Publications by authors named "Jason A Wykoff"
The severe acute respiratory syndrome coronavirus 2 pandemic is characterized by the emergence of novel variants of concern (VOCs) that replace ancestral strains. Here, we dissect the complex selective pressures by evaluating variant fitness and adaptation in human respiratory tissues. We evaluate viral properties and host responses to reconstruct forces behind D614G through Omicron (BA.
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- Human airway epithelia obtain oxygen from air rather than blood, which makes them susceptible to issues like mucus plugs due to various pulmonary diseases.
- Chronic hypoxia (CH) in airway epithelia has been linked to increased MUC5B mucin production and altered ion absorption, contributing to mucus accumulation and airway obstruction.
- This study reveals that chronic hypoxia may play a significant role in the progression of muco-obstructive lung diseases (MOLDs) by affecting airway remodeling and resulting in further airway damage.
Article Synopsis
- Mucus properties in lung diseases like asthma and cystic fibrosis are altered due to factors like excessive mucus secretion and airway dehydration, impacting respiratory function.
- A new benchtop device called Rheomuco can quickly and easily measure the viscoelastic properties of mucus, providing results in under 5 minutes, which is beneficial for clinical assessments.
- The study validated the device's performance against traditional methods and demonstrated its ability to detect significant changes in mucus consistency, highlighting its potential for optimizing treatments with mucoactive drugs.
Zoonotic transmission of coronaviruses poses an ongoing threat to human populations. Endemic outbreaks of swine acute diarrhea syndrome coronavirus (SADS-CoV) have caused severe economic losses in the pig industry and have the potential to cause human outbreaks. Currently, there are no vaccines or specific antivirals against SADS-CoV, and our limited understanding of SADS-CoV host entry factors could hinder prompt responses to a potential human outbreak.
View Article and Find Full Text PDFMuco-obstructive lung diseases are typically associated with high risks of COVID-19 severity; however, allergic asthma showed reduced susceptibility. To investigate viral spread, primary human airway epithelial (HAE) cell cultures were infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and host–virus interactions were examined via electron microscopy, immunohistochemistry, RNA in situ hybridization, and gene expression analyses. In HAE cell cultures, angiotensin-converting enzyme 2 (ACE2) expression governed cell tropism and viral load and was up-regulated by infection.
View Article and Find Full Text PDFQuestion: Cystic fibrosis (CF) is characterised by the accumulation of viscous adherent mucus in the lungs. While several hypotheses invoke a direct relationship with cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction ( acidic airway surface liquid (ASL) pH, low bicarbonate (HCO ) concentration, airway dehydration), the dominant biochemical alteration of CF mucus remains unknown.
Materials/methods: We characterised a novel cell line (CFTR-KO Calu3 cells) and the responses of human bronchial epithelial (HBE) cells from subjects with G551D or F508del mutations to ivacaftor and elexacaftor-tezacaftor-ivacaftor.