MafB protein stability is regulated by the JNK and ubiquitin-proteasome pathways

MafB is a basic leucine zipper transcription factor that plays important roles in development and differentiation processes. During osteoclastogenesis, its expression is downregulated at the transcriptional level via the JNK and p38 MAP kinase pathways. In the present study, we demonstrated that MafB protein stability is regulated by JNK and identified a phosphorylation site, Thr62. The expression of a constitutively active form of JNK (a fusion protein MKK7α1-JNK1β1) promoted the degradation of MafB in COS7 cells, and a T62A substitution significantly reduced the instability of MafB. The introduction of a four-fold (T58A/T62A/S70A/S74A) substitution in an acidic transcription-activating domain almost protected the instability resulting from the activation of JNK. Furthermore, treatment with proteasome inhibitors increased the MafB level, and a high-molecular-weight smear, characteristic of polyubiquitination, was observed in lysates from cells in which MafB, ubiquitin, and MKK7α1-JNK1β1 were co-expressed. These results suggest that phosphorylation of MafB by JNK confers susceptibility to proteasomal degradation.ArticleARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS. 494(1):94-100 (2010)journal articl

Automatic Filter Design for Synthesis of Haptic Textures from Recorded Acceleration Data

Sliding a probe over a textured surface generates a rich collection of vibrations that one can easily use to create a mental model of the surface. Haptic virtual environments attempt to mimic these real interactions, but common haptic rendering techniques typically fail to reproduce the sensations that are encountered during texture exploration. Past approaches have focused on building a representation of textures using a priori ideas about surface properties. Instead, this paper describes a process of synthesizing probe-surface interactions from data recorded from real interactions. We explain how to apply the mathematical principles of Linear Predictive Coding (LPC) to develop a discrete transfer function that represents the acceleration response under specific probe-surface interaction conditions. We then use this predictive transfer function to generate unique acceleration signals of arbitrary length. In order to move between transfer functions from different probe-surface interaction conditions, we develop a method for interpolating the variables involved in the texture synthesis process. Finally, we compare the results of this process with real recorded acceleration signals, and we show that the two correlate strongly in the frequency domain

Bendamustine Plus Rituximab as Salvage Treatment for Patients with Relapsed or Refractory Low-grade B-cell Lymphoma and Mantle Cell Lymphoma: A Single-Center Retrospective Study

Bendamustine plus rituximab (B-R) is an effective therapy for relapsed or refractory (r/r) low-grade B-cell lymphoma (LGBCL) and mantle cell lymphoma (MCL); however, clinical data from Japanese patients treated with B-R therapy are limited. We retrospectively evaluated the efficacy and safety of B-R therapy in 42 patients who received B-R therapy at our hospital for r/r LGBCL and MCL. All patients received intravenous (IV) ritux-imab 375 mg/m2 on day 1 and IV bendamustine 90 mg/m2 on days 2 and 3 every 28 days for up to 6 cycles. The common histologic subtypes were follicular lymphoma (n = 29, 70%), marginal zone lymphoma (n = 6, 14%), and MCL (n = 5, 12%). The overall response rate was 93%, with 62% complete response and complete response unconfirmed. The median progression-free survival (PFS) was 38 months (95% confidence interval [CI], 24.6 to not reached [NR]), and the median overall survival (OS) was 80 months (95% CI, 60.7 to NR). Patients receiving a cumulative dose of bendamustine ≥ 720 mg/m2 showed a significantly longer PFS and OS. Grade 3/4 adverse events (≥ 10%) included neutropenia (55%), lymphopenia (69%), and nausea (24%). B-R therapy was effective and well tolerated, and the cumulative dose of bendamustine was associated with a favorable outcome