PTEN is a PIP3 phosphatase that antagonizes oncogenic PI3-kinase signalling. Due to its critical role in suppressing the potent signalling pathway, it is one of the most mutated tumour suppressors, especially in brain tumours. It is generally thought that PTEN deficiencies predominantly result from either loss of expression or enzymatic activity. By analysing PTEN in malignant glioblastoma primary cells derived from 16 of our patients, we report mutations that block localization of PTEN at the plasma membrane and nucleus without affecting lipid phosphatase activity. Cellular and biochemical analyses as well as structural modelling revealed that two mutations disrupt intramolecular interaction of PTEN and open its conformation, enhancing polyubiquitination of PTEN and decreasing protein stability. Moreover, promoting mono-ubiquitination increases protein stability and nuclear localization of mutant PTEN. Thus, our findings provide a molecular mechanism for cancer-associated PTEN defects and may lead to a brain cancer treatment that targets PTEN mono-ubiquitination.

The nature of the stress in a suspension of equal homogeneous spheres all subject to the same force, such as weight, is considered; inertial effects are neglected. This study builds upon some of the well-known work devoted to this problem by the founder of the Journal of Fluid Mechanics, Professor George K. Batchelor. After developing a general theory, the antisymmetric part of the stress tensor is considered in detail. It is shown that, in addition to a term already found by Batchelor and characterized by an axial vector, the antisymmetric stress contains another term characterized by the curl of a polar vector. As a consequence, a suspension will possess, in addition to an axial vortex viscosity, a polar vortex viscosity. Appendix C presents a calculation of the hindrance function for rotation correct to the first order in the particle volume fraction.

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