Biology subjects

McGargill, M. A.

Publications and source records attributed to McGargill, M. A..

3 recordsLinked to original sources

bioRxiv2025

Discovery Stack Pilot: Feasibility and Outcomes of a Scientist-Designed Peer Review Model Separating Quality and Impact

Peer review serves as the cornerstone of scientific quality control. Yet, the current journal-centric system is hindered by long timelines, high publication costs, inconsistent review quality, systemic biases, and editorial gatekeeping. Notably, the system relies on misaligned measures of impact that are tethered to journal branding and conflate scientific rigor (Quality) with perceived significance (Impact). Here, we report findings from the Discovery Stack Pilot Study, which tested a scientist-designed, journal-independent peer review model. The Discovery Stack model integrates in-line reviewer comments to promote constructive feedback and separately evaluates scientific Quality and Impact using defined criteria. To examine feasibility and effectiveness, manuscripts were reviewed in parallel with traditional journal review. A total of 162 reviews were completed, and survey data from 86 participants were analyzed. The results showed that reviewers effectively evaluated Quality and Impact as separate dimensions, with Quality scores being more consistent across reviewers than Impact scores. Participants strongly supported the core elements of the Discovery Stack model and expressed enthusiasm for its broader adoption to enhance transparency, efficiency, and value in peer review. Future studies will explore integrating this model into a digital platform for reviewing and curating scientific discoveries to improve the production and dissemination of high-quality research.

scientific communication and education↗

bioRxiv2023

Utility of nasal swabs for assessing mucosal immune responses towards SARS-CoV-2

SARS-CoV-2 has caused millions of infections worldwide since its emergence in 2019. Understanding how infection and vaccination induce mucosal immune responses and how they fluctuate over time is important, especially since they are key in preventing infection and reducing disease severity. We established a novel methodology for assessing SARS-CoV-2 cytokine and antibody responses at the nasal epithelium by using nasopharyngeal swabs collected longitudinally before and after either SARS-CoV-2 infection or vaccination. We then compared responses between mucosal and systemic compartments. We demonstrate that cytokine and antibody profiles differ markedly between compartments. Nasal cytokines show a wound healing phenotype while plasma cytokines are consistent with pro-inflammatory pathways. We found that nasal IgA and IgG have different kinetics after infection, with IgA peaking first. Although vaccination results in low nasal IgA, IgG induction persists for up to 180 days post-vaccination. This research highlights the importance of studying mucosal responses in addition to systemic responses to respiratory infections to understand the correlates of disease severity and immune memory. The methods described herein can be used to further mucosal vaccine development by giving us a better understanding of immunity at the nasal epithelium providing a simpler, alternative clinical practice to studying mucosal responses to infection. TeaserA nasopharyngeal swab can be used to study the intranasal immune response and yields much more information than a simple viral diagnosis.

immunology↗

bioRxiv2020

Broadly reactive influenza antibodies are not limited by germinal center competition with high affinity antibodies

Enhancing the generation of broadly reactive influenza antibodies is a pertinent goal towards developing a universal influenza vaccine. While antibodies that bind conserved influenza epitopes have been identified in humans, the frequency of these antibodies is typically very low. The predominant theory is that antibodies specific for conserved influenza epitopes are limited in germinal centers by competition with high affinity antibodies specific for the variable region of the virus. Here, we show that reducing germinal center formation and removing competition with high affinity antibodies was not sufficient to increase broadly reactive influenza antibodies or enhance protection against distinct influenza subtypes. These data disprove the prevailing hypothesis that broadly reactive influenza antibodies are rare due to competition in germinal centers. Additionally, levels of IgM antibodies specific for the variable region of HA persisted in mice in the absence of germinal centers, further demonstrating that immunodominance can be established independent of germinal centers. Our data also highlight the protective capacity of germinal center-independent IgM antibodies, which are not typically considered when testing correlates of protection, and offer an alternate target for delivering a universal influenza vaccine. IMPORTANCEIt is estimated that 250,000 - 650,000 individuals worldwide die each year from seasonal influenza infections. Current vaccines provide little protection against newly emerging strains. Thus, considerable effort is focused on enhancing the generation of broadly reactive influenza antibodies in order to develop a universal influenza vaccine. However, broadly reactive antibodies are rare and the factors that limit their generation are not completely understood. Our data disprove the prevailing hypothesis that broadly reactive influenza antibodies are rare due to completion in the germinal centers with antibodies to the variable HA head. Understanding the factors limiting antibodies specific for conserved regions of the influenza virus is imperative for developing a universal vaccine, which could potentially circumvent a global pandemic

immunology↗