However, the CYB5D1 negatively correlates with a patients risk, suggesting that it has the opposite effect. It seems nevertheless plausible that the expression of this gene also interferes with drug metabolism. This hypothesis is compatible with the fact that the strongest predictive power of this gene was seen in a data set primarily composed of patients which received adjuvant chemotherapy before surgery. African trypanosomes are masters of extracellular survival in the mammalian bloodstream, where they multiply in the face of continuous host immune attack both from antibodies and the complement system. Of critical importance for the bloodstream form trypanosome is a dense protective layer of Variant Surface Glycoprotein, which shields invariant surface receptors from recognition. Eventually the host mounts an effective antibody response against a given VSG variant, whereby B-cell responses against the predominant VSG play a critical role. However, as new VSG switch variants continuously arise within the population, these escape recognition and form the next wave of infection. This highly sophisticated strategy of antigenic variation allows the trypanosome to maintain a chronic infection. An individual trypanosome encodes a vast repertoire of more than 1500 VSGs which are highly divergent in sequence. In fact, it has been estimated that in T. Mepiroxol brucei 927 about 60% of the VSGs are unique, with the rest occurring in very small subfamilies. Despite this great dissimilarity at the sequence level, VSGs with different amino acid sequences have a highly conserved tertiary structure. This conservation in VSG shape presumably allows a trypanosome switching from one VSG type to another to form a protective coat composed of different VSG types. There are about 56106 VSG dimers per cell, which are attached to the cell surface through a glycosylphosphatidylinositol anchor. This makes the VSG layer on the trypanosome cell surface a very dense but highly fluid barrier. Extremely high rates of VSG endocytosis allow the trypanosome to continuously exchange the VSG on its surface. Trypanosome motility coupled with these high rates of endocytosis allow the trypanosome to rapidly remove VSG-antibody complexes, providing protection from low titres of anti-VSG antibodies. We have shown previously that VSG is essential in bloodstream form T. brucei, even in vitro in the absence of antibodies or complement. Blocking VSG synthesis results in a very striking and precise Gentamycin Sulfate precytokinesis cell-cycle arrest with no re-initiation of S phase. The precision of this cell-cycle arrest argues that VSG synthesis is monitored as part of a cell-cycle checkpoint, whereby progression is halted in the absence of sufficient VSG. The unusually tight nature of this precytokinesis cell cycle arrest phenotype is unique in bloodstream form T. brucei, as other bloodstream form RNAi cytokinesis mutants described thus far have phenotypes whereby cells continue to attempt cytokinesis while subsequently re-entering S-phase in a new cell-cycle. For example, depletion of the GPI8 catalytic subunit of the GPI: protein transamidase complex in bloodstream form T. brucei results in a precytokinesis arrest. Alternatively, inhibition of synthesis of a variety of flagellar proteins in bloodstream form T. brucei including the basal body and flagellar protein KMP-11 or aurora kinase-1 and related proteins results in an inhibition of cytokinesis. However these different precytokinesis cell-cycle arrest phenotypes are all imprecise, as the arrested cells repeatedly re-enter S-phase, and show characteristic multinuclear, multikinetoplast and multiflagellar phenotypes.