1,285 research outputs found

    The mTORC2 Component Rictor Contributes to Cisplatin Resistance in Human Ovarian Cancer Cells

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    This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Resistance to cisplatin-based therapy is a major cause of treatment failure in human ovarian cancer. A better understanding of the mechanisms of cisplatin resistance will offer new insights for novel therapeutic strategies for this deadly disease. Akt and p53 are determinants of cisplatin sensitivity. Rictor is a component of mTOR protein kinase complex 2, which is required for Akt phosphorylation (Ser473) and full activation. However, the precise role of rictor and the relationship between rictor and p53 in cisplatin resistance remains poorly understood. Here, using sensitive wild-type p53 (OV2008 and A2780s), resistant wild-type p53 (C13* and OVCAR433), and p53 compromised (A2780cp, OCC1, and SKOV-3) ovarian cancer cells, we have demonstrated that (i) rictor is a determinant of cisplatin resistance in chemosensitive human ovarian cancer cells; (ii) cisplatin down-regulates rictor content by caspase-3 cleavage and proteasomal degradation; (iii) rictor down-regulation sensitizes chemo-resistant ovarian cancer cells to cisplatin-induced apoptosis in a p53-dependent manner; (iv) rictor suppresses cisplatin-induced apoptosis and confers resistance by activating and stabilizing Akt. These findings extend current knowledge on the molecular and cellular basis of cisplatin resistance and provide a rationale basis for rictor as a potential therapeutic target for chemoresistant ovarian cancer

    Azide-Alkyne Huisgen [3+2] Cycloaddition Using CuO Nanoparticles

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    Recent developments in the synthesis of CuO nanoparticles (NPs) and their application to the [3+2] cycloaddition of azides with terminal alkynes are reviewed. With respect to the importance of click chemistry, CuO hollow NPs, CuO hollow NPs on acetylene black, water-soluble double-hydrophilic block copolymer (DHBC) nanoreactors and ZnO-CuO hybrid NPs were synthesized. Non-conventional energy sources such as microwaves and ultrasound were also applied to these click reactions, and good catalytic activity with high regioselectivity was observed. CuO hollow NPs on acetylene black can be recycled nine times without any loss of activity, and water-soluble DHBC nanoreactors have been developed for an environmentally friendly process.open6

    Air-stable van der Waals PtTe2 conductors with high current-carrying capacity and strong spin- orbit interaction

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    High-performance van der Waals (vdW) integrated electronics and spintronics require reliable current-carrying capacity. However, it is challenging to achieve high current density and air-stable performance using vdW metals owing to the fast electrical breakdown triggered by defects or oxidation. Here, we report that spin-orbit interacted synthetic PtTe2 layers exhibit significant electrical reliability and robustness in ambient air. The 4-nm-thick PtTe2 synthesized at a low temperature (similar to 400 degrees C) shows intrinsic metallic transport behavior and a weak antilocalization effect attributed to the strong spin-orbit scattering. Remarkably, PtTe2 sustains a high current density approaching approximate to 31.5 MA cm(-2), which is the highest value among electrical interconnect candidates under oxygen exposure. Electrical failure is caused by the Joule heating of PtTe2 rather than defect-induced electromigration, which was achievable by the native TeOx passivation. The high-quality growth of PtTe2 and the investigation of its transport behaviors lay out essential foundations for the development of emerging vdW spin-orbitronics

    Global Industry Reorganization and Market Concentration : Automobiles, Steel, and Airlines

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    Glioblastoma multiforme (GBM) is a deadly primary brain malignancy. Glioblastoma stem cells (GSC), which have the ability to self-renew and differentiate into tumor lineages, are believed to cause tumor recurrence due to their resistance to current therapies. A subset of GSCs is marked by cell surface expression of CD133, a glycosylated pentaspan transmembrane protein. The study of CD133-expressing GSCs has been limited by the relative paucity of genetic tools that specifically target them. Here, we present CD133-LV, a lentiviral vector presenting a single chain antibody against CD133 on its envelope, as a vehicle for the selective transduction of CD133-expressing GSCs. We show that CD133-LV selectively transduces CD133+ human GSCs in dose-dependent manner and that transduced cells maintain their stem-like properties. The transduction efficiency of CD133-LV is reduced by an antibody that recognizes the same epitope on CD133 as the viral envelope and by shRNA-mediated knockdown of CD133. Conversely, the rate of transduction by CD133-LV is augmented by overexpression of CD133 in primary human GBM cultures. CD133-LV selectively transduces CD133-expressing cells in intracranial human GBM xenografts in NOD.SCID mice, but spares normal mouse brain tissue, neurons derived from human embryonic stem cells and primary human astrocytes. Our findings indicate that CD133-LV represents a novel tool for the selective genetic manipulation of CD133-expressing GSCs, and can be used to answer important questions about how these cells contribute to tumor biology and therapy resistance

    First Among Equals: The Effect of Team Leader Characteristics on the Internal Dynamics of Cross-Functional Product Development Teams

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    Drawing upon the Path-Goal Theory of leadership, this study examines the effect of team leader characteristics on an array of conflict resolution behavior, collaboration, and communication patterns of cross-functional new product development (NPD) teams. A hierarchical linear model analysis based on a survey of 246 members from 64 NPD teams suggests that participative management style and initiation of goal structure by the team leader exert the strongest influence on internal team dynamics. Both these leadership characteristics had a positive effect on functional conflict resolution, collaboration, and communication quality within the NPD team; while discouraging dysfunctional conflict resolution and formal communications. Comparatively, team leaderā€™s consideration, initiation of process structure, and position had a surprisingly weak effect on internal team dynamics. Further the findings underscore the differential effects on various dimensions of team dynamics, the importance of controlling for project and team characteristics, and the use of multi-level modeling for studying nested phenomena related to NPD teams. Implications of these findings are discussed

    Earlier snowmelt may lead to late season declines in plant productivity and carbon sequestration in Arctic tundra ecosystems

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    Arctic warming is affecting snow cover and soil hydrology, with consequences for carbon sequestration in tundra ecosystems. The scarcity of observations in the Arctic has limited our understanding of the impact of covarying environmental drivers on the carbon balance of tundra ecosystems. In this study, we address some of these uncertainties through a novel record of 119 site-years of summer data from eddy covariance towers representing dominant tundra vegetation types located on continuous permafrost in the Arctic. Here we found that earlier snowmelt was associated with more tundra net CO2 sequestration and higher gross primary productivity (GPP) only in June and July, but with lower net carbon sequestration and lower GPP in August. Although higher evapotranspiration (ET) can result in soil drying with the progression of the summer, we did not find significantly lower soil moisture with earlier snowmelt, nor evidence that water stress affected GPP in the late growing season. Our results suggest that the expected increased CO2 sequestration arising from Arctic warming and the associated increase in growing season length may not materialize if tundra ecosystems are not able to continue sequestering CO2 later in the season

    Earlier snowmelt may lead to late season declines in plant productivity and carbon sequestration in Arctic tundra ecosystems

    Get PDF
    Arctic warming is affecting snow cover and soil hydrology, with consequences for carbon sequestration in tundra ecosystems. The scarcity of observations in the Arctic has limited our understanding of the impact of covarying environmental drivers on the carbon balance of tundra ecosystems. In this study, we address some of these uncertainties through a novel record of 119 site-years of summer data from eddy covariance towers representing dominant tundra vegetation types located on continuous permafrost in the Arctic. Here we found that earlier snowmelt was associated with more tundra net CO2 sequestration and higher gross primary productivity (GPP) only in June and July, but with lower net carbon sequestration and lower GPP in August. Although higher evapotranspiration (ET) can result in soil drying with the progression of the summer, we did not find significantly lower soil moisture with earlier snowmelt, nor evidence that water stress affected GPP in the late growing season. Our results suggest that the expected increased CO2 sequestration arising from Arctic warming and the associated increase in growing season length may not materialize if tundra ecosystems are not able to continue sequestering CO2 later in the season.Peer reviewe

    Characterization of grapevine leafroll-associated virus 3 genetic variants and application towards RT-qPCR assay design

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    Grapevine leafroll-associated virus 3 (GLRaV-3) is the most widely prevalent and economically important of the complex of RNA viruses associated with grapevine leafroll disease (GLD). Phylogenetic studies have grouped GLRaV-3 isolates into nine different monophyletic groups and four supergroups, making GLRaV-3 a genetically highly diverse virus species. In addition, new divergent variants have been discovered recently around the world. Accurate identification of the virus is an essential component in the management and control of GLRaV-3; however, the diversity of GLRaV-3, coupled with the limited sequence information, have complicated the development of a reliable detection assay. In this study, GLRaV-3 sequence data available in GenBank and those generated at Foundation Plant Services, University of California-Davis, was used to develop a new RT-qPCR assay with the capacity to detect all known GLRaV-3 variants. The new assay, referred to as FPST, was challenged against samples that included plants infected with different GLRaV-3 variants and originating from 46 countries. The FPST assay detected all known GLRaV-3 variants, including the highly divergent variants, by amplifying a small highly conserved region in the 3' untranslated terminal region (UTR) of the virus genome. The reliability of the new RT-qPCR assay was confirmed by an enzyme linked immunosorbent assay (ELISA) that can detect all known GLRaV-3 variants characterized to date. Additionally, three new GLRaV-3 divergent variants, represented by four isolates, were identified using a hierarchical testing process involving the FPST assay, GLRaV-3 variant-specific assays and high-throughput sequencing analysis. These variants were distantly related to groups I, II, III, V, VI, VII and IX, but much similar to GLRaV-3 variants with no assigned group; thus, they may represent new clades. Finally, based on the phylogenetic analysis, a new GLRaV-3 subclade is proposed and named as group X.Alfredo Diaz-Lara, Vicki Klaassen, Kristian Stevens, Mysore R. Sudarshana, Adib Rowhani ... Nuredin Habili ... et al
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