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In the original article, there was an error. Justine Mbabazi was named instead of Justine Uvuza in the Acknowledgments. The corrected paragraph appears below. “Without the interest from a number of women leaders in Rwanda and Bangladesh, this work would not have been possible.We express our thanks to the seven women who provided the written statements on which this study is based: Baby Rani Karmakar, Colette Nyinawumuntu, Dimitrie Sissi Mukanyiligira, Jebunnessa, Justine Uvuza, Rosette Adera, and Tajkera Khair.” The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.

© Copyright © 2020 Randell and Yerbury. This paper is developed from qualitative data exploring the metaphors used to describe women’s leadership in differing cultural contexts. Metaphors are a useful communication tool, allowing us to understand an idea or concept through some other phenomenon. Understandably, studies of metaphor tend to focus on metaphors deriving from the English language and from Western cultures. Our everyday language literature abounds with metaphors that evoke images of the masculine – including of machines, war and fighting, competition, games and sport. Leadership is generally thought of as “a good thing,” as something important, carried out by people with desirable attributes, such as courage and insight, or with attractive personalities and good communication skills. Metaphors used in discussing women’s leadership in many countries may support this approach, but they do so by highlighting the obstacles women face, for example, the glass ceiling, glass cliff, sticky floors, and the labyrinth. This study attempts to break the mold, investigating the understanding of women’s leadership as expressed in metaphors that is contextualized differently across the continents. Taking an interpretive approach, this study seeks to present leadership through the understanding of female leaders involved in the field of education broadly defined, from Rwanda and Bangladesh, who gave accounts of their metaphorical conceptualisation of leadership. Using narrative analysis, these accounts were analyzed to identify and interpret the metaphors emerging from descriptions of leadership experiences. The analysis shows that these leaders used metaphors determined by a dynamic interplay of personal, situational, and cultural factors. Somewhat surprisingly, the metaphors used to present leadership are not always based on a local cultural context, with some explicitly including references to European plants, which could be considered exotic. However, they are not metaphors that fit neatly into the taxonomies recognized in the literature. This study makes an important contribution to the literature on leadership, especially leadership in education. It is one of the few studies focussing on the stories of women from a non-Western background. The pool of case studies presented here is limited, but these metaphors represent thinking tools enabling a scholarly and imaginative understanding of women’s leadership in education.

Objectives: Smoking is a common risk factor for chronic obstructive pulmonary disease (COPD) and lung cancer. Although COPD patients have higher risk of lung cancer compared to non-COPD smokers, the molecular links between these diseases are not well-defined. This study aims to identify genes that are downregulated by cigarette smoke and commonly repressed in COPD and lung cancer. Materials and methods: Primary human airway epithelial cells (HAEC) were exposed to cigarette-smoke-extract (CSE) for 10-weeks and significantly suppressed genes were identified by transcriptome array. Epigenetic abnormalities of these genes in lung adenocarcinoma (LUAD) from patients with or without COPD were determined using genome-wide and gene-specific assays and by in vitro treatment of cell lines with trichostatin-A or 5-aza-2-deoxycytidine. Results: The ten most commonly downregulated genes following chronic CSE exposure of HAEC and show promoter hypermethylation in LUAD were selected. Among these, expression of CCNA1, SNCA, and ZNF549 was significantly reduced in lung tissues from COPD compared with non-COPD cases while expression of CCNA1 and SNCA was further downregulated in tumors with COPD. The promoter regions of all three genes were hypermethylated in LUAD but not normal or COPD lungs. The reduced expression and aberrant promoter hypermethylation of these genes in LUAD were independently validated using data from the Cancer Genome Atlas project. Importantly, SNCA and ZNF549 methylation detected in sputum DNA from LUAD (52% and 38%) cases were more prevalent compared to cancer-free smokers (26% and 15%), respectively (p < 0.02). Conclusions: Our data show that suppression of CCNA1, SNCA, and ZNF549 in lung cancer and COPD occurs with or without promoter hypermethylation, respectively. Detecting methylation of these and previously identified genes in sputum of cancer-free smokers may serve as non-invasive biomarkers for early detection of lung cancer among high risk smokers including COPD patients.

The airways of the lungs are lined by ciliated and secretory epithelial cells important for mucociliary clearance. When these cells are damaged or lost, they are replaced by the differentiation of basal stem cells. Little is known about how this repair is orchestrated by signaling pathways in the epithelium and underlying stroma. We present evidence using cultured airway cells and genetic manipulation of a mouse model of airway repair that the cytokine IL-6 promotes the differentiation of ciliated vs. secretory cells. This process involves direct Stat3 regulation of genes controlling both cell fate (Notch1) and the differentiation of multiciliated cells (Multicilin and forkhead box protein J1). Moreover, the major producer of IL-6 appears to be mesenchymal cells in the stroma rather than immune cells.

Cystic Fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR). Newly developed “correctors” such as lumacaftor (VX-809) that improve CFTR maturation and trafficking and “potentiators” such as ivacaftor (VX-770) that enhance channel activity may provide important advances in CF therapy. Although VX-770 has demonstrated substantial clinical efficacy in the small subset of patients with a mutation (G551D) that affects only channel activity, a single compound is not sufficient to treat patients with the more common CFTR mutation, ΔF508. Thus, patients with ΔF508 will likely require treatment with both correctors and potentiators to achieve clinical benefit. However, whereas the effectiveness of acute treatment with this drug combination has been demonstrated in vitro, the impact of chronic therapy has not been established. In studies of human primary airway epithelial cells, we found that both acute and chronic treatment with VX-770 improved CFTR function in cells with the G551D mutation, consistent with clinical studies. In contrast, chronic VX-770 administration caused a dose-dependent reversal of VX-809-mediated CFTR correction in ΔF508 homozygous cultures. This result reflected the destabilization of corrected ΔF508 CFTR by VX-770, dramatically increasing its turnover rate. Chronic VX-770 treatment also reduced mature wild-type CFTR levels and function. These findings demonstrate that chronic treatment with CFTR potentiators and correctors may have unexpected effects that cannot be predicted from short-term studies. Combining of these drugs to maximize rescue of ΔF508 CFTR may require changes in dosing and/or development of new potentiator compounds that do not interfere with CFTR stability.

In the early 1900s, old-growth baldcypress (Taxodium distichum) was completely logged out of what is now the Manchac Wildlife Management Area, located in the Lake Pontchartrain Basin, Louisiana. Natural regeneration of swamp did not occur; the area is currently dominated by bulltongue (Sagittaria lancifolia) marsh. This study was conducted to isolate the major factors prohibiting cypress restoration. Specifically, four hundred baldcypress seedlings were planted in a three-way factorial treatment arrangement that included nutrient augmentation (fertilized vs. unfertilized), management of entangling vegetation (managed vs. unmanaged), herbivore protection (Tubex tree shelters, PVC sleeves, Tanglefoot), and elevation (included as a covariable). Highly significant differences in diameter growth were found for all main effects. For the herbivore protection treatment, relatively inexpensive PVC sleeves were as effective as Tubex Tree Shelters; unprotected trees experienced 100% mortality. Seedlings that received Osmocote 18-6-12 fertilizer showed nearly a two-fold increase in diameter growth. Similarly, seedlings that were managed grew nearly two times greater in diameter than unmanaged seedlings. However, seedlings that wereunmanaged grew nearly two times greater in height than managed seedlings. This study indicates that biotic factors are primarily responsible for the lack of cypress regeneration in southeastern Louisiana, not the prevalent, but largely untested, hypothesis of salt-water intrusion. Moreover, it is likely that, with a combination of management techniques, it is possible to restore swamp habitat in this area. Though labor intensive in the short run (i.e., first few years), once established, these trees may survive for hundreds of years.

The combination of irradiated fibroblast feeder cells and Rho kinase inhibitor, Y-27632, conditionally induces an indefinite proliferative state in primary mammalian epithelial cells. These conditionally reprogrammed cells (CRCs) are karyotype-stable and nontumorigenic. Because self-renewal is a recognized property of stem cells, we investigated whether Y-27632 and feeder cells induced a stem-like phenotype. We found that CRCs share characteristics of adult stem cells and exhibit up-regulated expression of α6 and β1 integrins, ΔNp63α, CD44, and telomerase reverse transcriptase, as well as decreased Notch signaling and an increased level of nuclear β-catenin. The induction of CRCs is rapid (occurs within 2 d) and results from reprogramming of the entire cell population rather than the selection of a minor subpopulation. CRCs do not overexpress the transcription factor sets characteristic of embryonic or induced pluripotent stem cells (e.g., Sox2, Oct4, Nanog, or Klf4). The induction of CRCs is also reversible, and removal of Y-27632 and feeders allows the cells to differentiate normally. Thus, when CRCs from ectocervical epithelium or tracheal epithelium are placed in an air–liquid interface culture system, the cervical cells form a well differentiated stratified squamous epithelium, whereas the tracheal cells form a ciliated airway epithelium. We discuss the diagnostic and therapeutic opportunities afforded by a method that can generate adult stem-like cells in vitro without genetic manipulation.

Wnt–β-catenin signaling regulates cell fate during organ development and postnatal tissue maintenance, but its contribution to specification of distinct lung epithelial lineages is still unclear. To address this question, we used a Cre recombinase (Cre)-LoxP approach to activate canonical Wnt signaling ectopically in developing lung endoderm. We found that persistent activation of canonical Wnt signaling within distal lung endoderm was permissive for normal development of alveolar epithelium, yet led to the loss of developing bronchiolar epithelium and ectasis of distal conducting airways. Activation of canonical Wnt led to ectopic expression of a lymphoid-enhancing factor and a T-cell factor (LEF and TCF, respectively) and absence of SRY (sex-determining region Y)-box 2 (SOX2) and tumor protein p63 (p63) expression in proximal derivatives. Conditional loss of SOX2 in airways phenocopied epithelial differentiation defects observed with ectopic activation of canonical Wnt. Our data suggest that Wnt negatively regulates a SOX2-dependent signaling program required for developmental progression of the bronchiolar lineage.

INTRODUCTION ......... 238 The Need jor Understanding Hwnan Resource Management (HRM) in Context ... 238 Theoretical Perspectives Relevant to Understanding HRM in Context 238 REVIEW OF EMPIRICAL RESEARCH 244 HRM and the Internal Contexts of Organizations .... . . . . . . . . . . . . . . . . . . . . 244 HRM and the External Contexts oj Organizations 248 AN INTEGRATIVE PERSPECTIVE FOR RESEARCH ON HRM IN CONTEXT . . . . . . . . . . . . . . 253 Theory-Driven Research 255 Methodological Issues 256

The pseudostratified epithelium of the mouse trachea and human airways contains a population of basal cells expressing Trp-63 (p63) and cytokeratins 5 (Krt5) and Krt14. Using a KRT5-CreERT2 transgenic mouse line for lineage tracing, we show that basal cells generate differentiated cells during postnatal growth and in the adult during both steady state and epithelial repair. We have fractionated mouse basal cells by FACS and identified 627 genes preferentially expressed in a basal subpopulation vs. non-BCs. Analysis reveals potential mechanisms regulating basal cells and allows comparison with other epithelial stem cells. To study basal cell behaviors, we describe a simple in vitro clonal sphere-forming assay in which mouse basal cells self-renew and generate luminal cells, including differentiated ciliated cells, in the absence of stroma. The transcriptional profile identified 2 cell-surface markers, ITGA6 and NGFR, which can be used in combination to purify human lung basal cells by FACS. Like those from the mouse trachea, human airway basal cells both self-renew and generate luminal daughters in the sphere-forming assay.

The identity of the endogenous epithelial cells in the adult lung that are responsible for normal turnover and repair after injury is still controversial. In part, this is due to a paucity of highly specific genetic lineage tools to follow efficiently the fate of the major epithelial cell populations: the basal, secretory, ciliated, neuroendocrine, and alveolar cells. As part of a program to address this problem we have used a 1-kb FOXJ1 promoter to drive CreER in the ciliated cells of the embryonic and adult lung. Analysis of FOXJ1-GFP transgenic lungs shows that labeled cells appear in a proximal-distal pattern during embryogenesis and that the promoter drives expression in all ciliated cells. Using FOXJ1CreER adult mice, we have followed the fate of ciliated cells after epithelial injury by naphthalene or sulfur dioxide. From quantitative analysis and confocal microscopy we conclude that ciliated cells transiently change their morphology in response to lung injury but do not proliferate or transdifferentiate as part of the repair process.

Airway surface liquid is comprised of mucus and an underlying, watery periciliary liquid (PCL). In contrast to the well-described axial transport of mucus along airway surfaces via ciliary action, theoretical analyses predict that the PCL is nearly stationary. Conventional and confocal microscopy of fluorescent microspheres and photoactivated fluorescent dyes were used with well-differentiated human tracheobronchial epithelial cell cultures exhibiting spontaneous, radial mucociliary transport to study the movements of mucus and PCL. These studies showed that the entire PCL is transported at approximately the same rate as mucus, 39.2+/-4.7 and 39.8+/-4.2 micrometer/sec, respectively. Removing the mucus layer reduced PCL transport by > 80%, to 4.8+/-0.6 micrometer/sec, a value close to that predicted from theoretical analyses of the ciliary beat cycle. Hence, the rapid movement of PCL is dependent upon the transport of mucus. Mucus-dependent PCL transport was spatially uniform and exceeded the rate expected for pure frictional coupling with the overlying mucus layer; hence, ciliary mixing most likely accelerates the diffusion of momentum from mucus into the PCL. The cephalad movement of PCL along airway epithelial surfaces makes this mucus-driven transport an important component of salt and water physiology in the lung in health and disease.