Spliceosome-targeted therapies trigger an antiviral immune response in triple-negative breast cancer

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Importance of glucose-6-phosphate dehydrogenase in taxol biosynthesis in <Emphasis Type="Italic">Taxus chinensis</Emphasis> cultures

The roles of glucose-6-phosphate dehydrogenase (G6PDH) in paclitaxel production were investigated in cell suspension cultures of Taxus chinensis. In the normal cultures, the trend of G6PDH activity was similar to that of cell growth. Addition of glutamate increased G6PDH activity, while dehydroepiandrosterone (DHEA) decreased G6PDH activity. In elicitor-treated cultures, cell growth was depressed, while G6PDH activity and taxol production were enhanced compared with the control. Glutamate recovered the depression of cell growth, and resulted in further increase in G6PDH activity and taxol production. Contrarily, DHEA exacerbated the depression of cell growth, and decreased G6PDH activity and taxol production induced by fungal elicítor. The results indicated that G6PDH played a critic role of taxol production by affecting cell viability.     

A taxonomy of application scheduling tools for high performance cluster computing

Application scheduling plays an important role in high-performance cluster computing. Application scheduling can be classified as job scheduling and task scheduling. This paper presents a survey on the software tools for the graph-based scheduling on cluster systems with the focus on task scheduling. The tasks of a parallel or distributed application can be properly scheduled onto multi-processors in order to optimize the performance of the program (e.g., execution time or resource utilization). In general, scheduling algorithms are designed based on the notion of task graph that represents the relationship of parallel tasks. The scheduling algorithms map the nodes of a graph to the processors in order to minimize overall execution time. Although many scheduling algorithms have been proposed in the literature, surprisingly not many practical tools can be found in practical use. After discussing the fundamental scheduling techniques, we propose a framework and taxonomy for the scheduling tools on clusters. Using this framework, the features of existing scheduling tools are analyzed and compared. We also discuss the important issues in improving the usability of the scheduling tools. This work is supported by the Hong Kong Polytechnic University under grant H-ZJ80 and by NASA Ames Research Center by a cooperative grant agreement with the University of Texas at Arlington. Jiannong Cao received the BSc degree in computer science from Nanjing University, Nanjing, China in 1982, and the MSc and the Ph.D degrees in computer science from Washington State University, Pullman, WA, USA, in 1986 and 1990 respectively. He is currently an associate professor in Department of Computing at the Hong Kong Polytechnic University, Hong Kong. He is also the director of the Internet and Mobile Computing Lab in the department. He was on the faculty of computer science at James Cook University and University of Adelaide in Australia, and City University of Hong Kong. His research interests include parallel and distributed computing, networking, mobile computing, fault tolerance, and distributed software architecture and tools. He has published over 120 technical papers in the above areas. He has served as a member of editorial boards of several international journals, a reviewer for international journals/conference proceedings, and also as an organizing/programme committee member for many international conferences. Dr. Cao is a member of the IEEE Computer Society, the IEEE Communication Society, IEEE, and ACM. He is also a member of the IEEE Technical Committee on Distributed Processing, IEEE Technical Committee on Parallel Processing, IEEE Technical Committee on Fault Tolerant Computing, and Computer Architecture Professional Committee of the China Computer Federation. Alvin Chan is currently an assistant professor at the Hong Kong Polytechnic University. He graduated from the University of New South Wales with a Ph.D. degree in 1995 and was subsequently employed as a Research Scientist by the CSIRO, Australia. From 1997 to 1998, he was employed by the Centre for Wireless Communications, National University of Singapore as a Program Manager. Dr. Chan is one of the founding members and director of a university spin-off company, Information Access Technology Limited. He is an active consultant and has been providing consultancy services to both local and overseas companies. His research interests include mobile computing, context-aware computing and smart card applications. Yudong Sun received the B.S. and M.S. degrees from Shanghai Jiao Tong University, China. He received Ph.D. degree from the University of Hong Kong in 2002, all in computer science. From 1988 to 1996, he was among the teaching staff in Department of Computer Science and Engineering at Shanghai Jiao Tong University. From 2002 to 2003, he held a research position at the Hong Kong Polytechnic University. At present, he is a Research Associate in School of Computing Science at University of Newcastle upon Tyne, UK. His research interests include parallel and distributed computing, Web services, Grid computing, and bioinformatics. Sajal K. Das is currently a Professor of Computer Science and Engineering and the Founding Director of the Center for Research in Wireless Mobility and Networking (CReWMaN) at the University of Texas at Arlington. His current research interests include resource and mobility management in wireless networks, mobile and pervasive computing, sensor networks, mobile internet, parallel processing, and grid computing. He has published over 250 research papers, and holds four US patents in wireless mobile networks. He received the Best Paper Awards in ACM MobiCom’99, ICOIN-16, ACM, MSWiM’00 and ACM/IEEE PADS’97. Dr. Das serves on the Editorial Boards of IEEE Transactions on Mobile Computing, ACM/Kluwer Wireless Networks, Parallel Processing Letters, Journal of Parallel Algorithms and Applications. He served as General Chair of IEEE PerCom’04, IWDC’04, MASCOTS’02 ACM WoWMoM’00-02; General Vice Chair of IEEE PerCom’03, ACM MobiCom’00 and IEEE HiPC’00-01; Program Chair of IWDC’02, WoWMoM’98-99; TPC Vice Chair of ICPADS’02; and as TPC member of numerous IEEE and ACM conferences. Minyi Guo received his Ph.D. degree in information science from University of Tsukuba, Japan in 1998. From 1998 to 2000, Dr. Guo had been a research scientist of NEC Soft, Ltd. Japan. He is currently a professor at the Department of Computer Software, The University of Aizu, Japan. From 2001 to 2003, he was a visiting professor of Georgia State University, USA, Hong Kong Polytechnic University, Hong Kong. Dr. Guo has served as general chair, program committee or organizing committee chair for many international conferences, and delivered more than 20 invited talks in USA, Australia, China, and Japan. He is the editor-in-chief of the Journal of Embedded Systems. He is also in editorial board of International Journal of High Performance Computing and Networking, Journal of Embedded Computing, Journal of Parallel and Distributed Scientific and Engineering Computing, and International Journal of Computer and Applications. Dr. Guo’s research interests include parallel and distributed processing, parallelizing compilers, data parallel languages, data mining, molecular computing and software engineering. He is a member of the ACM, IEEE, IEEE Computer Society, and IEICE. He is listed in Marquis Who’s Who in Science and Engineering.     

Zinc Transporter 7 Induced by High Glucose Attenuates Epithelial-to-Mesenchymal Transition of Peritoneal Mesothelial Cells

Zinc (Zn) is an essential micronutrient and cytoprotectant involved in preventing many types of epithelial-to-mesenchymal transition (EMT)-driven fibrosis in vivo. The zinc-transporter family SLC30A (ZnT) is a pivotal factor in the regulation of Zn homeostasis. However, its function in EMT in peritoneal mesothelial cells (PMCs) remains unknown. This study explored the regulation of zinc transporters and the role they play in cell EMT, particularly in rat peritoneal mesothelial cells (RPMCs), surrounding glucose concentrations and the molecular mechanism involved. The effects of high glucose (HG) on zinc transporter gene expression were measured in RPMCs by real-time PCR. We explored ZnT7 (Slc30A7): the effect of ZnT7 over-expression and siRNA-mediated knock-down on HG-induced EMT was investigated as well as the underlying molecular mechanisms. Over-expression of ZnT7 resulted in significantly inhibited HG-induced EMT in RPMCs, while inhibition of ZnT7 expression using a considerable siRNA-mediated knock-down of RPMCs increased the levels of EMT. Furthermore, over-expression of ZnT7 is accompanied by down-regulation of TGF-β/Smad pathway, phospho-Smad3,4 expression levels. The finding suggests that the zinc-transporting system in RPMCs is influenced by the exposure to HG. The ZnT7 may account for the inhibition of HG-induced EMT in RPMCs, likely through targeting TGF-β/Smad signaling.     

Growth on Geological Time Scales in the Antarctic Cryptoendolithic Microbial Community

In the process of biogenous weathering of Beacon sandstone in the McMurdo Dry Valleys (Ross Desert), Antarctica, periods of microbial growth, on the time scale of 103-104 years, alternate with sudden exfoliation events. The present study addressed the question of whether microbial growth is continuous between exfoliation events or whether each exfoliation is followed by a period of comparatively rapid growth and then an extended period of steady state. The color intensity (Munsell lightness value) of the rock surface is an indicator of relative age of the crust within the exfoliation cycle, permitting measurement of changes in microbial biomass on a geological time scale. Results indicate that microbial growth is continuous and that exfoliation occurs when the microbial biomass reaches the carrying capacity of the cryptoendolithic habitat.     

Influence of Arsenate on Lipid Peroxidation Levels and Antioxidant Enzyme Activities in Bacillus cereus Strain XZM002 Isolated from High Arsenic Aquifer Sediments

Bacillus cereus strain XZM002 isolated from high arsenic aquifer sediments of Datong Basin was applied to examine the effects of arsenate stress on antioxidant enzyme activities, lipid peroxidation levels and cell growth inhibition rate. After 2 d exposure, the cell growth inhibition rate enhanced with an increase of As(V) concentrations (0, 800, 1600 μg/l). Reactive oxygen species and glutathione contents, lipid peroxidation levels, and antioxidant enzymes (glutathione peroxidase, and other three) activities of the treated cells were significantly higher than those of the controls during 3 d exposure (p < 0.05). Besides, the levels of nine parameters reached maximum after 2 d exposure and increased significantly with increasing arsenate stress (p < 0.05). However, they returned to levels similar to those of the control on the fourth day of exposure. The results suggested that the antioxidant defense system in B. cereus strain XZM002 could protect the cells from oxidative damage induced by arsenate.     

Sinomenine hydrochloride enhancement of the inhibitory effects of anti-transferrin receptor antibody-dependent on the COX-2 pathway in human hepatoma cells

Transferrin receptor (TfR) has been used as a target for the antibody-based therapy of cancer due to its higher expression in tumors relative to normal tissues. Great potential has been shown by anti-TfR antibodies combined with chemotherapeutic drugs as a possible cancer therapeutic strategy. In our study, we investigated the anti-tumor effects of anti-TfR monoclonal antibody (mAb) alone or in combination with sinomenine hydrochloride in vitro. Results suggested that anti-TfR mAb or sinomenine hydrochloride could induce apoptosis, inhibit proliferation, and affect the cell cycle. A synergistic effect was found in relation to tumor growth inhibition and the induction of apoptosis when anti-TfR mAb and sinomenine hydrochloride were used simultaneously. The expression of COX-2 and VEGF protein in HepG2 cells treated with anti-TfR mAb alone was increased in line with increasing dosage of the agent. In contrast, COX-2 expression was dramatically decreased in HepG2 cells treated with sinomenine hydrochloride alone. Furthermore, we demonstrated that the inhibitory effects of sinomenine hydrochloride and anti-TfR mAb administered in combination were more prominent than when the agents were administered singly. To sum up, these results showed that the combined use of sinomenine hydrochloride and anti-TfR mAb may exert synergistic inhibitory effects on human hepatoma HepG2 cells in a COX-2-dependent manner. This finding provides new insight into how tumor cells overcome the interference of iron intake to survive and forms the basis of a new therapeutic strategy involving the development of anti-TfR mAb combined with sinomenine hydrochloride for liver cancer.     

Characterization of Basal and Morphine-Induced Uridine Release in the Striatum: An In Vivo Microdialysis Study in Mice

Uridine, a pyrimidine nucleoside, has been proposed to be a potential signaling molecule in the central nervous system. The understanding of uridine release in the brain is therefore of fundamental importance. The present study was performed to determine the characteristics of basal and morphine-induced uridine release in the striatum of freely moving mice by using the microdialysis technique. To ascertain whether extracellular uridine was derived from neuronal release, the following criteria were applied: sensitivity to (a) K⁺ depolarization, (b) Na⁺ channel blockade and (c) removal of extracellular Ca²⁺. Uridine levels were not greatly affected by infusion of tetrodotoxin (TTX) and were unaffected by either Ca²⁺-free medium or in the presence of EGTA (a calcium chelator), suggesting that basal extracellular uridine levels were maintained mainly by non-vesicular release mechanisms. In addition, both systemic and local application of morphine increased striatal uridine release. The morphine-induced release was reversed by naloxone pretreatment, but was unaffected by TTX or EGTA infusion. Moreover, co-administration of morphine and nitrobenzylthioinosine (NBTI, an inhibitor of nucleotide transporter) produced increases of uridine levels similar to that produced by NBTI or morphine alone, suggesting a nucleotide transporter mechanism involved. Taken together, these findings suggest that morphine produces a μ-opioid receptor-mediated uridine release via nucleoside transporters in a TTX- and calcium-independent manner.     

Inhibition of DNA damage repair by artificial activation of PARP with siDNA

One of the major early steps of repair is the recruitment of repair proteins at the damage site, and this is coordinated by a cascade of modifications controlled by phosphatidylinositol 3-kinase-related kinases and/or poly (ADP-ribose) polymerase (PARP). We used short interfering DNA molecules mimicking double-strand breaks (called Dbait) or single-strand breaks (called Pbait) to promote DNA-dependent protein kinase (DNA-PK) and PARP activation. Dbait bound and induced both PARP and DNA-PK activities, whereas Pbait acts only on PARP. Therefore, comparative study of the two molecules allows analysis of the respective roles of the two signaling pathways: both recruit proteins involved in single-strand break repair (PARP, XRCC1 and PCNA) and prevent their recruitment at chromosomal damage. Dbait, but not Pbait, also inhibits recruitment of proteins involved in double-strand break repair (53BP1, NBS1, RAD51 and DNA-PK). By these ways, Pbait and Dbait disorganize DNA repair, thereby sensitizing cells to various treatments. Single-strand breaks repair inhibition depends on direct trapping of the main proteins on both molecules. Double-strand breaks repair inhibition may be indirect, resulting from the phosphorylation of double-strand breaks repair proteins and chromatin targets by activated DNA-PK. The DNA repair inhibition by both molecules is confirmed by their synthetic lethality with BRCA mutations.