A Unique Cellular Organization of Human Distal Airways and Its Disarray in Chronic Obstructive Pulmonary Disease

Rationale: Remodeling and loss of distal conducting airways, including preterminal and terminal bronchioles (pre-TBs/TBs), underlie progressive airflow limitation in chronic obstructive pulmonary disease (COPD). The cellular basis of these structural changes remains unknown. Objectives: To identify biological changes in pre-TBs/TBs in COPD at single-cell resolution and determine their cellular origin. Methods: We established a novel method of distal airway dissection and performed single-cell transcriptomic profiling of 111,412 cells isolated from different airway regions of 12 healthy lung donors and pre-TBs of 5 patients with COPD. Imaging CyTOF and immunofluorescence analysis of pre-TBs/TBs from 24 healthy lung donors and 11 subjects with COPD were performed to characterize cellular phenotypes at a tissue level. Region-specific differentiation of basal cells isolated from proximal and distal airways was studied using an air-liquid interface model. Measurements and Main Results: The atlas of cellular heterogeneity along the proximal-distal axis of the human lung was assembled and identified region-specific cellular states, including SCGB3A2+ SFTPB+ terminal airway-enriched secretory cells (TASCs) unique to distal airways. TASCs were lost in COPD pre-TBs/TBs, paralleled by loss of region-specific endothelial capillary cells, increased frequency of CD8+ T cells normally enriched in proximal airways, and augmented IFN-γ signaling. Basal cells residing in pre-TBs/TBs were identified as a cellular origin of TASCs. Regeneration of TASCs by these progenitors was suppressed by IFN-γ. Conclusions: Altered maintenance of the unique cellular organization of pre-TBs/TBs, including loss of the region-specific epithelial differentiation in these bronchioles, represents the cellular manifestation and likely the cellular basis of distal airway remodeling in COPD

Optical Light Curves of Supernovae

Photometry is the most easily acquired information about supernovae. The light curves constructed from regular imaging provide signatures not only for the energy input, the radiation escape, the local environment and the progenitor stars, but also for the intervening dust. They are the main tool for the use of supernovae as distance indicators through the determination of the luminosity. The light curve of SN 1987A still is the richest and longest observed example for a core-collapse supernova. Despite the peculiar nature of this object, as explosion of a blue supergiant, it displayed all the characteristics of Type II supernovae. The light curves of Type Ib/c supernovae are more homogeneous, but still display the signatures of explosions in massive stars, among them early interaction with their circumstellar material. Wrinkles in the near-uniform appearance of thermonuclear (Type Ia) supernovae have emerged during the past decade. Subtle differences have been observed especially at near-infrared wavelengths. Interestingly, the light curve shapes appear to correlate with a variety of other characteristics of these supernovae. The construction of bolometric light curves provides the most direct link to theoretical predictions and can yield sorely needed constraints for the models. First steps in this direction have been already made.Comment: To be published in:"Supernovae and Gamma Ray Bursters", Lecture Notes in Physics (http://link.springer.de/series/lnpp

Variants associated withHHIP expression have sex-differential effects on lung function

Background: Lung function is highly heritable and differs between the sexes throughout life. However, little is known about sex-differential genetic effects on lung function. We aimed to conduct the first genome-wide genotype-by-sex interaction study on lung function to identify genetic effects that differ between males and females. Methods: We tested for interactions between 7,745,864 variants and sex on spirometry-based measures of lung function in UK Biobank (N=303,612), and sought replication in 75,696 independent individuals from the SpiroMeta consortium. Results: Five independent single-nucleotide polymorphisms (SNPs) showed genome-wide significant (P</p