Posted by: sarahhansenweb | June 7, 2016

June 2016

Davies, Daniel R., Dawne Olson, Danielle L. Meyer, Jamie L. Scholl, Michael J. Watt, Pasquale Manzerra, . . . Gina L. Forster. (2016). Mild traumatic brain injury with social defeat stress alters anxiety, contextual fear extinction, and limbic monoamines in adult rats. Frontiers in Behavioral Neuroscience, 10.
Mild traumatic brain injury (mTBI) produces symptoms similar to those typifying posttraumatic stress disorder (PTSD) in humans. We sought to determine whether a rodent model of stress concurrent with mTBI produces characteristics of PTSD such as impaired contextual fear extinction, while also examining concurrent alterations to limbic monoamine activity in brain regions relevant to fear and anxiety states. Male rats were exposed to social stress or control conditions immediately prior to mTBI induction, and 6 days later were tested either for anxiety-like behavior using the elevated plus maze (EPM), or for contextual fear conditioning and extinction. Brains were collected 24 h after EPM testing, and tissue from various limbic regions analyzed for content of monoamines, their precursors and metabolites using HPLC with electrochemical detection. Either social defeat or mTBI alone decreased time spent in open arms of the EPM, indicating greater anxiety-like behavior. However, this effect was enhanced by the combination of treatments. Further, rats exposed to both social defeat and mTBI exhibited greater freezing within extinction sessions compared to all other groups, suggesting impaired contextual fear extinction. Social defeat combined with mTBI also had greater effects on limbic monoamines than either insult alone, particularly with respect to serotonergic effects associated with anxiety and fear learning. The results suggest social stress concurrent with mTBI produces provides a relevant animal model for studying the prevention and treatment of post-concussive psychobiological outcomes. (PsycINFO Database Record (c) 2016 APA, all rights reserved). (journal abstract)
Fercho, Kelene, & Lee A. Baugh. (2016). Cognitive attribution of the source of an error in object-lifting results in differences in motor generalization. Experimental Brain Research.
To lift an object, the motor system must predict the weight of the object and use this information to program appropriate lifting forces. If this prediction is erroneous, people may assign blame for the error to either themselves or an external source—a process called credit assignment. In the present study, we explored the role of credit assignment on weight predictions during a lifting task. Participants were told that the EMG surface electrodes attached to their lifting hand were either part of a “passive” system that recorded muscular activity, or part of an “active” system that would apply energy to the muscle, influencing weight perception. Participants performed 90 lifts of the training blocks, followed by 10 lifts of a newly encountered larger test block. In between training and test trials, the experimenter turned off the recording system and removed the surface electrodes for participants in the “active” group. For each lift, we determined the initial peak rate of change of vertical load force rate and load-phase duration, estimates of predicted object weight. Analysis of the first 10 training lifts and the last 10 training lifts revealed no effect of Active versus Passive EMG on weight predictions. However, after removing the EMG equipment, participants in the “active” group failed to scale their predictive load forces in the same manner as those in the “passive” condition when lifting a novel block. We conclude that cognitive information may play a role in credit assignment, influencing weight prediction when lifting novel objects. (PsycINFO Database Record (c) 2016 APA, all rights reserved). (journal abstract)
Basic Biomedical Sciences, Vermillion Campus.
Zhang, Fan, Sigurd Hartnett, Alex Sample, Sabrina Schnack, & Yifan Li. (2016). High fat diet induced alterations of atrial electrical activities in mice. American journal of cardiovascular disease, 6(1), 1-9.
Obesity is a well-known risk factor for various cardiovascular diseases. Recent clinical data showed that overweight and obese patients have higher incidence of atrial fibrillation (AF) compared with individuals with normal body weights, but the underlying mechanisms remain to be elucidated. In this study, we investigated the effects of a high fat diet on atrial activities in mice. ICR male mice were fed a regular diet (RD) or a high fat diet (HFD) for 8 weeks. Mice fed HFD showed significantly greater body weight gains and visceral fat accumulation compared with RD mice. Under anesthetic condition, baseline arterial blood pressure and heart rate were not significantly different between RD and HFD groups. Although no spontaneous or atrial stimulation-induced atrial fibrillation was observed, this study revealed several alterations in the activities and protein levels in the atria in HFD mice. Surface electrocardiogram (ECG) revealed significantly shortened PR interval in HFD mice. In the atrial stimulation experiments, the sinoatrial (SA) node recovery time was significantly prolonged whereas the atrial effective refractory period was significantly reduced in HFD mice as compared with RD mice. Western blot showed protein levels of two major potassium channels, Kv1.5 and Kv4.2/3, were significantly increased in atria of HFD mice. These data indicate that HFD induces atrial electrophysiological remodeling in mice, which may be a potential mechanism underlying the increased risk for atrial arrhythmias in obesity and metabolic disorders.
Basic Biomedical Sciences, Vermillion Campus.
Pan, Yaoqian, Ruizhu Liu, Erin TerpstraYanqing WangFangfang Qiao, Jin Wang, . . . Bo Pan. (2015). Dysregulation and diagnostic potential of microRNA in Alzheimer’s disease. Journal of Alzheimer’s Disease, 49(1), 1-12.
Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases and is considered to be the main cause of cognitive impairment in elderly people. The major symptom of AD is progressive dementia that eventually results in dysfunction of daily life. Due to the fact that AD has a long period of incubation before clinical symptoms emerge, the available therapeutic treatments can only improve the symptoms but not delay the progression of AD. Therefore, there is an urgent need to explore effective diagnostic approaches to catch and better treat the disease before clinical symptoms appear. Recent research revealed that abnormal expression of certain miRNA could have a crucial role in the pathological process of neurodegenerative disease including AD. Furthermore, given that AD patients show increased level of miRNAs in the blood and cerebrospinal fluid, miRNAs are considered promising non-invasive candidates for AD diagnosis and prognosis. Here, we reviewed the current research related to implications of miRNAs during the development of AD, summarized of actively used approaches to identifying potential miRNA biomarkers in body fluids, and discussed the diagnostic potential of microRNAs as biomarkers for AD. (PsycINFO Database Record (c) 2016 APA, all rights reserved). (journal abstract)
Basic Biomedical Sciences, Vermillion Campus.
Elliott, Amy J.Emily R. W. HatJyoti AngalVictoria G. OwlSusan E. Puumala, & DanYelle B. Kenyon. (2016). Fostering Social Determinants of Health Transdisciplinary Research: The Collaborative Research Center for American Indian Health. International Journal of Environmental Research and Public Health, 13(1), 12.
The Collaborative Research Center for American Indian Health (CRCAIH) was established in September 2012 as a unifying structure to bring together tribal communities and health researchers across South Dakota, North Dakota and Minnesota to address American Indian/Alaska Native (AI/AN) health disparities. CRCAIH is based on the core values of transdisciplinary research, sustainability and tribal sovereignty. All CRCAIH resources and activities revolve around the central aim of assisting tribes with establishing and advancing their own research infrastructures and agendas, as well as increasing AI/AN health research. CRCAIH is comprised of three divisions (administrative; community engagement and innovation; research projects), three technical cores (culture, science and bioethics; regulatory knowledge; and methodology), six tribal partners and supports numerous multi-year and one-year pilot research projects. Under the ultimate goal of improving health for AI/AN, this paper describes the overarching vision and structure of CRCAIH, highlighting lessons learned in the first three years.
Sanford School of Medicine, Sioux Falls Campus.
Sapp, WendiRanjit Koodali, & Dmitri Kilin. (2016). Charge Transfer Mechanism in Titanium-Doped Microporous Silica for Photocatalytic Water-Splitting Applications. Catalysts, 6(3), 12.
Solar energy conversion into chemical form is possible using artificial means. One example of a highly-efficient fuel is solar energy used to split water into oxygen and hydrogen. Efficient photocatalytic water-splitting remains an open challenge for researchers across the globe. Despite significant progress, several aspects of the reaction, including the charge transfer mechanism, are not fully clear. Density functional theory combined with density matrix equations of motion were used to identify and characterize the charge transfer mechanism involved in the dissociation of water. A simulated porous silica substrate, using periodic boundary conditions, with Ti4+ ions embedded on the inner pore wall was found to contain electron and hole trap states that could facilitate a chemical reaction. A trap state was located within the silica substrate that lengthened relaxation time, which may favor a chemical reaction. A chemical reaction would have to occur within the window of photoexcitation; therefore, the existence of a trapping state may encourage a chemical reaction. This provides evidence that the silica substrate plays an integral part in the electron/hole dynamics of the system, leading to the conclusion that both components (photoactive materials and support) of heterogeneous catalytic systems are important in optimization of catalytic efficiency.
Chemistry Department.
Stelloh, C., M. H. Reimer, …., Samuel Milanovich, G. C. Yuan, & S. Rao. (2016). The cohesin-associated protein Wapal is required for proper Polycomb-mediated gene silencing. Epigenetics & Chromatin, 9, 18.
Background: The cohesin complex consists of multiple core subunits that play critical roles in mitosis and transcriptional regulation. The cohesin-associated protein Wapal plays a central role in off-loading cohesin to facilitate sister chromatid separation, but its role in regulating mammalian gene expression is not understood. We used embryonic stem cells as a model, given that the well-defined transcriptional regulatory circuits were established through master transcription factors and epigenetic pathways that regulate their ability to maintain a pluripotent state. Results: RNAi-mediated depletion of Wapal causes a loss of pluripotency, phenocopying loss of core cohesin subunits. Using chromatin immunoprecipitation coupled with next-generation sequencing (ChIP-seq), we determine that Wapal occupies genomic sites distal to genes in combination with CTCF and core cohesin subunits such as Rad21. Interestingly, genomic sites occupied by Wapal appear enriched for cohesin, implying that Wapal does not off-load cohesin at regions it occupies. Wapal depletion induces derepression of Polycomb group (PcG) target genes without altering total levels of Polycomb-mediated histone modifications, implying that PcG enzymatic activity is preserved. By integrating ChIP-seq and gene expression changes data, we identify that Wapal binding is enriched at the promoters of PcG-silenced genes and is required for proper Polycomb repressive complex 2 (PRC2) recruitment. Lastly, we demonstrate that Wapal is required for the interaction of a distal cis-regulatory element (CRE) with the c-Fos promoter. Conclusions: Collectively, this work indicates that Wapal plays a critical role in silencing of PcG target genes through the interaction of distal CREs with promoters.
Sanford School of Medicine, Sioux Falls Campus.
Rice, H. B., A. Bernasconi, K. C. Maki, William S. Harris, C. von Schacky, & P. C. Calder. (2016). Conducting omega-3 clinical trials with cardiovascular outcomes: Proceedings of a workshop held at ISSFAL 2014. Prostaglandins Leukotrienes and Essential Fatty Acids, 107, 30-42.
In contrast to earlier long-chain (LC) omega-3 (i.e. EPA and DHA) investigations, some recent studies have not demonstrated significant effects of EPA and DHA on cardiovascular disease (CVD) outcomes. The neutral findings may have been due to experimental design issues, such as: maintenance on aggressive cardiovascular drug treatment overshadowing the benefits of LC omega-3s, high background LC omega-3 intake, too few subjects in the study, treatment duration too short, insufficient LC omega-3 dosage, increase in omega-6 fatty acid intake during the study, failure to assess the LC omega-3 status of the subjects prior to and during treatment and lack of clarity concerning which mechanisms were expected to produce benefits. At the 11th ISSFAL Congress, a workshop was held on conducting LC omega-3 clinical trials with cardiovascular outcomes, with the goal of gaining a better understanding concerning aspects of experimental design that should be considered when planning clinical studies related to EPA and DHA and potential cardiovascular benefits. (C) 2016 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (
Sanford School of Medicine, Sioux Falls Campus.
Darling, Warren G., Marc A. Pizzimenti, Diane L. Rotella, Stephanie M. Hynes, Jizhi GeKimberly Stilwell-Morecraft, & Robert J. Morecraft. (2016). Sensorimotor cortex injury effects on recovery of contralesional dexterous movements in Macaca mulatta. Experimental Neurology, 281, 37-52.
The effects of primary somatosensory cortex (S1) injury on recovery of contralateral upper limb reaching and grasping were studied by comparing the consequences of isolated lesions to the arm/hand region of primary motor cortex (M1) and lateral premotor cortex (LPMC) to lesions of these same areas plus anterior parietal cortex (S1 and rostral area PE). We used multiple linear regression to assess the effects of gray and white matter lesion volumes on deficits in reaching and fine motor performance during the first month after the lesion, and during recovery of function over 3, 6 and 12 months post-injury in 13 monkeys. Subjects with frontoparietal lesions exhibited larger deficits and poorer recovery as predicted, including one subject with extensive peri-Rolandic injury developing learned nonuse after showing signs of recovery. Regression analyses showed that total white matter lesion volume was strongly associated with initial post-lesion deficits in motor performance and with recovery of skill in reaching and manipulation. Multiple regression analyses using percent damage to caudal M1 (M1c), rostral S1 (S1r), LPMC and area PE as predictor variables showed that S1r lesion volumes were closely related to delayed post-lesion recovery of upper limb function, as well as lower skill level of recovery. In contrast, M1c lesion volume was related primarily to initial post-lesion deficits in hand motor performance. Overall, these findings demonstrate that frontoparietal injury impairs hand motor function more so than frontal motor injury alone, and results in slower and poorer recovery than lesions limited to frontal motor cortex.
Basic Biomedical Sciences, Vermillion Campus.
Lonsdale, Damian J. (2016). The effects of leader–member exchange and the feedback environment on organizational citizenship and withdrawal. The Psychologist-Manager Journal, 19(1), 41-59.
Although leader–member exchange (LMX) and the feedback environment both capture elements of the supervisor–subordinate social dynamic, their combined effects have never been explored. In this study, significant interactions were hypothesized and found for a sample of university employees in the prediction of organizational citizenship behaviors (OCBs), but were not found in the prediction of organizational withdrawal. Interactive effects of LMX and the feedback environment were also hypothesized to be stronger for jobs of greater complexity than for jobs of lesser complexity, and this was generally supported for OCBs, but not for organizational withdrawal. Limitations and implications for future research are discussed. (PsycINFO Database Record (c) 2016 APA, all rights reserved). (journal abstract)
Beacom School of Business.
Raizada, AmolNachiket Apte, & Scott Pham. (2016). Q Fever Endocarditis Presenting with Superior Mesenteric Artery Embolism and Renal Infarction. Texas Heart Institute Journal, 43(1), 91-93.
Q fever is a zoonotic disease with a reservoir in mammals, birds, and ticks. Acute cases in human beings can be asymptomatic, or they can present with a flu-like illness, pneumonia, or hepatitis. Approximately 5% of cases progress to chronic Q fever. Endocarditis, the most typical manifestation of chronic Q fever, is usually associated with small vegetations that occur in patients who have had prior valvular damage or who are immunocompromised. We present what we think is the first reported case of superior mesenteric artery embolism from Q fever endocarditis of the aortic valve, in a 39-year-old woman who needed surgical embolectomy and subsequent aortic valve replacement.
Sanford School of Medicine, Sioux Falls Campus.
Jones, Nick, & Matthew Moffitt. (2016). Ethical Guidelines for Mobile App Development Within Health and Mental Health Fields. Professional Psychology-Research and Practice, 47(2), 155-162.
Currently there are no ethical guidelines for mobile health (mHealth) applications (apps) despite the rapid innovation and use of mobile technologies in the health care field. As such, we address existing policies from the federal government, development guidelines from the mobile industry, and ethical guidelines from the American Psychological Association that apply to the development of mHealth apps intended for psychological use. Privacy and confidentiality are of primary concerns when developing and using mHealth apps for the purpose of research, assessment, and ongoing therapy. Specifically, the use of app notifications and widgets can put app user’s privacy at risk unless used properly. Methods in which app developers and providers can safeguard against violations of privacy and confidentiality are examined. In addition, special considerations are made for the use of apps with inpatient and rural populations and for those with cognitive impairments. This discussion serves to inform those who develop and utilize mHealth apps of the ethical guidelines that should be followed when creating and using such apps.
Psychology Department.
Riley, Lynn, Mitchell E. McGlaughlin, & Kaius Helenurm. (2016). Narrow water barriers prevent multiple colonizations and limit gene flow among California Channel Island wild buckwheats ( Eriogonum: Polygonaceae). Botanical Journal of the Linnean Society, 181(2), 246-268.
The relative roles of chance colonization and subsequent gene flow in the development of insular endemic biotas have been extensively studied in remote oceanic archipelagos, but are less well characterized on nearshore island systems. The current study investigated patterns of colonization and divergence between and within two wild buckwheat species (Polygonaceae), Eriogonum arborescens and E. giganteum, endemic to the California Channel Islands to determine whether geographical isolation is driving diversification. Using plastid and nuclear sequence data and microsatellite allele frequencies, we determined that gene flow in these Eriogonum spp. is restricted by isolation. The data suggest that successful colonization of and gene flow among the islands are infrequent. Colonization appears to have followed a stepping-stone model that is consistent with a north-to-south pattern across the islands. This colonization pattern coupled with relatively little post-colonization inter-island gene flow, particularly among southern islands, has generated a pattern of more divergent lineages on the isolated southern islands. These results run counter to the general expectation that all islands close to a continental source should receive a high level of gene flow. Finally, management recommendations focused on protecting the lineages from loss of private alleles and the erosion of the remaining genetic diversity are offered.
Biology Department.
Wilkerson, Rachel J.Theresa ElderOlivia SowinksiJade I. Fostvedt, & James D. Hoefelmeyer. (2016). Phase transfer of oleic acid stabilized rod-shaped anatase TiO2 nanocrystals. Surface Science, 648, 333-338.
Three methods were evaluated for phase transfer of oleic acid stabilized TiO2 nanorods from non-polar phase to an aqueous phase. Three alkyltrimethylammonium bromide (C-6, C-8, C-12) surfactants were tested and compared with an amphiphilic polymer as interdigitation agents. Ligand substitutions with catechol derivatives with polar functional groups para to the -enediol were evaluated as well. The molecular surfactants were ineffective compared to the amphiphilic polymer in the interdigitation phase transfer approach. Ligand substitution with catechols proceeded efficiently with phase transfer. The ligand substitution reactions were accompanied by gas evolution, which was found to result from decarboxylation of oleic acid in alkaline aqueous conditions. (C) 2015 Elsevier B.V. All rights reserved.
Chemistry Department.
Jensen, JamieDanYelle B. Kenyon, & Jessica D. Hanson. (2016). Preventing alcohol-exposed pregnancy among American-Indian youth. Sex Education-Sexuality Society and Learning, 16(4), 368-378.
Research has determined that the prevention of alcohol-exposed pregnancies (AEP) must occur preconceptually, either by reducing alcohol intake in women planning pregnancy or at risk for becoming pregnant, or by preventing pregnancy in women drinking at risky levels. One such AEP prevention programme with non-pregnant American-Indian (AI) women is the Oglala Sioux Tribe (OST) Changing High-risk alcohOl use and Increasing Contraception Effectiveness Study (CHOICES) Programme, which shows promise in reducing AEP risk in AI women aged 18 or older. A community needs assessment was conducted with key informant interviews and focus groups with an emphasis on how to expand OST CHOICES. To identify relevant inter-related themes, a content analysis was conducted on qualitative feedback from the focus groups and interviews. Altogether, key informant interviews were completed with 25 health and social service professionals. Eight focus groups were held with 58 AI participants, including adult women of child-bearing age, elder women, and adult men. Several sub-themes regarding the prevention of AEP with youth were identified, expanding the OST CHOICES curriculum into the schools, and the role of family and culture within AEP prevention.
Sanford School of Medicine, Sioux Falls Campus.
Xu, R., G. D. Zhang, J. H. Mai, …., Yu Huang, J. Liu, . . . H. F. Shen. (2016). An injectable nanoparticle generator enhances delivery of cancer therapeutics. Nature Biotechnology, 34(4), 414-+.
The efficacy of cancer drugs is often limited because only a small fraction of the administered dose accumulates in tumors. Here we report an injectable nanoparticle generator (iNPG) that overcomes multiple biological barriers to cancer drug delivery. The iNPG is a discoidal micrometer-sized particle that can be loaded with chemotherapeutics. We conjugate doxorubicin to poly(l-glutamic acid) by means of a pH-sensitive cleavable linker, and load the polymeric drug (pDox) into iNPG to assemble iNPG-pDox. Once released from iNPG, pDox spontaneously forms nanometer-sized particles in aqueous solution. Intravenously injected iNPG-pDox accumulates at tumors due to natural tropism and enhanced vascular dynamics and releases pDox nanoparticles that are internalized by tumor cells. Intracellularly, pDox nanoparticles are transported to the perinuclear region and cleaved into Dox, thereby avoiding excretion by drug efflux pumps. Compared to its individual components or current therapeutic formulations, iNPG-pDox shows enhanced efficacy in MDA-MB-231 and 4T1 mouse models of metastatic breast cancer, including functional cures in 40-50% of treated mice.
Biomedical Engineering, Sioux Falls Campus.
Schuurs-Hoeijmakers, J. H. M., Megan L. Landsverk, N. Foulds, M. K. Kukolich, & et. al. (2016). Clinical Delineation of the PACS1-Related Syndrome-Report on 19 Patients. American Journal of Medical Genetics Part A, 170(3), 670-675.
We report on 19 individuals with a recurrent de novo c.607C>T mutation in PACS1. This specific mutation gives rise to a recognizable intellectual disability syndrome. There is a distinctive facial appearance (19/19), characterized by full and arched eyebrows, hypertelorism with downslanting palpebral fissures, long eye lashes, ptosis, low set and simple ears, bulbous nasal tip, wide mouth with downturned corners and a thin upper lip with an unusual “wavy” profile, flat philtrum, and diastema of the teeth. Intellectual disability, ranging from mild to moderate, was present in all. Hypotonia is common in infancy (8/19). Seizures are frequent (12/19) and respond well to anticonvulsive medication. Structural malformations are common, including heart (10/19), brain (12/16), eye (10/19), kidney (3/19), and cryptorchidism (6/12 males). Feeding dysfunction is presenting in infancy with failure to thrive (5/19), gastroesophageal reflux (6/19), and gastrostomy tube placement (4/19). There is persistence of oral motor dysfunction. We provide suggestions for clinical work-up and management and hope that the present study will facilitate clinical recognition of further cases. (c) 2016 Wiley Periodicals, Inc.
Sanford School of Medicine, Sioux Falls Campus.
Zook, Heather G., Anupam B. Kharbanda, Andrew Flood, Brian Harmon, Susan E. Puumala, & Nathaniel R. Payne. (2016). Racial Differences in Pediatric Emergency Department Triage Scores. Journal of Emergency Medicine (0736-4679), 50(5), 720-727.
<bold>Background: </bold>Racial disparities are frequently reported in emergency department (ED) care.<bold>Objectives: </bold>To examine racial differences in triage scores of pediatric ED patients. We hypothesized that racial differences existed but could be explained after adjusting for sociodemographic and clinical factors.<bold>Methods: </bold>We examined all visits to two urban, pediatric EDs between August 2009 and March 2010. Demographic and clinical data were electronically extracted from the medical record. We used logistic regression to analyze racial differences in triage scores, controlling for possible covariates.<bold>Results: </bold>There were 54,505 ED visits during the study period, with 7216 (13.2%) resulting in hospital admission. White patients accounted for 36.4% of visits, African Americans 28.5%, Hispanics 18.0%, Asians 4.1%, and American Indians 1.8%. After adjusting for potential confounders, African American (adjusted odds ratio [aOR] 1.89, 95% confidence interval [CI] 1.69-2.12), Hispanic (aOR 1.77, 95% CI 1.55-2.02), and American Indian (aOR 2.57, 95% CI 1.80-3.66) patients received lower-acuity triage scores than Whites. In three out of four subgroup analyses based on presenting complaints (breathing difficulty, abdominal pain, fever), African Americans and Hispanics had higher odds of receiving low-acuity triage scores. No racial differences were detected for patients with presenting complaints of laceration/head injury/arm injury. However, among patients admitted to the hospital, African Americans (aOR 1.47, 95% CI 1.13-1.90) and Hispanics (aOR 1.71, CI 1.22-2.39) received lower-acuity triage scores than Whites.<bold>Conclusion: </bold>After adjusting for available sociodemographic and clinical covariates, African American, Hispanic, and American Indian patients received lower-acuity triage scores than Whites.
Sanford School of Medicine, Sioux Falls Campus.
Hersrud, Samantha L.Attila D. Kovács, & David A. Pearce. (2016). Antigen presenting cell abnormalities in the Cln3−/− mouse model of juvenile neuronal ceroid lipofuscinosis. BBA – Molecular Basis of Disease, 1862(7), 1324-1336.
Mutations of the CLN3 gene lead to juvenile neuronal ceroid lipofuscinosis (JNCL), an autosomal recessive lysosomal storage disorder that causes progressive neurodegeneration in children and adolescents. There is evidence of immune system involvement in pathology that has been only minimally investigated. We characterized bone marrow stem cell-derived antigen presenting cells (APCs), peritoneal macrophages, and leukocytes from spleen and blood, harvested from the Cln3 −/− mouse model of JNCL. We detected dramatically elevated CD11c surface levels and increased total CD11c protein in Cln3 −/− cell samples compared to wild type. This phenotype was specific to APCs and also to a loss of CLN3, as surface levels did not differ from wild type in other leukocyte subtypes nor in cells from two other NCL mouse models. Subcellularly, CD11c was localized to lipid rafts, indicating that perturbation of surface levels is attributable to derangement of raft dynamics, which has previously been shown in Cln3 mutant cells. Interrogation of APC function revealed that Cln3 −/− cells have increased adhesiveness to CD11c ligands as well as an abnormal secretory pattern that closely mimics what has been previously reported for Cln3 mutant microglia. Our results show that CLN3 deficiency alters APCs, which can be a major contributor to the autoimmune response in JNCL.
Sanford School of Medicine, Sioux Falls Campus.
Mariappan, KadarkaraisamyMadhubabu AlaparthiMariah HoffmanMyriam Alcantar RamaVinothini BalasubramanianDanielle M. John, & Andrew G. Sykes. (2015). Improved selectivity for Pb(ii) by sulfur, selenium and tellurium analogues of 1,8-anthraquinone-18-crown-5: synthesis, spectroscopy, X-ray crystallography and computational studies. Dalton Transactions: An International Journal of Inorganic Chemistry, 44(26), 11774-11787.
We report here a series of heteroatom-substituted macrocycles containing an anthraquinone moiety as a fluorescent signaling unit and a cyclic polyheteroether chain as the receptor. Sulfur, selenium, and tellurium derivatives of 1,8-anthraquinone-18-crown-5 (1) were synthesized by reacting sodium sulfide (Na2S), sodium selenide (Na2Se) and sodium telluride (Na2Te) with 1,8-bis(2-bromoethylethyleneoxy)anthracene-9,10-dione in a 1:1 ratio. The optical properties of the new compounds are examined and the sulfur and selenium analogues produce an intense green emission enhancement upon association with Pb(ii) in acetonitrile. Selectivity for Pb(ii) is markedly improved as compared to the oxygen analogue 1 which was also competitive for Ca(ii) ion. UV-Visible and luminescence titrations reveal that 2 and 3 form 1:1 complexes with Pb(ii), confirmed by single-crystal X-ray studies where Pb(ii) is complexed within the macrocycle through coordinate covalent bonds to neighboring carbonyl, ether and heteroether donor atoms. Cyclic voltammetry of 2–8 showed classical, irreversible oxidation potentials for sulfur, selenium and tellurium heteroethers in addition to two one-electron reductions for the anthraquinone carbonyl groups. DFT calculations were also conducted on 1, 2, 3, 6, 6 + Pb(ii) and 6 + Mg(ii) to determine the trend in energies of the HOMO and the LUMO levels along the series.
Chemistry Department.
Hammerquist, Rhonda J.Kimberly A. Messerschmidt, April A. Pottebaum, & Thaddaus R. Hellwig. (2016). Vaccinations in asplenic adults. American Journal of Health-System Pharmacy, 73(9), e220-e228.
Purpose. The recommended immunizations for adult asplenic patients are reviewed. Summary. Patients without a spleen are at risk of developing overwhelming postsplenectomy infections due to encapsulated organisms, mainly pneumococcal, meningococcal, and Haemophilus influenzae type b (Hib). Due to the high mortality rates associated with these infections, vaccinations are recommended as a preventive measure. It is challenging to ensure optimal immunizations in these high-risk patients due to the number of recommended vaccines, the availability of multiple formulations, and the inability to administer specific formulations at the same time, as well as differences in subsequent vaccine administration schedules. Pharmacists play a key role in recommending specific vaccines and timing for these patients in order to achieve the most robust immune response. This article reviews the specific recommendations for pneumococcal, meningococcal, Hib, and influenza vaccinations in asplenic patients. Conclusion. In order to prevent potentially life-threatening infections, asplenic individuals should be vaccinated against S. pneumoniae, N. meningitidis, Hib, and influenza. The optimal timing of vaccination in relation to splenectomy depends on the nature of the splenectomy.
Sanford School of Medicine, Sioux Falls Campus.

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