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Article ; Online: Baseline immune states (BIS) associated with vaccine responsiveness and factors that shape the BIS.

Nehar-Belaid, Djamel / Sokolowski, Mark / Ravichandran, Sathyabaarathi / Banchereau, Jacques / Chaussabel, Damien / Ucar, Duygu

Seminars in immunology

2023 Volume 70, Page(s) 101842

Abstract: Vaccines are among the greatest inventions in medicine, leading to the elimination or control of numerous diseases, including smallpox, polio, measles, rubella, and, most recently, COVID-19. Yet, the effectiveness of vaccines varies among individuals. In ...

Abstract	Vaccines are among the greatest inventions in medicine, leading to the elimination or control of numerous diseases, including smallpox, polio, measles, rubella, and, most recently, COVID-19. Yet, the effectiveness of vaccines varies among individuals. In fact, while some recipients mount a robust response to vaccination that protects them from the disease, others fail to respond. Multiple clinical and epidemiological factors contribute to this heterogeneity in responsiveness. Systems immunology studies fueled by advances in single-cell biology have been instrumental in uncovering pre-vaccination immune cell types and genomic features (i.e., the baseline immune state, BIS) that have been associated with vaccine responsiveness. Here, we review clinical factors that shape the BIS, and the characteristics of the BIS associated with responsiveness to frequently studied vaccines (i.e., influenza, COVID-19, bacterial pneumonia, malaria). Finally, we discuss potential strategies to enhance vaccine responsiveness in high-risk groups, focusing specifically on older adults.
MeSH term(s)	Humans ; Aged ; Vaccines ; Measles/prevention & control ; Vaccination ; COVID-19/prevention & control
Chemical Substances	Vaccines
Language	English
Publishing date	2023-09-15
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1018141-6
ISSN	1096-3618 ; 1044-5323
ISSN (online)	1096-3618
ISSN	1044-5323
DOI	10.1016/j.smim.2023.101842
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Article ; Online: The Th1/Tfh-like biased responses elicited by the rASP-1 innate adjuvant are dependent on TRIF and Type I IFN receptor pathways.

George, Parakkal Jovvian / Marches, Radu / Nehar-Belaid, Djamel / Banchereau, Jacques / Lustigman, Sara

Frontiers in immunology

2022 Volume 13, Page(s) 961094

Abstract: ... ...

Abstract	Ov
MeSH term(s)	Adaptor Proteins, Vesicular Transport/metabolism ; Adjuvants, Immunologic/pharmacology ; Adjuvants, Pharmaceutic ; Animals ; Chemokine CXCL10/metabolism ; Humans ; Influenza A Virus, H1N1 Subtype ; Influenza Vaccines ; Interleukin-12 Subunit p40 ; Interleukin-17/metabolism ; Mice ; Myeloid Differentiation Factor 88/metabolism ; Receptor, Interferon alpha-beta/genetics ; Receptor, Interferon alpha-beta/metabolism ; Toll-Like Receptor 4/metabolism ; Tumor Necrosis Factor-alpha/metabolism
Chemical Substances	Adaptor Proteins, Vesicular Transport ; Adjuvants, Immunologic ; Adjuvants, Pharmaceutic ; Chemokine CXCL10 ; Influenza Vaccines ; Interleukin-12 Subunit p40 ; Interleukin-17 ; Myeloid Differentiation Factor 88 ; Toll-Like Receptor 4 ; Tumor Necrosis Factor-alpha ; Receptor, Interferon alpha-beta (156986-95-7)
Language	English
Publishing date	2022-09-02
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.2022.961094
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Article ; Online: The Tsallis generalized entropy enhances the interpretation of transcriptomics datasets.

Dérian, Nicolas / Pham, Hang-Phuong / Nehar-Belaid, Djamel / Tchitchek, Nicolas / Klatzmann, David / Eric, Vicaut / Six, Adrien

PloS one

2022 Volume 17, Issue 4, Page(s) e0266618

Abstract: Background: Identifying differentially expressed genes between experimental conditions is still the gold-standard approach to interpret transcriptomic profiles. Alternative approaches based on diversity measures have been proposed to complement the ... ...

Abstract	Background: Identifying differentially expressed genes between experimental conditions is still the gold-standard approach to interpret transcriptomic profiles. Alternative approaches based on diversity measures have been proposed to complement the interpretation of such datasets but are only used marginally. Methods: Here, we reinvestigated diversity measures, which are commonly used in ecology, to characterize mice pregnancy microenvironments based on a public transcriptome dataset. Mainly, we evaluated the Tsallis entropy function to explore the potential of a collection of diversity measures for capturing relevant molecular event information. Results: We demonstrate that the Tsallis entropy function provides additional information compared to the traditional diversity indices, such as the Shannon and Simpson indices. Depending on the relative importance given to the most abundant transcripts based on the Tsallis entropy function parameter, our approach allows appreciating the impact of biological stimulus on the inter-individual variability of groups of samples. Moreover, we propose a strategy for reducing the complexity of transcriptome datasets using a maximation of the beta diversity. Conclusions: We highlight that a diversity-based analysis is suitable for capturing complex molecular events occurring during physiological events. Therefore, we recommend their use through the Tsallis entropy function to analyze transcriptomics data in addition to differential expression analyses.
MeSH term(s)	Animals ; Ecology ; Entropy ; Mice ; Transcriptome
Language	English
Publishing date	2022-04-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0266618
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Article ; Online: Distinct baseline immune characteristics associated with responses to conjugated and unconjugated pneumococcal polysaccharide vaccines in older adults.

Ravichandran, Sathyabaarathi / Erra-Diaz, Fernando / Karakaslar, Onur E / Marches, Radu / Kenyon-Pesce, Lisa / Rossi, Robert / Chaussabel, Damien / Nehar-Belaid, Djamel / LaFon, David C / Pascual, Virginia / Palucka, Karolina / Paust, Silke / Nahm, Moon H / Kuchel, George A / Banchereau, Jacques / Ucar, Duygu

Nature immunology

2024 Volume 25, Issue 2, Page(s) 316–329

Abstract: Pneumococcal infections cause serious illness and death among older adults. The capsular polysaccharide vaccine PPSV23 and conjugated alternative PCV13 can prevent these infections; yet, underlying immunological responses and baseline predictors remain ... ...

Abstract	Pneumococcal infections cause serious illness and death among older adults. The capsular polysaccharide vaccine PPSV23 and conjugated alternative PCV13 can prevent these infections; yet, underlying immunological responses and baseline predictors remain unknown. We vaccinated 39 older adults (>60 years) with PPSV23 or PCV13 and observed comparable antibody responses (day 28) and plasmablast transcriptional responses (day 10); however, the baseline predictors were distinct. Analyses of baseline flow cytometry and bulk and single-cell RNA-sequencing data revealed a baseline phenotype specifically associated with weaker PCV13 responses, which was characterized by increased expression of cytotoxicity-associated genes, increased frequencies of CD16
MeSH term(s)	Male ; Humans ; Female ; Aged ; Vaccines, Conjugate ; Antibodies, Bacterial ; Double-Blind Method ; Streptococcus pneumoniae ; Vaccination ; Pneumococcal Vaccines ; Polysaccharides
Chemical Substances	Vaccines, Conjugate ; Antibodies, Bacterial ; Pneumococcal Vaccines ; Polysaccharides
Language	English
Publishing date	2024-01-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	2016987-5
ISSN	1529-2916 ; 1529-2908
ISSN (online)	1529-2916
ISSN	1529-2908
DOI	10.1038/s41590-023-01717-5
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Article: An unconventional mechanism of IL-1β secretion that requires Type I IFN in lupus monocytes.

Caielli, Simone / Balasubramanian, Preetha / Rodriguez-Alcazar, Juan / Balaji, Uthra / Wan, Zurong / Baisch, Jeanine / Smitherman, Cynthia / Walters, Lynnette / Sparagana, Paola / Nehar-Belaid, Djamel / Marches, Radu / Nassi, Lorien / Stewart, Katie / Fuller, Julie / Banchereau, Jacques F / Gu, Jinghua / Wright, Tracey / Pascual, Virginia

bioRxiv : the preprint server for biology

2023

Abstract: Systemic Lupus Erythematosus (SLE) is characterized by autoreactive B cell activation, upregulation of Type I Interferon (IFN) and widespread inflammation. Mitochondrial nucleic acids (NAs) are increasingly recognized as triggers of ... ...

Abstract	Systemic Lupus Erythematosus (SLE) is characterized by autoreactive B cell activation, upregulation of Type I Interferon (IFN) and widespread inflammation. Mitochondrial nucleic acids (NAs) are increasingly recognized as triggers of IFN
Language	English
Publishing date	2023-08-03
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.08.03.551696
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Article ; Online: Young infants display heterogeneous serological responses and extensive but reversible transcriptional changes following initial immunizations.

Nouri, Nima / Cao, Raquel Giacomelli / Bunsow, Eleonora / Nehar-Belaid, Djamel / Marches, Radu / Xu, Zhaohui / Smith, Bennett / Heinonen, Santtu / Mertz, Sara / Leber, Amy / Smits, Gaby / van der Klis, Fiona / Mejías, Asunción / Banchereau, Jacques / Pascual, Virginia / Ramilo, Octavio

Nature communications

2023 Volume 14, Issue 1, Page(s) 7976

Abstract: Infants necessitate vaccinations to prevent life-threatening infections. Our understanding of the infant immune responses to routine vaccines remains limited. We analyzed two cohorts of 2-month-old infants before vaccination, one week, and one-month post- ...

Abstract	Infants necessitate vaccinations to prevent life-threatening infections. Our understanding of the infant immune responses to routine vaccines remains limited. We analyzed two cohorts of 2-month-old infants before vaccination, one week, and one-month post-vaccination. We report remarkable heterogeneity but limited antibody responses to the different antigens. Whole-blood transcriptome analysis in an initial cohort showed marked overexpression of interferon-stimulated genes (ISGs) and to a lesser extent of inflammation-genes at day 7, which normalized one month post-vaccination. Single-cell RNA sequencing in peripheral blood mononuclear cells from a second cohort identified at baseline a predominantly naive immune landscape including ISG
MeSH term(s)	Humans ; Infant ; Leukocytes, Mononuclear/metabolism ; Interferons/metabolism ; Vaccination ; Gene Expression Profiling ; Inflammation/metabolism
Chemical Substances	Interferons (9008-11-1)
Language	English
Publishing date	2023-12-02
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-43758-2
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Article: Comprehensive single cell aging atlas of mammary tissues reveals shared epigenomic and transcriptomic signatures of aging and cancer.

Angarola, Brittany L / Sharma, Siddhartha / Katiyar, Neerja / Gu Kang, Hyeon / Nehar-Belaid, Djamel / Park, SungHee / Gott, Rachel / Eryilmaz, Giray N / LaBarge, Mark A / Palucka, Karolina / Chuang, Jeffrey H / Korstanje, Ron / Ucar, Duygu / Anczukow, Olga

bioRxiv : the preprint server for biology

2023

Abstract: Aging is the greatest risk factor for breast cancer; however, how age-related cellular and molecular events impact cancer initiation is unknown. We investigate how aging rewires transcriptomic and epigenomic programs of mouse mammary glands at single ... ...

Abstract	Aging is the greatest risk factor for breast cancer; however, how age-related cellular and molecular events impact cancer initiation is unknown. We investigate how aging rewires transcriptomic and epigenomic programs of mouse mammary glands at single cell resolution, yielding a comprehensive resource for aging and cancer biology. Aged epithelial cells exhibit epigenetic and transcriptional changes in metabolic, pro-inflammatory, or cancer-associated genes. Aged stromal cells downregulate fibroblast marker genes and upregulate markers of senescence and cancer-associated fibroblasts. Among immune cells, distinct T cell subsets (
Language	English
Publishing date	2023-10-23
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.10.20.563147
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Article: AMULET: a novel read count-based method for effective multiplet detection from single nucleus ATAC-seq data

Thibodeau, Asa / Eroglu, Alper / McGinnis, Christopher S. / Lawlor, Nathan / Nehar-Belaid, Djamel / Kursawe, Romy / Marches, Radu / Conrad, Daniel N. / Kuchel, George A. / Gartner, Zev J. / Banchereau, Jacques / Stitzel, Michael L. / Cicek, A. Ercument / Ucar, Duygu

Genome biology. 2021 Dec., v. 22, no. 1

2021

Abstract: Detecting multiplets in single nucleus (sn)ATAC-seq data is challenging due to data sparsity and limited dynamic range. AMULET (ATAC-seq MULtiplet Estimation Tool) enumerates regions with greater than two uniquely aligned reads across the genome to ... ...

Abstract	Detecting multiplets in single nucleus (sn)ATAC-seq data is challenging due to data sparsity and limited dynamic range. AMULET (ATAC-seq MULtiplet Estimation Tool) enumerates regions with greater than two uniquely aligned reads across the genome to effectively detect multiplets. We evaluate the method by generating snATAC-seq data in the human blood and pancreatic islet samples. AMULET has high precision, estimated via donor-based multiplexing, and high recall, estimated via simulated multiplets, compared to alternatives and identifies multiplets most effectively when a certain read depth of 25K median valid reads per nucleus is achieved.
Keywords	blood ; genome ; humans ; islets of Langerhans
Language	English
Dates of publication	2021-12
Size	p. 252.
Publishing place	BioMed Central
Document type	Article
ZDB-ID	2040529-7
ISSN	1474-760X
ISSN	1474-760X
DOI	10.1186/s13059-021-02469-x
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Single Cell Analysis of Blood Mononuclear Cells Stimulated Through Either LPS or Anti-CD3 and Anti-CD28.

Lawlor, Nathan / Nehar-Belaid, Djamel / Grassmann, Jessica D S / Stoeckius, Marlon / Smibert, Peter / Stitzel, Michael L / Pascual, Virginia / Banchereau, Jacques / Williams, Adam / Ucar, Duygu

Frontiers in immunology

2021 Volume 12, Page(s) 636720

Abstract: Immune cell activation assays have been widely used for immune monitoring and for understanding disease mechanisms. However, these assays are typically limited in scope. A holistic study of circulating immune cell responses to different activators is ... ...

Abstract	Immune cell activation assays have been widely used for immune monitoring and for understanding disease mechanisms. However, these assays are typically limited in scope. A holistic study of circulating immune cell responses to different activators is lacking. Here we developed a cost-effective high-throughput multiplexed single-cell RNA-seq combined with epitope tagging (CITE-seq) to determine how classic activators of T cells (anti-CD3 coupled with anti-CD28) or monocytes (LPS) alter the cell composition and transcriptional profiles of peripheral blood mononuclear cells (PBMCs) from healthy human donors. Anti-CD3/CD28 treatment activated all classes of lymphocytes either directly (T cells) or indirectly (B and NK cells) but reduced monocyte numbers. Activated T and NK cells expressed senescence and effector molecules, whereas activated B cells transcriptionally resembled autoimmune disease- or age-associated B cells (e.g., CD11c, T-bet). In contrast, LPS specifically targeted monocytes and induced two main states: early activation characterized by the expression of chemoattractants and a later pro-inflammatory state characterized by expression of effector molecules. These data provide a foundation for future immune activation studies with single cell technologies (https://czi-pbmc-cite-seq.jax.org/).
MeSH term(s)	Adult ; Antibodies, Monoclonal/immunology ; CD28 Antigens/immunology ; CD3 Complex/immunology ; Cells, Cultured ; Cellular Senescence/genetics ; Chemotaxis/genetics ; Female ; Gene Expression Profiling ; High-Throughput Screening Assays ; Humans ; Immunization ; Leukocytes, Mononuclear/immunology ; Lipopolysaccharides/immunology ; Lymphocyte Activation/genetics ; Male ; Single-Cell Analysis ; Young Adult
Chemical Substances	Antibodies, Monoclonal ; CD28 Antigens ; CD3 Complex ; Lipopolysaccharides
Language	English
Publishing date	2021-03-17
Publishing country	Switzerland
Document type	Journal Article ; 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.2021.636720
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Article ; Online: Regulatory T Cells Orchestrate Similar Immune Evasion of Fetuses and Tumors in Mice.

Nehar-Belaid, Djamel / Courau, Tristan / Dérian, Nicolas / Florez, Laura / Ruocco, Maria Grazia / Klatzmann, David

Journal of immunology (Baltimore, Md. : 1950)

2016 Volume 196, Issue 2, Page(s) 678–690

Abstract: Embryos and tumors are both masses of dividing cells expressing foreign Ags, but they are not rejected by the immune system. We hypothesized that similar tolerogenic mechanisms prevent their rejection. Global comparison of fetal and tumor ... ...

Abstract	Embryos and tumors are both masses of dividing cells expressing foreign Ags, but they are not rejected by the immune system. We hypothesized that similar tolerogenic mechanisms prevent their rejection. Global comparison of fetal and tumor microenvironments through transcriptomics in mice revealed strikingly similar and dramatic decreases in expression of numerous immune-related pathways, including Ag presentation and T cell signaling. Unsupervised analyses highlighted the parallel kinetics and similarities of immune signature downregulation, from the very first days after tumor or embryo implantation. Besides upregulated signatures related to cell proliferation, the only significant signatures shared by the two conditions across all biological processes and all time points studied were downmodulated immune response signatures. Regulatory T cell depletion completely reverses this immune downmodulation to an immune upregulation that leads to fetal or tumor immune rejection. We propose that evolutionarily selected mechanisms that protect mammalian fetuses from immune attack are hijacked to license tumor development.
MeSH term(s)	Animals ; Female ; Fetal Development/immunology ; Fetus/immunology ; Immune Tolerance/immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Neoplasms/immunology ; T-Lymphocytes, Regulatory/immunology ; Transcriptome ; Tumor Escape/immunology
Language	English
Publishing date	2016-01-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
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.1501834
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Zs.MG 28: Show issues

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