Roles of calpain-calpastatin system (CCS) in human T cell activation
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
// Anna Mikosik 1 , Aleksandra Jasiulewicz 1 , Agnieszka Daca 2 , Izabella Henc 2 , Joanna E. Frąckowiak 1 , Katarzyna Ruckemann-Dziurdzińska 2 , Jerzy Foerster 3 , Aurelie Le Page 4 , Ewa Bryl 2 , Tamas Fulop 4 and Jacek M. Witkowski 1 1 Department of Pathophysiology, Medical University of Gdańsk, Gdańsk, Poland 2 Department of Pathology and Experimental Rheumatology, Medical University of Gdańsk, Gdańsk, Poland 3 Department of Clinical and Social Gerontology, Medical University of Gdańsk, Gdańsk, Poland 4 Research Center on Ageing, University of Sherbrooke, Sherbrooke, Quebec, Canada Correspondence to: Jacek M. Witkowski, email: // Keywords : T cells, calpain, calpastatin, proliferation, cytokines, Immunology and Microbiology Section, Immune response, Immunity Received : August 25, 2016 Accepted : November 02, 2016 Published : November 09, 2016 Abstract The immune response is determined by the speed of the T cell reaction to antigens assured by a state of readiness for proliferation and cytokine secretion. Proliferation, apoptosis and motion of many cell types are controlled by cytoplasmic proteases - µ- and m-calpain - and their inhibitor calpastatin, together forming the “calpain-calpastatin system” (CCS), assumed to modify their targets only upon activation-dependent cytoplasmic Ca 2+ increase. Contrastingly to this notion, using quantitative real time PCR and semiquantitative flow cytometry respectively, we show here that the CCS genes are constitutively expressed, and that both calpains are constitutively active in resting, circulating human CD4 + and CD8 + lymphocytes. Furthermore, we demonstrate that calpain inhibition in the resting T cells prevents them from proliferation in vitro and greatly reduces secretion of multiple cytokines. The mechanistic reason for these effects of calpain inhibition on T cell functions might be the demonstrated significant reduction of the expression of active (phosphorylated) upstream signalling molecules, including the phospholipase C gamma, p56Lck and NFκB, in the inhibitor-treated cells. Thus, we propose that the constitutive, self-regulatory calpain-calpastatin system activity in resting human T cells is a necessary, controlling element of their readiness for complex and effective response to antigenic challenge.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it