Curcumin induces apoptosis of upper aerodigestive tract cancer cells by targeting multiple pathways

Curcumin, a natural compound isolated from the Indian spice Haldi or curry powder , has been used for centuries as a traditional remedy for many ailments. Recently, the potential use of curcumin in cancer prevention and therapy urges studies to uncover the molecular mechanisms associated with its anti-tumor effects. In the current manuscript, we investigated the mechanism of curcumin-induced apoptosis in upper aerodigestive tract cancer cell lines and showed that curcumin-induced apoptosis is mediated by the modulation of multiple pathways such as induction of p73, and inhibition of p-AKT and Bcl-2. Treatment of cells with curcumin induced both p53 and the related protein p73 in head and neck and lung cancer cell lines. Inactivation of p73 by dominant negative p73 significantly protected cells from curcumin-induced apoptosis, whereas ablation of p53 by shRNA had no effect. Curcumin treatment also strongly inhibited p-AKT and Bcl-2 and overexpression of constitutively active AKT or Bcl-2 significantly inhibited curcumin-induced apoptosis. Taken together, our findings suggest that curcumin-induced apoptosis is mediated via activating tumor suppressor p73 and inhibiting p-AKT and Bcl-2

GPU Concurrency: Weak Behaviours and Programming Assumptions

Concurrency is pervasive and perplexing, particularly on graphics processing units (GPUs). Current specifications of languages and hardware are inconclusive; thus programmers often rely on folklore assumptions when writing software. To remedy this state of affairs, we conducted a large empirical study of the concurrent behaviour of deployed GPUs. Armed with litmus tests (i.e. short concurrent programs), we questioned the assumptions in programming guides and vendor documentation about the guarantees provided by hardware. We developed a tool to generate thousands of litmus tests and run them under stressful workloads. We observed a litany of previously elusive weak behaviours, and exposed folklore beliefs about GPU programming---often supported by official tutorials---as false. As a way forward, we propose a model of Nvidia GPU hardware, which correctly models every behaviour witnessed in our experiments. The model is a variant of SPARC Relaxed Memory Order (RMO), structured following the GPU concurrency hierarchy

A role for SHPS-1/SIRPα in concanavalin A-dependent production of MMP-9

SHPS‐1/SIRPα1 is a transmembrane glycoprotein that belongs to the immunoglobulin (Ig) super family. In the present study, we show that SHPS‐1 strongly associates with Concanavalin A (Con A), a plant lectin obtained from jack beans. Further studies with SHPS‐1 mutants reveal that the extracellular domain of SHPS‐1 containing the Ig sequence is responsible for its association with Con A. Con A treatment induces cross‐linking and multimerization of the SHPS‐1 protein in the plasma membrane, accompanied by its tyrosine phosphorylation and recruitment of SHP‐2. In contrast, Ricinus communis agglutinin (RCA), another lectin obtained from castor bean, does not bind or activate tyrosine phosphorylation of SHPS‐1. Moreover, Con A activates Akt in a SHP‐2‐dependent manner. Treatment of mouse embryonic fibroblasts (MEFs) with Con A induces secretion of matrix metalloproteinase (MMP)‐9, a phenomenon that is inhibited in cells expressing YF mutant of SHPS‐1, a dominant negative form of Akt or in cells pre‐treated with an Akt inhibitor, LY294002 or extracellular‐signal regulated kinase (Erk) inhibitor, U0126. In addition, expression of the YF mutant of SHPS‐1 inhibits Con A‐dependent activation of Akt and Erk kinases. Taken together, our results suggest that SHPS‐1 is a receptor for Con A that mediates Con A‐dependent MMP‐9 secretion through SHP‐2‐promoted activation of both Akt and Erk pathways

SHP-2 tyrosine phosphatase inhibits p73-dependent apoptosis and expression of a subset of p53-target genes induced by the green tea polyphenol EGCG

Green tea polyphenol, epigallocatechin-3-gallate (EGCG) differentially regulates the cellular growth of cancer cells in a p53-dependent manner through apoptosis and/or cell cycle arrest. In an effort to further elucidate the mechanism of differential growth regulation by EGCG, we have investigated the role of the tyrosine phosphatase, SHP-2. Comparing the responses of mouse embryonic fibroblasts (MEFs), expressing either WT or functionally inactive/truncated SHP-2, we find that inactivation of SHP-2 remarkably sensitizes cells to EGCG-mediated killing. MEFs lacking functional SHP-2 undergo massive apoptosis upon treatment with EGCG. By comparing gene expression profiles, we have identified a set of transcriptional targets of p53 that are differentially modulated in cells undergoing apoptosis. Western blot and real-time PCR analyses of a select group of genes further confirm that the expression is SHP-2-dependent. Similar observations were made in MEFs lacking p53, confirming that the expression of these “p53 target genes” is p53-independent. In addition, EGCG treatment induced the expression of p73 mRNA and protein in both cell types, but not p63. Inactivation of p73 in cells expressing nonfunctional SHP-2 markedly inhibited apoptosis and p53 target gene expression. Although phosphorylation of JNK is differentially regulated by SHP2, it was found to be dispensable for EGCG-induced apoptosis and p53 target gene expression. Our results have identified SHP-2 as a negative regulator of EGCG-induced-apoptosis and have identified a subset of p53 target genes whose expression is paradoxically not mediated by p53 but by one of its family members, p73

Fetal movement counting using optical fibre sensors

Daily fetal movement counting based on maternal perception is widely deployed to monitor fetal wellbeing. However, the counting performed by the mother is prone to errors for various reasons. There are limited devices on the market that can provide reliable and automatic counting. This paper presents a prototype of a novel fetal movement monitoring device based on fibre Bragg grating sensors. Deformation of the skin caused by a fetal movement can lead to a change of the strain and stress on the optical fibre sensors, therefore can induce distortions to the breathing pattern of the mother. In the study data was gathered by the sensors through strain measurement and was post-processed using Independent Component Analysis and high-pass filtering to show the instances of the fetal movements. Information gathered during user trials with the prototype suggests that the system detects significantly higher numbers of fetus movements than that observed based on the mother's perception. Among the various techniques available for fetal movement monitoring, fibre optic sensing provides many advantages including; multiplex capability, flexibility and minimal size, making the concept an attractive solution for reliable monitoring of antenatal fetal movements

Antitumor Activity of 2,9-Di-\u3cem\u3eSec\u3c/em\u3e-Butyl-1,10-Phenanthroline

The anti-tumor effect of a chelating phen-based ligand 2,9-di-sec-butyl-1,10-phenanthroline (dsBPT) and its combination with cisplatin were examined in both lung and head and neck cancer cell lines and xenograft animal models in this study. The effects of this agent on cell cycle and apoptosis were investigated. Protein markers relevant to these mechanisms were also assessed. We found that the inhibitory effect of dsBPT on lung and head and neck cancer cell growth (IC50 ranged between 0.1–0.2 μM) was 10 times greater than that on normal epithelial cells. dsBPT alone induced autophagy, G1 cell cycle arrest, and apoptosis. Our in vivo studies indicated that dsBPT inhibited tumor growth in a dose-dependent manner in a head and neck cancer xenograft mouse model. The combination of dsBPT with cisplatin synergistically inhibited cancer cell growth with a combination index of 0.3. Moreover, the combination significantly reduced tumor volume as compared with the untreated control (p = 0.0017) in a head and neck cancer xenograft model. No organ related toxicities were observed in treated animals. Our data suggest that dsBPT is a novel and potent antitumor drug that warrants further preclinical and clinical development either as a single agent or in combination with known chemotherapy drugs such as cisplatin

Environmentally friendly analysis of emerging contaminants by pressurized hot water extraction-stir bar sorptive extraction-derivatization and gas chromatography-mass spectrometry

This work describes the development, optimiza- tion, and validation of a new method for the simultaneous determination of a wide range of pharmaceuticals (beta- blockers, lipid regulators ... ) and personal care products (fragrances, UV filters, phthalates ... ) in both aqueous and solid environmental matrices. Target compounds were extracted from sediments using pressurized hot water ex- traction followed by stir bar sorptive extraction. The first stage was performed at 1,500 psi during three static extrac- tion cycles of 5 min each after optimizing the extraction temperature (50 – 150 °C) and addition of organic modifiers (% methanol) to water, the extraction solvent. Next, aqueous extracts and water samples were processed using polydime- thylsiloxane bars. Several parameters were optimized for this technique, including extraction and desorption time, ionic strength, presence of organic modifiers, and pH. Fi- nally, analytes were extracted from the bars by ultrasonic irradiation using a reduced amount of solvent (0.2 mL) prior to derivatization and gas chromatography – mass spectrome- try analysis. The optimized protocol uses minimal amounts of organic solvents (<10 mL/sample) and time ( ≈ 8 h/sam- ple) compared to previous ex isting methodologies. Low standard deviation (usually below 10 %) and limits of de- tection (sub-ppb) vouch for the applicability of the method- ology for the analysis of target compounds at trace levels. Once developed, the method was applied to determin

CSR Communication Research: A Theoretical-cum-Methodological Perspective From Semiotics

Despite the proliferation of studies on corporate social responsibility (CSR), there is a lack of consensus and a cardinal methodological base for research on the quality of CSR communication. Over the decades, studies in this space have remained conflicting, unintegrated, and sometimes overlapping. Drawing on semiotics—a linguistic-based theoretical and analytical tool, our article explores an alternative perspective to evaluating the quality and reliability of sustainability reports. Our article advances CSR communication research by introducing a theoretical-cum-methodological perspective which provides unique insights into how to evaluate the quality of CSR communication. Particularly, we illustrate the application of our proposed methodology on selected U.K. FTSE 100 companies. Our two-phased analysis employed the Greimas Canonical Narrative Schema and the Semiotic Square of Veridiction in drawing meanings from selected sustainability/CSR reports. In addition, we present a distinctive CSR report quality model capable of guiding policy makers and firms in designing sustainability/CSR reporting standards