Eosinophil adhesion under flow conditions activates mechanosensitive signaling pathways in human endothelial cells

Leukocyte transmigration can be affected by shear stress; however, the mechanisms by which shear stress modulates transmigration are unknown. We found that adhesion of eosinophils or an eosinophilic cell line to intereukin 4–stimulated endothelial cells led to a shear-dependent increase in endothelial cell intracellular calcium and increased phosphorylation of extracellular signal-regulated kinase (ERK) 2, but not c-Jun NH2-terminal kinase or p38 mitogen-activated protein kinase. Latex beads coated with antibodies were used to characterize the role of specific endothelial cell surface molecules in initiating signaling under shear conditions. We found that ligation of either vascular cell adhesion molecule–1 or E-selectin, but not major histocompatibility complex class I, induced a shear-dependent increase in ERK2 phosphorylation in cytokine-stimulated endothelial cells. Disassembly of the actin cytoskeleton with latrunculin A prevented ERK2 phosphorylation after adhesion under flow conditions, supporting a role for the cytoskeleton in mechanosensing. Rapid phosphorylation of focal adhesion kinase and paxillin occurred under identical conditions, suggesting that focal adhesions were also involved in mechanotransduction. Finally, we found that Rho-associated protein kinase and calpain were both critical in the subsequent transendothelial migration of eosinophils under flow conditions. These data suggest that ligation of leukocyte adhesion molecules under flow conditions leads to mechanotransduction in endothelial cells, which can regulate subsequent leukocyte trafficking

Is it possible to separate the graft-versus-leukemia (GVL) effect against B cell acute lymphoblastic leukemia from graft-versus-host disease (GVHD) after hematopoietic cell transplant?

Hematopoietic cell transplant is a curative therapy for many pediatric patients with high risk acute lymphoblastic leukemia. Its therapeutic mechanism is primarily based on the generation of an alloreactive graft-versus-leukemia effect that can eliminate residual leukemia cells thus preventing relapse. However its efficacy is diminished by the concurrent emergence of harmful graft-versus-host disease disease which affects healthly tissue leading to significant morbidity and mortality. The purpose of this review is to describe the interventions that have been trialed in order to augment the beneficial graft-versus leukemia effect post-hematopoietic cell transplant while limiting the harmful consequences of graft-versus-host disease. This includes many emerging and promising strategies such a

A novel approach to screen and compare emission inventories

A methodology is proposed to support the evaluation and comparison of different types of emission inventories. The strengths and weaknesses of the methodology are presented and discussed based on an example. The approach results in a “diamond” diagram useful to flag out anomalous behaviors in the emission inventories and to get insight in possible explanations. In particular, the “diamond” diagram is shown to provide meaningful information in terms of: discrepancies between the total emissions reported by macrosector and pollutant, contribution of each macro-sector to the total amount of emissions released by pollutant, and the identification and quantification of the different factors causing the discrepancies between total emissions. A practical example in Barcelona is used for testing and to provide relevant information for the analyzed emission datasets. The tests show the capability of the proposed methodology to flag inconsistencies in the existing inventories. The proposed methodology system may be useful for regional and urban inventory developers as an initial evaluation of the consistency of their inventories

An inverse finite element method with an application to extrusion with solidification

The flow and solidification of planar jets are analysed by means of an efficient inverse isotherm finite element method. The method is based on a tessellation that is constructed by isotherms as characteristic co-ordinate lines transverse to the flow direction. Thus opposite sides of finite elements lie on isotherms. The method allows the simultaneous determination of the location of the isotherms with the primary unknowns, namely, the velocity, the pressure, the temperature and the location of the free surface. Thus the determination of the location of the solidification front (which is known to pose significant computational difficulties) is automatic. This facilitates the control of the location of the solidification front by controlling macroscopic variables such as the flow rate, the cooling rate and the capillary design. The location of the solidification may then be suitably chosen to influence the frozen-in orientation and structure in extrusion of high-performance materials such as composites and polymers, in continuous casting of metals and in growth of crystals.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50200/1/1650090505_ftp.pd

A multi-model study of the hemispheric transport and deposition of oxidised nitrogen.

Fifteen chemistry-transport models are used to quantify, for the first time, the export of oxidised nitrogen (NOy) to and from four regions (Europe, North America, South Asia, and East Asia), and to estimate the uncertainty in the results. Between 12 and 24% of the NOx emitted is exported from each region annually. The strongest impact of each source region on a foreign region is: Europe on East Asia, North America on Europe, South Asia on East Asia, and East Asia on North America. Europe exports the most NOy, and East Asia the least. East Asia receives the most NOy from the other regions. Between 8 and 15% of NOx emitted in each region is transported over distances larger than 1000 km, with 3–10% ultimately deposited over the foreign regions

The effect of cigarette smoke exposure on the development of inflammation in lungs, gut and joints of TNFΔARE mice

The inflammatory cytokine TNF-alpha is a central mediator in many immune-mediated diseases, such as Crohn's disease (CD), spondyloarthritis (SpA) and chronic obstructive pulmonary disease (COPD). Epidemiologic studies have shown that cigarette smoking (CS) is a prominent common risk factor in these TNF-dependent diseases. We exposed TNF Delta ARE mice; in which a systemic TNF-alpha overexpression leads to the development of inflammation; to 2 or 4 weeks of air or CS. We investigated the effect of deregulated TNF expression on CS-induced pulmonary inflammation and the effect of CS exposure on the initiation and progression of gut and joint inflammation. Upon 2 weeks of CS exposure, inflammation in lungs of TNF Delta ARE mice was significantly aggravated. However, upon 4 weeks of CS-exposure, this aggravation was no longer observed. TNF Delta ARE mice have no increases in CD4+ and CD8+ T cells and a diminished neutrophil response in the lungs after 4 weeks of CS exposure. In the gut and joints of TNF Delta ARE mice, 2 or 4 weeks of CS exposure did not modulate the development of inflammation. In conclusion, CS exposure does not modulate gut and joint inflammation in TNF Delta ARE mice. The lung responses towards CS in TNF Delta ARE mice however depend on the duration of CS exposure