Vaccinia-Related Kinase 2 Mediates Accumulation of Polyglutamine Aggregates via Negative Regulation of the Chaperonin TRiC

Misfolding of proteins containing abnormal expansions of polyglutamine (polyQ) repeats is associated with cytotoxicity in several neurodegenerative disorders, including Huntington's disease. Recently, the eukaryotic chaperonin TRiC hetero-oligomeric complex has been shown to play an important role in protecting cells against the accumulation of misfolded polyQ protein aggregates. It is essential to elucidate how TRiC function is regulated to better understand the pathological mechanism of polyQ aggregation. Here, we propose that vaccinia-related kinase 2 (VRK2) is a critical enzyme that negatively regulates TRiC. In mammalian cells, overexpression of wild-type VRK2 decreased endogenous TRiC protein levels by promoting TRiC ubiquitination, but a VRK2 kinase-dead mutant did not. Interestingly, VRK2-mediated downregulation of TRiC increased aggregate formation of a polyQ-expanded huntingtin fragment. This effect was ameliorated by rescue of TRiC protein levels. Notably, small interference RNA-mediated knockdown of VRK2 enhanced TRiC protein stability and decreased polyQ aggregation. The VRK2-mediated reduction of TRiC protein levels was subsequent to the recruitment of COP1 E3 ligase. Among the members of the COP1 E3 ligase complex, VRK2 interacted with RBX1 and increased E3 ligase activity on TRiC in vitro. Taken together, these results demonstrate that VRK2 is crucial to regulate the ubiquitination-proteosomal degradation of TRiC, which controls folding of polyglutamine proteins involved in Huntington's disease.open118Ysciescopu

Selective requirement of H2B N-Terminal tail for p14ARF-induced chromatin silencing

The N-terminal tail of histone H2B is believed to be involved in gene silencing, but how it exerts its function remains elusive. Here, we report the biochemical characterization of p14ARF tumor suppressor as a transcriptional repressor that selectively recognizes the unacetylated H2B tails on nucleosomes. The p14ARF–H2B tail interaction is functional, as the antagonistic effect of p14ARF on chromatin transcription is lost upon deletion or acetylation of H2B tails. Gene expression profiling and chromatin immunoprecipitation studies emphasize the significance of H2B deacetylation and p14ARF recruitment in establishing a repressive environment over the cell cycle regulatory genes. Moreover, HDAC1-mediated H2B deacetylation, especially at K20, constitutes an essential step in tethering p14ARF near target promoters. Our results thus reveal a hitherto unknown role of p14ARF in the regulation of chromatin transcription, as well as molecular mechanisms governing the repressive action of p14ARF

Vacuum Leak Detection Method Using Index Regression and Correction for Semiconductor Equipment in a Vacuum Chamber

In semiconductor manufacturing, fault detection is an important method for monitoring equipment condition and examining the potential causes of a fault. Vacuum leakage is considered one of the major faults that can occur in semiconductor processing. An unnecessary O2 and N2 mixture, a major component of the atmosphere, creates unexpected process results and hence drops in yield. Vacuum leak detection systems that are currently available in the vacuum industry are based on helium mass spectrometers. They are used for detecting the vacuum leakage at the sole isolation condition where the chamber is fully pumped but cannot be used for in situ detection while the process is ongoing in the chamber. In this article, a chamber vacuum leak detection method named Index Regression and Correction (IRC) is presented, utilizing common data which were gathered during normal chamber operation. This method was developed by analyzing a simple list of data, such as pressure, the temperature of the chamber body, and the position of the auto pressure control (APC), to detect any leakages in the vacuum chamber. The proposed method was experimentally verified and the results showed a high accuracy of up to 97% when a vacuum leak was initiated in the chamber. The proposed method is expected to improve the process yield of the chamber by detecting even small vacuum leakages at very early stages of the process

Vacuum Leak Detection Method Using Index Regression and Correction for Semiconductor Equipment in a Vacuum Chamber

In semiconductor manufacturing, fault detection is an important method for monitoring equipment condition and examining the potential causes of a fault. Vacuum leakage is considered one of the major faults that can occur in semiconductor processing. An unnecessary O2 and N2 mixture, a major component of the atmosphere, creates unexpected process results and hence drops in yield. Vacuum leak detection systems that are currently available in the vacuum industry are based on helium mass spectrometers. They are used for detecting the vacuum leakage at the sole isolation condition where the chamber is fully pumped but cannot be used for in situ detection while the process is ongoing in the chamber. In this article, a chamber vacuum leak detection method named Index Regression and Correction (IRC) is presented, utilizing common data which were gathered during normal chamber operation. This method was developed by analyzing a simple list of data, such as pressure, the temperature of the chamber body, and the position of the auto pressure control (APC), to detect any leakages in the vacuum chamber. The proposed method was experimentally verified and the results showed a high accuracy of up to 97% when a vacuum leak was initiated in the chamber. The proposed method is expected to improve the process yield of the chamber by detecting even small vacuum leakages at very early stages of the process

Eventually Periodic Points of Infra-Nil Endomorphisms

<p/> <p>Hyperbolic toral automorphisms provide important examples of chaotic dynamical systems. Generalizing automorphisms on tori, we study (infra-)nil endomorphisms defined on (infra-)nilmanifolds. In particular, we show that every infra-nil endomorphism has dense eventually periodic points.</p

Dual Roles of Serine-Threonine Kinase Receptor-Associated Protein (STRAP) in Redox-Sensitive Signaling Pathways Related to Cancer Development

Serine-threonine kinase receptor-associated protein (STRAP) is a transforming growth factor β (TGF-β) receptor-interacting protein that has been implicated in both cell proliferation and cell death in response to various stresses. However, the precise roles of STRAP in these cellular processes are still unclear. The mechanisms by which STRAP controls both cell proliferation and cell death are now beginning to be unraveled. In addition to its biological roles, this review also focuses on the dual functions of STRAP in cancers displaying redox dysregulation, where it can behave as a tumor suppressor or an oncogene (i.e., it can either inhibit or promote tumor formation), depending on the cellular context. Further studies are needed to define the functions of STRAP and the redox-sensitive intracellular signaling pathways that enhance either cell proliferation or cell death in human cancer tissues, which may help in the development of effective treatments for cancer

Capsaicin inhibits platelet-activating factor-induced cytosolic Ca2+ rise and superoxide production.

Platelet-activating factor (PAF) is an important participant in the inflammatory process. We studied the regulation of PAF activity by capsaicin in human promyelocytic leukemia HL-60 cells. Capsaicin inhibited PAF-induced superoxide production in a concentration-dependent manner. In addition to PAF, the fMLP- and extracellular ATP-induced superoxide productions were inhibited by capsaicin, whereas PMA-induced superoxide production was not affected. In the PAF-stimulated cytosolic Ca21 increase, capsaicin inhibited in particular the sustained portion of the raised Ca21 level without attenuation of the peak height. In the absence of extracellular Ca21, the PAF-induced Ca21 elevation was not inhibited by capsaicin because capsaicin only inhibited the Ca21 influx from the extracellular space. In addition, capsaicin did not affect PAF-induced inositol 1,4,5-trisphosphate production, suggesting that phospholipase C activation by PAF is not affected by capsaicin. Store-operated Ca21 entry (SOCE) induced by thapsigargin was inhibited by capsaicin in a concentration-dependent manner. This capsaicin effect was also observed on thapsigargin-induced Ba21 and Mn21 influx. Furthermore, capsaicins inhibitory effect on the thapsigargin-induced Ca21 rise overlapped with that of SK&F96365, an inhibitor of SOCE. Both capsaicin and SK&F96365 also inhibited PAF-induced cytosolic superoxide generation in HL-60 cells differentiated by all-trans-retinoic acid. Our data suggest that capsaicin exerts its anti-inflammatory effect by inhibiting SOCE elicited via PLC activation, which occurs upon PAF activation and results in the subsequent superoxide production.This work was supported by grants from the Korea Research Foundation, National Research Laboratory Program by the Ministry of Science and Technology, and the Brain Science and Engineering Research Program sponsored by the Ministry of Science and Technology (1998). This study was also supported by the Brain Korea Program from the Ministry of Education