Functional enhancement of neuronal cell behaviors and differentiation by elastin-mimetic recombinant protein presenting Arg-Gly-Asp peptides

Background: Integrin-mediated interaction of neuronal cells with extracellular matrix (ECM) is important for the control of cell adhesion, morphology, motility, and differentiation in both in vitro and in vivo systems. Arg-Gly-Asp (RGD) sequence is one of the most potent integrin-binding ligand found in many native ECM proteins. An elastin-mimetic recombinant protein, TGPG[VGRGD(VGVPG)6]20WPC, referred to as [RGD-V6]20, contains multiple RGD motifs to bind cell-surface integrins. This study aimed to investigate how surface-adsorbed recombinant protein can be used to modulate the behaviors and differentiation of neuronal cells in vitro. For this purpose, biomimetic ECM surfaces were prepared by isothermal adsorption of [RGD-V6]20 onto the tissue culture polystyrene (TCPS), and the effects of protein-coated surfaces on neuronal cell adhesion, spreading, migration, and differentiation were quantitatively measured using N2a neuroblastoma cells.Results: The [RGD-V6]20 was expressed in E. coli and purified by thermally-induced phase transition. N2a cell attachment to either [RGD-V6]20 or fibronectin followed hyperbolic binding kinetics saturating around 2 μM protein concentration. The apparent maximum cell binding to [RGD-V6]20 was approximately 96% of fibronectin, with half-maximal adhesion on [RGD-V6]20 and fibronectin occurring at a coating concentration of 2.4 × 10-7 and 1.4 × 10-7 M, respectively. The percentage of spreading cells was in the following order of proteins: fibronectin (84.3% ± 6.9%) > [RGD-V6]20 (42.9% ± 6.5%) > [V7]20 (15.5% ± 3.2%) > TCPS (less than 10%). The migration speed of N2a cells on [RGD-V6]20 was similar to that of cells on fibronectin. The expression of neuronal marker proteins Tuj1, MAP2, and GFAP was approximately 1.5-fold up-regulated by [RGD-V6]20 relative to TCPS. Moreover, by the presence of both [RGD-V6]20 and RA, the expression levels of NSE, TuJ1, NF68, MAP2, and GFAP were significantly elevated.Conclusion: We have shown that an elastin-mimetic protein consisting of alternating tropoelastin structural domains and cell-binding RGD motifs is able to stimulate neuronal cell behaviors and differentiation. In particular, adhesion-induced neural differentiation is highly desirable for neural development and nerve repair. In this context, our data emphasize that the combination of biomimetically engineered recombinant protein and isothermal adsorption approach allows for the facile preparation of bioactive matrix or coating for neural tissue regeneration. © 2012 Jeon et al.; licensee BioMed Central Ltd.1

H727 Cells Are Inherently Resistant to the Proteasome Inhibitor Carfilzomib, Yet Require Proteasome Activity for Cell Survival and Growth

The second-in-class proteasome inhibitor (PI) carfilzomib (Kyprolis, Cfz) has contributed to a substantial advancement in multiple myeloma treatment by improving patient survival and quality of life. A considerable portion of patients however display intrinsic resistance to Cfz. Our mechanistic understanding of intrinsic Cfz resistance is limited due to a lack of suitable cell-based models. We report that H727 human bronchial carcinoid cells are inherently resistant to Cfz, yet susceptible to other PIs and inhibitors targeting upstream components of the ubiquitin-proteasome system (UPS). These results indicate that H727 cells remain dependent on the UPS for cell survival and growth despite harboring intrinsic resistance to Cfz. Alterations in the composition of proteasome catalytic subunits via interferon-γ treatment or siRNA knockdown results in sensitization of H727 cells to Cfz. We postulate that a potential link may exist between the composition of proteasome catalytic subunits and the cellular response to Cfz. Overall, H727 cells may serve as a useful cell-based model for de novo Cfz resistance and our results suggest previously unexplored mechanisms of de novo PI resistance

Pengaruh Tingkat Inflasi, Tingkat Suku Bunga SBI, Nilai Tukar Rupiah, Indeks Dow Jones, Dan Indeks Klse Terhadap Indeks Harga Saham Gabungan (Ihsg) Studi Pada Bursa Efek Indonesia Periode Januari 2010 – Desember 2013

This research aimed to know the effect of inflation rate, SBI rate, Rupiah exchange rate, Dow Jones index, KLSE index towards Composite Stock Price Index (CSPI). Types of research used in explanatory research with quantitative approach. The sample was based on monthly time series data from January 2010 - December 2013, used full sampling method which consist of 48 samples. This research used multiple linear regression method. The value coefficient of determination (R2) 0,84, means the independent variables inflation rate, SBI rate, Rupiah exchange rate, Dow Jones index, KLSE index, explain the dependent variable Composite Stock Price Index (CSPI) up to 84% and the remaining 16% explained by the other that had not been examined. Simultaneous test result (F test), indicating that inflation rate, SBI rate, Rupiah exchange rate, Dow Jones index, KLSE index has significant effect on the Composite Stock Price Index (CSPI) simultaneously. Partial test result (t test), indicates that inflation rate showed a insignificant influence on CSPI, while SBI rate and Rupiah exchange rate had a negative effect and significant to CSPI, Dow Jones index and KLSE index had a positive and significant to CSPI. The most dominant influential variable in this research is Dow Jones Index

Efficient hybrid organic-inorganic light emitting diodes with self-assembled dipole molecule deposited metal oxides

We investigate the effect of self-assembled dipole molecules (SADMs) on ZnO surface in hybrid organic-inorganic polymeric light-emitting diodes (HyPLEDs). Despite the SADM being extremely thin, the magnitude and orientation of SADM dipole moment effectively influenced the work function of the ZnO. As a consequence, the charge injection barrier between the conduction band of the ZnO and the lowest unoccupied molecular orbital of poly(9,9(')-dioctylfluorene)-co-benzothiadiazole could be efficiently controlled resulting that electron injection efficiency is remarkably enhanced. The HyPLEDs modified with a negative dipolar SADM exhibited enhanced device performances, which correspond to approximately a fourfold compared to those of unmodified HyPLEDs.open442

β-Lapachone Significantly Increases the Effect of Ionizing Radiation to Cause Mitochondrial Apoptosis via JNK Activation in Cancer Cells

β-lapachone (β-lap), has been known to cause NQO1-dependnet death in cancer cells and sensitize cancer cells to ionizing radiation (IR). We investigated the mechanisms underlying the radiosensitization caused by β-lap. cells induced ROS generation, triggered ER stress and stimulated activation of ERK and JNK. Inhibition of ROS generation by NAC effectively attenuated the activation of ERK and JNK, induction of ER stress, and subsequent apoptosis. Importantly, inhibition of ERK abolished ROS generation and ER stress, whereas inhibition of JNK did not, indicating that positive feedback regulation between ERK activation and ROS generation triggers ER stress in response to combined treatment. Furthermore, prevention of ER stress completely blocked combination treatment-induced JNK activation and subsequent apoptotic cell death. In addition, combined treatment efficiently induced the mitochondrial translocation of cleaved Bax, disrupted mitochondrial membrane potential, and the nuclear translocation of AIF, all of which were efficiently blocked by a JNK inhibitor. Caspases 3, 8 and 9 were activated by combined treatment but inhibition of these caspases did not abolish apoptosis indicating caspase activation played a minor role in the induction of apoptosis. cells are treated with combination of IR and β-lap, positive feedback regulation between ERK and ROS leads to ER stress causing JNK activation and mitochondrial translocation of cleaved Bax. The resultant decrease in mitochondrial membrane leads to translocation of AIF and apoptosis

Asymptomatic subjects with diabetes have a comparable risk of coronary artery disease to Non-diabetic subjects presenting chest pain: a 4-year community-based prospective study

This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background Although diabetes mellitus is an important risk factor of coronary artery disease (CAD), routine screening for CAD is not recommended for asymptomatic diabetic patients. We assessed the impact of chest pain on CAD risk according to the presence or absence of diabetes mellitus. Methods We investigated the future CAD event rate in subjects with and without chest pain according to the presence or absence of diabetes in a prospective large-scale community-based study in Korea. Results Among 8,574 subjects (4,032 men and 4,542 women) without a history of CAD, 0.8% and 2.2% of non-diabetic and diabetic subjects, respectively, reported newly developed CAD events during 4 years of follow-up. Although the presence of chest pain at baseline was also significantly associated with an increased risk of CAD of more than 2-fold in both non-diabetic and diabetic subjects (P < 0.01), the risk of future CVD event in asymptomatic diabetic patients was not significantly different from that in non-diabetic subjects with chest pain (hazard ratio, 0.907; 95% confidence interval, 0.412 – 1.998). Conclusions The CAD event rate of asymptomatic subjects with diabetes was comparable to that of non-diabetic subjects reporting chest pain. Considering the high risk of CAD in asymptomatic diabetic patients, more clinical trials aimed at formulating strategies to screen asymptomatic diabetic subjects should be carried out