Posted by: kelsijo97 | November 12, 2013

November 2013

Doorn, Joshua M., & Michael C. Kruer. (2013). Newly characterized forms of neurodegeneration with brain iron accumulation. Current neurology and neuroscience reports, 13(12), 413.
 
Neurodegeneration with brain iron accumulation (NBIA) comprises a group of brain iron deposition syndromes that lead to mixed extrapyramidal features and progressive dementia. Historically, there has not been a clearly identifiable molecular cause for many patients with clinical and radiologic features of NBIA. Recent discoveries have shown that mutations in C19orf12 or WDR45 can lead to NBIA. C19orf12 mutations are inherited in an autosomal recessive manner, and lead to a syndrome similar to that caused by mutations in PANK2 or PLA2G6. In contrast, WDR45 mutations lead to a distinct form of NBIA characterized by spasticity and intellectual disability in childhood followed by the subacute onset of dystonia-parkinsonism in adulthood. WDR45 mutations act in an X-linked dominant manner. Although the function of C19orf12 is largely unknown, WDR45 plays a key role in autophagy. Each of these new forms of NBIA thus leads to a distinct clinical syndrome, and together they implicate new cellular pathways in the pathogenesis of these disorders.
 
Basic Biomedical Sciences, Vermillion Campus.
 
 
Morecraft, Robert J., Jizhi Ge, Kimberly S. Stilwell-Morecraft, David W. McNeal, Marc A. Pizzimenti, & Warren G. Darling. (2013). Terminal distribution of the corticospinal projection from the hand/arm region of the primary motor cortex to the cervical enlargement in rhesus monkey. The Journal of comparative neurology, 521(18), 4205-4235.
 
To further our understanding of the corticospinal projection (CSP) from the hand/arm representation of the primary motor cortex (M1), high-resolution anterograde tracing methodology and stereology were used to investigate the terminal distribution of this connection at spinal levels C5 to T1. The highest number of labeled terminal boutons occurred contralaterally (98%) with few ipsilaterally (2%). Contralaterally, labeled boutons were located within laminae I-X, with the densest distribution found in lamina VII and, to a lesser extent, laminae IX and VI. Fewer terminals were found in other contralateral laminae. Within lamina VII, terminal boutons were most prominent in the dorsomedial, dorsolateral, and ventrolateral subsectors. Within lamina IX, the heaviest terminal labeling was distributed dorsally. Ipsilaterally, boutons were found in laminae V-X. The most pronounced distribution occurred in the dorsomedial and ventromedial sectors of lamina VII and fewer labeled boutons were located in other ipsilateral laminae. Segmentally, contralateral lamina VII labeling was highest at levels C5-C7. In contrast, lamina IX labeling was highest at C7-T1 and more widely dispersed among the quadrants at C8-T1. Our findings suggest dominant contralateral influence of the M1 hand/arm CSP, a contralateral innervation pattern in lamina VII supporting Kuypers (1982) conceptual framework of a “lateral motor system,” and a projection to lamina IX indicating significant influence on motoneurons innervating flexors acting on the shoulder and elbow rostrally (C5-C7), along with flexors, extensors, abductors and adductors acting on the digits, hand and wrist caudally (C8-T1). J. Comp. Neurol. 521:4205-4235, 2013. 2013 Wiley Periodicals, Inc. Copyright 2013 Wiley Periodicals, Inc.
 
Basic Biomedical Sciences, Vermillion Campus.
 
 
Dececchi, T. Alexander, & H. C. E. Larsson. (2013). BODY AND LIMB SIZE DISSOCIATION AT THE ORIGIN OF BIRDS: UNCOUPLING ALLOMETRIC CONSTRAINTS ACROSS A MACROEVOLUTIONARY TRANSITION. Evolution, 67(9), 2741-2752.
 
The origin of birds and powered flight is a classic major evolutionary transition. Research on their origin often focuses on the evolution of the wing with trends of forelimb elongation traced back through many nonavian maniraptoran dinosaurs. We present evidence that the relative forelimb elongation within avian antecedents is primarily due to allometry and is instead driven by a reduction in body size. Once body size is factored out, there is no trend of increasing forelimb length until the origin of birds. We report that early birds and nonavian theropods have significantly different scaling relationships within the forelimb and hindlimb skeleton. Ancestral forelimb and hindlimb allometric scaling to body size is rapidly decoupled at the origin of birds, when wings significantly elongate, by evolving a positive allometric relationship with body size from an ancestrally negative allometric pattern and legs significantly shorten by keeping a similar, near isometric relationship but with a reduced intercept. These results have implications for the evolution of powered flight and early diversification of birds. They suggest that their limb lengths first had to be dissociated from general body size scaling before expanding to the wide range of fore and hindlimb shapes and sizes present in today’s birds.
 
Biology Department.
 
 
Feller, K. D., T. W. Cronin, S. T. Ahyong, & Megan L. Porter. (2013). Morphological and molecular description of the late-stage larvae of Alima Leach, 1817 (Crustacea: Stomatopoda) from Lizard Island, Australia. Zootaxa, 3722(1), 22-32.
 
Alima pacifica and A. orientalis are stomatopods commonly found at Lizard Island, Great Barrier Reef, Australia. There are currently no descriptions that link the larvae to the adult morphotype despite the frequent occurrence of the last larval stage of these two species. We used DNA barcoding of the cytochrome oxidase I (COI) gene to link the last stage larvae of A. pacifica and A. orientalis to the respective adult morphotype. Detailed morphological descriptions of the late larva of each species are provided and compared to other described last- stage Alima larvae. These data support previous studies that suggest paraphyly of the genus Alima.
 
Biology Department.
 
 
Scott, M. L., G. T. Auble, Mark D. Dixon, W. C. Johnson, & L. A. Rabbe. (2013). LONG-TERM COTTONWOOD FOREST DYNAMICS ALONG THE UPPER MISSOURI RIVER, USA. River Research and Applications, 29(8), 1016-1029.
 
The upper Missouri River bottomland in north-central Montana, USA, retains much of the physical character it had when traversed by Lewis and Clark around 1805. We used geospatial data to quantify long-term changes in the distribution of bottomland vegetation, land use patterns and channel planform for a 257-rkm segment of the Missouri River above Fort Peck Reservoir. This segment is less ecologically altered than downstream segments, but two dams completed in the mid-1950s have decreased the frequency and magnitude of floods. The area of forest is sparse because of geomorphic setting but, contrary to public perception, has remained relatively constant during the past century. However, the stability of forest area obscures its spatial and temporal dynamics. We used state and transition models to quantify fates and sources of forest during two periods: 1890s-1950s and 1950s-2006. Total forest area was 6% greater in 2006 than it was in the 1890s, largely due to reduced forest loss to erosional processes and gains related to progressive channel narrowing. Channel narrowing resulted in part from human-caused peak flow attenuation. A modified transition matrix, used to examine future steady-state conditions, projected little change in forest area; however, these projections are likely an overestimate. The extent to which 2006 forest area represents a transient adjustment to a new flow regime versus a dynamic, quasi-steady state will be determined by the long-term interplay among hydrologic factors, channel processes, water management and land use practices. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.
 
Biology Department.
 
 
Kibombo, Harrison S., A. S. Weber, Chia-Ming Wu, K. R. Raghupathi, & Ranjit T. Koodali. (2013). Effectively dispersed europium oxide dopants in TiO2 aerogel supports for enhanced photocatalytic pollutant degradation. Journal of Photochemistry and Photobiology a-Chemistry, 269, 49-58.
 
The influence of supercritical drying and the europium oxide content on the physicochemical properties and the resultant photocatalytic activity of Eu-TiO2 aerogels for the degradation of salicylic acid were explored for the first time. It was demonstrated that the efficiencies might be influenced by a combination of factors such as enhanced adsorption, presence of trap states, and/or suppression of rutile phase formation. The well dispersed europium oxide dopants may act as trap states. A subsequent enhancement of charge separation avails electrons for oxygen attack to form superoxide ions, from which (OH)-O-center dot radicals can be generated, and are postulated to be primary contributors toward the degradation efficiencies in this study. (C) 2013 Elsevier B.V. All rights reserved.
 
Chemistry Department
 
 
Kone, K. Y., C. Druon, Etienne Z. Gnimpieba, M. Delmotte, A. Duquenoy, & J. C. Laguerre. (2013). Power density control in microwave assisted air drying to improve quality of food. Journal of Food Engineering, 119(4), 750-757.
 
Currently, the new trend is the development of microwave hot air drying control in order to solve the problem of hot spots on the product. So in this study, a microwave/hot air drying system with the ability of automatic power density control was developed for tomato drying. Three power densities (3, 5 and 7 W/g) at 40 degrees C air temperature were applied and the output, reflected microwave power and the mass of the sample were registered online. Two different drying strategies were implemented. The first consisted of a microwave drying without specific power control. The second one introduced power control. A feedback control based on specific power related to the actual sample mass resulted in the best power control and the improvement of product quality compared to the dry sample without power control. (C) 2013 Elsevier Ltd. All rights reserved.
 
Computer Science Department.
 
 
Dutkay, D. E., Gabriel Picioroaga, & M. S. Song. (2014). Orthonormal bases generated by Cuntz algebras. Journal of Mathematical Analysis and Applications, 409(2), 1128-1139.
 
We show how some orthonormal bases can be generated by representations of the Cuntz algebra; these include Fourier bases on fractal measures, generalized Walsh bases on the unit interval and piecewise exponential bases on the middle third Cantor set. (C) 2013 Published by Elsevier Inc.
 
Mathematics Department.
 
 
Lio, Y. L., T. R. Tsai, M. Aslam, & Nan Jiang. (2014). Control Charts for Monitoring Burr Type-X Percentiles. Communications in Statistics-Simulation and Computation, 43(4), 761-776.
 
When the sampling distribution of a parameter estimator is unknown, using normality asymptotically, the Shewhart-type chart may provide improper control limits. To monitor Burr type-X percentiles, two parametric bootstrap charts (PBCs) are proposed and compared with the Shewhart-type chart via a Monte Carlo simulation. Simulation results exhibit that the proposed PBCs perform well with a short average run length to signal out-of-control when the process is out-of-control, and have more adequate control limits than the Shewhart-type chart in view of in-control false alarm rate. An example regarding single fiber strength is presented for illustrating the proposed PBCs.
 
Mathematics Department.
 
 
Barker, D., W. Z. Wei, D. M. Mei, & C. Zhang. (2013). Ionization efficiency study for low energy nuclear recoils in germanium. Astroparticle Physics, 48, 8-15.
 
We used the internal conversion (E-0 transition) of germanium-72 to indirectly measure the low energy nuclear recoils of germanium. Together with a reliable Monte Carlo package, in which we implement the internal conversion process, the data was compared to the Lindhard (k = 0.159) and Barker-Mei models. A shape analysis indicates that both models agree well with data in the region of interest within 4%. The most probable value (MPV) of the nuclear recoils obtained from the shape analysis is 17.5 +/- 0.12 (sys) +/- 0.035 (stat) keV with an average path-length of 0.014 mu m. Published by Elsevier B.V.
 
Physics Department.
 
 
Wang, Guojian, Xifa Long, Lizhen Zhang, Zhoubin Lin, & Guofu Wang. (2013). Growth and spectral properties of Nd3+:Ba2LiNb5O15 crystal. Optical Materials, 35(12), 2703-2706.
 
Highlights: [•] Nd3+:Ba2LiNb5O15 crystal was obtained by Czochralski method. [•] The refractive index was measured by the minimum deviation method. [•] The polarized absorption and luminescence spectra were investigated. [•] The spectral parameters were calculated according to Judd–Ofelt theory.
 
Physics Department.
 
 
Dvorak, R. D., Tyler B. Wray, Nicholas J. Kuvaas, & Tess M. Kilwein. (2013). Mania and sexual risk: Associations with behavioral self-regulation. Journal of Affective Disorders, 150(3), 1076-1081.
 
Introduction: Risky sexual behavior among young adults is a central public health concern. Hallmark cognitive effects of mania involve grandiose extrinsic goal-setting, which may be part of a tendency to approach rewarding cues while understanding potential negative consequences. Poor impulse control also reflects a tendency to seek reward and rely on emotional decision-making. In contrast, effortful control is associated with adaptive decision making. Methods: Participants (n=595) completed measures of impulsivity, risk for mania, and risky sexual behavior. Relationships between risk for mania, behavioral self-regulation, and risky sexual behavior were examined in a negative binomial hurdle model. Results: For the hurdle portion, sensation-seeking was positively associated with the likelihood of engaging in risky sexual behavior. Effortful control was inversely associated with the likelihood of engaging in risky sexual behavior, but only among those high in risk for mania. Among those endorsing engagement in risky sex, urgency was positively, and effortful control negatively, associated with frequency of risky sex. Risk for mania was positively associated with frequency of risky sex, but only for those low in effortful control. Limitations: Findings were among a homogeneous, young adult, nonclinical population, limiting generalizability. Examining these associations among a clinical population in an active manic episodic is warranted. Conclusion: Results suggest high levels of effortful control may diminish the hallmark effects of mania on cognition thereby reducing engagement in risky sexual behavior. Treatments targeting emotion-based rash action and effortful decision making may be particularly important for those experiencing manic symptoms. (C) 2013 Elsevier B.V. All rights reserved.
 
Psychology Department.
 
 
Ammann, Eric M., James V. Pottala, William S. Harris, Mark A. Espeland, Robert Wallace, Natalie L. Denburg, . . . Jennifer G. Robinson. (2013). Omega-3 fatty acids and domain-specific cognitive aging: Secondary analyses of data from WHISCA. Neurology, 81(17), 1484-1491.
 
OBJECTIVE: To test the hypothesis that higher levels of red blood cell (RBC) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have a protective association with domain-specific cognitive function in women aged 65 years and older.; METHODS: A total of 2,157 women with normal cognition enrolled in a clinical trial of postmenopausal hormone therapy were followed with annual cognitive testing for a median of 5.9 years. In this retrospective cohort study, we assessed the relationship between prerandomization RBC DHA + EPA levels and a) cognitive measures at baseline, and b) cognitive change over time. Endpoints were composite cognitive function and performance in 7 cognitive domains: fine motor speed, verbal memory, visual memory, spatial ability, verbal knowledge, verbal fluency, and working memory.; RESULTS: After adjustment for demographic, clinical, and behavioral characteristics, no significant (p < 0.01) cross-sectional cognitive differences were found between women in the high and low DHA + EPA tertiles at the time of the first annual cognitive battery. In addition, no significant (p < 0.01) differences were found between the high and low DHA + EPA tertiles in the rate of cognitive change over time.; CONCLUSIONS: We did not find an association between RBC DHA + EPA levels and age-associated cognitive decline in a cohort of older, dementia-free women.
 
Sanford School of Medicine, Sioux Falls Campus.
 
 
De, Pradip, M. Hasmann, & Brian Leyland-Jones. (2013). Molecular determinants of trastuzumab efficacy: What is their clinical relevance? Cancer Treatment Reviews, 39(8), 925-934.
 
Trastuzumab-containing therapy is a standard of care for human epidermal growth factor receptor-2 (HER2)-positive breast cancer. In pre-clinical models, a wide range of molecular mechanisms have been associated with reduced sensitivity to trastuzumab in vitro. These include expression of the truncated HER2 receptor fragment p95(HER2), activating mutation of the gene encoding the class 1A catalytic subunit of phosphatidylinositol 3-kinase (PIK3CA), loss of phosphatase and tensin homolog (PTEN), activation of other downstream signal transducers, prevention of cell cycle arrest, increased signaling through alternative (HER or non-HER) tyrosine kinase receptors, and resistance to antibody-dependent cellular cytotoxicity. However, the clinical significance of these mechanisms as determinants of trastuzumab efficacy in vivo has been unclear. Here, we review clinical studies of potential predictive biomarkers of trastuzumab efficacy in HER2-positive breast cancer and consider whether evaluation of such markers might inform patient selection for therapy. We find that clinical evidence relating to potential predictive biomarkers is mostly limited to small, retrospective studies, many of which have yielded conflicting findings. Some trends are evident in the retrospective data and in biomarker analyses from randomized clinical trials, particularly relating to activation of the phosphatidylinositol 3-kinase pathway, but none is sufficiently strong to form a basis for patient selection. This may be explained by the fact that multiple mechanisms of action determine the clinical efficacy of trastuzumab. In the absence of novel, validated biomarkers of efficacy, trastuzumab eligibility should continue to be based on evaluation of HER2 status according to standard methods. (C) 2013 Elsevier Ltd. All rights reserved.
 
Sanford School of Medicine, Sioux Falls Campus.
 
 
Dey, Nandini, Brandon Young, Mark Abramovitz, Mark Bouzyk, Benjamin Barwick, Pradip De, & Brian Leyland-Jones. (2013). Differential Activation of Wnt-beta-Catenin Pathway in Triple Negative Breast Cancer Increases MMP7 in a PTEN Dependent Manner. PloS one, 8(10), e77425.
 
Mutations of genes in tumor cells of Triple Negative subset of Breast Cancer (TNBC) deregulate pathways of signal transduction. The loss of tumor suppressor gene PTEN is the most common first event associated with basal-like subtype (Martins, De, Almendro, Gonen, and Park, 2012). Here we report for the first time that the functional upregulation of secreted-MMP7, a transcriptional target of Wnt-beta-catenin signature pathway in TNBC is associated to the loss of PTEN. We identified differential expression of mRNAs in several key-components genes, and transcriptional target genes of the Wnt-beta-catenin pathway (WP), including beta-catenin, FZD7, DVL1, MMP7, c-MYC, BIRC5, CD44, PPARD, c-MET, and NOTCH1 in FFPE tumors samples from TNBC patients of two independent cohorts. A similar differential upregulation of mRNA/protein for beta-catenin, the functional readout of WP, and for MMP7, a transcriptional target gene of beta-catenin was observed in TNBC cell line models. Genetic or pharmacological attenuation of beta-catenin by SiRNA or WP modulators (XAV939 and sulindac sulfide) and pharmacological mimicking of PTEN following LY294002 treatment downregulated MMP7 levels as well as enzymatic function of the secreted MMP7 in MMP7 positive PTEN-null TNBC cells. Patient data revealed that MMP7 mRNA was high in only a subpopulation of TNBC, and this subpopulation was characterized by a concurrent low expression of PTEN mRNA. In cell lines, a high expression of casein-zymograph-positive MMP7 was distinguished by an absence of functional PTEN. A similar inverse relationship between MMP7 and PTEN mRNA levels was observed in the PAM50 data set (a correlation coefficient of -0.54). The PAM50 subtype and outcome data revealed that the high MMP7 group had low pCR (25%) and High Rd (74%) in clinical stage T3 pathologic response in contrast to the high pCR (40%) and low residual disease (RD) (60%) of the low MMP7 group.
 
Sanford School of Medicine, Sioux Falls Campus.
 
 
Flock, Michael R., William S. Harris, & Penny M. Kris-Etherton. (2013). Long-chain omega-3 fatty acids: time to establish a dietary reference intake. Nutrition Reviews, 71(10), 692-707.
 
The beneficial effects of consuming omega-3 polyunsaturated fatty acids (n-3 PUFAs), specifically eicosapentaenoic acid ( EPA) and docosahexaenoic acid ( DHA), on cardiovascular health have been studied extensively. To date, there is no dietary reference intake ( DRI) for EPA and DHA, although many international authorities and expert groups have issued dietary recommendations for them. Given the substantial new evidence published since the last Institute of Medicine ( IOM) report on energy and macronutrients, released in 2002, there is a pressing need to establish a DRI for EPA and DHA. In order to set a DRI, however, more information is needed to define the intakes of EPA and DHA required to reduce the burden of chronic disease. Information about potential gender- or race-based differences in requirements is also needed. Given the many health benefits of EPA and DHA that have been described since the 2002 IOM report, there is now a strong justification for establishing a DRI for these fatty acids.
 
Sanford School of Medicine, Sioux Falls Campus.
 
 
Gara, Rishi Kumar, Vasudha Sundram, Subhash C. Chauhan, & Meena Jaggi. (2013). Anti-Cancer Potential of a Novel SERM Ormeloxifene. Current Medicinal Chemistry, 20(33), 4177-4184.
 
Ormeloxifene is a non-steroidal Selective Estrogen Receptor Modulator (SERM) that is used as an oral contraceptive. Recent studies have shown its potent anti-cancer activities in breast, head and neck, and chronic myeloid leukemia cells. Several in vivo and clinical studies have reported that ormeloxifene possesses an excellent therapeutic index and has been well-tolerated, without any haematological, biochemical or histopathological toxicity, even with chronic administration. A reasonably long period of time and an enormous financial commitment are required to develop a lead compound into a clinically approved anti-cancer drug. For these reasons and to circumvent these obstacles, ormeloxifene is a promising candidate on a fast track for the development or repurposing established drugs as anti-cancer agents for cancer treatment. The current review summarizes recent findings on ormeloxifene as an anti-cancer agent and future prospects of this clinically safe pharmacophore.
 
Sanford School of Medicine, Sioux Falls Campus.
 
 
Grenon, S. Marlene, Christopher D. Owens, Hugh Alley, ….., William Harris, Millie Hughes-Fulford, & Michael S. Conte. (2013). n-3 Polyunsaturated fatty acids supplementation in peripheral artery disease: the OMEGA-PAD trial. Vascular Medicine, 18(5), 263-274.
 
Despite current consensus guidelines recommending intensive cardiovascular risk factor management for peripheral artery disease (PAD), patients suffering from PAD continue to experience significant morbidity and mortality. This excess morbid burden is at least partially related to impaired vascular function and systemic inflammation. Interventions bridging this gap are critical. Dietary supplementation of n-3 polyunsaturated fatty acids (n-3 PUFA) has been shown to improve endothelial function and reduce inflammation in different cohorts, as well as to decrease cardiovascular events in secondary prevention trials in patients with coronary artery disease. Their effects in the PAD population are, however, less well understood. The OMEGA-PAD trial is a double-blinded, randomized, placebo-controlled trial that examines the impact of a high-dose, short-duration dietary oral supplementation of n-3 PUFA on vascular function and inflammation in patients with established PAD. The purpose of this article is to provide a detailed description of the design and methods of the OMEGA-PAD trial, and a summary of baseline characteristics of the cohort.
 
Sanford School of Medicine, Sioux Falls Campus.
 
 
Harris, William S., S. A. Varvel, J. V. Pottala, G. R. Warnick, & J. P. McConnell. (2013). Comparative effects of an acute dose of fish oil on omega-3 fatty acid levels in red blood cells versus plasma: Implications for clinical utility. Journal of Clinical Lipidology, 7(5), 433-440.
 
BACKGROUND: Omega-3 fatty acid (n-3 FA) biostatus can be estimated with red blood cell (RBC) membranes or plasma. The matrix that exhibits the lower within-person variability and is less affected by an acute dose of n-3 FA is preferred in clinical practice. OBJECTIVE: We compared the acute effects of a large dose of n-3 FA on RBC and plasma levels of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA). METHODS: Healthy volunteers (n = 20) were given 4 capsules containing 3.6 g of n-3 FA with a standardized breakfast. Blood samples were drawn at 0, 2, 4, 6, 8, and 24 hours. The EPA + DHA content of RBC membranes and plasma (the latter expressed as a percentage of total FA and as a concentration) were determined. General linear mixed models were used to analyze the mean response profiles in FA changes over time for plasma and RBCs. RESULTS: At 6 hours after load, the plasma concentration of EPA + DHA had increased by 47% (95% confidence interval [CI], 24% to 73%) and the plasma EPA + DHA percentage of total FA by 19% (95% CI, 4.7% to 36%). The RBC EPA + DHA percentage of composition was unchanged [-0.6% (95% CI, -2.6% to 1.5%)]. At 24 hours, the change in both of the plasma EPA + DHA markers was 10-fold greater than that in RBCs. CONCLUSIONS: An acute dose of n-3 FA (eg, a meal of oily fish or fish oil supplements) taken within a day before a doctor’s visit can elevate levels of EPA + DHA in plasma, whether expressed as a percentage or a concentration, but not in RBC membranes. Similar to hemoglobin A(1c), which is not affected by an acute glycemic deviation, RBCs provide a more reliable estimate of a patient’s chronic EPA + DHA status than does plasma. (c) 2013 National Lipid Association. All rights reserved.
 
Sanford School of Medicine, Sioux Falls Campus.
 
 
Horn, H. F., D. I. Kim, G. D. Wright, ….., & Kyle J. Roux. (2013). A mammalian KASH domain protein coupling meiotic chromosomes to the cytoskeleton. Journal of Cell Biology, 202(7), 1023-1039.
 
Chromosome pairing is an essential meiotic event that ensures faithful haploidization and recombination of the genome. Pairing of homologous chromosomes is facilitated by telomere-led chromosome movements and formation of a meiotic bouquet, where telomeres cluster to one pole of the nucleus. In metazoans, telomere clustering is dynein and microtubule dependent and requires Sun1, an inner nuclear membrane protein. Here we provide a functional analysis of KASH5, a mammalian dynein-binding protein of the outer nuclear membrane that forms a meiotic complex with Sun1. This protein is related to zebrafish futile cycle (Fue), a nuclear envelope (NE) constituent required for pronuclear migration. Mice deficient in this Fue homologue are infertile. Males display meiotic arrest in which pairing of homologous chromosomes fails. These findings demonstrate that telomere attachment to the NE is insufficient to promote pairing and that telomere attachment sites must be coupled to cytoplasmic dynein and the microtubule system to ensure meiotic progression.
 
Sanford School of Medicine, Sioux Falls Campus.
 
 
Judd, Kyle T., Sean Burns, & Karen Hand. (2013). Finding a job in an overcrowded market: getting what you want. Journal of orthopaedic trauma, 27 Suppl 1, S2-4.
 
As the number of fellowship-trained orthopaedic trauma surgeons entering the workforce increases, so does the competition for available practice opportunities. The process of finding employment has seemingly become more involved as the relative availability of positions has declined over recent years. To manage this new environment, new graduates need to become much more proactive in the process of seeking and obtaining orthopaedic trauma positions.
 
Sanford School of Medicine, Sioux Falls Campus.
 
 
May, Philip A., Jason Blankenship, Anna-Susan Marais, ….., H. Eugene Hoyme, Barbara Tabachnick, & Soraya Seedat. (2013). Maternal alcohol consumption producing fetal alcohol spectrum disorders (FASD): Quantity, frequency, and timing of drinking. Drug & Alcohol Dependence, 133(2), 502-512.
 
Abstract: Background: Concise, accurate measures of maternal prenatal alcohol use are needed to better understand fetal alcohol spectrum disorders (FASD). Methods: Measures of drinking by mothers of children with specific FASD diagnoses and mothers of randomly-selected controls are compared and also correlated with physical and cognitive/behavioral outcomes. Results: Measures of maternal alcohol use can differentiate maternal drinking associated with FASD from that of controls and some from mothers of alcohol-exposed normals. Six variables that combine quantity and frequency concepts distinguish mothers of FASD children from normal controls. Alcohol use variables, when applied to each trimester and three months prior to pregnancy, provide insight on critical timing of exposure as well. Measures of drinking, especially bingeing, correlate significantly with increased child dysmorphology and negative cognitive/behavioral outcomes in children, especially low non-verbal IQ, poor attention, and behavioral problems. Logistic regression links (p <.001) first trimester drinking (vs. no drinking) with FASD, elevating FASD likelihood 12 times; first and second trimester drinking increases FASD outcomes 61 times; and drinking in all trimesters 65 times. Conversely, a similar regression (p =.008) indicates that drinking only in the first trimester makes the birth of a child with an FASD 5 times less likely than drinking in all trimesters. Conclusions: There is significant variation in alcohol consumption both within and between diagnostic groupings of mothers bearing children diagnosed within the FASD continuum. Drinking measures are empirically identified and correlated with specific child outcomes. Alcohol use, especially heavy use, should be avoided throughout pregnancy.
 
Sanford School of Medicine, Sioux Falls Campus.
 
 
Pothula, S., H. E. P. Bazan, & Gudiseva Chandrasekher. (2013). Regulation of Cdc42 Expression and Signaling Is Critical for Promoting Corneal Epithelial Wound Healing. Investigative Ophthalmology & Visual Science, 54(8), 5343-5352.
 
PURPOSE. Cdc42, a member of Rho GTPases (guanosine triphosphatases), participates in cytokine-and growth factor-controlled biological functions in mammalian tissues. Here, we examined Cdc42 role in corneal epithelial wound healing and the influence of hepatocyte, keratinocyte, and epidermal growth factor (HGF, KGF, and EGF)-mediated signaling on Cdc42. METHODS. Epithelial wounds were created on the corneas of live rabbits by complete debridement and in rabbit corneal epithelial primary cultures through scratch injury. Cdc42 expression in cultures was suppressed using Cdc42 siRNA. Cdc42 activation was determined by pull-down assays with PAK-agarose beads. Cdc42 expression was analyzed by immunoblotting and immunofluorescence. Association of Cdc42 with cell-cycle proteins was identified by immunoprecipitation. RESULTS. In rabbit corneas, significant increase in Cdc42 expression that occurred 2 to 4 days after the injury coincided with wound closure, and by 8 days the expression reached near basal levels. Silencing of Cdc42 expression in cultures caused inhibition of wound closure as a result of 60% to 75% decrease in epithelial migration and growth. HGF, KGF, and EGF increased Cdc2 expression, activation, and its phosphorylation on ser71. Inhibition of growth factor-mediated PI-3K signaling resulted in the downregulation of Cdc42 expression and its phosphorylation. Increased association of cell-cycle proteins p27(kip) and cyclin-dependent kinase 4 (CDK4) with Cdc42; and phosphorylated Cdc42 with plasma membrane leading edges was also observed in the presence of growth factors. CONCLUSIONS. Cdc42 is an important regulator of corneal epithelial wound repair. To promote healing, Cdc42 may interact with receptor tyrosine kinase-activated signaling cascades that participate in cell migration and cell-cycle progression.
 
Sanford School of Medicine, Sioux Falls Campus.
 
 
Sharma, Jitendra, A. Nanda, R. S. Jung, S. Mehta, J. Pooria, & D. P. Hsu. (2013). Risk of contrast-induced nephropathy in patients undergoing endovascular treatment of acute ischemic stroke. Journal of Neurointerventional Surgery, 5(6), 543-545.
 
Background and purpose We report the incidence and risk factors for contrast-induced nephropathy after the use of iodinated contrast for endovascular treatment of acute ischemic stroke. Methods A retrospective chart review was performed in 194 consecutive patients who underwent endovascular treatment for acute ischemic stroke between January 2006 and January 2011. No patients were excluded from treatment for elevated creatinine (Cr). Each patient received approximately 150ml intra-arterial non-ionic low-osmolar contrast agent (Optiray 320) during the endovascular procedure. Contrast-induced nephropathy (CIN) was defined according to the Acute Kidney Injury Network criteria as a relative increase of serum Cr 50% above the baseline or an absolute increase of 0.3mg/dl at 48h following the endovascular procedure. Results Of 194 patients (mean age 6514years), 52% were women (n=100) and 25% (n=48) were diabetic. Baseline Cr levels for 191 patients ranged between 0.4 and 2.7mg/dl. Three patients on chronic hemodialysis had baseline Cr levels ranging between 5.3 and 6.1mg/dl. Cr was 1.5mg/dl in 163 patients (84%) and 1.5mg/dl in 31 (16%). Three of the 191 patients (1.5%) developed CIN as noted from Cr measurements between baseline and within 48h. One patient who developed an elevated Cr level had a known history of chronic renal insufficiency (Cr >1.5mg/dl) and two had baseline Cr levels within the normal range. An additional CT angiogram was obtained in 44 patients, none of which developed CIN. Female gender and diabetes were not associated with a higher risk of developing CIN. Conclusions The risk of developing CIN is low among patients with acute stroke who undergo emergency endovascular treatment. Treatment of acute stroke should be performed irrespective of Cr levels.
 
Sanford School of Medicine, Sioux Falls Campus.
 
 
Smythe, Maureen A., John Fanikos, Michael P. Gulseth, Ann K. Wittkowsky, Sarah A. Spinler, William E. Dager, & Edith A. Nutescu. (2013). Rivaroxaban: Practical Considerations for Ensuring Safety and Efficacy. Pharmacotherapy, 33(11), 1223-1245.
 
Rivaroxaban is the first agent available within a new class of anticoagulants called direct factor Xa inhibitors. Rivaroxaban is approved for use in the United States for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, for the prevention of deep vein thrombosis in patients undergoing total hip replacement and total knee replacement, for the treatment of deep vein thrombosis and pulmonary embolism, and for the reduction in risk of recurrence of deep vein thrombosis and pulmonary embolism (with additional indications under review). Rivaroxaban dose and frequency of administration vary depending on the indication. As of result of predictable pharmacokinetics and pharmacodynamics, a fixed dose of rivaroxaban is administered without routine coagulation testing. Rivaroxaban has a short half-life, undergoes a dual mode of elimination (hepatic and renal), and is a substrate for P-glycoprotein. Rivaroxaban has a lower potential for drug interactions compared with warfarin. Despite the advantages of a once/day fixed-dose oral agent, in many clinical situations limited evidence is available to guide optimal management of rivaroxaban therapy. In this article, we review the available evidence and provide recommendations where possible for such situations including the desire to monitor the anticoagulation intensity, use in special patient populations, managing drug interactions, and transitioning across anticoagulant agents. Potential strategies for reversing rivaroxaban’s anticoagulant effect are reviewed. Health systems will need to perform a systematic safety evaluation and ensure that numerous hospital policies related to anticoagulation are updated to include rivaroxaban. A comprehensive approach to education is needed for clinicians, patients, and technical support personnel involved in patient interactions to ensure safe use.
 
Sanford School of Medicine, Sioux Falls Campus.
 
 
Sun, Yuliang, Nandini Dey, M. Brammer, Pradip De, & Brian Leyland-Jones. (2013). Bevacizumab confers additional advantage to the combination of trastuzumab plus pertuzumab in trastuzumab-refractory breast cancer model. Cancer Chemotherapy and Pharmacology, 72(4), 733-745.
 
We investigated antitumor activity of trastuzumab (T)/T-DM1 + pertuzumab (P) + bevacizumab (B) in T-sensitive (BT474) and T-resistant (BT474HerR) BC models in order to test whether or not the addition of an anti-angiogenic drug can provide a supplementary advantage to the antitumor activity of double HER2-mAB combination. In addition to the antitumor activity (xenograft model), we tested antiproliferative effect, and HER2-mediated signals of different antibodies (T or P or T-DM1) in HER2-amplified T-sensitive, T-resistant and HER2-amplified/PIK3CA mutated (HCC1954) BT cell lines by 3D ON-TOP clonogenic growth assay and Western blots. Data show (1) T, T-DM1 or P blocked p-AKT (> 60 %), p-ERK (> 50 %) following heregulin in only T-sensitive cells, (2) T/T-DM1 + P, T/T-DM1 + B, and P + B reduced tumor growth as compared to any single-agent treatment, (3) T + P + B achieved almost complete regression of tumor growth, decreased cell proliferation, and inhibited tumor-induced angiogenesis, in both models, (4) antitumor activity of T + P + B was associated with the pharmacodynamic knockdown of p-AKT, and (5) T-DM1 + P caused complete regression of tumor volume in both models. Our data demonstrate that B imparts a significant advantage when combined with T + P in the resistant model, in contrast to T-DM1 + P, as the triple combination of T-DM1 + P + B and the double combination of T-DM1 + P showed a comparable antitumor activity. Our study reveals the preclinical evidence in favor of the inclusion of B when combined with T + P in T-resistant BC patients.
 
Sanford School of Medicine, Sioux Falls Campus.
 
 
Ikiugu, Moses N. (2013). The validity of occupational performance assessments: a validity generalization meta-analysis. Occupational therapy in health care, 27(4), 372-391.
 
ABSTRACT The purpose of this meta-analysis was to determine sample weighted mean validity effect sizes for occupational performance assessments, and their generalizability from research to clinical settings. The bare-bones Validity Generalization (VG) guidelines developed by Hunter and Schmidt ( 2004 ) augmented by Maximum Likelihood (ML) procedures were used to complete the meta-analysis. The sample consisted of 27 studies in which convergent, divergent, and predictive validity estimates of occupational performance assessments were investigated. The mean coefficients of assessments validated in the studies constituting the sample for this meta-analysis ranged from medium to large. Further meta-analysis with complete dis-attenuation of observed mean validity coefficients is indicated.
 
School of Health Sciences.
 
 
Nick, Jan M., Nancy C. Sharts-Hopko, & Debra Woodard Leners. (2013). From Committee to Commission: The History of the NLN’s Academic Certified Nurse Educator Program. Nursing Education Perspectives, 34(5), 298-302.
 
AIM: To describe the historical events surrounding the development of the National League for Nursing (NLN) Academic Nurse Educator Certification Program (ANECP) and document its transition from a committee to a commission. BACKGROUND: During the latter half of the 20th century, certification became a demonstrated standard of excellence in nursing. A few visionaries suggested that nursing education itself was a specialty, but the timing for certification was not right. METHOD: The events have been studied through three primary sources: archived minutes, oral interviews, and the authors’ eyewitness accounts. RESULTS: Growing pains, personnel changes and the rapid growth from committee to commission occurred during a few short years. While the NLN made sound decisions during the change process by seeking evidence and the guidance of experts and consultants, unexpected challenges occurred. CONCLUSION: The tremendous growth of the ANECP in its first years demonstrated that change was clearly desired so long as it was anchored in an evidence-based process focused on quality.
 
School of Health Sciences.

 

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