Robust Glyoxalase activity of Hsp31, a ThiJ/DJ-1/PfpI Family Member Protein, Is Critical for Oxidative Stress Resistance in Saccharomyces cerevisiae

Methylglyoxal (MG) is a reactive metabolic intermediate generated during various cellular biochemical reactions, including glycolysis. The accumulation of MG indiscriminately modifies proteins, including important cellular antioxidant machinery, leading to severe oxidative stress, which is implicated in multiple neurodegenerative disorders, aging, and cardiac disorders. Although cells possess efficient glyoxalase systems for detoxification, their functions are largely dependent on the glutathione cofactor, the availability of which is self-limiting under oxidative stress. Thus, higher organisms require alternate modes of reducing the MG-mediated toxicity and maintaining redox balance. In this report, we demonstrate that Hsp31 protein, a member of the ThiJ/DJ-1/PfpI family in Saccharomyces cerevisiae, plays an indispensable role in regulating redox homeostasis. Our results show that Hsp31 possesses robust glutathione-independent methylglyoxalase activity and suppresses MG-mediated toxicity and ROS levels as compared with another paralog, Hsp34. On the other hand, glyoxalase-defective mutants of Hsp31 were found highly compromised in regulating the ROS levels. Additionally, Hsp31 maintains cellular glutathione and NADPH levels, thus conferring protection against oxidative stress, and Hsp31 relocalizes to mitochondria to provide cytoprotection to the organelle under oxidative stress conditions. Importantly, human DJ-1, which is implicated in the familial form of Parkinson disease, complements the function of Hsp31 by suppressing methylglyoxal and oxidative stress, thus signifying the importance of these proteins in the maintenance of ROS homeostasis across phylogeny.

Lack of Critical Slowing Down Suggests that Financial Meltdowns Are Not Critical Transitions, yet Rising Variability Could Signal Systemic Risk

Complex systems inspired analysis suggests a hypothesis that financial meltdowns are abrupt critical transitions that occur when the system reaches a tipping point. Theoretical and empirical studies on climatic and ecological dynamical systems have shown that approach to tipping points is preceded by a generic phenomenon called critical slowing down, i.e. an increasingly slow response of the system to perturbations. Therefore, it has been suggested that critical slowing down may be used as an early warning signal of imminent critical transitions. Whether financial markets exhibit critical slowing down prior to meltdowns remains unclear. Here, our analysis reveals that three major US (Dow Jones Index, S&P 500 and NASDAQ) and two European markets (DAX and FTSE) did not exhibit critical slowing down prior to major financial crashes over the last century. However, all markets showed strong trends of rising variability, quantified by time series variance and spectral function at low frequencies, prior to crashes. These results suggest that financial crashes are not critical transitions that occur in the vicinity of a tipping point. Using a simple model, we argue that financial crashes are likely to be stochastic transitions which can occur even when the system is far away from the tipping point. Specifically, we show that a gradually increasing strength of stochastic perturbations may have caused to abrupt transitions in the financial markets. Broadly, our results highlight the importance of stochastically driven abrupt transitions in real world scenarios. Our study offers rising variability as a precursor of financial meltdowns albeit with a limitation that they may signal false alarms.

On the critical thickness for non-localized to localized plastic flow transition in metallic glasses: A molecular dynamics study

Molecular dynamics simulations were employed to investigate the specimen thickness-dependent tensile behavior of a series of Cu(x)Z(100-x) (x = 20, 40, 50, 64 and 80 at%) metallic glass (MG) films, with a particular focus on the critical thickness, tc, below which non-localized plastic flow takes place. The simulation results reveal that while the transition occurs in all the alloys examined, t(c) is sensitive to the composition. We rationalize t(c) by postulating that the strain energy stored in the sample at the onset of plastic deformation has to be sufficient for the formation of shear bands. The composition-dependence of t(c) was found to correlate with the average activation energy of the atomic level plastic deformation events. (C) 2015 Elsevier Ltd. All rights reserved.

Atomistic Simulation of Stacked Nucleosome Core Particles: Tail Bridging, the H4 Tail, and Effect of Hydrophobic Forces

We report the first atomistic simulation of two stacked nucleosome core particles (NCPs), with an aim to understand, in molecular detail, how they interact, the effect of salt concentration, and how different histone tails contribute to their interaction, with a special emphasis on the H4 tail, known to have the largest stabilizing effect on the NCP-NCP interaction. We do not observe specific K16-mediated interaction between the H4 tail and the H2A-H2B acidic patch, in contrast with the findings from crystallographic studies, but find that the stacking was stable even in the absence of this interaction. We perform simulations with the H4 tail (partially/completely) removed and find that the region between LYS-16 and LYS-20 of the H4 tail holds special importance in mediating the inter-NCP interaction. Performing similar tail-clipped simulations with the H3 tail removed, we compare the roles of the H3 and H4 tails in maintaining the stacking. We discuss the relevance of our simulation results to the bilayer and other liquid-crystalline phases exhibited by NCPs in vitro and, through an analysis of the histone-histone interface, identify the interactions that could possibly stabilize the inter-NCP interaction in these columnar mesophases. Through the mechanical disruption of the stacked nucleosome system using steered molecular dynamics, we quantify the strength of inter-NCP stacking in the presence and absence of salt. We disrupt the stacking at some specific sites of internucleosomal tail-DNA contact and perform a comparative quantification of the binding strengths of various tails in stabilizing the stacking. We also examine how hydrophobic interactions may contribute to the overall stability of the stacking and find a marked difference in the role of hydrophobic forces as compared with electrostatic forces in determining the stability of the stacked nucleosome system.

Critical investigation of high performance spin-coated high-kappa titania thin films based MOS capacitor

We report the tunable dielectric constant of titania films with low leakage current density. Titanium dioxide (TiO2) films of three different thicknesses (36, 63 and 91 nm) were deposited by the consecutive steps of solution preparation, spin-coating, drying, and firing at different temperatures. The problem of poor adhesion between Si substrate and TiO2 insulating layer was resolved by using the plasma activation process. The surface roughness was found to increase with increasing thickness and annealing temperature. The electrical investigation was carried out using metal-oxide-semiconductor structure. The flat band voltage (V-FB), oxide trapped charge (Q(ot)), dielectric constant (kappa) and equivalent oxide thicknesses are calculated from capacitance-voltage (C-V) curves. The C-V characteristics indicate a thickness dependent dielectric constant. The dielectric constant increases from 31 to 78 as thickness increases from 36 to 91 nm. In addition to that the dielectric constant was found to be annealing temperature and frequency dependent. The films having thickness 91 nm and annealed at 600 A degrees C shows the low leakage current density. Our study provides a broad insight of the processing parameters towards the use of titania as high-kappa insulating layer, which might be useful in Si and polymer based flexible devices.

On the issues of resolving a low melting combination as a definite eutectic or an elusive cocrystal: A critical evaluation

Cocrystals and eutectics are different yet related crystalline multi-component adducts with diverse applications in pharmaceutical and materials fields. Recently, they were shown to be alternate products of cocrystallization experiments. Whereas a cocrystal shows distinct diffraction, spectroscopic and thermal signatures as compared to parent components, the hallmark of a eutectic is its low melting nature. However, in certain cases, there can be a problem when one resorts to design a cocrystal and assess its formation vis-A -vis a eutectic. In the absence of a gold standard method to make a cocrystal, it is often difficult to judge how exhaustive should the cocrystallization trials be to ensure the accomplishment of a desired/putative cocrystal. Further, a cocrystal can manifest with intermolecular interactions and/or crystal structure similar to that of its parent compounds such that the conventional diffraction and spectroscopic techniques will be of little help to conclusively infer the formation of cocrystal in the lack of single crystals. Such situations combined with low melting behavior of a combination brings the complication of resolving the combination as a cocrystal or eutectic since now both the adducts share common features. Based on the curious case of Caffeine-Benzoic acid combination, this study aims to unfold the intricate issues related to the design, formation and characterization of cocrystals and eutectics for a way forward. The utility of heteronuclear seeding methodology in establishing a given combination as a cocrystal-forming one or a eutectic-forming one in four known systems is appraised.