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1761. ALC1/CHD1L, a chromatin-remodeling enzyme, is required for efficient base excision repair

Title Tesim:
ALC1/CHD1L, a chromatin-remodeling enzyme, is required for efficient base excision repair
Creator:
Hirota, Kouji, Takeda, Shunichi, Harada, Hiroshi, Pommier, Yves, Koike, Kaoru, Fujiike, Haruna, Nakamura, Jun, Murai, Junko, Tsuda, Masataka, Shimizu, Naoto, Yamamoto, Takashi, Asada, Ryuta, Sakuma, Tetsushi, Ooka, Masato, Agama, Keli, Nakazawa, Yuka, Yasui, Akira, Cho, Kosai, Hiraoka, Masahiro, Watanabe, Reiko, and Ogi, Tomoo
Date of publication:
2017
Abstract Tesim:
ALC1/CHD1L is a member of the SNF2 superfamily of ATPases carrying a macrodomain that binds poly(ADP-ribose). Poly(ADP-ribose) polymerase (PARP) 1 and 2 synthesize poly(ADP-ribose) at DNA-strand cleavage sites, promoting base excision repair (BER). Although depletion of ALC1 causes increased sensitivity to various DNA-damaging agents (H2O2, UV, and phleomycin), the role played by ALC1 in BER has not yet been established. To explore this role, as well as the role of ALC1’s ATPase activity in BER, we disrupted the ALC1 gene and inserted the ATPase-dead (E165Q) mutation into the ALC1 gene in chicken DT40 cells, which do not express PARP2. The resulting ALC1-/- and ALC1-/E165Q cells displayed an indistinguishable hypersensitivity to methylmethane sulfonate (MMS), an alkylating agent, and to H2O2, indicating that ATPase plays an essential role in the DNA-damage response. PARP1-/- and ALC1-/-/PARP1-/- cells exhibited a very similar sensitivity to MMS, suggesting that ALC1 and PARP1 collaborate in BER. Following pulse-exposure to H2O2, PARP1-/- and ALC1-/-/PARP1-/- cells showed similarly delayed kinetics in the repair of single-strand breaks, which arise as BER intermediates. To ascertain ALC1’s role in BER in mammalian cells, we disrupted the ALC1 gene in human TK6 cells. Following exposure to MMS and to H2O2, the ALC1-/- TK6 cell line showed a delay in single-strand-break repair. We therefore conclude that ALC1 plays a role in BER. Following exposure to H2O2,ALC1-/- cells showed compromised chromatin relaxation. We thus propose that ALC1 is a unique BER factor that functions in a chromatin context, most likely as a chromatin-remodeling enzyme.
Resource type:
Article
Affiliation Label Tesim:
Department of Environmental Sciences and Engineering
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/e2/82/bb/5c/e282bb5c-ecfc-4dd2-8603-2a46b5cc8e4b
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/kwy9-bf30
Identifier:
Publisher DOI: https://doi.org/10.1371/journal.pone.0188320, PMID: 29149203, Onescience id: ff416da8e7f55497eaa64a764a449b805b9d8680, and PMCID: PMC5693467
ISSN:
1932-6203
Journal Issue:
11
Journal Title:
PloS One
Journal Volume:
12
Keyword:
DNA Helicases, Chromatin, B-Lymphocytes, Humans, Gene Expression Regulation, Chromatin Assembly and Disassembly, DNA-Binding Proteins, Animals, DNA Repair, Cell Line, Transformed, Hydrogen Peroxide, Cell Line, Tumor, Chickens, Methyl Methanesulfonate, and HeLa Cells
Language Label:
English
ORCID:
Other Affiliation:
Department of Chemistry; Tokyo Metropolitan University, Department of Radiation Genetics; Graduate School of Medicine; Kyoto University, Laboratory of Cancer Cell Biology; Radiation Biology Center; Kyoto University, Laboratory of Molecular Pharmacology; Developmental Therapeutics Branch; Center for Cancer Research; National Cancer Institute; National Institutes of Health, Department of Primary Care and Emergency Medicine; Kyoto University Graduate School of Medicine, Department of Mathematical and Life Sciences; Graduate School of Science; Hiroshima University, Department of Genetics; Research Institute of Environmental Medicine (RIeM); Nagoya University, Department of Genome Repair; Atomic Bomb Disease Institute; Nagasaki University Sakamoto, Division of Dynamic Proteome; Institute of Development; Aging and Cancer; Tohoku University, Department of Radiation Oncology; Japanese Red Cross Society Wakayama Medical Center, and National Institutes of Biomedical Innovation; Health and Nutrition
Page Start:
e0188320
Person:
Hirota, Kouji, Takeda, Shunichi, Harada, Hiroshi, Pommier, Yves, Koike, Kaoru, Fujiike, Haruna, Nakamura, Jun, Murai, Junko, Tsuda, Masataka, Shimizu, Naoto, Yamamoto, Takashi, Asada, Ryuta, Sakuma, Tetsushi, Ooka, Masato, Agama, Keli, Nakazawa, Yuka, Yasui, Akira, Cho, Kosai, Hiraoka, Masahiro, Watanabe, Reiko, and Ogi, Tomoo
Rights Statement Label:
In Copyright
Source:
08612t83c

1762. Admixture mapping of pelvic organ prolapse in African Americans from the Women’s Health Initiative Hormone Therapy trial

Title Tesim:
Admixture mapping of pelvic organ prolapse in African Americans from the Women’s Health Initiative Hormone Therapy trial
Creator:
Ward, Renee M., Wallace, Robert B., O'Sullivan, Mary J., North, Kari E., Qi, Lihong, Wu, Jennifer M., Aldrich, Melinda C., Edwards, Digna R. Velez, Gr, Mariaelisa, Giri, Ayush, Edwards, Todd L., Park, Amy J., Hartmann, Katherine E., and Nassir, Rami
Date of publication:
2017
Abstract Tesim:
Evidence suggests European American (EA) women have two- to five-fold increased odds of having pelvic organ prolapse (POP) when compared with African American (AA) women. However, the role of genetic ancestry in relation to POP risk is not clear. Here we evaluate the association between genetic ancestry and POP in AA women from the Women’s Health Initiative Hormone Therapy trial. Women with grade 1 or higher classification, and grade 2 or higher classification for uterine prolapse, cystocele or rectocele at baseline or during follow-up were considered to have any POP (N = 805) and moderate/severe POP (N = 156), respectively. Women with at least two pelvic exams with no indication for POP served as controls (N = 344). We performed case-only, and case-control admixture-mapping analyses using multiple logistic regression while adjusting for age, BMI, parity and global ancestry. We evaluated the association between global ancestry and POP using multiple logistic regression. European ancestry at the individual level was not associated with POP risk. Case-only and case-control local ancestry analyses identified two ancestry-specific loci that may be associated with POP. One locus (Chromosome 15q26.2) achieved empirically-estimated statistical significance and was associated with decreased POP odds (considering grade ≥2 POP) with each unit increase in European ancestry (OR: 0.35; 95% CI: 0.30, 0.57; p-value = 1.48x10-5). This region includes RGMA, a potent regulator of the BMP family of genes. The second locus (Chromosome 1q42.1-q42.3) was associated with increased POP odds with each unit increase in European ancestry (Odds ratio [OR]: 1.69; 95% confidence interval [CI]: 1.28, 2.22; p-value = 1.93x10-4). Although this region did not reach statistical significance after considering multiple comparisons, it includes potentially relevant genes including TBCE, and ACTA1. Unique non-overlapping European and African ancestry-specific susceptibility loci may be associated with increased POP risk.
Resource type:
Article
Affiliation Label Tesim:
Department of Epidemiology and Department of Obstetrics and Gynecology
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/e2/82/bb/5c/e282bb5c-ecfc-4dd2-8603-2a46b5cc8e4b
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/f6bq-wy87
Identifier:
Onescience id: e555118aa7445278b72b4ac793ef400ac462ae17, Publisher DOI: https://doi.org/10.1371/journal.pone.0178839, PMID: 28582460, and PMCID: PMC5459562
ISSN:
1932-6203
Journal Issue:
6
Journal Title:
PloS One
Journal Volume:
12
Keyword:
Nerve Tissue Proteins, Population groupings, Genetic Loci, Evolutionary Biology, African Americans, Molecular Biology Techniques, Rectocele, Gene Mapping, Alleles, Science, Uterine Prolapse, People and places, Molecular Biology, Women's Health, Human Genetics, Q, Molecular Chaperones, Genetics, Ethnicities, Biology and Life Sciences, Population Genetics, Medicine and Health Sciences, Research Article, Research and Analysis Methods, Humans, Actins, R, Medicine, Population Biology, Body Mass Index, Severity, and Chromosome Mapping
Language Label:
English
ORCID:
Other Affiliation:
Department of Obstetrics and Gynecology; Vanderbilt University; Medical Center, Department of Epidemiology; University of Iowa; College of Public Health, Department of Obstetrics and Gynecology; Miller School of Medicine, Division of Biostatistics; Department of Public Health Sciences; School of Medicine; University of California; Davis, Department of Thoracic Surgery; Vanderbilt University; Medical Center, Vanderbilt Genetics Institute; Vanderbilt University; Medical Center, Division of Epidemiology; Department of Medicine; Vanderbilt University; Medical Center, Vanderbilt Epidemiology Center; Institute for Medicine and Public Health; Vanderbilt University; Medical Center, Department of Obstetrics and Gynecology; Georgetown University; School of Medicine, Department of Biochemistry and Molecular Medicine; University of California; Davis, and Department of Internal Medicine; University of California; Davis
Page Start:
e0178839
Person:
Ward, Renee M., Wallace, Robert B., O'Sullivan, Mary J., North, Kari E., Qi, Lihong, Wu, Jennifer M., Aldrich, Melinda C., Edwards, Digna R. Velez, Gr, Mariaelisa, Giri, Ayush, Edwards, Todd L., Park, Amy J., Hartmann, Katherine E., and Nassir, Rami
Rights Statement Label:
In Copyright
Source:
3f462b54z

1763. Admixture mapping in the Hispanic Community Health Study/Study of Latinos reveals regions of genetic associations with blood pressure traits

Title Tesim:
Admixture mapping in the Hispanic Community Health Study/Study of Latinos reveals regions of genetic associations with blood pressure traits
Creator:
Reiner, Alex P., Hanson, Robert, Daviglus, Martha L., Thornton, Timothy A., Talavera, Gregory A., Baier, Leslie J., Levy, Daniel, Wassertheil-Smoller, Sylvia, Franceschini, Nora, Sofer, Tamar, Browning, Sharon R., Kobes, Sayuko, Cooper, Richard S., and Cai, Jianwen
Date of publication:
2017
Abstract Tesim:
Admixture mapping can be used to detect genetic association regions in admixed populations, such as Hispanics/Latinos, by estimating associations between local ancestry allele counts and the trait of interest. We performed admixture mapping of the blood pressure traits systolic and diastolic blood pressure (SBP, DBP), mean arterial pressure (MAP), and pulse pressure (PP), in a dataset of 12,116 participants from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Hispanics/Latinos have three predominant ancestral populations (European, African, and Amerindian), for each of which we separately tested local ancestry intervals across the genome. We identified four regions that were significantly associated with a blood pressure trait at the genome-wide admixture mapping level. A 6p21.31 Amerindian ancestry association region has multiple known associations, but none explained the admixture mapping signal. We identified variants that completely explained this signal. One of these variants had p-values of 0.02 (MAP) and 0.04 (SBP) in replication testing in Pima Indians. A 11q13.4 Amerindian ancestry association region spans a variant that was previously reported (p-value = 0.001) in a targeted association study of Blood Pressure (BP) traits and variants in the vitamin D pathway. There was no replication evidence supporting an association in the identified 17q25.3 Amerindian ancestry association region. For a region on 6p12.3, associated with African ancestry, we did not identify any candidate variants driving the association. It may be driven by rare variants. Whole genome sequence data may be necessary to fine map these association signals, which may contribute to disparities in BP traits between diverse populations.
Resource type:
Article
Affiliation Label Tesim:
Department of Epidemiology and Department of Biostatistics
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/e2/82/bb/5c/e282bb5c-ecfc-4dd2-8603-2a46b5cc8e4b
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/pchc-4641
Identifier:
Publisher DOI: https://doi.org/10.1371/journal.pone.0188400, PMID: 29155883, PMCID: PMC5695820, and Onescience id: ad75aa82731af4eced5f7ec9722da7c147c0ea04
ISSN:
1932-6203
Journal Issue:
11
Journal Title:
PloS One
Journal Volume:
12
Keyword:
Chromosome Mapping, Molecular Biology Techniques, Genetic Mapping, Genome Analysis, Variant Genotypes, Blood Pressure, Heredity, Medicine and Health Sciences, Genomic Signal Pro, Human Genetics, Molecular Biology, Genomics, Biology and Life Sciences, Cell Signaling, Computational Biology, People and places, Mexican People, Population groupings, Genetics, Cell Biology, Signal Transduction, Latin American people, Gene Mapping, Ethnicities, Genome-Wide Association Studies, Gene Identification and Analysis, and Vascular Medicine
Language Label:
English
ORCID:
Other Affiliation:
Division of Public Health Sciences; Fred Hutchinson Cancer Research Center, Phoenix Epidemiology and Clinical Research Branch; NIDDK; NIH, Institute for Minority Health Research; University of Illinois at Chicago, Feinberg School of Medicine; Northwestern University, Department of Biostatistics; University of Washington, Division of Health Promotion and Behavioral Science; San Diego State University, Population Sciences Branch; National Heart; Lung; and Blood Institute; National Institutes of Health, Framingham Heart Study, Department of Epidemiology and Population Health; Albert Einstein College of Medicine, Department of Medicine; Harvard Medical School, Division of Sleep and Circadian Disorders; Brigham and Women’s Hospital, and Department of Public Health Sciences; Stritch School of Medicine; Loyola University Chicago
Page Start:
e0188400
Person:
Reiner, Alex P., Hanson, Robert, Daviglus, Martha L., Thornton, Timothy A., Talavera, Gregory A., Baier, Leslie J., Levy, Daniel, Wassertheil-Smoller, Sylvia, Franceschini, Nora, Sofer, Tamar, Browning, Sharon R., Kobes, Sayuko, Cooper, Richard S., and Cai, Jianwen
Rights Statement Label:
In Copyright
Source:
9593v1617

1764. Adaptations of an RNA virus to increasing thermal stress

Title Tesim:
Adaptations of an RNA virus to increasing thermal stress
Creator:
Cierra, M Leon Guerrero, Whang, Stella G, Singhal, Sonia, Kerr, Benjamin, Busch, Hannah G, and McClure, Erin M
Date of publication:
2017
Abstract Tesim:
Environments can change in incremental fashions, where a shift from one state to another occurs over multiple organismal generations. The rate of the environmental change is expected to influence how and how well populations adapt to the final environmental state. We used a model system, the lytic RNA bacteriophage Φ6, to investigate this question empirically. We evolved viruses for thermostability by exposing them to heat shocks that increased to a maximum temperature at different rates. We observed increases in the ability of many heat-shocked populations to survive high temperature heat shocks. On their first exposure to the highest temperature, populations that experienced a gradual increase in temperature had higher average survival than populations that experienced a rapid temperature increase. However, at the end of the experiment, neither the survival of populations at the highest temperature nor the number of mutations per population varied significantly according to the rate of thermal change. We also evaluated mutations from the endpoint populations for their effects on viral thermostability and growth. As expected, some mutations did increase viral thermostability. However, other mutations decreased thermostability but increased growth rate, suggesting that benefits of an increased replication rate may have sometimes outweighed the benefits of enhanced thermostability. Our study highlights the importance of considering the effects of multiple selective pressures, even in environments where a single factor changes.
Resource type:
Article
Affiliation Label Tesim:
Department of Biology
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/e2/82/bb/5c/e282bb5c-ecfc-4dd2-8603-2a46b5cc8e4b
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/3k5k-by88
Identifier:
Onescience id: f99f7f13f444f7ff0e59d535af6bfd7569acde1a, PMID: 29267297, PMCID: PMC5739421, and Publisher DOI: https://doi.org/10.1371/journal.pone.0189602
ISSN:
1932-6203
Journal Issue:
12
Journal Title:
PloS One
Journal Volume:
12
Keyword:
Bacteriology, Viral Evolution, Mutation, Hot Temperature, Microbial Mutation, Population Genetics, Bacteriophage phi 6, Organismal Evolution, Microbial Evolution, Population Biology, Q, Adaptation, Microbiology, Bacterial Evolution, Medicine, Evolutionary Adaptation, Research Article, Biology and Life Sciences, Organisms, Virology, R, Stress, Evolutionary Processes, Physiological, Viral Replication, Bacteriophages, Substitution Mutation, Viruses, Science, Evolutionary Biology, and Genetics
Language Label:
English
ORCID:
Other Affiliation:
Department of Biology; University of Washington
Page Start:
e0189602
Person:
Cierra, M Leon Guerrero, Whang, Stella G, Singhal, Sonia, Kerr, Benjamin, Busch, Hannah G, and McClure, Erin M
Rights Statement Label:
In Copyright
Source:
jm214v47w

1765. A SNP panel and online tool for checking genotype concordance through comparing QR codes

Title Tesim:
A SNP panel and online tool for checking genotype concordance through comparing QR codes
Creator:
Kong, Xuejun, Li, Yun, Yang, Yuchen, Zhou, Eric Lingfeng, Liu, Eric Yi, Geihs, Matthias, Martin, Joshua S., Du, Yonghong, McGee, John, Huang, Jie, and Sun, Yingrui
Date of publication:
2017
Abstract Tesim:
In the current precision medicine era, more and more samples get genotyped and sequenced. Both researchers and commercial companies expend significant time and resources to reduce the error rate. However, it has been reported that there is a sample mix-up rate of between 0.1% and 1%, not to mention the possibly higher mix-up rate during the down-stream genetic reporting processes. Even on the low end of this estimate, this translates to a significant number of mislabeled samples, especially over the projected one billion people that will be sequenced within the next decade. Here, we first describe a method to identify a small set of Single nucleotide polymorphisms (SNPs) that can uniquely identify a personal genome, which utilizes allele frequencies of five major continental populations reported in the 1000 genomes project and the ExAC Consortium. To make this panel more informative, we added four SNPs that are commonly used to predict ABO blood type, and another two SNPs that are capable of predicting sex. We then implement a web interface (http://qrcme.tech), nicknamed QRC (for QR code based Concordance check), which is capable of extracting the relevant ID SNPs from a raw genetic data, coding its genotype as a quick response (QR) code, and comparing QR codes to report the concordance of underlying genetic datasets. The resulting 80 fingerprinting SNPs represent a significant decrease in complexity and the number of markers used for genetic data labelling and tracking. Our method and web tool is easily accessible to both researchers and the general public who consider the accuracy of complex genetic data as a prerequisite towards precision medicine.
Resource type:
Article
Affiliation Label Tesim:
Department of Genetics, Department of Biostatistics, Department of Computer Science, and North Carolina Translational and Clinical Sciences Institute
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/e2/82/bb/5c/e282bb5c-ecfc-4dd2-8603-2a46b5cc8e4b
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/36zd-dq05
Identifier:
Onescience id: bef1b85acb8045f7163e5c3e3fc1ba94d1d012a8, Publisher DOI: https://doi.org/10.1371/journal.pone.0182438, PMCID: PMC5604942, and PMID: 28926565
ISSN:
1932-6203
Journal Issue:
9
Journal Title:
PloS One
Journal Volume:
12
Keyword:
Medicine and Health Sciences, Variant Genotypes, Genotyping, Molecular Biology, Genetic Mapping, Genomics, Genetic Fingerprinting and Footprinting, Web-Based Applications, Computer Architecture, User Interfaces, Computer and Information Sciences, Computer Applications, Heredity, Blood, Anatomy, Physiology, Genomic Medicine, Journal Article, Genetics, Body Fluids, Genetic Fingerprinting, Molecular Biology Techniques, Biology and Life Sciences, and Molecular Genetics
Language Label:
English
ORCID:
Other Affiliation:
Beth Israel Deaconess Medical Center, Department of Computer Science, Department of Biostatistics, Department of Computer Science; Technische Universität Darmstadt, School of Statistics; Beijing Normal University, Boston VA Research Institute, Brigham Women’s Hospital Division of Aging; Harvard Medical School, and Department of Mathematics and Statistics; Boston University
Page Start:
e0182438
Person:
Kong, Xuejun, Li, Yun, Yang, Yuchen, Zhou, Eric Lingfeng, Liu, Eric Yi, Geihs, Matthias, Martin, Joshua S., Du, Yonghong, McGee, John, Huang, Jie, and Sun, Yingrui
Rights Statement Label:
In Copyright
Source:
5t34sq87v

1766. A qualitative study of secondary distribution of HIV self-test kits by female sex workers in Kenya

Title Tesim:
A qualitative study of secondary distribution of HIV self-test kits by female sex workers in Kenya
Creator:
Mavedzenge, Sue Napierala, Murray, Katherine R., Thirumurthy, Harsha, Sijenje, Florence, Agot, Kawango, Maman, Suzanne, and Oluoch, Lennah
Date of publication:
2017
Abstract Tesim:
Promoting awareness of serostatus and frequent HIV testing is especially important among high risk populations such as female sex workers (FSW) and their sexual partners. HIV self-testing is an approach that is gaining ground in sub-Saharan Africa as a strategy to increase knowledge of HIV status and promote safer sexual decisions. However, little is known about self-test distribution strategies that are optimal for increasing testing access among hard-to-reach and high risk individuals. We conducted a qualitative study with 18 FSW who participated in a larger study that provided them with five oral fluid-based self-tests, training on how to use the tests, and encouragement to offer the self-tests to their sexual partners using their discretion. Women demonstrated agency in the strategies they used to introduce self-tests to their partners and to avoid conflict with partners. They carefully considered with whom to share self-tests, often assessing the possibility for negative reactions from partners as part of their decision making process. When women faced negative reactions from partners, they drew on strategies they had used before to avoid conflict and physical harm from partners, such as not responding to angry partners and forgoing payment to leave angry partners quickly. Some women also used self-tests to make more informed sexual decisions with their partners.
Resource type:
Article
Affiliation Label Tesim:
Department of Health Policy and Management and Department of Health Behavior
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/e2/82/bb/5c/e282bb5c-ecfc-4dd2-8603-2a46b5cc8e4b
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/dy9h-rg60
Identifier:
Publisher DOI: https://doi.org/10.1371/journal.pone.0174629, PMID: 28346527, Onescience id: 39453244694e85078be6aca860d93daad1da2fd9, and PMCID: PMC5367822
ISSN:
1932-6203
Journal Issue:
3
Journal Title:
PloS One
Journal Volume:
12
Keyword:
Sex Workers, Qualitative Research, Humans, Adolescent, Risk-Taking, Adult, Decision Making, Sex Work, Reagent Kits, Diagnostic, Diagnostic Self Evaluation, Female, Kenya, Sexual Partners, HIV Infections, Young Adult, and Unsafe Sex
Language Label:
English
ORCID:
Other Affiliation:
Research Triangle International, FHI360, and Impact Research and Development Organization
Page Start:
e0174629
Person:
Mavedzenge, Sue Napierala, Murray, Katherine R., Thirumurthy, Harsha, Sijenje, Florence, Agot, Kawango, Maman, Suzanne, and Oluoch, Lennah
Rights Statement Label:
In Copyright
Source:
v405sg68b

1767. A purified MAA-based ELISA is a useful tool for determining anti-MAA antibody titer with high sensitivity

Title Tesim:
A purified MAA-based ELISA is a useful tool for determining anti-MAA antibody titer with high sensitivity
Creator:
Shimomoto, Takasumi, Uchida, Koji, Hörkkö, Sohvi, Gold, Avram, Holley, Darcy W., Willis, Monte S., Yi, Xianwen, Tian, Xu, Collins, Leonard B., Zhang, Zhenfa, Nakamura, Jun, Bultman, Scott J., and Wang, Chunguang
Date of publication:
2017
Abstract Tesim:
Atherosclerosis is widely accepted to be a chronic inflammatory disease, and the immunological response to the accumulation of LDL is believed to play a critical role in the development of this disease. 1,4-Dihydropyridine-type MAA-adducted LDL has been implicated in atherosclerosis. Here, we have demonstrated that pure MAA-modified residues can be chemically conjugated to large proteins without by-product contamination. Using this pure antigen, we established a purified MAA-ELISA, with which a marked increase in anti-MAA antibody titer was determined at a very early stage of atherosclerosis in 3-month ApoE-/- mice fed with a normal diet. Our methods of Nε-MAA-L-lysine purification and purified antigen-based ELISA will be easily applicable for biomarker-based detection of early stage atherosclerosis in patients, as well as for the development of an adduct-specific Liquid Chromatography/Mass Spectrometry-based quantification of physiological and pathological levels of MAA.
Resource type:
Article
Affiliation Label Tesim:
Department of Environmental Sciences and Engineering, Department of Genetics, Department of Pathology and Laboratory Medicine, and University of North Carolina at Chapel Hill
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/e2/82/bb/5c/e282bb5c-ecfc-4dd2-8603-2a46b5cc8e4b
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/8kxq-m089
Identifier:
PMID: 28222187, PMCID: PMC5319763, Onescience id: e80d0e58aefbc0dc54cc0cd53443acdc9db0d42b, and Publisher DOI: https://doi.org/10.1371/journal.pone.0172172
ISSN:
1932-6203
Journal Issue:
2
Journal Title:
PloS One
Journal Volume:
12
Keyword:
Animals, Magnetic Resonance Spectroscopy, Autoantibodies, Mice, Malondialdehyde, Enzyme-Linked Immunosorbent Assay, Sensitivity and Specificity, Acetaldehyde, Female, and Mice, Inbred C57BL
Language Label:
English
ORCID:
Other Affiliation:
School of Bioagricultural Sciences; Nagoya University, Medical Research Center and Nordlab Oulu; University Hospital and University of Oulu, Medical Microbiology and Immunology; Research Unit of Biomedicine; Faculty of Medicine; University of Oulu, and School of Medicine
Page Start:
e0172172
Person:
Shimomoto, Takasumi, Uchida, Koji, Hörkkö, Sohvi, Gold, Avram, Holley, Darcy W., Willis, Monte S., Yi, Xianwen, Tian, Xu, Collins, Leonard B., Zhang, Zhenfa, Nakamura, Jun, Bultman, Scott J., and Wang, Chunguang
Rights Statement Label:
In Copyright
Source:
dn39x663f

1768. A prospective cohort study of safety and patient satisfaction of voluntary medical male circumcision in Botswana

Title Tesim:
A prospective cohort study of safety and patient satisfaction of voluntary medical male circumcision in Botswana
Creator:
Ledikwe, Jenny H., Ntsuape, Conrad, Wirth, Kathleen E., Semo, Bazghina-werq, Barnhart, Scott, and Spees, Lisa P.
Date of publication:
2017
Abstract Tesim:
Randomized trials have shown that voluntary medical male circumcision (VMMC) significantly reduces the risk of HIV acquisition in men. However, the rate of complications associated with the surgical procedure varies from 0.7% to 37.4% in real-world settings. We assessed the frequency, type and severity of adverse events following VMMC among 427 adult men surgically circumcised in southeastern Botswana; 97% completed ≥1 follow-up visit within seven days post-circumcision. Thirty moderate AEs were observed in 28 men resulting in an overall AE rate of 6.7%. Patient satisfaction was high: >95% were very or somewhat satisfied with the procedure and subsequent follow-up care.
Resource type:
Article
Affiliation Label Tesim:
Cecil G. Sheps Center for Health Services Research
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/e2/82/bb/5c/e282bb5c-ecfc-4dd2-8603-2a46b5cc8e4b
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/qjmm-4z88
Identifier:
PMID: 29112959, Publisher DOI: https://doi.org/10.1371/journal.pone.0185904, PMCID: PMC5675416, and Onescience id: d82537b9bd6ab69aa3daae2de462e8e9f2c226bf
ISSN:
1932-6203
Journal Issue:
11
Journal Title:
PloS One
Journal Volume:
12
Keyword:
Africa, Adults, Engineering and Technology, Adverse Events, Clinical Research Design, Geographical Locations, Surgical and Invasive Medical Procedures, Diagnostic Medicine, Telephones, Hemorrhage, Circumcision, Equipment, Population Groupings, Biotechnology, People and Places, Signs and Symptoms, Medicine and Health Sciences, Medical Devices and Equipment, Biology and Life Sciences, Vascular Medicine, Age Groups, Pathology and Laboratory Medicine, Botswana, and Reproductive System Procedures
Language Label:
English
ORCID:
Other Affiliation:
Botswana International Training and Education Center for Health (I-TECH), Department of Global Health; University of Washington, Department of HIV/AIDS Prevention and Care; Botswana Ministry of Health, Department of Epidemiology; Harvard T.H. Chan School of Public Health, Department of Immunology and Infectious Diseases; Harvard T.H. Chan School of Public Health, and Family Health International
Page Start:
e0185904
Person:
Ledikwe, Jenny H., Ntsuape, Conrad, Wirth, Kathleen E., Semo, Bazghina-werq, Barnhart, Scott, and Spees, Lisa P.
Rights Statement Label:
In Copyright
Source:
b8515t71b

1769. Who Treats Patients with Diabetes and Compensated Cirrhosis

Title Tesim:
Who Treats Patients with Diabetes and Compensated Cirrhosis
Creator:
Trogdon, Justin G., Liu, Tsai-Ling, Fried, Bruce, Paul, John E., Sidney Barritt, , and Weinberger, Morris
Date of publication:
2016
Abstract Tesim:
Increasingly, patients with multiple chronic conditions are being managed in patient-centered medical homes (PCMH) that coordinate primary and specialty care. However, little is known about the types of providers treating complex patients with diabetes and compensated cirrhosis.
Resource type:
Article
Affiliation Label Tesim:
Department of Health Policy and Management and Division of Gastroenterology and Hepatology
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/e2/82/bb/5c/e282bb5c-ecfc-4dd2-8603-2a46b5cc8e4b
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/nfzy-m280
Identifier:
PMCID: PMC5082637, Onescience id: 639c50a3104f03ba86f1a0e7c241ad4eafc5634f, PMID: 27783702, and Publisher DOI: https://doi.org/10.1371/journal.pone.0165574
ISSN:
1932-6203
Journal Issue:
10
Journal Title:
PloS One
Journal Volume:
11
Keyword:
Middle Aged, Diabetes Complications, Aged, Retrospective Studies, Liver Cirrhosis, Primary Health Care, Diabetes Mellitus, Cross-Sectional Studies, Adult, Male, Humans, Databases, Factual, and Female
Language Label:
English
ORCID:
Other Affiliation:
Center for Outcomes Research and Evaluation (CORE); Carolinas HealthCare System and Durham VAMC Center for Health Services Research
Page Start:
e0165574
Person:
Trogdon, Justin G., Liu, Tsai-Ling, Fried, Bruce, Paul, John E., Sidney Barritt, , and Weinberger, Morris
Rights Statement Label:
In Copyright
Source:
1831cq963

1770. Variant Discovery and Fine Mapping of Genetic Loci Associated with Blood Pressure Traits in Hispanics and African Americans

Title Tesim:
Variant Discovery and Fine Mapping of Genetic Loci Associated with Blood Pressure Traits in Hispanics and African Americans
Creator:
Franceschini, Nora, Kooperberg, Charles, Zubair, Niha, Schwander, Karen, North, Kari E., Hindorff, Lucia A., Guo, Xiuqing, Ehret, Georg, Carty, Cara L., Lu, Yingchang, Buyske, Steven, Rao, , Fornage, Myriam, Barrett, Paula Q., Tao, Ran, Bielinski, Suzette J., Haessler, Jeff, Manichaikul, Ani, Bien, Stephanie, Loos, Ruth J. F., Chakravarti, Aravinda, Bottinger, Erwin P., Carlson, Christopher S., Kaufman, Joel D., Sung, Yun Ju, and Rich, Stephen S.
Date of publication:
2016
Abstract Tesim:
Despite the substantial burden of hypertension in US minority populations, few genetic studies of blood pressure have been conducted in Hispanics and African Americans, and it is unclear whether many of the established loci identified in European-descent populations contribute to blood pressure variation in non-European descent populations. Using the Metabochip array, we sought to characterize the genetic architecture of previously identified blood pressure loci, and identify novel cardiometabolic variants related to systolic and diastolic blood pressure in a multi-ethnic US population including Hispanics (n = 19,706) and African Americans (n = 18,744). Several known blood pressure loci replicated in African Americans and Hispanics. Fourteen variants in three loci (KCNK3, FGF5, ATXN2-SH2B3) were significantly associated with blood pressure in Hispanics. The most significant diastolic blood pressure variant identified in our analysis, rs2586886/KCNK3 (P = 5.2 x 10−9), also replicated in independent Hispanic and European-descent samples. African American and trans-ethnic meta-analysis data identified novel variants in the FGF5, ULK4 and HOXA-EVX1 loci, which have not been previously associated with blood pressure traits. Our identification and independent replication of variants in KCNK3, a gene implicated in primary hyperaldosteronism, as well as a variant in HOTTIP (HOXA-EVX1) suggest that further work to clarify the roles of these genes may be warranted. Overall, our findings suggest that loci identified in European descent populations also contribute to blood pressure variation in diverse populations including Hispanics and African Americans—populations that are understudied for hypertension genetic risk factors.
Resource type:
Article
Affiliation Label Tesim:
Department of Epidemiology and Department of Biostatistics
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/e2/82/bb/5c/e282bb5c-ecfc-4dd2-8603-2a46b5cc8e4b
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/9zf8-8r14
Identifier:
Onescience id: 68b9f3ad72943cc49f81878b100beadeb9000024, Publisher DOI: https://doi.org/10.1371/journal.pone.0164132, PMCID: PMC5063457, and PMID: 27736895
ISSN:
1932-6203
Journal Issue:
10
Journal Title:
PloS One
Journal Volume:
11
Keyword:
potassium channel subfamily K member 3, long noncoding RNA HOTTIP, human, Genome-Wide Association Study, Potassium Channels, Tandem Pore Domain, Quantitative Trait Loci, Hispanic Americans, Blood Pressure, Humans, Nerve Tissue Proteins, RNA, Long Noncoding, African Americans, and Genetic Variation
Language Label:
English
ORCID:
Other Affiliation:
Division of Public Health Sciences; Fred Hutchinson Cancer Research Center, Division of Biostatistics; Washington University, Division of Genomic Medicine; National Human Genome Research Institute; National Institutes of Health, Institute for Translational Genomics and Population Sciences; Department of Pediatrics; LABiomed at Harbor-University of California at Los Angeles Medical Center, Department of Specialties of Internal Medicine; Geneva University Hospital, Center for Complex Disease Genomics; Johns Hopkins University School of Medicine, Center for Translational Science; George Washington University; Children's National Medical Center, Genetics of Obesity and Related Metabolic Traits Program; Charles Bronfman Institute for Personalized Medicine; Icahn School of Medicine at Mount Sinai, Department of Statistics and Biostatistics; Rutgers University, Brown Foundation Institute of Molecular Medicine; Human Genetics Center; University of Texas Health Science Center, Department of Pharmacology; University of Virginia, Division of Epidemiology; Department of Health Sciences Research; Mayo Clinic, Center for Public Health Genomics; University of Virginia, and Department of Environmental and Occupational Health Sciences; Epidemiology; and Medicine; University of Washington
Page Start:
e0164132
Person:
Franceschini, Nora, Kooperberg, Charles, Zubair, Niha, Schwander, Karen, North, Kari E., Hindorff, Lucia A., Guo, Xiuqing, Ehret, Georg, Carty, Cara L., Lu, Yingchang, Buyske, Steven, Rao, , Fornage, Myriam, Barrett, Paula Q., Tao, Ran, Bielinski, Suzette J., Haessler, Jeff, Manichaikul, Ani, Bien, Stephanie, Loos, Ruth J. F., Chakravarti, Aravinda, Bottinger, Erwin P., Carlson, Christopher S., Kaufman, Joel D., Sung, Yun Ju, and Rich, Stephen S.
Rights Statement Label:
In Copyright
Source:
73666955c