Biology subjects

Flores, J. R.

Publications and source records attributed to Flores, J. R..

3 recordsLinked to original sources

bioRxiv2020

Rooting morphologically divergent taxa - slow-evolving sequence data might help

When fossils are sparse and the lineages studied are very divergent morphologically, analyses based exclusively on morphology may lead to conflicting and unexpected hypotheses. Through integration of data from conservative genes/gene regions the terminals including these data can anchor or constrain the search, thereby practically circumscribing the search space of the combined analyses. In this study, we revisit the phylogeny of a highly divergent group of mosses, class Polytrichopsida. We supplemented the morphological matrix by adding sequence data of the nuclear gene 18S, chloroplast genes rbcL and rps4, plus the mitochondrial gene nad5. For the phylogenetic analyses we used parsimony as the optimality criterion. Analyses that included all the terminals resulted in one most parsimonious tree with a clade comprised of Alophosia azorica and the fossil Meantoinea alophosioides representing the basal-most lineage. Analyses with different outgroup sampling produced the same topology for most ingroup relationships. An analysis excluding morphological characters and the four terminals for which only morphological characters were scored (the two fossil and two extant terminals) resulted in one optimal tree with identical topology to the one obtained when including all terminals. These results are largely congruent with those obtained in the recent analyses based exclusively on sequence level data of a larger number of terminals. Our results indicate that large size and complexity of the gametophyte have evolved independently in several lineages. Notably, the nodes of the backbone of the most parsimonious tree have very low support values, thus these inferred relationships could change if new additional information conflicts with the current data. Future studies should be aimed at incorporating all terminals into phylogenetic analyses, which is not an unrealistic goal for a group with less than 200 species. Also, additional fossils, some of which await detailed examination and description, need to be included. Whether these will affect the overall pattern of phylogeny presented here remains to be seen. In a group that is obviously very ancient, we cannot assume, a priori, that currently known fossil taxa, which go back in time less than 140 Ma, represent the oldest lineages of the group.

evolutionary biology↗

bioRxiv2020

Inducible epithelial resistance improves survival of Sendai virus pneumonia in mice by both inactivating virus and preventing CD8+ T cell-mediated immunopathology

Viral pneumonias remain a global health threat necessitating novel strategies to prevent and treat these lower respiratory tract infections. We have reported that mice treated with a combination of inhaled Toll-like receptor (TLR) 2/6 and TLR 9 agonists (Pam2-ODN) are broadly protected against respiratory pathogens. Although a single inhalation of Pam-ODN prevents acute morbidity and chronic complications associated with viral pneumonias, the mechanisms underlying this protection remain incompletely elucidated. Here, we show in a lethal paramyxovirus model that Pam2-ODN-enhanced survival is associated with robust virus inactivation that occurs prior to internalization by lung epithelial cells. However, it was also noted that viral mortality in sham-treated mice temporally corresponded with CD8+ T cell-enriched lung inflammation that peaks after the viral burden wanes. Pam2-ODN treatment also blocked this injurious inflammation, but the attenuation of lymphocytic inflammation and the reduction in virus burden were both lost when inducible reactive oxygen species generation was inhibited. Depleting CD8+ T cells before or after viral challenge underscored the balanced roles of CD8+ T cells in antiviral immunity and fatal immunopathology, but did not obviate the Pam2-ODN antiviral protection. These findings identify multifunctional inducible antiviral mechanisms and may reveal means to protect susceptible individuals against respiratory infections.

immunology↗

bioRxiv2019

Aerosolized TLR Agonists Suppress Acute Sendai Virus Lung Infection and Chronic Airway Disease in Mice

Respiratory viral infections play central roles in the initiation, exacerbation and progression of asthma in humans. An acute paramyxoviral infection in mice can cause a chronic lung disease that resembles human asthma. We sought to determine whether reduction of Sendai virus lung burden in mice by stimulating innate immunity with aerosolized Toll-like receptor (TLR) agonists could attenuate the severity of chronic asthma-like lung disease. Treatment with 1 {micro}M oligodeoxynucleotide (ODN) M362, an agonist of the TLR9 homodimer, and 4 {micro}M Pam2CSK4 (Pam2), an agonist of the TLR2/6 heterodimer, within a few days before or after Sendai virus challenge, resulted in a [~]75% reduction in lung Sendai virus burden five days after challenge. The reduction in acute lung virus burden was associated with marked reductions 49 days after viral challenge in eosinophilic and lymphocytic lung inflammation, airway mucous metaplasia, lumenal mucus occlusion, and hyperresponsiveness to methacholine. Mechanistically, ODN/Pam2 treatment attenuated the chronic asthma phenotype by suppressing IL-33 production by type 2 pneumocytes, both by reducing the severity of acute infection and by downregulating Type 2 (allergic) inflammation. These data suggest that treatment of susceptible human hosts with aerosolized ODN and Pam2 at the time of a respiratory viral infection might attenuate the severity of the acute infection and reduce progression of asthma.\n\nOne Sentence SummaryRespiratory viral infections can induce chronic airway disease, and we find that stimulating innate immunity within the lungs of mice reduces the severity of acute infection and development of a chronic asthma phenotype.

immunology↗