Synthesis of phosphatidic acids via cobalt(salen) catalyzed epoxide ring-opening with dibenzyl phosphate

With a CoIII(salen)OTs catalyst, dibenzyl phosphate ring-opens a variety of terminal epoxides with excellent regio-selectively and yields up to 85%. The reaction is used in a highly efficient synthesis of enantiopure mixed-diacyl phosphatidic acids, including a photoswitchable phosphatidic acid mimic

Periostin:contributor to abnormal airway epithelial function in asthma?

Periostin may serve as a biomarker for type-2-mediated eosinophilic airway inflammation in asthma. We hypothesised that type-2 cytokine IL-13 induces airway epithelial expression of periostin, which in turn contributes to epithelial changes observed in asthma.We studied the effect of IL-13 on periostin expression in BEAS-2B and air-liquid interface (ALI)-differentiated primary bronchial epithelial cells (PBECs). Additionally, effects of recombinant human periostin on epithelial-to-mesenchymal transition (EMT) markers and mucin genes were assessed. In bronchial biopsies and induced sputum from asthma patients and healthy controls, we analysed periostin single cell gene expression and protein levels.IL-13 increased POSTN expression in both cell types, which was accompanied by EMT-related features in BEAS-2B. In ALI-differentiated PBECs, IL-13 increased periostin basolateral and apical release. Apical administration of periostin increased the expression of MMP9, MUC5B and MUC5AC In bronchial biopsies, POSTN expression was mainly confined to basal epithelial cells, ionocytes, endothelial cells and fibroblasts, showing higher expression in basal epithelial cells from asthma patients versus controls. Higher protein levels of periostin, expressed in epithelial and subepithelial layers, was confirmed in bronchial biopsies from asthma patients compared to healthy controls. Although sputum periostin levels were not higher in asthma, levels correlated with eosinophil numbers and coughing up mucus.Periostin expression is increased by IL-13 in bronchial epithelial cells and higher in bronchial biopsies from asthma patients. This may have important consequences, as administration of periostin increased epithelial expression of mucin genes, supporting the relationship of periostin with type-2 mediated asthma and mucus secretion

Importance of Warping in Beams with Narrow Rectangular Cross-Sections: An Analytical, Numerical and Experimental Flexible Cross-Hinge Case Study

This paper reports on the significance of warping deformation on the stability analysis of a flexible cross-hinge mechanism, which consists of two leaf springs with rectangular cross-section. The effect of misalignments in this mechanism is studied analytically, numerically and experimentally. An analytical buckling analysis is carried out to determine the theoretical critical load of a generalized cross-hinge mechanism on the basis of first principles. A geometrically nonlinear beam finite element with a non-uniform torsion description is used to model the leaf springs numerically. The change in natural mode frequencies and stiffness as a function of the misalignment is determined by a multibody program. Measurements from a dedicated experimental set-up confirm that the inclusion of warping effects is crucial, even for narrow rectangular cross-sections: it is found that the effects of warping increase the analytical critical buckling load of the system by 55%

A cellular census of human lungs identifies novel cell states in health and in asthma.

Human lungs enable efficient gas exchange and form an interface with the environment, which depends on mucosal immunity for protection against infectious agents. Tightly controlled interactions between structural and immune cells are required to maintain lung homeostasis. Here, we use single-cell transcriptomics to chart the cellular landscape of upper and lower airways and lung parenchyma in healthy lungs, and lower airways in asthmatic lungs. We report location-dependent airway epithelial cell states and a novel subset of tissue-resident memory T cells. In the lower airways of patients with asthma, mucous cell hyperplasia is shown to stem from a novel mucous ciliated cell state, as well as goblet cell hyperplasia. We report the presence of pathogenic effector type 2 helper T cells (TH2) in asthmatic lungs and find evidence for type 2 cytokines in maintaining the altered epithelial cell states. Unbiased analysis of cell-cell interactions identifies a shift from airway structural cell communication in healthy lungs to a TH2-dominated interactome in asthmatic lungs.This work was funded by OpenTargets, an open innovation public-private partnership (http://www.opentargets.org), a GlaxoSmithKline collaborative agreement with University Medical Center Groningen, Wellcome (WT206194), EMBO and HFSP Long Term fellowships to R. Vento-Tormo, the Marie Curie ENLIGHT-TEN training network for Tomas Gomes, the Lung Foundation Netherlands (projects no 5.1.14.020 and 4.1.18.226), and Health-Holland, Top Sector Life Sciences & Health. LMS acknowledges funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 753039, HBS acknowledges funding by the Helmholtz Association and the German Center for Lung Research (DZL). F.J.T. acknowledges financial support by the German Research Foundation (DFG) within the Collaborative Research Centre 1243, Subproject A17, by the Helmholtz Association (Incubator grant sparse2big, grant number ZT-I-0007) and by the Chan Zuckerberg Initiative DAF (advised fund of Silicon Valley Community Foundation), grant number 182835

vieira19_Nasal_anonymised-processed.csv

Nasal Datase