45 research outputs found
American Advocacy - Foundation of the American Dream
Colloquium: The Federal Judiciary: Essays from the Benc
The Summary Jury Trial
The American judicial system must necessarily rely on a steady flow of dispositions of cases by settlement lest it collapse because of a demand for trials beyond the ability of the courts to try cases. Settlements are achieved through a variety of procedures and techniques, yet many cases result in trials because of the uncertainty about prospective juror perceptions that pervades settlement discussions. Summary trial helps to eliminate this element of uncertainty and, at the same time, provides an additional basis for settlement of cases otherwise committed to trial. This is not to suggest that trial is to be avoided at all costs, but trial should result only in those cases incapable of alternative solutions. The summary jury trial provides one viable alternative
The Summary Jury Trial
The American judicial system must necessarily rely on a steady flow of dispositions of cases by settlement lest it collapse because of a demand for trials beyond the ability of the courts to try cases. Settlements are achieved through a variety of procedures and techniques, yet many cases result in trials because of the uncertainty about prospective juror perceptions that pervades settlement discussions. Summary trial helps to eliminate this element of uncertainty and, at the same time, provides an additional basis for settlement of cases otherwise committed to trial. This is not to suggest that trial is to be avoided at all costs, but trial should result only in those cases incapable of alternative solutions. The summary jury trial provides one viable alternative
3rd Annual Federal Practice Institute
Outline of speakers\u27 presentations from the 3rd Annual Federal Practice Institute held by UK/CLE on September 23, 1988
Childhood papillary thyroid cancer as second malignancy after successful treatment of rhabdomyosarcoma
Distinct External Signals Trigger Sequential Release of Apical Organelles during Erythrocyte Invasion by Malaria Parasites
The invasion of erythrocytes by Plasmodium merozoites requires specific interactions between host receptors and parasite ligands. Parasite proteins that bind erythrocyte receptors during invasion are localized in apical organelles called micronemes and rhoptries. The regulated secretion of microneme and rhoptry proteins to the merozoite surface to enable receptor binding is a critical step in the invasion process. The sequence of these secretion events and the external signals that trigger release are not known. We have used time-lapse video microscopy to study changes in intracellular calcium levels in Plasmodium falciparum merozoites during erythrocyte invasion. In addition, we have developed flow cytometry based methods to measure relative levels of cytosolic calcium and study surface expression of apical organelle proteins in P. falciparum merozoites in response to different external signals. We demonstrate that exposure of P. falciparum merozoites to low potassium ion concentrations as found in blood plasma leads to a rise in cytosolic calcium levels through a phospholipase C mediated pathway. Rise in cytosolic calcium triggers secretion of microneme proteins such as the 175 kD erythrocyte binding antigen (EBA175) and apical membrane antigen-1 (AMA-1) to the merozoite surface. Subsequently, interaction of EBA175 with glycophorin A (glyA), its receptor on erythrocytes, restores basal cytosolic calcium levels and triggers release of rhoptry proteins. Our results identify for the first time the external signals responsible for the sequential release of microneme and rhoptry proteins during erythrocyte invasion and provide a starting point for the dissection of signal transduction pathways involved in regulated exocytosis of these key apical organelles. Signaling pathway components involved in apical organelle discharge may serve as novel targets for drug development since inhibition of microneme and rhoptry secretion can block invasion and limit blood-stage parasite growth
clag9 Is Not Essential for PfEMP1 Surface Expression in Non-Cytoadherent Plasmodium falciparum Parasites with a Chromosome 9 Deletion
BACKGROUND: The expression of the clonally variant virulence factor PfEMP1 mediates the sequestration of Plasmodium falciparum infected erythrocytes in the host vasculature and contributes to chronic infection. Non-cytoadherent parasites with a chromosome 9 deletion lack clag9, a gene linked to cytoadhesion in previous studies. Here we present new clag9 data that challenge this view and show that surface the non-cytoadherence phenotype is linked to the expression of a non-functional PfEMP1. METHODOLOGY/PRINCIPAL FINDINGS: Loss of adhesion in P. falciparum D10, a parasite line with a large chromosome 9 deletion, was investigated. Surface iodination analysis of non-cytoadherent D10 parasites and COS-7 surface expression of the CD36-binding PfEMP1 CIDR1α domain were performed and showed that these parasites express an unusual trypsin-resistant, non-functional PfEMP1 at the erythrocyte surface. However, the CIDR1α domain of this var gene expressed in COS-7 cells showed strong binding to CD36. Atomic Force Microscopy showed a slightly modified D10 knob morphology compared to adherent parasites. Trafficking of PfEMP1 and KAHRP remained functional in D10. We link the non-cytoadherence phenotype to a chromosome 9 breakage and healing event resulting in the loss of 25 subtelomeric genes including clag9. In contrast to previous studies, knockout of the clag9 gene from 3D7 did not interfere with parasite adhesion to CD36. CONCLUSIONS/SIGNIFICANCE: Our data show the surface expression of non-functional PfEMP1 in D10 strongly indicating that genes other than clag9 deleted from chromosome 9 are involved in this virulence process possibly via post-translational modifications