The actomyosin systems in apicomplexa

The phylum of Apicomplexa groups obligate intracellular parasites that exhibit unique classes of unconventional myosin motors. These parasites also encode a limited repertoire of actins, actin-like proteins, actin-binding proteins and nucleators of filamentous actin (F-actin) that display atypical properties. In the last decade, significant progress has been made to visualize F-actin and to unravel the functional contribution of actomyosin systems in the biology of Toxoplasma and Plasmodium, the most genetically-tractable members of the phylum. In addition to assigning specific roles to each myosin, recent biochemical and structural studies have begun to uncover mechanistic insights into myosin function at the atomic level. In several instances, the myosin light chains associated with the myosin heavy chains have been identified, helping to understand the composition of the motor complexes and their mode of regulation. Moreover, the considerable advance in proteomic methodologies and especially in assignment of posttranslational modifications is offering a new dimension to our understanding of the regulation of actin dynamics and myosin function. Remarkably, the actomyosin system contributes to three major processes in Toxoplasma gondii: (i) organelle trafficking, positioning and inheritance, (ii) basal pole constriction and intravacuolar cell-cell communication and (iii) motility, invasion, and egress from infected cells. In this chapter, we summarize how the actomyosin system harnesses these key events to ensure successful completion of the parasite life cycle

Theileria in ruminants

Theileria are important hemoprotozoan parasites of domestic and wild ruminants, transmitted by ixodid ticks leading to diseases which range from mild in apparent reactions to highly fatal diseases. Bovine-infecting T. parva and T. annulata and ovine-infecting T. lestoquardi are of major global economic importance, but other Theileria spp. are also briefly mentioned. Classification of Theileria has been a subject of great controversy without consensus on whether many taxons are different species, synonyms, or subspecies of the same parasite. However, with the development of new molecular tools, many of the outstanding difficulties could be resolved. Theileria have complex life cycles both in the vertebrate host and the tick vector, many of which are not clearly understood. One unique feature of some Theileria is their ability to transform infected host cells into a reversible cancer-like proliferation conferring to them an ability to proliferate without apoptosis. The transformation is not permanent because it can be reversed by treatment with anti-theilerial drugs. Understanding this mechanism could give insights into treatment of cancer. Control of the diseases caused by Theileria has largely relied on chemical drugs either to treat infected hosts or prevent infection by controlling the tick vectors. But resistance to chemicals by the parasites or vectors has led to the development of more sustainable control methods such as live vaccination against the three most pathogenic Theileria spp. of ruminants. Efforts are also under way to develop subunit vaccines against these parasites

Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation

BACKGROUND: A substantial proportion of patients receiving fibrinolytic therapy for myocardial infarction with ST-segment elevation have inadequate reperfusion or reocclusion of the infarct-related artery, leading to an increased risk of complications and death. METHODS: We enrolled 3491 patients, 18 to 75 years of age, who presented within 12 hours after the onset of an ST-elevation myocardial infarction and randomly assigned them to receive clopidogrel (300-mg loading dose, followed by 75 mg once daily) or placebo. Patients received a fibrinolytic agent, aspirin, and when appropriate, heparin (dispensed according to body weight) and were scheduled to undergo angiography 48 to 192 hours after the start of study medication. The primary efficacy end point was a composite of an occluded infarct-related artery (defined by a Thrombolysis in Myocardial Infarction flow grade of 0 or 1) on angiography or death or recurrent myocardial infarction before angiography. RESULTS: The rates of the primary efficacy end point were 21.7 percent in the placebo group and 15.0 percent in the clopidogrel group, representing an absolute reduction of 6.7 percentage points in the rate and a 36 percent reduction in the odds of the end point with clopidogrel therapy (95 percent confidence interval, 24 to 47 percent; P<0.001). By 30 days, clopidogrel therapy reduced the odds of the composite end point of death from cardiovascular causes, recurrent myocardial infarction, or recurrent ischemia leading to the need for urgent revascularization by 20 percent (from 14.1 to 11.6 percent, P=0.03). The rates of major bleeding and intracranial hemorrhage were similar in the two groups. CONCLUSIONS: In patients 75 years of age or younger who have myocardial infarction with ST-segment elevation and who receive aspirin and a standard fibrinolytic regimen, the addition of clopidogrel improves the patency rate of the infarct-related artery and reduces ischemic complications