ArticleScience signaling2011
In vivo systems analysis identifies spatial and temporal aspects of the modulation of TNF-α-induced apoptosis and proliferation by MAPKs.
Article in Science signaling, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
69 citing papers in PubMed, 8 citations in OpenAlex.
- Multivariate Computational Analysis of Gamma Delta T Cell Inhibitory Receptor Signatures Reveals the Divergence of Healthy and ART-Suppressed HIV+ Aging.Frontiers in immunology · 2018Trial
- Distinct genital tract HIV-specific antibody profiles associated with tenofovir gel.Mucosal immunology · 2016Trial
- Distinct Antibody Fc-profiles in Lymph During Homeostasis and Chronic HIV Infection.Pathogens & immunity · 2026Article
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- Oxysophocarpine Inhibits Apoptosis of Lung Epithelial Cells to Alleviate Acute Lung Injury via KIT/PI3K Signaling Pathway.Drug design, development and therapy · 2025Article
- Accumulation of Neutrophil Phagocytic Antibody Features Tracks With Naturally Acquired Immunity Against Malaria in Children.The Journal of infectious diseases · 2023Article
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- Lipopolysaccharide-induced chronic inflammation increases female serum gonadotropins and shifts the pituitary transcriptomic landscape.Frontiers in endocrinology · 2023Article
- Maternal HIV infection drives altered placentalFrontiers in microbiology · 2023Article
- Altered Maternal Antibody Profiles in Women With Human Immunodeficiency Virus Drive Changes in Transplacental Antibody Transfer.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Article
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- Cell surface integrin α5ß1 clustering negatively regulates receptor tyrosine kinase signaling in colorectal cancer cells via glycogen synthase kinase 3.Integrative biology : quantitative biosciences from nano to macro · 2021Article
- Antibody Subclass and Glycosylation Shift Following Effective TB Treatment.Frontiers in immunology · 2021Article
- IgG3 collaborates with IgG1 and IgA to recruit effector function in RV144 vaccinees.JCI insight · 2020Article
- Article
- Identification of a unique temporal signature in blood and BAL associated with IPF progression.Scientific reports · 2020Article
- Protein-based, but not viral vector alone, HIV vaccine boosting drives an IgG1-biased polyfunctional humoral immune response.JCI insight · 2020Article
- Robust latent-variable interpretation of in vivo regression models by nested resampling.Scientific reports · 2019Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Cellular responses to external stimuli depend on dynamic features of multipathway network signaling; thus, cell behavior is influenced in a complex manner by the environment and by intrinsic properties. Methods of multivariate systems analysis have provided an understanding of these convoluted effects, but only for relatively simplified examples in vitro. To determine whether such approaches could be successfully used in vivo, we analyzed the signaling network that determines the response of intestinal epithelial cells to tumor necrosis factor-α (TNF-α). We built data-driven, partial least-squares discriminant analysis (PLSDA) models based on signaling, apoptotic, and proliferative responses in the mouse small intestinal epithelium after systemic exposure to TNF-α. The extracellular signal-regulated kinase (ERK) signaling axis was a critical modulator of the temporal variation in apoptosis at different doses of TNF-α and of the spatial variation in proliferation in distinct intestinal regions. Inhibition of MEK, a mitogen-activated protein kinase kinase upstream of ERK, altered the signaling network and changed the temporal and spatial phenotypes consistent with model predictions. Our results demonstrate the dynamic, adaptive nature of in vivo signaling networks and identify natural, tissue-level variation in responses that can be deconvoluted only with quantitative, multivariate computational modeling. This study lays a foundation for the use of systems-based approaches to understand how dysregulation of the cellular network state underlies complex diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.