Finding the facts in an infodemic: framing effective COVID-19 messages to connect people to authoritative content.

The public's need for timely and trusted COVID-19 information remains high. Governments and global health agencies such as the WHO have sought to disseminate accurate and timely information to counteract misinformation and disinformation that has arisen as part of an 'infodemic'-the overabundance of information on COVID-19-some accurate and some not. In early 2020, WHO began a collaboration with Google to run online public service announcements on COVID-19, in the form of search ads displayed above results of Google Search queries. Web-based text ads can drive online searchers of COVID-19 information to authoritative COVID-19 content but determining what message is most effective is a challenge. WHO wanted to understand which message framing, that is, the way in which ad information is worded for the public, leads searchers to click through to WHO content. WHO tested 71 text ads in English across four COVID-19 topics using a mix of message frames: descriptive, collective, gain, loss, appeals to values and emphasising reasons. Between 11 September 2020 and 23 November 2020, there were 13 million views of the experimental WHO text ads leading to 1.4 million click-throughs to the WHO website. Within the set of 71 ads, there was a large spread between the most effective and least effective messages; for messages on COVID-19, the best performing framings were more than twice as effective as the worst performing framings (18.7% vs 8.5% engagement rate). Health practitioners can apply the messaging tactics WHO found to be successful to rapidly optimise messages for their own public health campaigns and better reach the public with authoritative information. Similar collaboration between big technology companies and governments and global health agencies has the potential to advance public health.

Elastin receptor (S-gal) occupancy by elastin peptides modulates T-cell response during murine emphysema.

Chronic obstructive pulmonary disease and emphysema are associated with increased elastin peptides (EP) production because of excessive breakdown of lung connective tissue. We recently reported that exposure of mice to EP elicited hallmark features of emphysema. EP effects are largely mediated through a receptor complex that includes the elastin-binding protein spliced-galactosidase (S-gal). In previous studies, we established a correlation between cytokine production and S-gal protein expression in EP-treated immune cells. In this study, we investigated the S-gal-dependent EP effects on T-helper (Th) and T-cytotoxic (Tc) responses during murine EP-triggered pulmonary inflammation. C57BL/6J mice were endotracheally instilled with the valine-glycine-valine-alanine-proline-glycine (VGVAPG) elastin peptide, and, 21 days after treatment, local and systemic T-lymphocyte phenotypes were analyzed at cytokine and transcription factor expression levels by multicolor flow cytometry. Exposure of mice to the VGVAPG peptide resulted in a significant increase in the proportion of the CD4+ and CD8+ T cells expressing the cytokines IFN-γ or IL-17a and the transcription factors T-box expressed in T cells or retinoic acid-related orphan receptor-γt (RORγt) without effects on IL-4 and Gata-binding protein 3 to DNA sequence [A/T]GATA[A/G] expression. These effects were maximized when each T-cell subpopulation was challenged ex vivo with EP, and they were inhibited in vivo when an analogous peptide antagonizing the EP/S-gal interactions was instilled together with the VGVAPG peptide. This study demonstrates that, during murine emphysema, EP-S-gal interactions contribute to a Th-1 and Th-17 proinflammatory T-cell response combined with a Tc-1 response. Our study also highlights the S-gal receptor as a putative pharmacological target to modulate such an immune response.

Induction and regulation of murine emphysema by elastin peptides.

Emphysema is the major component of chronic obstructive pulmonary disease (COPD). During emphysema, elastin breakdown in the lung tissue originates from the release of large amounts of elastase by inflammatory cells. Elevated levels of elastin-derived peptides (EP) reflect massive pulmonary elastin breakdown in COPD patients. Only the EP containing the GXXPG conformational motif with a type VIII ß-turn are elastin receptor ligands inducing biological activities. In addition, the COOH-terminal glycine residue of the GXXPG motif seems a prerequisite to the biological activity. In this study, we endotracheally instilled C57BL/6J mice with GXXPG EP and/or COOH-terminal glycine deleted-EP whose sequences were designed by molecular dynamics and docking simulations. We investigated their effect on all criteria associated with the progression of murine emphysema. Bronchoalveolar lavages were recovered to analyze cell profiles by flow cytometry and lungs were prepared to allow morphological and histological analysis by immunostaining and confocal microscopy. We observed that exposure of mice to EP elicited hallmark features of emphysema with inflammatory cell accumulation associated with increased matrix metalloproteinases and desmosine expression and of remodeling of parenchymal tissue. We also identified an inactive COOH-terminal glycine deleted-EP that retains its binding-activity to EBP and that is able to inhibit the in vitro and in vivo activities of emphysema-inducing EP. This study demonstrates that EP are key actors in the development of emphysema and that they represent pharmacological targets for an alternative treatment of emphysema based on the identification of EP analogous antagonists by molecular modeling studies.

Rapid method of quantification of tight-junction organization using image analysis.

The spatial organization of proteins in a cell population or in tissues is an important parameter to study the functionality of biological specimens. In this article, we have focused on tight junctions which form network-like features in immunofluorescence microscopy images. Usually, the organization or disorganization of tight junctions is noticed qualitatively. The aim of this article is to present a simple method to quantify the organization level of tight junction network using image analysis with a dedicated macro developed with Image J software. The method has been validated with simulated images displaying regular decrease of network organization. Then, the macro has been applied to immunofluorescence microscopy images of cells in culture and of tissue sections.