Chemistry Department.
Qiu, Chao, L. Zhang, H. Wang, and  Chaoyang Jiang. (2012). Surface-Enhanced Raman Scattering on Hierarchical Porous Cuprous Oxide Nanostructures in Nanoshell and Thin-Film Geometries. [Article]. Journal of Physical Chemistry Letters, 3(5), 651-657.
Understanding the mechanism of surface-enhanced Raman scattering (SERS) of molecules on semiconductor nanostructures is directly related to our capabilities of designing and optimizing new SERS-active substrates for broad applications in the field of molecular detection and characterization. Here, we present an exploration of using cuprous oxide nanostructures with hierarchical porosity for enhancing Raman signals of adsorbed probe molecules. Distinct SERS signals were detected on both individual polycrystalline nanoshells and porous thin films composed of cuprous oxide nanocrystals. The observed enhancement of SERS signals can be interpreted as synergistic effects of strong chemical interactions between the probe molecules and cuprous oxide surfaces, localized electromagnetic field enhancement, and the unique hierarchical porosity of the nanostructures. Our work introduced a novel type of semiconductor substrates for high-performance SEAS and extended the applications of cuprous oxide nanostructures to spectroscopy-based molecular sensing and characterizations.
Chemistry Department.
Sun, Haorn R., Anjaneyulu Putta, Justin P. Kloster, and  Usha K. Tottempudi. (2012). Unexpected photostability improvement of aromatics in polyfluorinated solvents. [Article]. Chemical Communications, 48(99), 12085-12087.
The photostability of aromatic compounds in the presence of air is significantly improved through perfluoroalkylation of the corresponding aromatic cores and use of polyfluorinated solvents despite higher O(2) concentration in polyfluorinated solvents than in hydrocarbon solvents.
Chemistry Department.
Yao, Ge, Mary T. Berry, P. Stanley May, and  Dmitri S. Kilin. (2012). Optical properties of host material for phosphor computational modeling. [Article]. International Journal of Quantum Chemistry, 112(24), 3889-3895.
The lanthanide ions doped hexagon (β)-NaYF4 nanocrystals exhibit photoluminescence outputs, where β-NaYF4 with a strong cation disorder serve as host substance. The ab initio computation of β-NaYF4 with different atomic sizes Na mY mF4m, for m = 3, 6, 12, 24, 48, or 96 in periodic boundary conditions is simulated based on density functional theory with the generalized gradient approximation. With the increase of unit sizes, the energy of highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO), energy gap, and energy per atom exhibit asymptotic convergence as well as the interatomic distances. The calculation of first ionization energy appreciates the prediction of the Koopmans’ theorem. The investigation of orbital’s spatial distribution proves the ligand (F− −1e → F) to metal (Y3+ +1e → Y2+) transition during the excitations mainly through the p → d path. Two families of lifetimes are observed in the simulated results from the optical absorption spectrum, which indicates that transitions can be divided by two categories.
Chemistry Department.
Zhang, Yuchi, and  Dmitri S. Kilin. (2012). Computational modeling of wet TiO2 (001) anatase surfaces functionalized by transition metal doping. [Article]. International Journal of Quantum Chemistry, 112(24), 3867-3873.
Titanium dioxide anatase nanostructure is a photocatalyst under UV light. Our objective is to discover proper surface and functionalization, which facilitate the efficiency of photocatalytic water splitting on TiO2 crystals. We set up a periodic model of Ti32O64·8H2O as the neutral structure and expose the (001) crystallographic surface as it is more reactive. Using platinum, cobalt, and ruthenium to dope in the (001) crystallographic surface and get Ti30Me2O64·8H2O, which Me stands for either Pt, Co, or Ru. Based on density functional theory and Perdue Burke Ernzerhof functional (PBE) we calculate and optimize the doped nanostructures using VASP software. Through their density of states, we can analyze the possibility of charge transfer at the crystal surface and compare how the doping elements affect the charge transfer direction. A comparison of the computed absorption spectra and the charge density of the doping nanostructures help us in better understanding of the possibility of the bandgap tuning in photocatalytic energy nanomaterials.
Chemistry Department.
Sun, Haoran R., Usha K. Tottempudi, Jeffrey D. Mottishaw, Prem N. Basa, Anjaneyulu Putta, and  Andrew G. Sykes. (2012). Strengthening pi-pi Interactions While Suppressing C(sp2)-H center dot center dot center dot pi (T-Shaped) Interactions via Perfluoroalkylation: A Crystallographic and Computational Study That Supports the Beneficial Formation of 1-D pi-pi Stacked Aromatic Materials. [Article]. Crystal Growth & Design, 12(11), 5655-5662.
The design and synthesis of aromatic crystalline materials with controllable crystal structure packing is of particular interest in organic semiconductor and optoelectronic devices, where 1-D pi-pi stacked structures that enhance charge mobility are the most beneficial. We report here that the pi-pi interactions between aromatic molecules can be strengthened and the C(sp2)-H center dot center dot center dot pi (T-shape) interaction can be suppressed by perfluoroalkylation of corresponding aromatics. Both crystal structure data and ab initio calculations show that the pi-pi interaction is strengthened due to the electronic effects of perfluoroalkyl substituents, and the C(sp2)-H center dot center dot center dot pi interaction is suppressed by the steric effects of the perfluoroalkyl substituents. The C(sp3)-F center dot center dot center dot F-C(sp3) attractive interactions between perfluoroalkyl chains further stabilize the crystal structures. We also found that C(sp3)-F center dot center dot center dot pi interaction can be eliminated if an optimal electron deficiency of the pi system is tuned by adjusting the number of perfluoroalkyl substituents. The insight gained from this study is of particular interest in organic semiconductor research as well as the fields of molecular recognition, sensing, and design of enzyme inhibitors where pi-pi interactions are also important.
Chrmistry Department.
Cummins, R. G., W. T. Wise, and  Brandon H. Nutting. (2012). Excitation Transfer Effects Between Semantically Related and Temporally Adjacent Stimuli. [Article]. Media Psychology, 15(4), 420-442.
Although excitation transfer theory has been supported in numerous contexts, questions remain regarding transfer of arousal between events that are semantically and temporally related. This article summarizes two studies exploring excitation transfer between such events: sequential plays from a college football game. Study 1 failed to support the theory, instead suggesting contrast effects between stimuli. A follow-up study, which altered the method and incorporated psychophysiological measures, demonstrated that arousal may transfer between semantically related, temporally adjacent events. We suggest implications for the theory vis-a-vis misattribution of arousal, as well as opportunities to expand the application of excitation transfer.
Contemporary Media & Journalism.
Newswander, Chad B. (2012). Moral Leadership and Administrative Statesmanship: Safeguards of Democracy in a Constitutional Republic. [Article]. Public Administration Review, 72(6), 866-874.
The pursuit of the common good must be understood from the reality that governing is ugly. The ability to grapple with situations that are ambiguous requires administrators to be cognizant of action that might be suspect but necessary to accomplish the public interest. This often requires them to become active players. John Rohr postulates that the U.S. Supreme Court’s standards of strict scrutiny is one approach that could be used to justify such action. Building on this line of thinking, the strict scrutiny test can be used as a guide to shape the constitutive character of administrative statesmanship while simultaneously restraining it. The ability to balance formative action and restraint provides a different dimension to an understanding of administrative statesmanship. Even though this process is not easy, it helps administrators refrain from going beyond the mark and enables them to act like statesmen in seemingly unresolvable situations.
Political Science Department.
Wang, X. T., and  Joseph G. Johnson. (2012). A Tri-Reference Point Theory of Decision Making Under Risk. [Article]. Journal of Experimental Psychology-General, 141(4), 743-756.
The tri-reference point (TRP) theory takes into account minimum requirements (MR), the status quo (SQ), and goals (G) in decision making under risk. The 3 reference points demarcate risky outcomes and risk perception into 4 functional regions: success (expected value of x >= G), gain (SQ < X < G), loss (MR <= x < SQ), and failure (x < MR). The psychological impact of achieving or failing to achieve these reference points is rank ordered as MR > G > SQ. We present TRP assumptions and value functions and a mathematical formalization of the theory. We conducted empirical tests of crucial TRP predictions using both explicit and implicit reference points. We show that decision makers consider both G and MR and give greater weight to MR than G, indicating failure aversion (i.e., the disutility of a failure is greater than the utility of a success in the same task) in addition to loss aversion (i.e., the disutility of a loss is greater than the utility of the same amount of gain). Captured by a double-S shaped value function with 3 inflection points, risk preferences switched between risk seeking and risk aversion when the distribution of a gamble straddled a different reference point. The existence of MR (not G) significantly shifted choice preference toward risk aversion even when the outcome distribution of a gamble was well above the MR. Single reference point based models such as prospect theory cannot consistently account for these findings. The TRP theory provides simple guidelines for evaluating risky choices for individuals and organizational management.
Psychology Department.
Levenback, C. F., S. Ali, R. L. Coleman, Maria C. Bell, K. De Geest, N. M. Spirtos, R. K. Potkul, M. M. Leitao, J. N. Bakkum-Gamez, E. C. Rossi, S. S. Lentz, J. J. Burke, L. Van Le, and  C. L. Trimble. (2012). Lymphatic Mapping and Sentinel Lymph Node Biopsy in Women With Squamous Cell Carcinoma of the Vulva: A Gynecologic Oncology Group Study. [Article]. Journal of Clinical Oncology, 30(31), 3786-3791.
Purpose To determine the safety of sentinel lymph node biopsy as a replacement for inguinal femoral lymphadenectomy in selected women with vulvar cancer. Patients and Methods Eligible women had squamous cell carcinoma, at least 1-mm invasion, and tumor size >= 2 cm and <= 6 cm. The primary tumor was limited to the vulva, and there were no groin lymph nodes that were clinically suggestive of cancer. All women underwent intraoperative lymphatic mapping, sentinel lymph node biopsy, and inguinal femoral lymphadenectomy. Histologic ultra staging of the sentinel lymph node was prescribed. Results In all, 452 women underwent the planned procedures, and 418 had at least one sentinel lymph node identified. There were 132 node-positive women, including 11 (8.3%) with false-negative nodes. Twenty-three percent of the true-positive patients were detected by immunohistochemical analysis of the sentinel lymph node. The sensitivity was 91.7% (90% lower confidence bound, 86.7%) and the false-negative predictive value (1-negative predictive value) was 3.7% (90% upper confidence bound, 6.1%). In women with tumor less than 4 cm, the false-negative predictive value was 2.0% (90% upper confidence bound, 4.5%). Conclusion Sentinel lymph node biopsy is a reasonable alternative to inguinal femoral lymphadenectomy in selected women with squamous cell carcinoma of the vulva. J Clin Oncol 30:3786-3791. (C) 2012 by American Society of Clinical Oncology
Sanford School of Medicine
Berdahl, John P., D. Y. Yu, and  W. H. Morgan. (2012). The translaminar pressure gradient in sustained zero gravity, idiopathic intracranial hypertension, and glaucoma. [Article]. Medical Hypotheses, 79(6), 719-724.
Papilledema has long been associated with elevated intracranial pressure. Classically, tumors, idiopathic intracranial hypertension, and obstructive hydrocephalus have led to an increase in intracranial pressure causing optic nerve head edema and observable optic nerve swelling. Recent reports describe astronauts returning from prolonged space flight on the International Space Station with papilledema (Mader et al., 2011) [1]. Papilledema has not been observed in shorter duration space flight. Other recent work has shown that the difference in intraocular pressure (IOP) and cerebrospinal fluid pressure (CSFp) may be very important in the pathogenesis of diseases of the optic nerve, especially glaucoma (Berdahl and Allingham, 2009; Berdahl, Allingham, et al., 2008; Berdahl et al., 2008; Ren et al., 2009; Ren et al., 2011) [2-6]. The difference in IOP and CSFp across the lamina cribrosa is known as the translaminar pressure difference (TLPD). We hypothesize that in zero gravity, CSF no longer pools in the caudal spinal column as it does in the upright position on earth. Instead. CSF diffuses throughout the subarachnoid space resulting in a moderate but persistently elevated cranial CSF pressure, including the region just posterior to the lamina cribrosa known as the optic nerve subarachnoid space (ONSAS). This small but chronically elevated CSFp could lead to papilledema when CSFp is greater than the IOP. If the TLPD is the cause of optic nerve head edema in astronauts subjected to prolonged zero gravity, raising IOP and/or orbital pressure may treat this condition and protect astronauts in future space travels from the effect of zero gravity on the optic nerve head. Additionally, the same TLPD concept may offer a deeper understanding of the pathogenesis and treatment options of idiopathic intracranial hypertension (IIH), glaucoma and other diseases of the optic nerve head. (C) 2012 Elsevier Ltd. All rights reserved.
Sanford School of Medicine, Sioux Falls Campus.
Dey, Nandini, B. R. Smith, and  B. Leyland-Jones. (2012). Targeting Basal-Like Breast Cancers. [Review]. Current Drug Targets, 13(12), 1510-1524.
Basal-like breast tumors and triple negative breast tumors are high-risk breast cancers that typically carry the poorest prognoses compared with HR (Hormone Receptor)-positive tumors and HER2 (Human Epidermal growth factor Receptor 2)-amplified tumors for known therapies. These subsets of breast cancers exhibit aggressive clinical behavior, pushing margins of invasion, poor clinical outcome, and derive limited benefit from current therapy. This clinical situation is contributed and further aggravated by their less known biology, lack of obvious molecular targets, absence of favorable biomarkers, and their limited response to single-drug therapy. In 2010, Oakman et al., remarked that current therapy fails to curtail the innate aggressive behavior of TNBC (Triple Negative Breast Cancer) in the majority of patients. The poor prognosis coupled with a lack of targeted use of therapies is responsible for the high mortality in this subtype. The present review will examine the existing literature and scrutinize the difficulties that have, to date, limited the understanding of the biology of these tumor cells, and provide a rationale for the development of the concept of combining subtype-specific and pathway-specific drug targets for the therapeutic intervention of the disease.
Sanford School of Medicine, Sioux Falls Campus.
Harris, William S., James V. Pottala, S. M. Lacey, R. S. Vasan, M. G. Larson, and  S. J. Robins. (2012). Clinical correlates and heritability of erythrocyte eicosapentaenoic and docosahexaenoic acid content in the Framingham Heart Study. [Article]. Atherosclerosis, 225(2), 425-431.
Objectives: Red blood cell (RBC) levels of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA, the omega-3 index, expressed as a percent of total fatty acids) are inversely related to risk for cardiovascular disease (CVD). Although several mechanisms underlying this relationship have been proposed, understanding the associations between the omega-3 index and markers of CVD in the community can shed additional light on this question. The objectives of this study were to define the relations between the omega-3 index and clinical factors and to determine the heritability of the omega-3 index. Methods: RBC samples (n = 3196) drawn between 2005 and 2008 from participants in the Framingham Study [Examination 8 of the Offspring cohort plus Examination 3 of the Omni (minorities) cohort] were analyzed for fatty acid composition by gas chromatography. Results: The mean (SD) omega-3 index was 5.6% (1.7%). In multivariable regression models, the factors significantly and directly associated with the omega-3 index were age, female sex, higher education, fish oil supplementation, dietary intake of EPA + DHA, aspirin use, lipid pharmacotherapy, and LDL-cholesterol. Factors inversely associated were Offspring cohort, heart rate, waist girth, triglycerides and smoking. The total explained variability in the omega-3 index for the fully adjusted model was 73%, which included major components due to heritability (24%), EPA + DHA intake (25%), and fish oil supplementation (15%). Conclusion: The variability in the omega-3 index is determined primarily by dietary and genetic factors. An increased omega-3 index is associated with a generally cardioprotective risk factor milieu. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
Sanford School of Medicine, Sioux Falls Campus.
Higashisaka, K., Y. Yoshioka, K. Yamashita, Yahuhiro Abe, H. Kamada, S. Tsunoda, H. Nabeshi, T. Yoshikawa, and  Y. Tsutsumi. (2012). Hemopexin as biomarkers for analyzing the biological responses associated with exposure to silica nanoparticles. [Article]. Nanoscale Research Letters, 7.
Practical uses of nanomaterials are rapidly spreading to a wide variety of fields. However, potential harmful effects of nanomaterials are raising concerns about their safety. Therefore, it is important that a risk assessment system is developed so that the safety of nanomaterials can be evaluated or predicted. Here, we attempted to identify novel biomarkers of nanomaterial-induced health effects by a comprehensive screen of plasma proteins using two-dimensional differential in gel electrophoresis (2D-DIGE) analysis. Initially, we used 2D-DIGE to analyze changes in the level of plasma proteins in mice after intravenous injection via tail veins of 0.8 mg/mouse silica nanoparticles with diameters of 70 nm (nSP70) or saline as controls. By quantitative image analysis, protein spots representing > 2.0-fold alteration in expression were found and identified by mass spectrometry. Among these proteins, we focused on hemopexin as a potential biomarker. The levels of hemopexin in the plasma increased as the silica particle size decreased. In addition, the production of hemopexin depended on the characteristics of the nanomaterials. These results suggested that hemopexin could be an additional biomarker for analyzing the biological responses associated with exposure to silica nanoparticles. We believe that this study will contribute to the development of biomarkers to ensure the safety of silica nanoparticles.
Sanford School of Medicine, Sioux Falls Campus.
Hirai, T., Y. Yoshioka, H. Takahashi, K. Ichihashi, T. Yoshida, S. Tochigi, K. Nagano, Yahuhiro Abe, H. Kamada, S. Tsunoda, H. Nabeshi, T. Yoshikawa, and  Y. Tsutsumi. (2012). Amorphous silica nanoparticles enhance cross-presentation in murine dendritic cells. [Article]. Biochemical and Biophysical Research Communications, 427(3), 553-556.
Nanomaterials (NMs) exhibit unique physicochemical properties and innovative functions, and they are increasingly being used in a wide variety of fields. Ensuring the safety of NMs is now an urgent task. Recently, we reported that amorphous silica nanoparticles (nSPs), one of the most widely used NMs, enhance antigen-specific cellular immune responses and may therefore aggravate immune diseases. Thus, to ensure the design of safer nSPs, investigations into the effect of nSPs on antigen presentation in dendritic cells, which are central orchestrators of the adaptive immune response, are now needed. Here, we show that nSPs with diameters of 70 and 100 nm enhanced exogenous antigen entry into the cytosol from endosomes and induced cross-presentation, whereas submicron-sized silica particles (>100 nm) did not. Furthermore, we show that surface modification of nSPs suppressed cross-presentation. Although further studies are required to investigate whether surface-modified nSPs suppress immune-modulating effects in vivo, the current results indicate that appropriate regulation of the characteristics of nSPs, such as size and surface properties, will be critical for the design of safer nSPs. (C) 2012 Elsevier Inc. All rights reserved.
Sanford School of Medicine, Sioux Falls Campus.
Niewoehner, Patricia M., Rochelle R. Henderson, Jami Dalchow, Tracy L. Beardsley, Robert A. Stern, and  David B. Carr. (2012). Predicting Road Test Performance in Adults with Cognitive or Visual Impairment Referred to a Veterans Affairs Medical Center Driving Clinic. [Article]. Journal of the American Geriatrics Society, 60(11), 2070-2074.
Objectives To develop a screening battery for office-based clinicians that would assist with the prediction of impaired driving performance and deciding who should proceed to road testing in a sample of adults with cognitive or visual deficits. Design Prospective observational study. Setting Driving evaluation clinic at a Veterans Affairs Medical Center ( VAMC) in St. Louis, Missouri. Participants Seventy-seven individuals aged 23 to 91 with diagnoses of cognitive or visual impairment or both referred to an occupational therapy based driving clinic by VAMC providers because of concerns regarding driving safety. Measurements Predictor variables included tests of visual and cognitive functioning and activities of daily living. The major outcome was pass or fail on a standardized performance-based on-road driving test. Results Thirty percent of the referrals failed the road test. The best predictors of driving performance were the Trail- Making Test Part A and the Mazes Test from the Neuropsychological Assessment Battery. Conclusion Measures of visual search, psychomotor speed, and executive functioning accurately predicted road test performance in a significant number of participants. These brief tests may assist clinicians in deciding who should proceed with a road test in a driver rehabilitation clinic or perhaps to whom it should be recommended to cease driving.
Sanford School of Medicine, Sioux Falls Campus.
O’Connor, F. G., Michael F. Bergeron, J. Cantrell, P. Connes, K. G. Harmon, E. Ivy, J. Kark, D. Klossner, P. Lisman, B. K. Meyers, K. O’Brien, K. Ohene-Frempong, A. A. Thompson, J. Whitehead, and  P. A. Deuster. (2012). ACSM and CHAMP Summit on Sickle Cell Trait: Mitigating Risks for Warfighters and Athletes. [Article]. Medicine and Science in Sports and Exercise, 44(11), 2045-2056.
An estimated 300 million people worldwide have sickle cell trait (SCT). Although largely benign, SCT has been associated with exertional rhabdomyolysis and exercise-related sudden death in warfighters/athletes (WA). The National Collegiate Athletic Association’s policy to confirm a student athlete’s SCT status during their preparticipation medical examination prompted reaction from some organizations regarding the rationale and ethical justification of the policy. Methods: On September 26 and 27, 2011, a summit, composed of military and civilian experts in sports medicine and SCT, was convened at the Uniformed Services University in Bethesda, MD. The expert panel was charged with two objectives: 1) to provide specific recommendations to further mitigate the apparent risk with strenuous exercise in WA with SCT and 2) to develop clinical guidelines to identify, treat, and return to duty/play WA suspected to have incurred nonfatal sickle cell collapse. Results: New terminology is introduced, areas of current controversy are explored, consensus recommendations for mitigating risk and managing the WA with SCT are reviewed, and important areas for future research are identified. Conclusion: Further research is needed before conclusions can be drawn regarding the etiology of the increased death rate observed in WA with SCT, and the possibility exists that SCT is a surrogate for as yet another contributing factor for the unexplained deaths.
Sanford School of Medicine, Sioux Falls Campus.
Skulas-Ray, Ann, Penny Kris-Etherton, William Harris, and  Sheila West. (2012). Effects of Marine-Derived Omega-3 Fatty Acids on Systemic Hemodynamics at Rest and During Stress: a Dose-Response Study. [Article]. Annals of Behavioral Medicine, 44(3), 301-308.
Background: Omega-3 fatty acids reduced heart rate (HR) and blood pressure (BP) in some studies, but dose-response studies are rare, and little is known about underlying mechanisms. Purpose: We examined effects of 0.85 g/day eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) (low dose) and 3.4 g/day EPA + DHA (high dose) on HR and systemic hemodynamics during rest, speech, and foot cold pressor tasks. Methods: This was a dose-response, placebo-controlled, double-blind, randomized, crossover trial (8-week treatment, 6-week washout) in 26 adults. Results: Throughout the testing sessions, HR was reduced in a dose-dependent manner. The high dose reduced BP and stroke volume and increased pre-ejection period. Reductions in BP were associated with increases in erythrocyte omega-3 fatty acids. Conclusions: High-dose long-chain omega-3 fatty acids can reduce BP and HR, at rest and during stress. These findings suggest that at-risk populations may achieve benefits with increased omega-3 intake. The trial was registered on (NCT00504309).
Sanford School of Medicine, Sioux Falls Campus.
Yoshida, T., Y. Yoshioka, K. Matsuyama, Y. Nakazato, Yahuhiro Abe, H. Kamada, S. Tsunoda, H. Nabeshi, T. Yoshikawa, and  Y. Tsutsumi. (2012). Surface modification of amorphous nanosilica particles suppresses nanosilica-induced cytotoxicity, ROS generation, and DNA damage in various mammalian cells. [Article]. Biochemical and Biophysical Research Communications, 427(4), 748-752.
Recently, nanomaterials have been utilized in various fields. In particular, amorphous nanosilica particles are increasingly being used in a range of applications, including cosmetics, food technology, and medical diagnostics. However, there is concern that the unique characteristics of nanomaterials might induce undesirable effects. The roles played by the physical characteristics of nanomaterials in cellular responses have not yet been elucidated precisely. Here, by using nanosilica particles (nSPs) with a diameter of 70 nm whose surface was either unmodified (nSP70) or modified with amine (nSP70-N) or carboxyl groups (nSP70-C), we examined the relationship between the surface properties of nSPs and cellular responses such as cytotoxicity, reactive oxygen species (ROS) generation, and DNA damage. To compare the cytotoxicity of nSP70, nSP70-N, or nSP70-N, we examined in vitro cell viability after nSP treatment. Although the susceptibility of each cell line to the nSPs was different, nSP70-C and nSP70-N showed lower cytotoxicity than nSP70 in all cell lines. Furthermore, the generation of ROS and induction of DNA damage in nSP70-C- and nSP70-N-treated cells were lower than those in nSP70-treated cells. These results suggest that the surface properties of nSP70 play an important role in determining its safety, and surface modification of nSP70 with amine or carboxyl groups may be useful for the development of safer nSPs. We hope that our results will contribute to the development of safer nanomaterials. (C) 2012 Elsevier Inc. All rights reserved.
Sanford School of Medicine, Sioux Falls Campus.
Ikiugu, Moses, Nick Pollard, Audrey Cross, Megan Willer, Jenna Everson, and  Jeanie Stockland. (2012). Meaning making through occupations and occupational roles: A heuristic study of worker-writer histories. The British Journal of Occupational Therapy, 75(6), 289-295.
Introduction: Occupations are recognised in occupational therapy and occupational science literature as vehicles to meaning and wellbeing. Yet, the question of how they are used to create meaning has not been investigated exhaustively. In this study, the researchers explored the life histories of worker-writers in the United Kingdom. These writers considered themselves as representatives of the most numerous but marginalised social class. The researchers considered how the worker-writers derived life meaning from their occupations and occupational roles. Method: Using heuristic research methods, 34 published autobiographies were analysed to elicit themes illuminating how meaning was created by the worker-writers through occupations and occupational roles. Results: Five themes emerged from the analysis. Worker-writers created meaning by engaging in occupations and occupational roles that fostered family life and other meaningful relationships; a sense of control over their lives; meaningful leisure pursuits; a contribution to or connection to greater causes; and a sense of wellbeing. Conclusion: No claims are being made in this study about the generalisability of the findings to clinical practice. However, occupational therapists may consider exploring ways of helping clients engage in occupations reflecting themes that emerged from the study, as a way of helping them to reconstruct their lives following life-changing events or conditions. (PsycINFO Database Record (c) 2012 APA, all rights reserved) (journal abstract)
School of Health Sciences.
Kusek, Edward R., Amanda J. Kusek, and  E. Alex Kusek. (2012). Five-year retrospective study of laser-assisted periodontal therapy. [Article]. General Dentistry, 60(6), 540-543.
This article outlines a five-year retrospective study involving a diode dental laser used on periodontally infected teeth. The present study utilized a specific protocol: scaling and root planing, light ultrasonic scaling, and the use of a diode laser. In 80% of cases, pocket depth of 3 mm or less was maintained.
School of Health Sciences.

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