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Record W3095430612 · doi:10.1038/s41467-020-19145-6

ACE2 localizes to the respiratory cilia and is not increased by ACE inhibitors or ARBs

2020· article· en· W3095430612 on OpenAlexfundno aff
Ivan T. Lee, Tsuguhisa Nakayama, Chien-Ting Wu, Yury Goltsev, Sizun Jiang, Phillip A. Gall, Chun‐Kang Liao, Liang-Chun Shih, Christian M. Schürch, David R. McIlwain, Pauline Chu, Nicole A. Borchard, David Zarabanda, Sachi S. Dholakia, Angela Yang, Dayoung Kim, Han Chen, Tomoharu Kanie, Chia-Der Lin, Ming-Hsui Tsai, Katie M. Phillips, Raymond Kim, Jonathan B. Overdevest, Matthew A. Tyler, Carol H. Yan, Chih-Feng Lin, Yi-Tsen Lin, Da‐Tian Bau, Gregory J. Tsay, Zara M. Patel, Yung-An Tsou, Alexandar Tzankov, Matthias S. Matter, Chih‐Jaan Tai, Te‐Huei Yeh, Peter H. Hwang, Garry P. Nolan, Jayakar V. Nayak, Peter K. Jackson

Bibliographic record

VenueNature Communications · 2020
Typearticle
Languageen
FieldMedicine
TopicSARS-CoV-2 and COVID-19 Research
Canadian institutionsnot available
FundersStanford Maternal and Child Health Research InstituteNational Institute of Allergy and Infectious DiseasesNational Institute of General Medical SciencesHamilton Health Sciences FoundationDefence Science and Technology LaboratoryNational Institutes of HealthSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungU.S. Food and Drug AdministrationParker Institute for Cancer ImmunotherapyUniversity of BernCalifornia Institute for Regenerative MedicineNational Institute of Diabetes and Digestive and Kidney DiseasesBill and Melinda Gates FoundationNational Cancer InstituteNational Science Foundation
KeywordsCiliumAngiotensin-converting enzyme 2ReceptorMotile ciliumRespiratory systemTropismTissue tropismAirwayBiologyPathogenesisImmunologyMedicineDiseaseCell biologyCoronavirus disease 2019 (COVID-19)VirusPathologyInternal medicineInfectious disease (medical specialty)

Abstract

fetched live from OpenAlex

The coronavirus SARS-CoV-2 is the causative agent of the ongoing severe acute respiratory disease pandemic COVID-19. Tissue and cellular tropism is one key to understanding the pathogenesis of SARS-CoV-2. We investigate the expression and subcellular localization of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), within the upper (nasal) and lower (pulmonary) respiratory tracts of human donors using a diverse panel of banked tissues. Here, we report our discovery that the ACE2 receptor protein robustly localizes within the motile cilia of airway epithelial cells, which likely represents the initial or early subcellular site of SARS-CoV-2 viral entry during host respiratory transmission. We further determine whether ciliary ACE2 expression in the upper airway is influenced by patient demographics, clinical characteristics, comorbidities, or medication use, and show the first mechanistic evidence that the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs) does not increase susceptibility to SARS-CoV-2 infection through enhancing the expression of ciliary ACE2 receptor. These findings are crucial to our understanding of the transmission of SARS-CoV-2 for prevention and control of this virulent pathogen.

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.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.010

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0030.001

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.

Opus teacher head0.069
GPT teacher head0.386
Teacher spread0.317 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations258
Published2020
Admission routes1
Has abstractyes

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