Comparative spatial proteomics of Plasmodium-infected erythrocytes.

Plasmodium parasites contribute to one of the highest global infectious disease burdens. To achieve this success, the parasite has evolved a range of specialized subcellular compartments to extensively remodel the host cell for its survival. The information to fully understand these compartments is likely hidden in the so far poorly characterized Plasmodium species spatial proteome. To address this question, we determined the steady-state subcellular location of more than 12,000 parasite proteins across five different species by extensive subcellular fractionation of erythrocytes infected by Plasmodium falciparum, Plasmodium knowlesi, Plasmodium yoelii, Plasmodium berghei, and Plasmodium chabaudi. This comparison of the pan-species spatial proteomes and their expression patterns indicates increasing species-specific proteins associated with the more external compartments, supporting host adaptations and post-transcriptional regulation. The spatial proteome offers comprehensive insight into the different human, simian, and rodent Plasmodium species, establishing a powerful resource for understanding species-specific host adaptation processes in the parasite.

High myeloid-related protein: 8/14 levels are related to an increased risk of cardiovascular events after carotid endarterectomy.

BACKGROUND AND PURPOSE: Myeloid-related protein (Mrp) 8/14 complex is the functional relevant form of Mrp-8 and Mrp-14. Mrp-8/14 complex is actively formed in the cytoplasm of circulating neutrophils and monocytes and then secreted. Plasma Mrp-8/14 complex is emerging as a new biomarker that may discriminate between patients with an acute coronary syndrome and those with stable coronary heart disease. Little is known about the predictive value of Mrp-8/14 plaque and plasma levels for cardiovascular events after atherectomy. METHODS: Plasma and plaque Mrp-8/14 levels were determined by ELISA in 230 consecutive patients (mean age 73) who underwent carotid endarterectomy. Patients were followed for 3 years for recurrent cardiovascular events (vascular death, nonfatal vascular event, and peripheral intervention). During follow-up, 62 patients experienced an event. Baseline Mrp-8/14 levels were higher in patients who experienced an event than in event-free patients (plasma 0.78+/-0.63 versus 0.57+/-0.67 mg/L; P=0.030 and plaque 0.54+/-1.23 versus 0.08+/-1.51 mg/kg; P=0.027). In a Cox model, a 1 U increase in log Mrp-8/14 was associated with an increased risk of recurrent events (plasma, hazard ratio [HR], 1.51; 95% CI, 1.02 to 2.23, P=0.040; and plaque, HR, 1.23, 95% CI, 1.04 to 1.46, P=0.018). After multivariate adjustment for risk factors (both plasma and plaque Mrp-8/14) and plaque characteristics (only plaque Mrp-8/14), the HR remained the same for both plasma (HR, 1.50, 95% CI, 1.01 to 2.30; P=0.046) and plaque (HR, 1.20, 95% CI, 1.01 to 1.44; P=0.042). CONCLUSIONS: High Mrp-8/14 plasma and plaque levels are related to an increased risk of adverse cardiovascular events after a carotid endarterectomy, independent of traditional cardiovascular risk factors.