Self-assembled arrays of zinc oxide nanoparticles from monolayer films of diblock copolymer micelles

A hexagonal array of optically active ZnO nanoparticles was synthesized in situ on the solid substrate by utilizing a single-layered film of diblock copolymer micelles as a nanostructured template.X1135sciescopu

DJ-1 interacts with and regulates paraoxonase-2, an enzyme critical for neuronal survival in response to oxidative stress.

Loss-of-function mutations in DJ-1 (PARK7) gene account for about 1% of all familial Parkinson's disease (PD). While its physiological function(s) are not completely clear, DJ-1 protects neurons against oxidative stress in both in vitro and in vivo models of PD. The molecular mechanism(s) through which DJ-1 alleviates oxidative stress-mediated damage remains elusive. In this study, we identified Paraoxonase-2 (PON2) as an interacting target of DJ-1. PON2 activity is elevated in response to oxidative stress and DJ-1 is crucial for this response. Importantly, we showed that PON2 deficiency hypersensitizes neurons to oxidative stress induced by MPP+ (1-methyl-4-phenylpyridinium). Conversely, over-expression of PON2 protects neurons in this death paradigm. Interestingly, PON2 effectively rescues DJ-1 deficiency-mediated hypersensitivity to oxidative stress. Taken together, our data suggest a model by which DJ-1 exerts its antioxidant activities, at least partly through regulation of PON2

Dynamic analysis of optimality in myocardial energy metabolism under normal and ischemic conditions

To better understand the dynamic regulation of optimality in metabolic networks under perturbed conditions, we reconstruct the energetic-metabolic network in mammalian myocardia using dynamic flux balance analysis (DFBA). Additionally, we modified the optimal objective from the maximization of ATP production to the minimal fluctuation of the profile of metabolite concentration under ischemic conditions, extending the hypothesis of original minimization of metabolic adjustment to create a composite modeling approach called M-DFBA. The simulation results are more consistent with experimental data than are those of the DFBA model, particularly the retentive predominant contribution of fatty acid to oxidative ATP synthesis, the exact mechanism of which has not been elucidated and seems to be unpredictable by the DFBA model. These results suggest that the systemic states of metabolic networks do not always remain optimal, but may become suboptimal when a transient perturbation occurs. This finding supports the relevance of our hypothesis and could contribute to the further exploration of the underlying mechanism of dynamic regulation in metabolic networks

Chemotactic response and adaptation dynamics in Escherichia coli

Adaptation of the chemotaxis sensory pathway of the bacterium Escherichia coli is integral for detecting chemicals over a wide range of background concentrations, ultimately allowing cells to swim towards sources of attractant and away from repellents. Its biochemical mechanism based on methylation and demethylation of chemoreceptors has long been known. Despite the importance of adaptation for cell memory and behavior, the dynamics of adaptation are difficult to reconcile with current models of precise adaptation. Here, we follow time courses of signaling in response to concentration step changes of attractant using in vivo fluorescence resonance energy transfer measurements. Specifically, we use a condensed representation of adaptation time courses for efficient evaluation of different adaptation models. To quantitatively explain the data, we finally develop a dynamic model for signaling and adaptation based on the attractant flow in the experiment, signaling by cooperative receptor complexes, and multiple layers of feedback regulation for adaptation. We experimentally confirm the predicted effects of changing the enzyme-expression level and bypassing the negative feedback for demethylation. Our data analysis suggests significant imprecision in adaptation for large additions. Furthermore, our model predicts highly regulated, ultrafast adaptation in response to removal of attractant, which may be useful for fast reorientation of the cell and noise reduction in adaptation.Comment: accepted for publication in PLoS Computational Biology; manuscript (19 pages, 5 figures) and supplementary information; added additional clarification on alternative adaptation models in supplementary informatio

Regulation of neutrophil senescence by microRNAs

Neutrophils are rapidly recruited to sites of tissue injury or infection, where they protect against invading pathogens. Neutrophil functions are limited by a process of neutrophil senescence, which renders the cells unable to respond to chemoattractants, carry out respiratory burst, or degranulate. In parallel, aged neutrophils also undergo spontaneous apoptosis, which can be delayed by factors such as GMCSF. This is then followed by their subsequent removal by phagocytic cells such as macrophages, thereby preventing unwanted inflammation and tissue damage. Neutrophils translate mRNA to make new proteins that are important in maintaining functional longevity. We therefore hypothesised that neutrophil functions and lifespan might be regulated by microRNAs expressed within human neutrophils. Total RNA from highly purified neutrophils was prepared and subjected to microarray analysis using the Agilent human miRNA microarray V3. We found human neutrophils expressed a selected repertoire of 148 microRNAs and that 6 of these were significantly upregulated after a period of 4 hours in culture, at a time when the contribution of apoptosis is negligible. A list of predicted targets for these 6 microRNAs was generated from http://mirecords.biolead.org and compared to mRNA species downregulated over time, revealing 83 genes targeted by at least 2 out of the 6 regulated microRNAs. Pathway analysis of genes containing binding sites for these microRNAs identified the following pathways: chemokine and cytokine signalling, Ras pathway, and regulation of the actin cytoskeleton. Our data suggest that microRNAs may play a role in the regulation of neutrophil senescence and further suggest that manipulation of microRNAs might represent an area of future therapeutic interest for the treatment of inflammatory disease

A Classification Method Based on Principal Components of SELDI Spectra to Diagnose of Lung Adenocarcinoma

Lung cancer is the leading cause of cancer death worldwide, but techniques for effective early diagnosis are still lacking. Proteomics technology has been applied extensively to the study of the proteins involved in carcinogenesis. In this paper, a classification method was developed based on principal components of surface-enhanced laser desorption/ionization (SELDI) spectral data. This method was applied to SELDI spectral data from 71 lung adenocarcinoma patients and 24 healthy individuals. Unlike other peak-selection-based methods, this method takes each spectrum as a unity. The aim of this paper was to demonstrate that this unity-based classification method is more robust and powerful as a method of diagnosis than peak-selection-based methods.The results showed that this classification method, which is based on principal components, has outstanding performance with respect to distinguishing lung adenocarcinoma patients from normal individuals. Through leaving-one-out, 19-fold, 5-fold and 2-fold cross-validation studies, we found that this classification method based on principal components completely outperforms peak-selection-based methods, such as decision tree, classification and regression tree, support vector machine, and linear discriminant analysis.The classification method based on principal components of SELDI spectral data is a robust and powerful means of diagnosing lung adenocarcinoma. We assert that the high efficiency of this classification method renders it feasible for large-scale clinical use

The Microscopic Origin of Residual Stress for Flat Self-Actuating Piezoelectric Cantilevers

In this study, flat piezoelectric microcantilevers were fabricated under low-stress Pb(Zr0.52Ti0.48)O3 (PZT) film conditions. They were analyzed using the Raman spectrum and wafer curvature methods. Based on the residual stress analysis, we found that a thickness of 1 μm was critical, since stress relaxation starts to occur at greater thicknesses, due to surface roughening. The (111) preferred orientation started to decrease when the film thickness was greater than 1 μm. The d33 value was closely related to the stress relaxation associated with the preferred orientation changes. We examined the harmonic response at different PZT cantilever lengths and obtained a 9.4-μm tip displacement at 3 Vp-p at 1 kHz. These analyses can provide a platform for the reliable operation of piezoelectric microdevices, potentially nanodevice when one needs to have simultaneous control of the residual stress and the piezoelectric properties