Airway derived emphysema-specific alveolar type II cells exhibit impaired regenerative potential in COPD.

Emphysema, the progressive destruction of gas exchange surfaces in the lungs, is a hallmark of chronic obstructive pulmonary disease (COPD) that is presently incurable. This therapeutic gap is largely due to a poor understanding of potential drivers of impaired tissue regeneration, such as abnormal lung epithelial progenitor cells, including alveolar type II (ATII) and airway club cells. We discovered an emphysema-specific sub-population of ATII cells located in enlarged distal alveolar sacs, termed asATII cells. Single cell RNA-seq and in situ localisation revealed that asATII cells co-express the alveolar marker surfactant protein C (SPC) and the club cell marker secretaglobin-3A2 (SCGB3A2). A similar ATII sub-population derived from club cells was also identified in mouse COPD models using lineage labeling. Human and mouse ATII sub-populations formed 80-90% fewer alveolar organoids than healthy controls, indicating reduced progenitor function. Targeting asATII cells or their progenitor club cells could reveal novel COPD treatment strategies.

The µ2 and λ1 Proteins of Mammalian Reovirus Modulate Early Events Leading to Induction of the Interferon Signaling Network.

It has been previously shown that amino acid polymorphisms in reovirus proteins µ2 and λ1 are associated with differing levels of interferon induction. In the present study, viruses carrying these polymorphisms in either or both proteins, were further studied. The two viral determinants exert a synergistic effect on the control of ß-interferon induction at the protein and mRNA level, with a concomitant increase in RIG-I. In contrast, levels of phospho-Stat1 and interferon-stimulated genes are increased in singly substituted viruses but with no further increase when both substitutions were present. This suggests that the viral determinants are acting during initial events of viral recognition. Accordingly, difference between viruses was reduced when infection was performed with partially uncoated virions (ISVPs) and transfection of RNA recovered from early-infected cells recapitulates the differences between viruses harboring the different polymorphisms. Altogether, the data are consistent with a redundant or complementary role of µ2 and λ1, affecting either early disassembly or the nature of the viral RNA in the incoming viral particle. Proteins involved in viral RNA synthesis are thus involved in this likely critical aspect of the ability of different reovirus variants to infect various cell types, and to discriminate between parental and transformed/cancer cells.

Colorimetric evaluation of facial skin and free flap donor sites in various ethnic populations.

OBJECTIVE: To determine the optimal colour match for free tissue donor sites transferred to defects of the cheek and neck in a multicultural population. DESIGN: A prospective measurement of the colour of potential free flap donor sites and recipient sites in healthy volunteers. SETTING: A tertiary care academic health science centre. METHODS: Sixty-four healthy volunteers (Caucasian, black, South Asian, Southeast Asian) underwent noninvasive skin colour measurement of the cheek and neck, as well as a standard set of potential free tissue donor sites using a Minolta CR 300 (Konica-Minolta Canada; Markham, ON, Canada) chromameter. MAIN OUTCOME MEASURES: Measurement was done using derived colour measurements based on the Commission Internationale de l'Eclairage or International Commission on Light (CIE) L*a*b* tristimulus values. E* is a derived value of colour difference between sites using the L*a*b* measures. Statistical analysis was done using the Wilcoxon signed rank test. RESULTS: Variations exist between optimal donor sites in individuals of different ethnic backgrounds. Mean E* values suggest that in Caucasians, Southeast Asians, and South Asians, the upper extremity and trapezius flaps most closely approximate the recipient sites. In blacks, the variation in mean E* values is small and a wide variety of flaps provide a colour match to the cheek and neck. Luminance values support the observations regarding E*. DISCUSSION: Wide variations exist between individuals of different ethnic backgrounds in terms of optimal donor sites for the best colour match to surgical defects of the cheek and neck. In Caucasians, it appears that upper extremity sites, including the forearm and lateral arm flaps, provide the best colour match. Similar observations can be made in South Asians and Southeast Asians, with upper extremity flaps providing the best colour match. In blacks, there does not seem to be much variation in colour across the commonly used donor site, and a larger panel of flaps will provide an appropriate colour match in this subset of patients.