Chemokines orchestrate immune cell trafficking by eliciting either directed or random migration and by activating integrins in order to induce cell adhesion. Analyzing dendritic cell (DC) migration, we showed that these distinct cellular responses depended on the mode of chemokine presentation within tissues. The surface-immobilized form of the chemokine CCL21, the heparan sulfate-anchoring ligand of the CC-chemokine receptor 7 (CCR7), caused random movement of DCs that was confined to the chemokine-presenting surface because it triggered integrin-mediated adhesion. Upon direct contact with CCL21, DCs truncated the anchoring residues of CCL21, thereby releasing it from the solid phase. Soluble CCL21 functionally resembles the second CCR7 ligand, CCL19, which lacks anchoring residues and forms soluble gradients. Both soluble CCR7 ligands triggered chemotactic movement, but not surface adhesion. Adhesive random migration and directional steering cooperate to produce dynamic but spatially restricted locomotion patterns closely resembling the cellular dynamics observed in secondary lymphoid organs.
To learn more about the effect of economic conditions on civil war, we examine whether Sub-Saharan civil wars are more likely to start following downturns in the international price of countries' main export commodities. The data show a robust effect of commodity price downturns on the outbreak of civil wars. We also find that Sub-Saharan countries are more likely to see civil wars following economic downturns in their main OECD export destinations.
Abstract. According to the economic approach to political transitions, negative transitory economic shocks can open a window of opportunity for democratic change. Testing the theory requires a source of transitory shocks to the aggregate economy. We rely on rainfall shocks in Sub-Saharan African countries. Our analysis yields that negative transitory shocks lead to significant democratic change.A transitory 10 percent drop in income is followed by an improvement in democracy scores of 9 percentage points, and by an increase in the probability of a transition to democracy of 13 percentage points.
Prostaglandin E(2) (PGE(2)) is the most abundant eicosanoid and a very potent lipid mediator. PGE(2) is produced predominantly from arachidonic acid by its tightly regulated cyclooxygenases (COX) and prostaglandin E synthases (PGES). Secreted PGE(2) acts in an autocrine or paracrine manner through its four cognate G protein coupled receptors EP1 to EP4. Under physiological conditions, PGE(2) is key in many biological functions, such as regulation of immune responses, blood pressure, gastrointestinal integrity, and fertility. Deregulated PGE(2) synthesis or degradation is associated with severe pathological conditions like chronic inflammation, Alzheimer's disease, or tumorigenesis. Therefore, pharmacological inhibition of COX enzymes and PGE(2) receptor antagonism is of great therapeutic interest.
Over a 34-month period (1989-1991), 791 patients were diagnosed at endoscopic retrograde cholangiography to have bile duct stones. All patients underwent sphincterotomy and attempted extraction by Dormia basket. This was successful in 683 patients (86%). The remaining 108 patients with "difficult stones" (mean age 72 years) underwent mechanical, electrohydraulic or extracorporeal shock wave lithotripsy according to the following algorithm: (1) Mechanical lithotripsy for stones which could not be extracted after entrapment in the Dormia basket (n = 33); (2) peroral cholangioscopic electrohydraulic lithotripsy for stones which could not be engaged in the Dormia basket (n = 65); or (3) extracorporeal shock wave lithotripsy for intrahepatic stones (n = 10). Stone fragmentation and clearance was successful in all patients treated by mechanical lithotripsy, was unsuccessful in one patient submitted to electrohydraulic lithotripsy due to inability to insert the cholangioscope into the bile duct and failed in 3 patients treated by extracorporeal shock wave lithotripsy. Overall, 95% of difficult bile duct stones refractory to conventional endoscopic basket extraction were removed using the above lithotripsy techniques. There were no serious procedure-related complications.
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