Lung Cancer in Pulmonary Fibrosis: Tales of Epithelial Cell Plasticity

Lung epithelial cells exhibit a high degree of plasticity. Alterations to lung epithelial cell function are critically involved in several chronic lung diseases such as pulmonary fibrosis. Pulmonary fibrosis is characterized by repetitive injury and subsequent impaired repair of epithelial cells, which leads to aberrant growth factor activation and fibroblast accumulation. Increased proliferation and hyper- and metaplasia of epithelial cells upon injury have also been observed in pulmonary fibrosis; this epithelial cell activation might represent the basis for lung cancer development. Indeed, several studies have provided histopathological evidence of an increased incidence of lung cancer in pulmonary fibrosis. The mechanisms involved in the development of cancer in pulmonary fibrosis, however, remain poorly understood. This review highlights recently uncovered molecular mechanisms shared between lung cancer and fibrosis, which extend the current evidence of a common trait of cancer and fibrosis, as provided by histopathological observations. Copyright (C) 2011 S. Karger AG, Base

Efficiency of primary saliva secretion: an analysis of parameter dependence in dynamic single-cell and acinus models, with application to aquaporin knockout studies

Secretion from the salivary glands is driven by osmosis following the establishment of osmotic gradients between the lumen, the cell and the interstitium by active ion transport. We consider a dynamic model of osmotically driven primary saliva secretion and use singular perturbation approaches and scaling assumptions to reduce the model. Our analysis shows that isosmotic secretion is the most efficient secretion regime and that this holds for single isolated cells and for multiple cells assembled into an acinus. For typical parameter variations, we rule out any significant synergistic effect on total water secretion of an acinar arrangement of cells about a single shared lumen. Conditions for the attainment of isosmotic secretion are considered, and we derive an expression for how the concentration gradient between the interstitium and the lumen scales with water- and chloride-transport parameters. Aquaporin knockout studies are interpreted in the context of our analysis and further investigated using simulations of transport efficiency with different membrane water permeabilities. We conclude that recent claims that aquaporin knockout studies can be interpreted as evidence against a simple osmotic mechanism are not supported by our work. Many of the results that we obtain are independent of specific transporter details, and our analysis can be easily extended to apply to models that use other proposed ionic mechanisms of saliva secretion

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Surfactant secretion in LRRK2 knock-out rats : changes in lamellar body morphology and rate of exocytosis

Leucine-rich repeat kinase 2 (LRRK2) is known to play a role in the pathogenesis of various diseases including Parkinson disease, morbus Crohn, leprosy and cancer. LRRK2 is suggested to be involved in a number of cell biological processes such as vesicular trafficking, transcription, autophagy and lysosomal pathways. Recent histological studies of lungs of LRRK2 knock-out (LRRK2 -/-) mice revealed significantly enlarged lamellar bodies (LBs) in alveolar type II (ATII) epithelial cells. LBs are large, lysosome-related storage organelles for pulmonary surfactant, which is released into the alveolar lumen upon LB exocytosis. In this study we used high-resolution, subcellular live-cell imaging assays to investigate whether similar morphological changes can be observed in primary ATII cells from LRRK2 -/- rats and whether such changes result in altered LB exocytosis. Similarly to the report in mice, ATII cells from LRRK2 -/- rats contained significantly enlarged LBs resulting in a >50% increase in LB volume. Stimulation of ATII cells with ATP elicited LB exocytosis in a significantly increased proportion of cells from LRRK2 -/- animals. LRRK2 -/- cells also displayed increased intracellular Ca2+ release upon ATP treatment and significant triggering of LB exocytosis. These findings are in line with the strong Ca2+-dependence of LB fusion activity and suggest that LRRK2 -/- affects exocytic response in ATII cells via modulating intracellular Ca2+ signaling. Post-fusion regulation of surfactant secretion was unaltered. Actin coating of fused vesicles and subsequent vesicle compression to promote surfactant expulsion were comparable in cells from LRRK2 -/- and wt animals. Surprisingly, surfactant (phospholipid) release from LRRK2 -/- cells was reduced following stimulation of LB exocytosis possibly due to impaired LB maturation and surfactant loading of LBs. In summary our results suggest that LRRK2 -/- affects LB size, modulates intracellular Ca2+ signaling and promotes LB exocytosis upon stimulation of ATII cells with ATP

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe

Clinical and radiographic outcomes of the treatment of adolescent idiopathic scoliosis with segmental pedicle screws and combined local autograft and allograft bone for spinal fusion: a retrospective case series

<p>Abstract</p> <p>Background</p> <p>High morbidity has been reported with iliac crest bone graft harvesting; however, donor bone is typically necessary for posterior spinal fusion. Autograft bone combined with allograft may reduce the morbidity associated with iliac crest bone harvesting and improve the fusion rate. Our aim in this study was to determine the presence of complications, pseudarthrosis, non-union, and infection using combined <it>in situ </it>local autograft bone and freeze-dried cancellous allograft bone in patients undergoing posterior spinal fusion for the treatment of adolescent idiopathic scoliosis.</p> <p>Methods</p> <p>A combination of <it>in situ </it>local autograft bone and freeze-dried cancellous allograft blocks were used in 50 consecutive patients with adolescent idiopathic scoliosis treated by posterior fusion and Moss Miami pedicle screw instrumentation. Results were assessed clinically and radiographically and quality of life and functional outcome was evaluated by administration of a Chinese version of the SRS-22 survey.</p> <p>Results</p> <p>There were 41 female and 9 male patients included for analysis with an average age of 14.7 years (range, 12-17). All patients had a minimum follow-up of 18 months (range, 18 to 40 months). The average preoperative Cobb angle was 49.8° (range, 40° to 86°). The average number of levels fused was 9.8 (range, 6-15). Patients had a minimum postoperative follow-up of 18 months. At final follow-up, the average Cobb angle correction was 77.8% (range, 43.4 to 92.5%). There was no obvious loss in the correction, and the average loss of correction was 1.1° (range, 0° to 4°). There was no pseudarthrosis and no major complications.</p> <p>Conclusions</p> <p><it>In situ </it>autograft bone combined with allograft bone may be a promising method enhances spinal fusion in AIS treated with pedicle screw placement. By eliminating the need for iliac crest bone harvesting, significant morbidity may be avoided.</p

In vivo clearance of surfactant lipids during acute pulmonary inflammation.

BACKGROUND: A decrease in pulmonary surfactant has been suggested to contribute to the lung dysfunction associated with pulmonary inflammation. A number of studies have implicated surfactant clearance as a possible mechanism for altered pool sizes. The objective of the current study was to specifically investigate the mechanisms of surfactant clearance in a rodent model of acute pulmonary inflammation. METHODS: Inflammation was induced by intrapulmonary instillation of lipopolysaccharide (LPS: 100 μg/kg). Lipid clearance was assessed at 18 and 72 hours post-LPS instillation by intratracheal administration of radiolabel surfactant-like liposomes 2 hours prior to isolation and analysis of inflammatory cells and type II cells. RESULTS: At both 18 and 72 hours after LPS instillation there was significantly less radioactivity recovered in the lavage fluid compared to respective control groups (p < 0.05). At both time points, the number of cells recovered by lavage and their associated radioactivity was greater compared to control groups (p < 0.01). There was no difference in recovery of radioactivity by isolated type II cells or other cells obtained from enzymatic digestion of lung tissue. CONCLUSION: These results show that increased clearance of surfactant lipids in our model of acute pulmonary inflammation is primarily due to the inflammatory cells recruited to the airspace and not increased uptake by alveolar type II cells

Comparative analysis between shape memory alloy-based correction and traditional correction technique in pedicle screws constructs for treating severe scoliosis

The three-dimensional correction of severe rigid scoliosis has been improved by segmental pedicle screw instrumentation. However, there can be significant difficulty related to the use of a rigid rod, especially in the apex region of severe scoliosis. This study is a retrospective matched cohort study to evaluate the advantages of Nitinol shape memory alloy (SMA) rod-based correction by comparing the clinical and radiographic results obtained from using a temporary SMA rod and those from a standard rod in the correction of severe scoliosis. From May 2004 to September 2006, patients with matched curve type, ages at surgery, operative methods and fusion levels in our institute and instrumented with either SMA rods (n = 14) or traditional correction techniques (n = 16) were reviewed. In SMA group, the SMA rods served as a temporary intraoperative tool for deformity correction and were replaced by standard rods. The blood loss at surgery averaged 778 ± 285 ml in the traditional group and 585 ± 188 ml in the SMA group (P < 0.05). Operative time averaged 284 ± 53 min in the SMA group and 324 ± 41 min in the traditional group (P < 0.05). In the SMA group, the preoperative major curve was 92.6° ± 13.7° with a flexibility of 25.5 ± 7.3% was corrected to 29.4° ± 5.7° demonstrating a 68.4% immediate postoperative correction. In the traditional group, the preoperative major curve was 88.6° ± 14.6° with a flexibility of 29.3 ± 6.6% was corrected to 37.2° ± 7.3° demonstrating a 57.8% immediate postoperative correction. There was a statistic difference between the SMA group and traditional group in correction rate of the major thoracic curve. In the SMA group, one case suffered from deep infection 2 months postoperatively. In the traditional group, 6 of 16 cases suffered pedicle screw pull out or loosening during placement of the standard rod at the apex vertebrae on the concave side. In three cases, the mono-axial pedicle screws near the apex were abandoned and in five cases replaced with poly-axial pedicle screws. This study shows that the temporary use of SMA rod may reduce the operative time, blood loss, while improve the correction of the coronal plane when compared with standard techniques