Editorial: Pannexin and connexin signaling in cell death and tissue health and disease
Bibliographic record
Abstract
Editorial on the Research Topic Pannexin and connexin signaling in cell death and tissue health and diseaseThis Research Topic of Frontiers in Cell and Developmental Biology, "Pannexin and connexin signaling in cell death and tissue health and disease," brings together seven new articles exemplifying the role of connexin and pannexin signaling in human health, with the aim of increasing understanding of the biology of this area and feeding into work developing novel related therapies.The first time that gap junctions were associated with a human disease was in 1966, when Loewenstein and Kanno observed a lack of gap junctional intercellular communication between liver cancer cells (Loewenstein and Kanno, 1966).During the following five decades, this association has been confirmed in many in vitro and in vivo models; however, there is yet no clear answer about the precise molecular involvement of gap junctions and their constitutive proteins, the connexins, in tumor progression.How connexins are involved in cancer cell growth and/or invasion is still an open question, whose possible answers depend on tumor stage and cancer type.The lack of clear molecular mechanisms linking connexin signaling to cancer is probably due to the complexity of the disease evolution and heterogeneity of its microenvironment (Aasen et al., 2019).Since the seminal observation of Loewenstein and Kanno, it took almost 30 years to causally link connexin gene mutations to a human disease (in X-linked Charcot-Marie-Tooth disease) outside the cancer field (Bergoffen et al., 1993).This finding was unexpected, as the particular connexin, Connexin32 (Cx32), which was thought to be an epithelialspecific connexin, was identified in Schwann cells with a critical role in myelin maintenance.This work inspired the description of many more connexin-related genetic diseases, growing over 20 years, with the parallel discovery of new connexin isoforms, establishing connexins as members of a multigene family.Connexin mutations are now known to cause a wide range of genetic diseases affecting hearing (cochlea), skin keratinization, heart function, lens transparency, etc., (Srinivas et al., 2018).Many of these discoveries were confirmed by the increased use of transgenic strategies in mice permitting visualization of the pathophysiological effects of modulating connexin expression.In parallel, investigations of connexin function and biology showed that at least some connexins could not only mediate direct intercellular communication through gap junctions, but also communicate between intracellular and extracellular domains through unopposed connexin channels (connexons) in the plasma membrane.This so-called hemichannel
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.006 | 0.015 |
| Meta-epidemiology (narrow) | 0.004 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.003 |
| Bibliometrics | 0.004 | 0.001 |
| Science and technology studies | 0.003 | 0.002 |
| Scholarly communication | 0.007 | 0.004 |
| Open science | 0.003 | 0.003 |
| Research integrity | 0.022 | 0.017 |
| Insufficient payload (model declined to judge) | 0.028 | 0.015 |
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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".