Evidence mapPaperPMID 31719909Full record

ArticleCellular and molecular bioengineering2019

Identifying Key Pathways and Components in Chemokine-Triggered T Lymphocyte Arrest Dynamics Using a Multi-Parametric Global Sensitivity Analysis.

Dooyoung Lee, Michael T Beste, Nicholas R Anderson, Gary A Koretzky, Daniel A Hammer

Open access · bronzeAbstract read
In one paragraph

Article in Cellular and molecular bioengineering, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.2field-weighted citation impact, top 49% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 4 institutions in 3 countries.

Dooyoung LeeDepartment of Bioengineering, University of Pennsylvania, 240 Skirkanich Hall, 210 South 33rd St., Philadelphia, PA 19104 USA.
Michael T BesteDepartment of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA 19104 USA.
Nicholas R AndersonDepartment of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA 19104 USA.
Gary A KoretzkyPerelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104 USA.
Daniel A HammerDepartment of Bioengineering, University of Pennsylvania, 240 Skirkanich Hall, 210 South 33rd St., Philadelphia, PA 19104 USA.ORCID 0000-0002-3522-3154
University of Pennsylvania · USCancer Research Institute · USMorpho (United States) · USNovartis (Switzerland) · CH

Funding

NIAID NIH HHS R01 AI082292NIGMS NIH HHS R01 GM123019
6 · The paper itself

Abstract

introductionThe arrest of rolling T lymphocytes at specific locations is crucial to proper immune response function. We previously developed a model of chemokine-driven integrin activation, termed integrative signaling adhesive dynamics (ISAD). In addition, we have shown that loss of diacylglycerol kinase (DGK) leads to a gain of function regarding adhesion under shear flow. We undertook this study to understand the sensitivity of adhesion to perturbations in other signaling molecules.

methodsWe adapted multi-parametric sensitivity analysis (MPSA) for use in our ISAD model to identify important parameters, including initial protein concentrations and kinetic rate constants, for T lymphocyte arrest. We also compared MPSA results to those obtained from a single parametric sensitivity analysis.

resultsIn addition to the previously shown importance of DGK in lymphocyte arrest, PIP

conclusionWe show here that the regulation of the amount of second messengers are, in general, more critical for determining T lymphocyte arrest over the initial signaling proteins, highlighting the importance of amplification of signaling in cell adhesion responses. Overall, this work provides a mechanistic insight of the contribution of key pathways and components, thus may help to identify potential therapeutic targets for drug development against immune disorders.

Indexed as

ChemokineFirm arrestLFA-1Sensitivity analysisT lymphocyte

Identifiers

PMID31719909
PMCPMC6816696
OpenAlexW2947726944

What Socratic holds

Textmetadata
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Registered trials

None linked

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 Socratic graph.