Single-cell RNA sequencing uncovers the nuclear decoy lincRNA PIRAT as a regulator of systemic monocyte immunity during COVID-19

The systemic immune response to viral infection is shaped by master transcription fac-tors, such as NF-κB, STAT1, or PU.1. Although long noncoding RNAs (lncRNAs)have been suggested as important regulators of transcription factor activity, their contri-butions to the systemic immunopathologies observed during SARS-CoV-2 infectionhave remained unknown. Here, we employed a targeted single-cell RNA sequencingapproach to reveal lncRNAs differentially expressed in blood leukocytes during severeCOVID-19. Our results uncover the lncRNA PIRAT (PU.1-induced regulator of alar-min transcription) as a major PU.1 feedback-regulator in monocytes, governing the pro-duction of the alarmins S100A8/A9, key drivers of COVID-19 pathogenesis. Knockoutand transgene expression, combined with chromatin-occupancy profiling, characterizedPIRATasanucleardecoyRNA,keepingPU.1frombindingtoalarminpromotersandpromoting its binding to pseudogenes in naïve monocytes. NF-κB–dependent PIRATdown-regulation during COVID-19 consequently releases a transcriptional brake, fuelingalarmin production. Alarmin expression is additionally enhanced by the up-regulation ofthe lncRNA LUCAT1, which promotes NF-κB–dependentgeneexpressionattheexpenseof targets of the JAK-STAT pathway. Our results suggest a major role of nuclear noncod-ing RNA networks in systemic antiviral responses to SARS-CoV-2 in humans

ADAM8 signaling drives neutrophil migration and ARDS severity

Acute respiratory distress syndrome (ARDS) results in catastrophic lung failure and has an urgent, unmet need for improved early recognition and therapeutic development. Neutrophil influx is a hallmark of ARDS and is associated with the release of tissue-destructive immune effectors, such as matrix metalloproteinases (MMPs) and membrane-anchored metalloproteinase disintegrins (ADAMs). Here, we observed using intravital microscopy that Adam8–/– mice had impaired neutrophil transmigration. In mouse pneumonia models, both genetic deletion and pharmacologic inhibition of ADAM8 attenuated neutrophil infiltration and lung injury while improving bacterial containment. Unexpectedly, the alterations of neutrophil function were not attributable to impaired proteolysis but resulted from reduced intracellular interactions of ADAM8 with the actin-based motor molecule Myosin1f that suppressed neutrophil motility. In 2 ARDS cohorts, we analyzed lung fluid proteolytic signatures and identified that ADAM8 activity was positively correlated with disease severity. We propose that in acute inflammatory lung diseases such as pneumonia and ARDS, ADAM8 inhibition might allow fine-tuning of neutrophil responses for therapeutic gain

Introduction

In his authoritative history on The Chemical Industry 1900-1930, the economic historian L. F. Haber summed up the role of the Solvay company: "Solvay’s own enterprises were relatively small, but their interests and connections within Belgium as well as outside were extensive." He continued: "A comprehensive history of Solvay is badly needed and would fill a major gap in our knowledge of the development of the European chemical industry."1 This book fills that gap. Solvay and its history stand out for several reasons. During most of its 150 years of existence Solvay remained one of the leaders in its fields, but, more interesting, it also was one of the earliest multinational, or "polynational,"2 groups, as well as being a family-controlled firm up to the present time. These two features taken together make the company unique in the chemical industry, and perhaps even among businesses more generally.Moreover, the influence of the Solvay family - as well as the company - extends far beyond the realm of business. Solvay has lent its name to a number of initiatives in the field of science and education, particularly to the famous international conferences on physics and chemistry that have been organized since 1911. In its home country Solvay is an icon, being one of the last independent crown jewels from when Belgium was the second most industrialized country in the world. The large number of institutes, schools, and streets named after Solvay in Belgium illustrates the enduring impact of Solvay’s legacy to that small nation. Paradoxically, the resilient tradition of secrecy that lay at the core of the company’s technological success has long hindered a better understanding of its multiple lives. The present book aims to end that obscurity

Validierung einer Skala zur Messung der Reizsensibilität von Schülerinnen und Schülern

In der Bildungsforschung besteht derzeit eine Forschungslücke hinsichtlich interindividueller Unterschiede in der Reizsensibilität. Dieses Temperamentsmerkmal ist durch Besonderheiten in der Aufmerksamkeit auf innere und äußere Reize gekennzeichnet und daher in Lern- und Leistungssituationen von Bedeutung. Die Entwicklung einer für Schüler geeigneten Reizsensibilitätsskala ist ein erster Schritt zur Überbrückung der Forschungslücke. Vierhundertsechzig Haupt- und Realschüler bearbeiteten die neue Reizsensibilitätsskala sowie Validierungsmaße (z.B. schulisches und wissenschaftliches Interesse, Selbstwirksamkeitserwartung). Konfirmatorische Faktorenanalysen bestätigten die Aufteilung der Reizsensibilität in die zwei korrelierten Faktoren Reizoffenheit und Überreizbarkeit. Daneben verweisen theoretisch sinnvolle Zusammenhänge der Subskalen Reizoffenheit und Überreizbarkeit mit den Validierungskriterien auf die Validität des neuen Messinstruments