Background:Although the proteasome is a validated anticancer target, the clinical application of its inhibitors has been limited because of inherent systemic toxicity. To broaden clinical utility of proteasome inhibitors as anticancer agents, it is critical to develop strategies to selectively target proteasomes in cancer cells. The immunoproteasome is an alternative form of the constitutive proteasome that is expressed at high levels in cancer tissues, but not in most normal cells in the body.Methods:To validate the immunoproteasome as a chemotherapeutic target, an immunoproteasome catalytic subunit LMP2-targeting inhibitor and siRNA were used. The sensitivity of PC-3 prostate cancer cells to these reagents was investigated using viability assays. Further, a xenograft model of prostate cancer was studied to test the in vivo effects of LMP2 inhibition.Results:A small molecule inhibitor of the immunoproteasome subunit LMP2, UK-101, induced apoptosis of PC-3 cells and resulted in significant inhibition (∼50–60%) of tumour growth in vivo. Interestingly, UK-101 did not block degradation of IκBα in PC-3 cells treated with TNF-α, suggesting that its mode of action may be different from that of general proteasome inhibitors, such as bortezomib, which block IκBα degradation.Conclusion:These results strongly suggest that the immunoproteasome has important roles in cancer cell growth and thus provide a rationale for targeting the immunoproteasome in the treatment of prostate cancer.

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Easy deformation-induced nanostructuring was found in a Ti–Nb–Ta–In β alloy with low stability against α″ martensitic transformation. Upon severe plastic deformation at the sample center, the reversible β→α″ martensitic transformation plays a significant role for grain refinement. A possible mechanism is proposed, in which the formation of fine martensite, the interaction among slip dislocations, martensite and twins, and the reversible transition from α″ back to β phase are considered as the main causes leading to pronounced grain refinement to the nanoscale.

We report ductile bulk metallic glasses based on martensitic alloys. The slowly cooled specimens contain a mixture of parent 'austenite' and martensite phase. The slightly faster cooled bulk metallic glasses with 2-5 nm sized 'austenite'-like crystalline cluster reveal high strength and large ductility (16%). Shear bands propagate in a slither mode in this spatially inhomogeneous glassy structure and undergo considerable 'thickening' from 5-25 nm. A 'stress induced displacive transformation' is proposed to be responsible for both plasticity and work-hardeninglike behavior of these 'M-Glasses'.

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Love waves, a variety of surface acoustic waves (SAWs), can be used to detect very small biological surface interactions and so have a wide range of potential applications. To demonstrate the practicality of a Love wave SAW biosensor, we fabricated a 155-MHz Love wave SAW biosensor and compared it with a commercial surface Plasmon resonance (SPR) using glycerol-water solution with known densities and viscosities to calibrate the response signals of the biosensors. And the mass per unit area of anti-mouse IgG bound with protein G onto the sensitive layer of the biosensor was calculated on the basis of the calibration result. The sensitivity of the Love wave SAW biosensor was the same as or greater than that of the SPR biosensor. Furthermore, the Love wave SAW biosensor was capable of measuring a much wider range of viscosities than the SPR biosensor. Although the operating principle of the Love wave SAW biosensor is completely different from that of the SPR biosensor, the subtle changes in the viscoelastic properties of the biological layer that accompany biological binding reactions on the sensitive layer can be monitored and measured in the same ways as with the SPR biosensor.

Accurate detection of oestrus is important for artificial insemination. The aim of this study was to identify oestrous-specific bovine cervical mucus proteins that could be used to determine the optimal time for artificial insemination. Non-oestrous and controlled internal drug release (CIDR)-induced oestrous-stage mucus proteins were purified and subjected to surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, sodium dodecyl sulphate polyacrylamide gel electrophoresis and MALDI-TOF/TOF. Among differentially expressed proteins, lactoferrin (LF) and glutamate receptor-interacting protein 1 (GRIP1) showed a twofold increase during the CIDR-induced oestrous stage compared to the levels in non-oestrous stage in bovine cervical mucus. The RT-PCR, Western blotting and immunohistochemistry results showed that LF and GRIP1 expression was significantly increased during the oestrous stage in the uterus. This study demonstrated that bovine LF and GRIP1 exist during the oestrous stage, but not during the non-oestrous stage, suggesting that cervical mucus LF and GRIP1 are useful oestrous detection markers in cattle.