Abstracts from the Virtual Symposium “Signal Transduction at the Blood–Brain Barriers”
Bibliographic record
Abstract
Fluids and Barriers of the CNS 2021, 18(1): A1 COVID-19 is a respiratory disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).COVID-19 pathogenesis causes vascular-mediated neurological disorders via still elusive mechanisms.SARS-CoV-2 infects host cells by binding to angiotensin-converting enzyme 2 (ACE2) that recognizes the viral spike (S) protein.Brain pericytes express ACE2 at the neurovascular interface, outlining their possible implication in microvasculature injury in COVID-19.Yet, pericyte responses to SARS-CoV-2 is not clear.Here we report that ACE2 expression in human brain vascular pericytes is highly dynamic and is increased upon S protein stimulation.Pericytes exposed to S protein underwent phenotypic changes translated by increased expression of contractile and myofibrogenic proteins and an altered intracellular calcium dynamic.Furthermore, S protein induced lipid peroxidation, oxidative and nitrosative stress in pericytes as well as triggered an immune reaction, which was potentiated by hypoxia, a condition associated with vascular comorbidities.S protein exposure combined with hypoxia enhanced the production of pro-inflammatory cytokines.Finally, we found that S protein could reach the mouse brain via the intranasal route and that reactive ACE2-expressing pericytes are recruited to the damaged tissue undergoing fibrotic scarring in a mouse model of cerebral multifocal micro-occlusions.Our data demonstrate that the released S protein is sufficient to mediate pericyte immunoreactivity, which may contribute to microvasculature injury in absence of a productive viral infection.
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How this classification was reachedexpand
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 | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".