Genome wide chromatin occupancy of mrhl RNA and its role in gene regulation in mouse spermatogonial cells

Mrhl RNA is a nuclear lncRNA encoded in the mouse genome and negatively regulates Wnt signaling in spermatogonial cells through p68/Ddx5 RNA helicase. Mrhl RNA is present in the chromatin fraction of mouse spermatogonial Gc1-Spg cells and genome wide chromatin occupancy of mrhl RNA by ChOP (Chromatin oligo affinity precipitation) technique identified 1370 statistically significant genomic loci. Among these, genes at 37 genomic loci also showed altered expression pattern upon mrhl RNA down regulation which are referred to as GRPAM (Genes Regulated by Physical Association of Mrhl RNA). p68 interacted with mrhl RNA in chromatin at these GRPAM loci. p68 silencing drastically reduced mrhl RNA occupancy at 27 GRPAM loci and also perturbed the expression of GRPAM suggesting a role for p68 mediated mrhl RNA occupancy in regulating GRPAM expression. Wnt3a ligand treatment of Gc1-Spg cells down regulated mrhl RNA expression and also perturbed expression of these 27 GRPAM genes that included genes regulating Wnt signaling pathway and spermatogenesis, one of them being Sox8, a developmentally important transcription factor. We also identified interacting proteins of mrhl RNA associated chromatin fraction which included Pc4, a chromatin organizer protein and hnRNP A/B and hnRNP A2/B1 which have been shown to be associated with lincRNA-Cox2 function in gene regulation. Our findings in the Gc1-Spg cell line also correlate with the results from analysis of mouse testicular tissue which further highlights the in vivo physiological significance of mrhl RNA in the context of gene regulation during mammalian spermatogenesis.

A critical review of the definition of FRA resonance frequency of transformers as per IEEE Std C57.149-2012

The explanation of resonance given in IEEE Std C57.149-2012 to define resonance during frequency response analysis (FRA) measurements on transformers implicitly uses the conditions prevalent during resonance in a series R-L-C circuit. This dependence is evident from the two assertions made in the definition, viz., resulting in zero net reactive impedance, and, accompanied by a zero value appearing in the phase angle of the frequency response function. These two conditions are satisfied (at resonance) only in a series R-L-C circuit and certainly not in a transformer, as has been assumed in the Standard. This can be proved by considering a ladder-network model. Circuit analysis of this ladder network reveals the origin of this fallacy and proves that, at resonance, neither is the ladder network purely resistive and nor is the phase angle (between input voltage and input current) always zero. Also, during FRA measurements, it is often seen that phase angle does not traverse the conventional cyclic path from +90 degrees to -90 degrees (or vice versa) at all resonant frequencies. This peculiar feature can also be explained using pole-zero maps. Simple derivations, simulations and experimental results on an actual winding are presented. In summary, authors believe that this study dispels existing misconceptions about definition of FRA resonance and provides material for its correction in IEEE Std C57.149-2012. (C) 2014 Elsevier B.V. All rights reserved.

A trade-off between maxima in efficiency and specific work output of super- and trans-critical CO2 Brayton cycles

Several operational aspects for thermal power plants in general are non-intuitive and involve simultaneous optimization of a number of operational parameters. In the case of solar operated power plants, it is even more difficult due to varying heat source temperatures induced by variability in insolation levels. This paper introduces a quantitative methodology for load regulation of a CO2 based Brayton cycle power plant using the `thermal efficiency and specific work output' coordinate system. The analysis shows that a transcritical CO2 cycle offers more flexibility under part load performance than the supercritical cycle in case of non-solar power plants. However, for concentrated solar power, where efficiency is important, supercritical CO2 cycle fares better than transcritical CO2 cycle. A number of empirical equations relating heat source temperature, high side pressure with efficiency and specific work output are proposed which could assist in generating control algorithms. (C) 2015 Elsevier B.V. All rights reserved.

Lactoylglutathione lyase, a critical enzyme in methylglyoxal detoxification, contributes to survival of Salmonella in the nutrient rich environment

Glyoxalase I which is synonymously known as lactoylglutathione lyase is a critical enzyme in methylglyoxal (MG) detoxification. We assessed the STM3117 encoded lactoylglutathione lyase (Lgl) of Salmonella Typhimurium, which is known to function as a virulence factor, due in part to its ability to detoxify methylglyoxal. We found that STM3117 encoded Lgl isomerises the hemithioacetal adduct of MG and glutathione (GSH) into S-lactoylglutathione. Lgl was observed to be an outer membrane bound protein with maximum expression at the exponential growth phase. The deletion mutant of S. Typhimurium (lgl) exhibited a notable growth inhibition coupled with oxidative DNA damage and membrane disruptions, in accordance with the growth arrest phenomenon associated with typical glyoxalase I deletion. However, growth in glucose minimal medium did not result in any inhibition. Endogenous expression of recombinant Lgl in serovar Typhi led to an increased resistance and growth in presence of external MG. Being a metalloprotein, Lgl was found to get activated maximally by Co2+ ion followed by Ni2+, while Zn2+ did not activate the enzyme and this could be attributed to the geometry of the particular protein-metal complex attained in the catalytically active state. Our results offer an insight on the pivotal role of the virulence associated and horizontally acquired STM3117 gene in non-typhoidal serovars with direct correlation of its activity in lending survival advantage to Salmonella spp.

A critical review on in situ reduction of graphene oxide during preparation of conducting polymeric nanocomposites

Graphene oxide (GO), prepared by chemical oxidation of graphite, serves as a building block for developing polymeric nanocomposites. However, their application in electrical conductivity is limited by the fact that the oxygen sites on GO trap electrons and impede charge transport. Conducting nanocomposites can be developed by reducing GO. Various strategies have been adopted to either reduce GO ex situ, before the composite preparation, or in situ during the development of the nanocomposites. The current state of research on in situ reduction of GO during the preparation of conducting polymeric nanocomposites is discussed in this review. The mechanism and the efficiency of reduction is discussed with respect to various strategies employed during the preparation of the nanocomposite, the type of polymer used, and the processing conditions employed, etc. Its overall effect on the electrical conductivity of the nanocomposites is also discussed and the future outlook in this area is presented.

A Critical Assessment of the Flux Transport Dynamo

We first discuss how the flux transport dynamo with reasonably high diffusion can explain both the regular and the irregular features of the solar cycle quite well. Then, we critically examine the inadequacies of the model and the challenge posed by some recent observational data about meridional circulation, arriving at a conclusion that this model can still work within the bounds of observational data.

Dependence of ``critical cloud fraction' on aerosol composition

Recent studies, over regions influenced by biomass burning aerosol, have shown that it is possible to define a critical cloud fraction' (CCF) at which the aerosol direct radiative forcing switch from a cooling to a warming effect. Using 4 years of multi-satellite data analysis, we show that CCF varies with aerosol composition and changed from 0.28 to 0.13 from postmonsoon to winter as a result of shift from less absorbing to moderately absorbing aerosol. Our results indicate that we can estimate aerosol absorption from space using independently measured top of the atmosphere (TOA) fluxes Cloud Aerosol Lidar with Orthogonal Polarization-Moderate resolution Imaging Spectroradiometer-Clouds and the Earth's Radiant Energy System (CALIPSO-MODIS-CERES)] combined algorithms for example.

Tailoring the interface in graphene/thermoset polymer composites: A critical review

With the emergence of scientific interest in graphene oxide (GO) in recent times, researchers have endeavored to incorporate GO in thermoset polymeric matrix to develop composites with extraordinary set of properties. The current state of research in graphene/thermoset polymer composites is highlighted here with a focus on the role of interface in dictating the overall properties of the composites. Different strategies like covalent and non-covalent functionalization of GO have been discussed with respect to improvement in mechanical, electrical, thermal and rheological properties. In addition, future prospects have been outlined. By assessing the current state of research in graphene/thermoset composites, it is obvious that graphene derivatives are promising materials in enhancing the structural properties of the nanocomposites at extremely low levels of filler loading. This opens new avenues in designing lightweight composites for myriad applications and by tailoring the interfacial adhesion with the polymer, ordered structure can be achieved at macroscopic processing scales. (C) 2015 Elsevier Ltd. All rights reserved.

Mapping Key Residues of ISD11 Critical for NFS1-ISD11 Subcomplex Stability IMPLICATIONS IN THE DEVELOPMENT OF MITOCHONDRIAL DISORDER, COXPD19

Biogenesis of the iron-sulfur (Fe-S) cluster is an indispensable process in living cells. In mammalian mitochondria, the initial step of the Fe-S cluster assembly process is assisted by the NFS1-ISD11 complex, which delivers sulfur to scaffold protein ISCU during Fe-S cluster synthesis. Although ISD11 is an essential protein, its cellular role in Fe-S cluster biogenesis is still not defined. Our study maps the important ISD11 amino acid residues belonging to putative helix 1 (Phe-40), helix 3 (Leu-63, Arg-68, Gln-69, Ile-72, Tyr-76), and C-terminal segment (Leu-81, Glu-84) are critical for in vivo Fe-S cluster biogenesis. Importantly, mutation of these conserved ISD11 residues into alanine leads to its compromised interaction with NFS1, resulting in reduced stability and enhanced aggregation of NFS1 in the mitochondria. Due to altered interaction with ISD11 mutants, the levels of NFS1 and Isu1 were significantly depleted, which affects Fe-S cluster biosynthesis, leading to reduced electron transport chain complex (ETC) activity and mitochondrial respiration. In humans, a clinically relevant ISD11 mutation (R68L) has been associated in the development of a mitochondrial genetic disorder, COXPD19. Our findings highlight that the ISD11 R68A/R68L mutation display reduced affinity to form a stable subcomplex with NFS1, and thereby fails to prevent NFS1 aggregation resulting in impairment of the Fe-S cluster biogenesis. The prime affected machinery is the ETC complex, which showed compromised redox properties, causing diminished mitochondrial respiration. Furthermore, the R68L ISD11 mutant displayed accumulation of mitochondrial iron and reactive oxygen species, leading to mitochondrial dysfunction, which correlates with the phenotype observed in COXPD19 patients.

Interrelationship between Interphase Boundaries and Phase Contents near the Critical Compositions of Lead-Free Ferroelectric (Na0.5Bi0.5)TiO3-BaTiO3

Heterophase structures in lead-free perovskite-type ferroelectric solid solutions of (1 - z)(Na0.5Bi0.5)TiO3 - zBaTiO(3) are analysed for a few critical compositions near the morphotropic phase boundary (z = 0.05-0.07). Examples of the phase coexistence and elastic matching of the phases from different symmetry groups are considered to find optimum volume fractions of specific domain types and coexisting phases at the complete stress relief in two-phase samples. Some interrelations between these volume fractions are described using variants of the domain arrangement at changes in the composition and unit-cell parameters. The evaluated room-temperature volume fractions of the ferroelectric monoclinic (Cm symmetry) and tetragonal (P4mm symmetry) phases near the morphotropic phase boundary are in agreement with experimental data.

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.

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.