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2101. Zn2+ Inhibits Coronavirus and Arterivirus RNA Polymerase Activity In Vitro and Zinc Ionophores Block the Replication of These Viruses in Cell Culture

Title Tesim:
Zn2+ Inhibits Coronavirus and Arterivirus RNA Polymerase Activity In Vitro and Zinc Ionophores Block the Replication of These Viruses in Cell Culture
Creator:
van den Worm, Sjoerd H.E., Sims, Amy C., Baric, Ralph S., te Velthuis, Aartjan J.W., Snijder, Eric J., and van Hemert, Martijn J.
Date of publication:
2010
Abstract Tesim:
Increasing the intracellular Zn2+ concentration with zinc-ionophores like pyrithione (PT) can efficiently impair the replication of a variety of RNA viruses, including poliovirus and influenza virus. For some viruses this effect has been attributed to interference with viral polyprotein processing. In this study we demonstrate that the combination of Zn2+ and PT at low concentrations (2 µM Zn2+ and 2 µM PT) inhibits the replication of SARS-coronavirus (SARS-CoV) and equine arteritis virus (EAV) in cell culture. The RNA synthesis of these two distantly related nidoviruses is catalyzed by an RNA-dependent RNA polymerase (RdRp), which is the core enzyme of their multiprotein replication and transcription complex (RTC). Using an activity assay for RTCs isolated from cells infected with SARS-CoV or EAV—thus eliminating the need for PT to transport Zn2+ across the plasma membrane—we show that Zn2+ efficiently inhibits the RNA-synthesizing activity of the RTCs of both viruses. Enzymatic studies using recombinant RdRps (SARS-CoV nsp12 and EAV nsp9) purified from E. coli subsequently revealed that Zn2+ directly inhibited the in vitro activity of both nidovirus polymerases. More specifically, Zn2+ was found to block the initiation step of EAV RNA synthesis, whereas in the case of the SARS-CoV RdRp elongation was inhibited and template binding reduced. By chelating Zn2+ with MgEDTA, the inhibitory effect of the divalent cation could be reversed, which provides a novel experimental tool for in vitro studies of the molecular details of nidovirus replication and transcription.
Resource type:
Article
Admin Note:
deposited as part of the 1Science upload
Affiliation Label Tesim:
Department of Epidemiology
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/rvb5-9y41
Identifier:
https://dx.doi.org/10.1371/journal.ppat.1001176
ISSN:
1553-7366
Journal Issue:
11
Journal Title:
PLoS Pathogens
Journal Volume:
6
Keyword:
Ionophores, RNA, Messenger, Vero Cells, Zinc Compounds, Severe Acute Respiratory Syndrome, RNA Replicase, Escherichia coli, Virus Replication, Animals, Cercopithecus aethiops, Arterivirus Infections, Reverse Transcriptase Polymerase Chain Reaction, Electrophoretic Mobility Shift Assay, Blotting, Western, SARS Virus, RNA, Viral, and Arterivirus
Language Label:
English
ORCID:
Other Affiliation:
Leiden University Medical Center and
Page Start:
e1001176
Person:
van den Worm, Sjoerd H.E., Sims, Amy C., Baric, Ralph S., te Velthuis, Aartjan J.W., Snijder, Eric J., and van Hemert, Martijn J.
Rights Statement Label:
In Copyright
Source:
zw12z9633

2102. Research on HIV cure: Mapping the ethics landscape

Title Tesim:
Research on HIV cure: Mapping the ethics landscape
Creator:
Bruton, Carl Dean, Greene, Sandra B., Adimora, Adaora, Taylor, Jeff, Evans, David, Rennie, Stuart, Gilbertson, Adam, Gralinski, Lisa, Corneli, Amy, Weiner, Bryan J., Dee, Lynda, Sylla, Laurie, Brown, Brandon, Dube, Karine, Tucker, Joseph D., and Skinner, Asheley
Date of publication:
2017
Abstract Tesim:
According to current estimates, 36.7 million people are infected with HIV worldwide. Despite large-scale and growing programs to prevent and treat HIV infection, possible approaches to achieve a cure for HIV infection are of strong interest. In the development of candidate approaches to achieve an HIV cure, issues of future translation to human study participants, evidence-based practice, clinical care, diverse populations, and populations in low- and middle-income countries should all be considered. An HIV cure should be effective, safe, simple, affordable, and scalable. Acceptability research is a critical adjunct to ongoing biomedical HIV cure research efforts. Anticipating some of the ethical and implementation challenges related to HIV cure strategies is necessary before the availability of effective interventions. Ongoing engagement of stakeholders is needed to resolve ethical, logistical, social, cultural, policy, regulatory, and implementation challenges at all stages of the HIV cure research development process.
Resource type:
Article
Admin Note:
deposited with permission of Lisa Gralinski
Affiliation Label Tesim:
Gillings School of Global Public Health, Institute for Global Health and Infectious Diseases, and Department of Social Medicine
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/q7np-vn69
Identifier:
https://doi.org/10.1371/journal.pmed.1002470
ISSN:
15491277
Journal Issue:
12
Journal Title:
PLoS Medicine
Journal Volume:
14
Language Label:
English
ORCID:
Other Affiliation:
Collaboratory of AIDS Researchers for Eradication Community Advisory Board, , amfAR Institute for HIV Cure Research Community Advisory Board, Delaney AIDS Research Enterprise Community Advisory Board, Duke Clinical Research Institute, defeatHIV Community Advisory Board, and University of California Riverside
Person:
Bruton, Carl Dean, Greene, Sandra B., Adimora, Adaora, Taylor, Jeff, Evans, David, Rennie, Stuart, Gilbertson, Adam, Gralinski, Lisa, Corneli, Amy, Weiner, Bryan J., Dee, Lynda, Sylla, Laurie, Brown, Brandon, Dube, Karine, Tucker, Joseph D., and Skinner, Asheley
Rights Statement Label:
In Copyright
Source:
0r9678446

2103. Human dengue virus serotype 2 neutralizing antibodies target two distinct quaternary epitopes

Title Tesim:
Human dengue virus serotype 2 neutralizing antibodies target two distinct quaternary epitopes
Creator:
Baric, Thomas J., Durbin, Anna, Gallichotte, Emily N., Yount, Jr., Boyd L., de Silva, Aravinda M., Whitehead, Steve, Baric, Ralph S., and Widman, Douglas G.
Date of publication:
2018
Abstract Tesim:
Dengue virus (DENV) infection causes dengue fever, dengue hemorrhagic fever and dengue shock syndrome. It is estimated that a third of the world’s population is at risk for infection, with an estimated 390 million infections annually. Dengue virus serotype 2 (DENV2) causes severe epidemics, and the leading tetravalent dengue vaccine has lower efficacy against DENV2 compared to the other 3 serotypes. In natural DENV2 infections, strongly neutralizing type-specific antibodies provide protection against subsequent DENV2 infection. While the epitopes of some human DENV2 type-specific antibodies have been mapped, it is not known if these are representative of the polyclonal antibody response. Using structure-guided immunogen design and reverse genetics, we generated a panel of recombinant viruses containing amino acid alterations and epitope transplants between different serotypes. Using this panel of recombinant viruses in binding, competition, and neutralization assays, we have finely mapped the epitopes of three human DENV2 type-specific monoclonal antibodies, finding shared and distinct epitope regions. Additionally, we used these recombinant viruses and polyclonal sera to dissect the epitope-specific responses following primary DENV2 natural infection and monovalent vaccination. Our results demonstrate that antibodies raised following DENV2 infection or vaccination circulate as separate populations that neutralize by occupying domain III and domain I quaternary epitopes. The fraction of neutralizing antibodies directed to different epitopes differs between individuals. The identification of these epitopes could potentially be harnessed to evaluate epitope-specific antibody responses as correlates of protective immunity, potentially improving vaccine design.
Resource type:
Article
Admin Note:
deposited with permission of Ralph Baric
Affiliation Label Tesim:
Department of Epidemiology and Department of Microbiology and Immunology
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/s1aq-5r81
Identifier:
https://doi.org/10.1371/journal.ppat.1006934
ISSN:
1553-7366
Journal Issue:
2
Journal Title:
PLoS Pathogens
Journal Volume:
14
Language Label:
English
ORCID:
Other Affiliation:
, Johns Hopkins Bloomberg School of Public Health, and National Institutes of Health
Person:
Baric, Thomas J., Durbin, Anna, Gallichotte, Emily N., Yount, Jr., Boyd L., de Silva, Aravinda M., Whitehead, Steve, Baric, Ralph S., and Widman, Douglas G.
Rights Statement Label:
In Copyright
Source:
xw42nd51n

2104. Shortening of Zika virus CD-loop reduces neurovirulence while preserving antigenicity

Title Tesim:
Shortening of Zika virus CD-loop reduces neurovirulence while preserving antigenicity
Creator:
Dinnon III, Kenneth H., Gallichotte, Emily N., Baric, Ralph S., Menachery, Vineet D., and Fritch, Ethan
Date of publication:
2019
Abstract Tesim:
Zika virus (ZIKV) is a mosquito-borne positive sense RNA virus. Recently, ZIKV emerged into the Western hemisphere as a human health threat, with severe disease associated with developmental and neurological complications. The structural envelope protein of ZIKV and other neurotropic flaviviruses contains an extended CD-loop relative to non-neurotropic flaviviruses, and has been shown to augment ZIKV stability and pathogenesis. Here we show that shortening the CD-loop in ZIKV attenuates the virus in mice, by reducing the ability to invade and replicate in the central nervous system. The CD-loop mutation was genetically stable following infection in mice, though secondary site mutations arise adjacent to the CD-loop. Importantly, while shortening of the CD-loop attenuates the virus, the CD-loop mutant maintains antigenicity in immunocompetent mice, eliciting an antibody response that similarly neutralizes both the mutant and wildtype ZIKV. These findings suggest that the extended CD-loop in ZIKV is a determinant of neurotropism and may be a target in live-attenuated vaccine design, for not only ZIKV, but for other neurotropic flaviviruses.
Resource type:
Article
Admin Note:
deposited by permission of Ralph Baric
Affiliation Label Tesim:
Department of Microbiology and Immunology
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/yzsr-7196
Identifier:
https://doi.org/10.1371/journal.pntd.0007212
ISSN:
1935-2727
Journal Issue:
3
Journal Title:
PLoS Neglected Tropical Diseases
Journal Volume:
13
Language Label:
English
ORCID:
Other Affiliation:
Person:
Dinnon III, Kenneth H., Gallichotte, Emily N., Baric, Ralph S., Menachery, Vineet D., and Fritch, Ethan
Rights Statement Label:
In Copyright
Source:
jh343z29q

2105. Increasing the translation of mouse models of MERS coronavirus pathogenesis through kinetic hematological analysis

Title Tesim:
Increasing the translation of mouse models of MERS coronavirus pathogenesis through kinetic hematological analysis
Creator:
Baric, Ralph S., Sheahan, Timothy P., Jensen, Kara L., and Leist, Sarah R.
Date of publication:
2019
Abstract Tesim:
Newly emerging viral pathogens pose a constant and unpredictable threat to human and animal health. Coronaviruses (CoVs) have a penchant for sudden emergence, as evidenced by severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome CoV (MERS-CoV) and most recently, swine acute diarrhea syndrome coronavirus (SADS-CoV). Small animal models of emerging viral pathogenesis are crucial to better understand the virus and host factors driving disease progression. However, rodent models are often criticized for their limited translatability to humans. The complete blood count is the most ordered clinical test in the United States serving as the cornerstone of clinical medicine and differential diagnosis. We recently generated a mouse model for MERS-CoV pathogenesis through the humanization of the orthologous entry receptor dipeptidyl peptidase 4 (DPP4). To increase the translatability of this model, we validated and established the use of an automated veterinary hematology analyzer (VetScan HM5) at biosafety level 3 for analysis of peripheral blood. MERS-CoV lung titer peaked 2 days post infection concurrent with lymphopenia and neutrophilia in peripheral blood, two phenomena also observed in MERS-CoV infection of humans. The fluctuations in leukocyte populations measured by Vetscan HM5 were corroborated by standard flow cytometry, thus confirming the utility of this approach. Comparing a sublethal and lethal dose of MERS-CoV in mice, analysis of daily blood draws demonstrates a dose dependent modulation of leukocytes. Major leukocyte populations were modulated before weight loss was observed. Importantly, neutrophil counts on 1dpi were predictive of disease severity with a lethal dose of MERS-CoV highlighting the predictive value of hematology in this model. Taken together, the inclusion of hematological measures in mouse models of emerging viral pathogenesis increases their translatability and should elevate the preclinical evaluation of MERS-CoV therapeutics and vaccines to better mirror the complexity of the human condition.
Resource type:
Article
Admin Note:
deposited with permission from Ralph Baric
Affiliation Label Tesim:
Department of Epidemiology
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/0w7a-vt47
Identifier:
https://doi.org/10.1371/journal.pone.0220126
ISSN:
1932-6203
Journal Issue:
7
Journal Title:
PLoS ONE
Journal Volume:
14
Language Label:
English
ORCID:
Other Affiliation:
Person:
Baric, Ralph S., Sheahan, Timothy P., Jensen, Kara L., and Leist, Sarah R.
Rights Statement Label:
In Copyright
Source:
0r967843x

2106. Unified feature association networks through integration of transcriptomic and proteomic data

Title Tesim:
Unified feature association networks through integration of transcriptomic and proteomic data
Creator:
Waters, Katrina M., Adkins, Joshua N., Swanstrom, Jesica, Deatherage Kaiser, Brooke L. , Oxford, Kristie, McDermott, Jason E., Wendler, Jason P., McClure, Ryan S., and Baric, Ralph S.
Date of publication:
2019
Abstract Tesim:
High-throughput multi-omics studies and corresponding network analyses of multi-omic data have rapidly expanded their impact over the last 10 years. As biological features of different types (e.g. transcripts, proteins, metabolites) interact within cellular systems, the greatest amount of knowledge can be gained from networks that incorporate multiple types of -omic data. However, biological and technical sources of variation diminish the ability to detect cross-type associations, yielding networks dominated by communities comprised of nodes of the same type. We describe here network building methods that can maximize edges between nodes of different data types leading to integrated networks, networks that have a large number of edges that link nodes of different–omic types (transcripts, proteins, lipids etc). We systematically rank several network inference methods and demonstrate that, in many cases, using a random forest method, GENIE3, produces the most integrated networks. This increase in integration does not come at the cost of accuracy as GENIE3 produces networks of approximately the same quality as the other network inference methods tested here. Using GENIE3, we also infer networks representing antibody-mediated Dengue virus cell invasion and receptor-mediated Dengue virus invasion. A number of functional pathways showed centrality differences between the two networks including genes responding to both GM-CSF and IL-4, which had a higher centrality value in an antibody-mediated vs. receptor-mediated Dengue network. Because a biological system involves the interplay of many different types of molecules, incorporating multiple data types into networks will improve their use as models of biological systems. The methods explored here are some of the first to specifically highlight and address the challenges associated with how such multi-omic networks can be assembled and how the greatest number of interactions can be inferred from different data types. The resulting networks can lead to the discovery of new host response patterns and interactions during viral infection, generate new hypotheses of pathogenic mechanisms and confirm mechanisms of disease.
Resource type:
Article
Admin Note:
deposited with permission of Ralph Baric
Affiliation Label Tesim:
Department of Microbiology and Immunology
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/z5gg-x726
Identifier:
https://doi.org/10.1371/journal.pcbi.1007241
ISSN:
1553-734X
Journal Issue:
9
Journal Title:
PLoS Computational Biology
Journal Volume:
15
Language Label:
English
License Label:
CC0 1.0 Universal
ORCID:
Other Affiliation:
Pacific Northwest National Laboratory, , and Oregon Health and Sciences University
Person:
Waters, Katrina M., Adkins, Joshua N., Swanstrom, Jesica, Deatherage Kaiser, Brooke L. , Oxford, Kristie, McDermott, Jason E., Wendler, Jason P., McClure, Ryan S., and Baric, Ralph S.
Rights Statement Label:
In Copyright
Source:
vx021k868

2107. Guidance for Developers of Health Research Reporting Guidelines

Title Tesim:
Guidance for Developers of Health Research Reporting Guidelines
Creator:
Moher, David, Schulz, Kenneth F., Simera, Iveta, and Altman, Douglas
Date of publication:
2010
Abstract Tesim:
enterprise. On any given month about 63,000 new articles are indexed in PubMed, the United States National Library of Medicine’s public access portal for health-related publications. However, the quality of reporting in most health care journals remains inadequate. Glasziou and colleagues [1] assessed descriptions of given treatments in 80 trials and systematic reviews for which summaries were published during one year (October 2005 to October 2006) in Evidence-Based Medicine, a journal that is aimed at physicians working in primary care and general medicine. Treatment descriptions were inadequate in 41 of the original published articles, which made their use in clinical practice difficult if not impossible to replicate. This is just one of numerous examples of a large and disturbing literature indicating the general failure in the quality of reporting health research [2–6]. Many publications lack clarity, transparency, and completeness in how the authors actually carried out their research
Resource type:
Article
Affiliation Label Tesim:
Department of Obstetrics and Gynecology
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/jnfm-rh87
Edition:
Publisher
Identifier:
https://dx.doi.org/10.1371/journal.pmed.1000217
ISSN:
1549-1277
Journal Issue:
2
Journal Title:
PLoS Medicine
Journal Volume:
7
Language Label:
English
ORCID:
Other Affiliation:
Person:
Moher, David, Schulz, Kenneth F., Simera, Iveta, and Altman, Douglas
Rights Statement Label:
In Copyright
Source:
4t64gs535

2108. Supplementary Tables to "Changes in protein function underlies the disease spectrum in patients with CHIP mutations"

Title Tesim:
Supplementary Tables to "Changes in protein function underlies the disease spectrum in patients with CHIP mutations"
Creator:
Schisler, Jonathan
Date Created:
April 25, 2019
Date of publication:
2019
Abstract Tesim:
Monogenetic disorders that cause cerebellar ataxia are characterized by defects in gait and atrophy of the cerebellum; however, patients often suffer from a spectrum of disease, complicating treatment options. Spinocerebellar ataxia autosomal recessive 16 (SCAR16) is caused by coding mutations in STUB1, a gene that encodes the multi-functional enzyme CHIP (C-terminus of HSC70-interacting protein). The spectrum of disease found in SCAR16 patients includes a wide range in the age of disease onset, cognitive dysfunction, increased tendon reflex, and hypogonadism. Although SCAR16 mutations span the multiple functional domains of CHIP, it is unclear if the location of the mutation contributes to the clinical spectrum of SCAR16 or with changes in the biochemical properties of CHIP. In this study, we examined the associations and relationships between the clinical phenotypes of SCAR16 patients and how they relate to changes in the biophysical, biochemical, and functional properties of the corresponding mutated protein. We found that the severity of ataxia did not correlate with age of onset; however, cognitive dysfunction, increased tendon reflex, and ancestry were able to predict 54% of the variation in ataxia severity. We further identified domain-specific relationships between biochemical changes in CHIP and clinical phenotypes, and specific biochemical activities that associate selectively to either increased tendon reflex or cognitive dysfunction, suggesting that specific changes to CHIP-HSC70 dynamics contributes to the clinical spectrum of SCAR16. Finally, linear models of SCAR16 as a function of the biochemical properties of CHIP support the concept that further inhibiting mutant CHIP activity lessens disease severity and may be useful in the design of patient-specific targeted approaches to treat SCAR16.
Resource type:
Dataset
Affiliation Label Tesim:
Department of Pharmacology
Deposit Record:
240abdf9-b0b8-4034-b47e-98b5cb976ede
Type:
http://purl.org/dc/dcmitype/Software
DOI:
https://doi.org/10.17615/8dqf-e678
Kind of Data:
Numeric
Language Label:
English
License Label:
CC0 1.0 Universal
Methodology:
Table S1 contains the clinical variables. Table S2 contains the bivariate analysis summary of SARA and AOO with SCAR16 patient phenotypes. Table S3 contains the biochemical data. Table S4 contains the multivariate analysis summary of CHIP biochemical properties. Table S5 contains the analysis summary of SCAR16 mutation locations with the biochemical properties of the encoded mutant CHIP proteins. Table S6 contains the analysis summary of either cognitive dysfunction or increased tendon reflex with the biochemical properties CHIP. Table S7 contains the analysis summary of either SARA or AOO associations with each biochemical property of CHIP. Figure S1 displays the regression model of AOO and SARA as a function of the biochemical properties of CHIP. All analyses were performed using JMP Pro (v14.2.0) as detailed below. SCAR16 patient data. Clinical data were obtained from published reports [1–8]. One measure of disease severity is the score from the Scale for the Assessment and Rating of Ataxia (SARA). When SARA scores were not implicitly stated, SARA was imputed based on the clinical report [9]. CHIP mutation data. All biophysical and biochemical properties of CHIP proteins with disease-associated substitution mutations were obtained from published data [10]. HSP70 ubiquitination was measured by densitometry analysis and represented by the total amount of HSP70 that was modified by ubiquitination; wild-type (WT) CHIP ubiquitinated 73% or 81% of the HSP70 total in the reaction, respectively. Multiplicity. Multiple test corrections to control false positives were applied by using the Benjamini-Hochberg false discovery rate (FDR) cutoff of <10% for dependent variable associations or across all pair-wise comparisons, in either bivariate or multivariate analyses, respectively, as described below. Both the raw P and FDR values are reported. Post hoc tests, when applicable, are described in the figure legends. Bivariate analysis. Bivariate analysis was performed using either t-test or ANOVA (comparing continuous to categorical variables), linear regression (comparing two continuous variables), or contingency analysis using Fisher’s exact test (comparing two categorical variables). The P value is the result of testing the null hypothesis that there is no association between the variables. Multivariate analysis. The Pearson product-moment correlation coefficient was used to measure the strength of the linear relationships between each pair of response variables. An exact linear relationship between two variables, has a correlation of 1 or –1, depending on whether the variables are positively or negatively related. The correlation tends toward zero as the strength of relationship decreases. The P value is the result of testing the null hypothesis that the correlation between the variables is zero. 1. Shi C-H, Schisler JC, Rubel CE, Tan S, Song B, McDonough H, et al. Ataxia and hypogonadism caused by the loss of ubiquitin ligase activity of the U box protein CHIP. Hum Mol Genet. 2014;23: 1013–1024. doi:10.1093/hmg/ddt497 2. Shi Y, Wang J, Li J-D, Ren H, Guan W, He M, et al. Identification of CHIP as a Novel Causative Gene for Autosomal Recessive Cerebellar Ataxia. PLoS ONE. 2013;8. doi:10.1371/journal.pone.0081884 3. Bettencourt C, de Yébenes JG, López-Sendón JL, Shomroni O, Zhang X, Qian S-B, et al. Clinical and Neuropathological Features of Spastic Ataxia in a Spanish Family with Novel Compound Heterozygous Mutations in STUB1. Cerebellum. 2015;14: 378–381. doi:10.1007/s12311-014-0643-7 4. Cordoba M, Rodriguez-Quiroga S, Gatto EM, Alurralde A, Kauffman MA. Ataxia plus myoclonus in a 23-year-old patient due to STUB1 mutations. Neurology. 2014;83: 287–288. doi:10.1212/WNL.0000000000000600 5. Depondt C, Donatello S, Simonis N, Rai M, van Heurck R, Abramowicz M, et al. Autosomal recessive cerebellar ataxia of adult onset due to STUB1 mutations. Neurology. 2014;82: 1749–1750. doi:10.1212/WNL.0000000000000416 6. Synofzik M, Schüle R, Schulze M, Gburek-Augustat J, Schweizer R, Schirmacher A, et al. Phenotype and frequency of STUB1 mutations: next-generation screenings in Caucasian ataxia and spastic paraplegia cohorts. Orphanet J Rare Dis. 2014;9: 57. doi:10.1186/1750-1172-9-57 7. Hayer SN, Deconinck T, Bender B, Smets K, Züchner S, Reich S, et al. STUB1/CHIP mutations cause Gordon Holmes syndrome as part of a widespread multisystemic neurodegeneration: evidence from four novel mutations. Orphanet J Rare Dis. 2017;12: 31. doi:10.1186/s13023-017-0580-x 8. Heimdal K, Sanchez-Guixé M, Aukrust I, Bollerslev J, Bruland O, Jablonski GE, et al. STUB1 mutations in autosomal recessive ataxias – evidence for mutation-specific clinical heterogeneity. Orphanet J Rare Dis. 2014;9. doi:10.1186/s13023-014-0146-0 9. Schmitz-Hübsch T, du Montcel ST, Baliko L, Berciano J, Boesch S, Depondt C, et al. Scale for the assessment and rating of ataxia: development of a new clinical scale. Neurology. 2006;66: 1717–1720. doi:10.1212/01.wnl.0000219042.60538.92 10. Kanack AJ, Newsom OJ, Scaglione KM. Most mutations that cause spinocerebellar ataxia autosomal recessive type 16 (SCAR16) destabilize the protein quality-control E3 ligase CHIP. J Biol Chem. 2018;293: 2735–2743. doi:10.1074/jbc.RA117.000477
ORCID:
http://orcid.org/0000-0001-7382-2783
Other Affiliation:
Person:
Schisler, Jonathan
Source:
ws859k68q

2109. Ghostwritten

Title Tesim:
Ghostwritten
Creator:
Orol, Joshua
Date Created:
April 25, 2014
Date of publication:
spring 2014
Abstract Tesim:
Table of Contents: Fancies: Adventure Fantasy; Fantasy Library; Everyone’s Flat Chested on a Computer Screen; Late Summer Planting; Carousel Trap; Ethnography: Ethnography; Conflict Resolution; Ghostwriters; My Friend The Naval Officer; PLO Offices In Ramallah; Modern Resurrections in Jerusalem; All Day Inside: Roommates’ Philosophy; Over Creation; Bad Weather; Chew; Reckoning; Succubus: Succubus; Exorcism; Civil Disobedience Arrest, June 3rd 2013; New Toaster; Endless; Family Man: Double Cross; Youth Advisor; Confessing the Worst I Did to You; Splendid Envy; 1995 Minivan; Southern Jews: Dissatisfied; The 5th Avenue Conservative Synagogue; The Last Jew of Goldsboro; Youth (I’ll Be an Old Man Here); Mongrel; Shiva at a Strangers House
Resource type:
Honors Thesis
Affiliation Label Tesim:
Creative Writing Program
Award:
Highest Honors
Degree:
Bachelor of Arts
Degree Granting Institution:
University of North Carolina at Chapel Hill
Deposit Record:
3ec546d5-60bc-42d9-ae21-0629d93dcc16
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/yv41-tg18
Extent:
54
Keyword:
Poems, Palestine, Verse, Factory Farming, Pantoum, Technology, Conflict, Love, Israel, and Poetry
Note:
Funding: None
ORCID:
Other Affiliation:
Person:
Shapiro, Alan and Orol, Joshua
Rights Statement Label:
In Copyright

2110. Intent to Receive Pandemic Influenza A (H1N1) Vaccine, Compliance with Social Distancing and Sources of Information in NC, 2009

Title Tesim:
Intent to Receive Pandemic Influenza A (H1N1) Vaccine, Compliance with Social Distancing and Sources of Information in NC, 2009
Creator:
MacDonald, Pia, Horney, Jennifer A., Moore, Zack, and Davis, Meredith
Date Created:
August 22, 2018
Date of publication:
June 10, 2010
Abstract Tesim:
Background: Public adherence to influenza vaccination recommendations has been low, particularly among younger adults and children under 2, despite the availability of safe and effective seasonal vaccine. Intention to receive 2009 pandemic influenza A (H1N1) vaccine has been estimated to be 50% in select populations. This report measures knowledge of and intention to receive pandemic vaccine in a population-based setting, including target groups for seasonal and H1N1 influenza. Methodology and Principal Findings: On August 28–29, 2009, we conducted a population-based survey in 2 counties in North Carolina. The survey used the 30 X 7 two-stage cluster sampling methodology to identify 210 target households. Prevalence ratios (PR) and 95% confidence intervals (CI) were estimated. Knowledge of pandemic influenza A (H1N1) vaccine was high, with 165 (80%) aware that a vaccine was being prepared. A total of 133 (64%) respondents intended to receive pandemic vaccine, 134 (64%) intended to receive seasonal vaccine, and 109 (53%) intended to receive both. Reporting great concern about H1N1 infection (PR 1.55; 95%CI: 1.30, 1.85), receiving seasonal influenza vaccine in 2008–09 (PR 1.47; 95%CI: 1.18, 1.82), and intending to receive seasonal influenza vaccine in 2009–10 (PR 1.27; 95%CI: 1.14, 1.42) were associated with intention to receive pandemic vaccine. Not associated were knowledge of vaccine, employment, having children under age 18, gender, race/ethnicity and age. Reasons cited for not intending to get vaccinated include not being at risk for infection, concerns about vaccine side effects and belief that illness caused by pandemic H1N1 would be mild. Forty-five percent of households with children under 18 and 65% of working adults reported ability to comply with self-isolation at home for 7–10 days if recommended by authorities. Conclusions and Significance: This is the first report of a population based rapid assessment used to assess knowledge and intent to receive pandemic vaccine in a community sample. Intention to receive pandemic and seasonal vaccines was higher than previously published reports. To reach persons not intending to receive pandemic vaccine, public health communications should focus on the perceived risk of infection and concerns about vaccine safety.
Resource type:
Article
Affiliation Label Tesim:
North Carolina Institute for Public Health
Deposit Record:
420016cd-0708-40a4-aa22-80a8a25d6b04
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/z87z-3n92
Edition:
Publisher
Identifier:
https://doi.org/10.1371/journal.pone.0011226
Journal Issue:
6
Journal Title:
PLoS One
Journal Volume:
5
Language Label:
English
ORCID:
Other Affiliation:
Person:
MacDonald, Pia, Horney, Jennifer A., Moore, Zack, and Davis, Meredith
Rights Statement Label:
In Copyright
Source:
z316q363m