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Article ; Online: Flexible Distance-Based TCR Analysis in Python with tcrdist3.

Mayer-Blackwell, Koshlan / Fiore-Gartland, Andrew / Thomas, Paul G

Methods in molecular biology (Clifton, N.J.)

2022 Volume 2574, Page(s) 309–366

Abstract: Paired- and single-chain T cell receptor (TCR) sequencing are now commonly used techniques for interrogating adaptive immune responses. TCRs targeting the same epitope frequently share motifs consisting of critical contact residues. Here we illustrate ... ...

Abstract	Paired- and single-chain T cell receptor (TCR) sequencing are now commonly used techniques for interrogating adaptive immune responses. TCRs targeting the same epitope frequently share motifs consisting of critical contact residues. Here we illustrate the key features of tcrdist3, a new Python package for distance-based TCR analysis through a series of three interactive examples. In the first example, we illustrate how tcrdist3 can integrate sequence similarity networks, gene-usage plots, and background-adjusted CDR3 logos to identify TCR sequence features conferring antigen specificity among sets of peptide-MHC-multimer sorted receptors. In the second example, we show how the TCRjoin feature in tcrdist3 can be used to flexibly query receptor sequences of interest against bulk repertoires or libraries of previously annotated TCRs based on matching of similar sequences. In the third example, we show how the TCRdist metric can be leveraged to identify candidate polyclonal receptors under antigenic selection in bulk repertoires based on sequence neighbor enrichment testing, a statistical approach similar to TCRNET and ALICE algorithms, but with added flexibility in how the neighborhood can be defined.
MeSH term(s)	Algorithms ; Antigens ; Epitopes ; Receptors, Antigen, T-Cell
Chemical Substances	Antigens ; Epitopes ; Receptors, Antigen, T-Cell
Language	English
Publishing date	2022-08-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-2712-9_16
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Merkel cell polyomavirus-specific and CD39

Ryu, Heeju / Bi, Timothy M / Pulliam, Thomas H / Sarkar, Korok / Church, Candice D / Kumar, Nandita / Mayer-Blackwell, Koshlan / Jani, Saumya / Ramchurren, Nirasha / Hansen, Ulla K / Hadrup, Sine R / Fling, Steven P / Koelle, David M / Nghiem, Paul / Newell, Evan W

Cell reports. Medicine

2024 Volume 5, Issue 2, Page(s) 101390

Abstract: Merkel cell carcinoma is a skin cancer often driven by Merkel cell polyomavirus (MCPyV) with high rates of response to anti-PD-1 therapy despite low mutational burden. MCPyV-specific CD8 T cells are implicated in anti-PD-1-associated immune responses and ...

Abstract	Merkel cell carcinoma is a skin cancer often driven by Merkel cell polyomavirus (MCPyV) with high rates of response to anti-PD-1 therapy despite low mutational burden. MCPyV-specific CD8 T cells are implicated in anti-PD-1-associated immune responses and provide a means to directly study tumor-specific T cell responses to treatment. Using mass cytometry and combinatorial tetramer staining, we find that baseline frequencies of blood MCPyV-specific cells correlated with response and survival. Frequencies of these cells decrease markedly during response to therapy. Phenotypes of MCPyV-specific CD8 T cells have distinct expression patterns of CD39, cutaneous lymphocyte-associated antigen (CLA), and CD103. Correspondingly, overall bulk CD39
MeSH term(s)	Humans ; Carcinoma, Merkel Cell/drug therapy ; Carcinoma, Merkel Cell/metabolism ; Carcinoma, Merkel Cell/pathology ; Merkel cell polyomavirus/metabolism ; Programmed Cell Death 1 Receptor/metabolism ; CD8-Positive T-Lymphocytes ; Skin Neoplasms/drug therapy ; Skin Neoplasms/metabolism ; Biomarkers/metabolism ; Sialyl Lewis X Antigen/analogs & derivatives ; Oligosaccharides
Chemical Substances	6-sulfo sialyl Lewis X ; Programmed Cell Death 1 Receptor ; Biomarkers ; Sialyl Lewis X Antigen ; Oligosaccharides
Language	English
Publishing date	2024-02-09
Publishing country	United States
Document type	Journal Article
ISSN	2666-3791
ISSN (online)	2666-3791
DOI	10.1016/j.xcrm.2023.101390
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Article: Strain-level characterization of health-associated bacterial consortia that colonize the human gut during infancy.

Minot, Samuel S / Mayer-Blackwell, Koshlan / Fiore-Gartland, Andrew / Johnson, Andrew / Self, Steven / Bhatti, Parveen / Yao, Lena / Liu, Lili / Sun, Xin / Jinfa, Yi / Kublin, James

medRxiv : the preprint server for health sciences

2023

Abstract: Background: The human gut microbiome develops rapidly during infancy, a key window of development coinciding with maturation of the adaptive immune system. However, little is known of the microbiome growth dynamics over the first few months of life and ... ...

Abstract	Background: The human gut microbiome develops rapidly during infancy, a key window of development coinciding with maturation of the adaptive immune system. However, little is known of the microbiome growth dynamics over the first few months of life and whether there are any generalizable patterns across human populations. We performed metagenomic sequencing on stool samples (n=94) from a cohort of infants (n=15) at monthly intervals in the first six months of life, augmenting our dataset with seven published studies for a total of 4,441 metagenomes from 1,162 infants. Results: Strain-level Conclusion: By augmenting published metagenomic datasets with data from a newly established cohort we were able to identify novel groups of organisms that are correlated with measures of robust human development. We hypothesize that the presence of these groups may impact human health in aggregate in ways that individual species may not in isolation.
Language	English
Publishing date	2023-12-17
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.12.16.23300077
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Article: The Regulation of Nucleic Acid Vaccine Responses by the Microbiome.

Johnson, Andrew M F / Hager, Kevin / Alameh, Mohamad-Gabriel / Van, Phuong / Potchen, Nicole / Mayer-Blackwell, Koshlan / Fiore-Gartland, Andrew / Minot, Samuel / Lin, Paulo J C / Tam, Ying K / Weissman, Drew / Kublin, James G

bioRxiv : the preprint server for biology

2023

Abstract: Nucleic acid vaccines, including both RNA and DNA platforms, are key technologies that have considerable promise in combating both infectious disease and cancer. However, little is known about the extrinsic factors that regulate nucleic acid vaccine ... ...

Abstract	Nucleic acid vaccines, including both RNA and DNA platforms, are key technologies that have considerable promise in combating both infectious disease and cancer. However, little is known about the extrinsic factors that regulate nucleic acid vaccine responses and which may determine their effectiveness. The microbiome is recognized as a significant regulator of immune development and response, whose role in regulating some traditional vaccine platforms has recently been discovered. Using germ-free and specific-pathogen-free mouse models in combination with different protein, DNA, and mRNA vaccine regimens, we demonstrate that the microbiome is a significant regulator of nucleic acid vaccine immunogenicity. While the presence of the microbiome enhances CD8+ T cell responses to mRNA lipid nanoparticle (LNP) immunization, the microbiome suppresses immunoglobulin and CD4+ T cell responses to DNA-prime, DNA-protein-boost immunization, indicating contrasting roles for the microbiome in the regulation of these different nucleic acid vaccine platforms. In the case of mRNA-LNP vaccination, germ-free mice display reduced dendritic cell/macrophage activation that may underlie the deficient vaccine response. Our study identifies the microbiome as a relevant determinant of nucleic acid vaccine response with implications for their continued therapeutic development and deployment.
Language	English
Publishing date	2023-02-19
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.02.18.529093
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Article ; Online: The Regulation of Nucleic Acid Vaccine Responses by the Microbiome.

Journal of immunology (Baltimore, Md. : 1950)

2023 Volume 211, Issue 11, Page(s) 1680–1692

Abstract	Nucleic acid vaccines, including both RNA and DNA platforms, are key technologies that have considerable promise in combating both infectious disease and cancer. However, little is known about the extrinsic factors that regulate nucleic acid vaccine responses and which may determine their effectiveness. The microbiome is recognized as a significant regulator of immune development and response, whose role in regulating some traditional vaccine platforms has recently been discovered. Using germ-free and specific pathogen-free mouse models in combination with different protein, DNA, and mRNA vaccine regimens, we demonstrate that the microbiome is a significant regulator of nucleic acid vaccine immunogenicity. Although the presence of the microbiome enhances CD8+ T cell responses to mRNA lipid nanoparticle immunization, the microbiome suppresses Ig and CD4+ T cell responses to DNA-prime, DNA-protein-boost immunization, indicating contrasting roles for the microbiome in the regulation of these different nucleic acid vaccine platforms. In the case of mRNA lipid nanoparticle vaccination, germ-free mice display reduced dendritic cell/macrophage activation that may underlie the deficient vaccine response. Our study identifies the microbiome as a relevant determinant of nucleic acid vaccine response with implications for continued therapeutic development and deployment of these vaccines.
MeSH term(s)	Mice ; Animals ; Nucleic Acid-Based Vaccines ; CD8-Positive T-Lymphocytes ; Vaccines, DNA ; DNA ; Microbiota ; RNA, Messenger ; Immunization, Secondary
Chemical Substances	Nucleic Acid-Based Vaccines ; Vaccines, DNA ; DNA (9007-49-2) ; RNA, Messenger
Language	English
Publishing date	2023-10-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.2300196
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Article ; Online: Durable Expansion of TCR-δ Meta-Clonotypes After BCG Revaccination in Humans.

James, Charlotte A / Yu, Krystle K Q / Mayer-Blackwell, Koshlan / Fiore-Gartland, Andrew / Smith, Malisa T / Layton, Erik D / Johnson, John L / Hanekom, Willem A / Scriba, Thomas J / Seshadri, Chetan

Frontiers in immunology

2022 Volume 13, Page(s) 834757

Abstract: Mycobacterium ... ...

Abstract	Mycobacterium bovis
MeSH term(s)	Adult ; BCG Vaccine ; Child ; Child, Preschool ; Humans ; Immunization, Secondary ; Leukocytes, Mononuclear ; Mycobacterium tuberculosis ; Receptors, Antigen, T-Cell
Chemical Substances	BCG Vaccine ; Receptors, Antigen, T-Cell
Language	English
Publishing date	2022-03-30
Publishing country	Switzerland
Document type	Clinical Trial, Phase I ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.834757
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Article ; Online: High-Throughput Multiparallel Enteropathogen Detection via Nano-Liter qPCR.

Grembi, Jessica A / Mayer-Blackwell, Koshlan / Luby, Stephen P / Spormann, Alfred M

Frontiers in cellular and infection microbiology

2020 Volume 10, Page(s) 351

Abstract: Quantitative molecular diagnostic methods can effectively detect pathogen-specific nucleic acid sequences, but costs associated with multi-pathogen panels hinder their widespread use in research trials. Nano-liter qPCR (nL-qPCR) is a miniaturized tool ... ...

Abstract	Quantitative molecular diagnostic methods can effectively detect pathogen-specific nucleic acid sequences, but costs associated with multi-pathogen panels hinder their widespread use in research trials. Nano-liter qPCR (nL-qPCR) is a miniaturized tool for quantification of multiple targets in large numbers of samples based on assay parallelization on a single chip, with potentially significant cost-savings due to rapid throughput and reduced reagent volumes. We evaluated a suite of novel and published assays to detect 17 enteric pathogens using a commercially available nL-qPCR technology. Amplification efficiencies ranged from 88 to 98% (mean 91%) and were reproducible across four operators at two separate facilities. When applied to fecal material, assays were sensitive and selective (99.8% of DNA amplified were genes from the target organism). Due to nanofluidic volumes, detection limits were 1-2 orders of magnitude less sensitive for nL-qPCR than an enteric TaqMan Array Card (TAC). However, higher detection limits do not hinder detection of diarrhea-causing pathogen concentrations. Compared to TAC, nL-qPCR displayed 99% (95% CI 0.98, 0.99) negative percent agreement and 62% (95% CI 0.59, 0.65) overall positive percent agreement for presence of pathogens across diarrheal and non-diarrheal fecal samples. Positive percent agreement was 89% among samples with concentrations above the nL-qPCR detection limits. nL-qPCR assays showed an underestimation bias of 0.34 log
MeSH term(s)	Diarrhea/diagnosis ; Feces ; Humans ; Molecular Diagnostic Techniques ; Real-Time Polymerase Chain Reaction ; Sensitivity and Specificity
Language	English
Publishing date	2020-07-15
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2020.00351
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Article: Open Book, Open Source: PCB Usage in Mass-Market Paperback Book Adhesives

Parker, Jeffrey S / Mayer-Blackwell, Koshlan

Environmental science & technology letters. 2019 Sept. 06, v. 6, no. 10

2019

Abstract: This study documents an unrecognized source of polychlorinated biphenyls (PCBs) to indoor and outdoor environments from mass-market paperback book adhesives. The PCB content of common consumer products like books is less documented than industrial ... ...

Abstract	This study documents an unrecognized source of polychlorinated biphenyls (PCBs) to indoor and outdoor environments from mass-market paperback book adhesives. The PCB content of common consumer products like books is less documented than industrial products. Patents describe PCBs as components for hot-melt adhesives used for “perfect” bound paperback bookbinding. However, the PCB formulations, concentrations, and dates of use for these adhesives have not been confirmed by chemical analysis. We tested production-dated paperback books manufactured between 1946 and 1974 from six major publishers. Chemical analysis of the binding adhesive confirms the widespread presence of PCBs in paperback books. PCBs were detected in adhesives from all tested books manufactured between 1948 and 1974 (n = 21). High PCB concentrations (6.1–18 wt %/wt), consistent with use as a plasticizer, were found in half the samples (n = 12). We tentatively identified polychlorinated terphenyls (PCTs) in four samples with lower, ppm-level PCB concentrations. From 1948 to 1974, we estimate that over 6 billion mass-market paperback books were sold domestically, many of which remain in homes, libraries, and stores. Therefore, book adhesives may be a potential PCB source to indoor air and to the environment via paper mill effluent, landfills, and recycled paper.
Keywords	adhesives ; air ; chemical analysis ; landfills ; patents ; plasticizers ; polychlorinated biphenyls ; products and commodities ; pulp and paper mill effluents ; recycled paper
Language	English
Dates of publication	2019-0906
Size	p. 565-570.
Publishing place	American Chemical Society
Document type	Article
ISSN	2328-8930
DOI	10.1021/acs.estlett.9b00489
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Multi-trial analysis of HIV-1 envelope gp41-reactive antibodies among global recipients of candidate HIV-1 vaccines.

Mayer-Blackwell, Koshlan / Johnson, Andrew M / Potchen, Nicole / Minot, Simon S / Heptinstall, Jack / Seaton, Kelly / Sawant, Sheetal / Shen, Xiaoying / Tomaras, Georgia D / Fiore-Gartland, Andrew / Kublin, James G

Frontiers in immunology

2022 Volume 13, Page(s) 983313

Abstract: Many participants in HIV-1 vaccine trials, who have not previously been exposed to or vaccinated against HIV-1, display serum immunoglobulin antibodies that bind the gp41 region of HIV-1 envelope prior to vaccination. Previous studies have hypothesized ... ...

Abstract	Many participants in HIV-1 vaccine trials, who have not previously been exposed to or vaccinated against HIV-1, display serum immunoglobulin antibodies that bind the gp41 region of HIV-1 envelope prior to vaccination. Previous studies have hypothesized that these pre-existing antibodies may be cross-reactive and may skew future vaccine responses. In 12 large studies conducted by the HIV Vaccine Trial Network (HVTN) (n=1470 individuals), we find wide variation among participants in the pre-vaccine levels of gp41-reactive antibodies as measured by the binding antibody multiplex assay (BAMA). In the absence of exposure to the gp41 immunogen, anti-gp41 IgG levels were temporally stable over 26-52 weeks in repeated measures of placebo recipients. The analysis revealed that the geometric mean of pre-vaccine anti-gp41 IgG response was greater among participants in South Africa compared with participants in the United States. With gene-level metagenomic sequencing of pre-vaccination fecal samples collected from participants in one trial (HVTN 106), we detected positive associations between pre-vaccine anti-gp41 IgG and abundance of genes from multiple taxa in the
MeSH term(s)	Humans ; HIV-1 ; HIV Antibodies ; AIDS Vaccines ; HIV Infections/prevention & control ; HIV Seropositivity ; Immunoglobulin G
Chemical Substances	HIV Antibodies ; AIDS Vaccines ; Immunoglobulin G
Language	English
Publishing date	2022-10-12
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.983313
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Article ; Online: mRNA vaccination boosts S-specific T cell memory and promotes expansion of CD45RA

Mayer-Blackwell, Koshlan / Ryu, Heeju / Codd, Amy S / Parks, K Rachael / MacMillan, Hugh R / Cohen, Kristen W / Stewart, Terri L / Seese, Aaron / Lemos, Maria P / De Rosa, Stephen C / Czartoski, Julie L / Moodie, Zoe / Nguyen, Long T / McGuire, Donald J / Ahmed, Rafi / Fiore-Gartland, Andrew / McElrath, M Juliana / Newell, Evan W

Cell reports. Medicine

2023 Volume 4, Issue 8, Page(s) 101149

Abstract: SARS-CoV-2 infection and mRNA vaccination both elicit spike (S)-specific T cell responses. To analyze how T cell memory from prior infection influences T cell responses to vaccination, we evaluated functional T cell responses in naive and previously ... ...

Abstract	SARS-CoV-2 infection and mRNA vaccination both elicit spike (S)-specific T cell responses. To analyze how T cell memory from prior infection influences T cell responses to vaccination, we evaluated functional T cell responses in naive and previously infected vaccine recipients. Pre-vaccine S-specific responses are predictive of subsequent CD8
MeSH term(s)	Humans ; CD8-Positive T-Lymphocytes ; COVID-19/prevention & control ; Memory T Cells ; SARS-CoV-2 ; Vaccination ; Epitopes ; Leukocyte Common Antigens
Chemical Substances	Epitopes ; Leukocyte Common Antigens (EC 3.1.3.48)
Language	English
Publishing date	2023-08-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ISSN	2666-3791
ISSN (online)	2666-3791
DOI	10.1016/j.xcrm.2023.101149
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