It should also be considered that destruction of HIFs can occur independently of oxygen requirements via a hydroxylation/ubiquitination/proteosome-independent degradation pathway that is calpain-mediated.23 Elevated protein expression and distribution of calpains are observed in these severe malaria cases.8 Anticipating that HIF responses may be difficult to detect, we also examined other ‘footprints’ of hypoxia, including downstream markers such as VEGF that can be activated by HIF, and the transcriptional regulator DEC-1 that is regulated by hypoxia and HIF-1α but is more stable. The gene discussed is BHLHE40; the disease is malaria.