A pandemic lesson for global lung diseases: exacerbations are preventable.

A dramatic global reduction in the incidence of common seasonal respiratory viral infections has resulted from measures to limit the transmission of SARS2-Cov-19 during the pandemic . This has been accompanied by falls reaching 50% internationally in the incidence of acute exacerbations of pre-existing chronic respiratory diseases that include asthma, Chronic Obstructive Pulmonary Disease (COPD) and Cystic Fibrosis (CF). At the same time, the incidence of acute bacterial pneumonia and sepsis has fallen steeply world-wide. Such findings demonstrate the profound impact of common respiratory viruses on the course of these global illnesses. Reduced transmission of common respiratory bacterial pathogens and their interactions with viruses appear also as central factors. This review summarises pandemic changes in exacerbation rates of asthma, COPD, Cystic Fibrosis (CF) and pneumonia. We draw attention to the substantial body of knowledge about respiratory virus infections in these conditions, and that it has not yet translated into clinical practice. Now the large-scale of benefits that could be gained by managing these pathogens is unmistakable, we suggest the field merits substantial academic and industrial investment. We consider how pandemic-inspired measures for prevention and treatment of common infections should become a cornerstone for managing respiratory diseases. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Thaxtomin A affects CESA-complex density, expression of cell wall genes, cell wall composition, and causes ectopic lignification in Arabidopsis thaliana seedlings

Thaxtomin A, a phytotoxin produced by Streptomyces eubacteria, is suspected to act as a natural cellulose synthesis inhibitor. This view is confirmed by the results obtained from new chemical, molecular, and microscopic analyses of Arabidopsis thaliana seedlings treated with thaxtomin A. Cell wall analysis shows that thaxtomin A reduces crystalline cellulose, and increases pectins and hemicellulose in the cell wall. Treatment with thaxtomin A also changes the expression of genes involved in primary and secondary cellulose synthesis as well as genes associated with pectin metabolism and cell wall remodelling, in a manner nearly identical to isoxaben. In addition, it induces the expression of several defence-related genes and leads to callose deposition. Defects in cellulose synthesis cause ectopic lignification phenotypes in A. thaliana, and it is shown that lignification is also triggered by thaxtomin A, although in a pattern different from isoxaben. Spinning disc confocal microscopy further reveals that thaxtomin A depletes cellulose synthase complexes from the plasma membrane and results in the accumulation of these particles in a small microtubule-associated compartment. The results provide new and clear evidence for thaxtomin A having a strong impact on cellulose synthesis, thus suggesting that this is its primary mode of action

Evidence of immunometabolic dysregulation and airway dysbiosis in athletes susceptible to respiratory illness

Background Respiratory tract infection (RTI) is a leading cause of training and in-competition time-loss in athlete health. The immune factors associated with RTI susceptibility remain unclear. In this study, we prospectively characterise host immune factors in elite athletes exhibiting RTI susceptibility. Methods Peripheral blood lymphocyte flow cytometry phenotyping and 16S rRNA microbial sequencing of oropharyngeal swabs was performed in a prospective elite athlete cohort study (n = 121). Mass cytometry, peripheral blood mononuclear cell (PBMC) stimulation and plasma metabolic profiling was performed in age-matched highly-susceptible (HS) athletes (≥4RTI in last 18 months) (n = 22) compared to non-susceptible (NS) (≤1RTI in last 18 months) (n = 23) athletes. Findings were compared to non-athletic healthy controls (HC) (n = 19). Findings Athletes (n = 121) had a reduced peripheral blood memory T regulatory cell compartment compared to HC (p = 0.02 (95%CI:0.1,1.0)) and reduced upper airway bacterial biomass compared to HC (p = 0.032, effect size r = 0.19). HS athletes (n = 22) had lower circulating memory T regulatory cells compared to NS (n = 23) athletes (p = 0.005 (95%CI:-1.5,-0.15)) and HC (p = 0.002 (95%CI:-1.9,-0.3) with PBMC microbial stimulation assays revealing a T-helper 2 skewed immune response compared to HC. Plasma metabolomic profiling showed differences in sphingolipid pathway metabolites (a class of lipids important in infection and inflammation regulation) in HS compared to NS athletes and HC, with sphingomyelin predictive of RTI infection susceptibility (p = 0.005). Interpretation Athletes susceptible to RTI have reduced circulating memory T regulatory cells, metabolic dysregulation of the sphingolipid pathway and evidence of upper airway bacterial dysbiosis. Funding This study was funded by the English Institute of Sport (UK)

Are Individuals Fickle-Minded?

Game theory has been used to model large-scale social events — such as constitutional law, democratic stability, standard setting, gender roles, social movements, communication, markets, the selection of officials by means of elections, coalition formation, resource allocation, distribution of goods, and war — as the aggregate result of individual choices in interdependent decision-making. Game theory in this way assumes methodological individualism. The widespread observation that game theory predictions do not in general match observation has led to many attempts to repair game theory by creating behavioral game theory, which adds corrective terms to the game theoretic predictions in the hope of making predictions that better match observations. But for game theory to be useful in making predictions, we must be able to generalize from an individual’s behavior in one situation to that individual’s behavior in very closely similar situations. In other words, behavioral game theory needs individuals to be reasonably consistent in action if the theory is to have predictive power. We argue on the basis of experimental evidence that the assumption of such consistency is unwarranted. More realistic models of individual agents must be developed that acknowledge the variance in behavior for a given individual

Anti-Arthritic Activity in Rats of Some Phosphinegold(I) Thionucleobases and Related Thiolates

A number of phosphinegold(I) thiolates where, generally, the thiolate is derived from a thionucleobase, have been screened for anti-arthritic activity in Dark Agouti rats, a gold sensitive model for arthritis. Potency and toxicity data showed that, generally, the Ph3P derivatives and species based on thiopurines were the most effective and that with other complexes enhanced activity was accompanied by greater toxicity