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New tuberculosis vaccines are urgently needed to reduce the threat of this devastating disease. An approach consisting of a fusion protein of three tuberculosis antigens provides significant protection in before- and after-exposure challenge mouse models, representing a crucial step forward in tackling tuberculosis in latently infected individuals (pages 189–194).
The antiplatelet drug clopidogrel helps prevent stent-associated thrombosis, but the antiplatelet effects are quite variable and the clinical consequences can be serious. New findings show that the variability in clopidogrel efficacy is affected by the enzyme paraoxonase-1 (PON1), which is required for clopidogrel bioactivation (pages 110–116).
Adenosine therapy for sickle cell disease has been proposed to improve blood flow, mediate cytoprotection and inhibit natural killer cell activity. Complicating this approach, adenosine signaling also induces hemoglobin S polymerization, promoting 'sickling', vasoocclusion, hemolysis and organ damage (pages 79–86).
Loss of kidney filter function during nephrotic syndrome results in loss of protein from the blood into the urine (proteinuria). A new study mechanistically links proteinuria to dysregulated expression and post-transcriptional modification of the secreted glycoprotein angiopoietin-like-4 in kidney glomerular podocytes (pages 117–122).
The adipocyte-derived secretory factor adiponectin promotes insulin sensitivity, decreases inflammation and promotes cell survival. A new study now shows that these beneficial effects of adiponectin are dependent on sphingolipid metabolism (pages 55–63).
Histamine produced by immature myeloid cells restricts the expression of inflammatory mediators and regulates leukocyte recruitment to sites of tissue stress. Unexpectedly, cancer susceptibility is increased in mice lacking histamine, thus revealing a previously unknown mechanism whereby immature myeloid cells contribute to cancer development (pages 87–95).
