Multiple inflammasomes may regulate the interleukin-1-driven inflammation in protracted bacterial bronchitis

Protracted bacterial bronchitis (PBB) in young children is characterised by prolonged wet cough, prominent airway interleukin (IL)-1β expression and infection, often with nontypeable Haemophilus influenzae (NTHi). The mechanisms responsible for IL-1-driven inflammation in PBB are poorly understood. We hypothesised that the inflammation in PBB involves the NLRP3 and/or AIM2 inflammasome/IL-1β axis. Lung macrophages obtained from bronchoalveolar lavage (BAL), peripheral blood mononuclear cells (PBMCs), blood monocytes and monocyte-derived macrophages from patients with PBB and age-matched healthy controls were cultured in control medium or exposed to live NTHi. In healthy adult PBMCs, CD14+ monocytes contributed to 95% of total IL-1β-producing cells upon NTHi stimulation. Stimulation of PBB PBMCs with NTHi significantly increased IL-1β expression (p<0.001), but decreased NLRC4 expression (p<0.01). NTHi induced IL-1β secretion in PBMCs from both healthy controls and patients with recurrent PBB. This was inhibited by Z-YVAD-FMK (a caspase-1 selective inhibitor) and by MCC950 (a NLRP3 selective inhibitor). In PBB BAL macrophages inflammasome complexes were visualised as fluorescence specks of NLRP3 or AIM2 colocalised with cleaved caspase-1 and cleaved IL-1β. NTHi stimulation induced formation of specks of cleaved IL-1β, NLRP3 and AIM2 in PBMCs, blood monocytes and monocyte-derived macrophages. We conclude that both the NLRP3 and AIM2 inflammasomes probably drive the IL-1β-dominated inflammation in PBB.Alice C-H. Chen, Hai B. Tran, Yang Xi, Stephanie T. Yerkovich, Katherine J. Baines, Susan J. Pizzutto, Melanie Carroll, Avril A.B. Robertson, Matthew A. Cooper, Kate Schroder, Jodie L. Simpson, Peter G. Gibson, Greg Hodge, Ian B. Masters, Helen M. Buntain, Helen L. Petsky, Samantha J. Prime, Anne B. Chang, Sandra Hodge, and John W. Upha

Should science educators deal with the science/religion issue?

I begin by examining the natures of science and religion before looking at the ways in which they relate to one another. I then look at a number of case studies that centre on the relationships between science and religion, including attempts to find mechanisms for divine action in quantum theory and chaos theory, creationism, genetic engineering and the writings of Richard Dawkins. Finally, I consider some of the pedagogical issues that would need to be considered if the science/religion issue is to be addressed in the classroom. I conclude that there are increasing arguments in favour of science educators teaching about the science/religion issue. The principal reason for this is to help students better to learn science. However, such teaching makes greater demands on science educators than has generally been the case. Certain of these demands are identified and some specific suggestions are made as to how a science educator might deal with the science/religion issue. © 2008 Taylor & Francis

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

CEDS-SatEM Gridded - Bulk Emissions

Release of gridded greenhouse gas emissions from 2000-2019 based on the 2021_04_21 CEDS release with direct inclusion of point sources as time series. This dataset contains just the primary emissions species covered by CEDS, both at 0.5° and 0.1° spatial resolution. Data for speciated VOC emissions can be found in the companion dataset, DOI 10.5281/zenodo.7526534

CEDS Version 2021-04-21 Aircraft Emissions Fix

This data release contains global CEDS aircraft emissions gridded over a 0.5° latitude x longitude grid, with 25 altitude levels of 0.61 km thickness. The center of these altitude levels range from 0.305 to 14.495 km above sea level. Grids are provided over the years 1950-2019 on a monthly time scale, with the exception of methane, which ranges from 1970-2019

CEDS-SatEM Gridded - Speciated-VOC Emissions

Release of gridded greenhouse gas emissions from 2000-2019 based on the 2021_04_21 CEDS release with direct inclusion of point sources as time series. This dataset contains just the speciated VOC emissions covered by CEDS, both at 0.5° and 0.1° spatial resolution. Data for the CEDS primary emission species can be found in the companion dataset, DOI: 10.5281/zenodo.7526345

'I can actually exercise if I want to; it isn't as hard as I thought' - A qualitative study of the experiences and views of obese adolescents participating in an exercise therapy intervention

A qualitative study nested within a randomized controlled trial explored obese adolescents' experiences of participation in an exercise therapy intervention. Semi- structured interviews were conducted with participants assigned to exercise therapy. Participants' reported feeling more energetic during and after exercise, than before. Many participants reported feeling happy/ happier and expressed feeling better about themselves as individuals after the intervention. Most participants felt more confident in their ability to exercise regularly. Greater emphasis needs to be placed upon educating obese adolescents about the wide range of health benefits that exercise can provide, and that weight loss, while important, is only one such benefit