Insights into the Regulatory Characteristics of the Mycobacterial Dephosphocoenzyme A Kinase: Implications for the Universal CoA Biosynthesis Pathway

Being vastly different from the human counterpart, we suggest that the last enzyme of the Mycobacterium tuberculosis Coenzyme A biosynthetic pathway, dephosphocoenzyme A kinase (CoaE) could be a good anti-tubercular target. Here we describe detailed investigations into the regulatory features of the enzyme, affected via two mechanisms. Enzymatic activity is regulated by CTP which strongly binds the enzyme at a site overlapping that of the leading substrate, dephosphocoenzyme A (DCoA), thereby obscuring the binding site and limiting catalysis. The organism has evolved a second layer of regulation by employing a dynamic equilibrium between the trimeric and monomeric forms of CoaE as a means of regulating the effective concentration of active enzyme. We show that the monomer is the active form of the enzyme and the interplay between the regulator, CTP and the substrate, DCoA, affects enzymatic activity. Detailed kinetic data have been corroborated by size exclusion chromatography, dynamic light scattering, glutaraldehyde crosslinking, limited proteolysis and fluorescence investigations on the enzyme all of which corroborate the effects of the ligands on the enzyme oligomeric status and activity. Cysteine mutagenesis and the effects of reducing agents on mycobacterial CoaE oligomerization further validate that the latter is not cysteine-mediated or reduction-sensitive. These studies thus shed light on the novel regulatory features employed to regulate metabolite flow through the last step of a critical biosynthetic pathway by keeping the latter catalytically dormant till the need arises, the transition to the active form affected by a delicate crosstalk between an essential cellular metabolite (CTP) and the precursor to the pathway end-product (DCoA).

Difference in spin state and covalence between La1-xSrxCoO3 and La2-xSrxLi0.5Co0.5O4

We present a comparative study of the spin states and electronic properties of La1-xSrxCoO3 and La2-xSrxLi0.5Co0.5O4 using X-ray absorption near-edge structure spectroscopy at both the O-K and Co-L-2.3 thresholds. In the La2-xSrxLi0.5Co0.5O4 system the CoO6 octahedra are isolated, the holes induced by Sr doping are trapped in the isolated Co(IV)O-6 octahedra, and a low-spin state is found for the Co ions, which does not change upon Sr doping. In the La1-xSrxCoO3 system, the interconnected CoO6 octahedra, with a 180degrees Co-O-Co bond angle, give rise to a transition from low-spin to intermediate-spin state with a ferromagnetic alignment of the Co spins. The double-exchange, ferromagnetic coupling between Co ions mediated by the 180degrees bond angle is responsible for suppressing the low spin-state. We find that the branching ratio of spectral intensities at the L-2 and L-3 thresholds in the Co-L-2.3 X-ray absorption spectra is sensitive to the spin state of the Co ions allowing its direct spectroscopic determination. (C) 2002 Published by Elsevier Science B.V.

Strong ground motion at Bhuj city during the Kutch earthquake

In the absence of near field strong motion records, the level of ground motion during the devastating 26 January 2001 earthquake has to be found by indirect means. For the city of Bhuj, three broad band velocity time histories have been recorded by India Meteorological Department. In this paper these data are processed to obtain an estimate of strong ground motion at Bhuj. It is estimated that the peak ground acceleration at Bhuj was of the order of 0.38 g. Ground motion in the surrounding region is indirectly found using available spectral response recorder (SRR) data. These instrument-based results are compared with analytical results obtained from a half-space regional model.

The collective dynamics of self-propelled particles

We propose a method for the dynamic simulation of a collection of self-propelled particles in a viscous Newtonian fluid. We restrict attention to particles whose size and velocity are small enough that the fluid motion is in the creeping flow regime. We propose a simple model for a self-propelled particle, and extended the Stokesian Dynamics method to conduct dynamic simulations of a collection of such particles. In our description, each particle is treated as a sphere with an orientation vector p, whose locomotion is driven by the action of a force dipole Sp of constant magnitude S0 at a point slightly displaced from its centre. To simplify the calculation, we place the dipole at the centre of the particle, and introduce a virtual propulsion force Fp to effect propulsion. The magnitude F0 of this force is proportional to S0. The directions of Sp and Fp are determined by p. In isolation, a self-propelled particle moves at a constant velocity u0 p, with the speed u0 determined by S0. When it coexists with many such particles, its hydrodynamic interaction with the other particles alters its velocity and, more importantly, its orientation. As a result, the motion of the particle is chaotic. Our simulations are not restricted to low particle concentration, as we implement the full hydrodynamic interactions between the particles, but we restrict the motion of particles to two dimensions to reduce computation. We have studied the statistical properties of a suspension of self-propelled particles for a range of the particle concentration, quantified by the area fraction φa. We find several interesting features in the microstructure and statistics. We find that particles tend to swim in clusters wherein they are in close proximity. Consequently, incorporating the finite size of the particles and the near-field hydrodynamic interactions is of the essence. There is a continuous process of breakage and formation of the clusters. We find that the distributions of particle velocity at low and high φa are qualitatively different; it is close to the normal distribution at high φa, in agreement with experimental measurements. The motion of the particles is diffusive at long time, and the self-diffusivity decreases with increasing φa. The pair correlation function shows a large anisotropic build-up near contact, which decays rapidly with separation. There is also an anisotropic orientation correlation near contact, which decays more slowly with separation. Movies are available with the online version of the paper.

Universality and scaling behavior of injected power in elastic turbulence in wormlike micellar gel

We study the statistical properties of spatially averaged global injected power fluctuations for Taylor-Couette flow of a wormlike micellar gel formed by surfactant cetyltrimethylammonium tosylate. At sufficiently high Weissenberg numbers the shear rate, and hence the injected power p(t), at a constant applied stress shows large irregular fluctuations in time. The nature of the probability distribution function (PDF) of p(t) and the power-law decay of its power spectrum are very similar to that observed in recent studies of elastic turbulence for polymer solutions. Remarkably, these non-Gaussian PDFs can be well described by a universal, large deviation functional form given by the generalized Gumbel distribution observed in the context of spatially averaged global measures in diverse classes of highly correlated systems. We show by in situ rheology and polarized light scattering experiments that in the elastic turbulent regime the flow is spatially smooth but random in time, in agreement with a recent hypothesis for elastic turbulence.

Synthesis and characterization of novel cationic lipid and cholesterol-coated gold nanoparticles and their interactions with dipalmitoylphosphatidylcholine membranes

Novel gold nanoparticles bearing cationic single-chain, double-chain, and cholesterol based amphiphilic units have been synthesized. These nanoparticles represent size-stable entities in which various cationic lipids have been immobilized through their thiol group onto the gold nanoparticle core. The resulting colloids have been characterized by UV-vis, (1)H NMR, FT-IR spectroscopy, and transmission electron microscopy. The average size of the resultant nanoparticles could be controlled by the relative bulkiness of the capping agent. Thus, the average diameters of the nanoparticles formed from the cationic single-chain, double-chain, and cholesterol based thiolate-coated materials were 5.9,2.9, and 2.04 nm, respectively. We also examined the interaction of these cationic gold nanoparticles with vesicular membranes generated from dipalmitoylphosphatidylcholine (DPPC) lipid suspensions. Nanoparticle doped DPPC vesicular suspensions displayed a characteristic surface plasmon band in their UV-vis spectra. Inclusion of nanoparticles in vesicular suspensions led to increases in the aggregate diameters, as evidenced from dynamic light scattering. Differential scanning calorimetric examination indicated that incorporation of single-chain, double-chain, and cholesteryl-linked cationic nanoparticles exert variable effects on the DPPC melting transitions. While increased doping of single-chain nanoparticles in DPPC resulted in the phases that melt at higher temperatures, inclusion of an incremental amount of double-chain nanoparticles caused the lowering of the melting temperature of DPPC. On the other hand, the cationic cholesteryl nanoparticle interacted with DPPC in membranes in a manner somewhat analogous to that of cholesterol itself and caused broadening of the DPPC melting transition.

Generalized asymptotic expansions for the wavenumbers in infinite flexible in vacuo orthotropic cylindrical shells

Analytical expressions are found for the wavenumbers and resonance frequencies in flexible, orthotropic shells using the asymptotic methods. These expressions are valid for arbitrary circumferential orders n. The Donnell-Mushtari shell theory is used to model the dynamics of the cylindrical shell. Initially, an in vacuo cylindrical isotropic shell is considered and expressions for all the wavenumbers (bending, near-field bending, longitudinal and torsional) are found. Subsequently, defining a suitable orthotropy parameter epsilon, the problem of wave propagation in an orthotropic shell is posed as a perturbation on the corresponding problem for an isotropic shell. Asymptotic expressions for the wavenumbers in the in vacuo orthotropic shell are then obtained by treating epsilon as an expansion parameter. In both cases (isotropy and orthotropy), a frequency-scaling parameter (eta) and Poisson's ratio (nu) are used to find elegant expansions in the different frequency regimes. The asymptotic expansions are compared with numerical solutions in each of the cases and the match is found to be good. The main contribution of this work lies in the extension of the existing literature by developing closed-form expressions for wavenumbers with arbitrary circumferential orders n in the case of both, isotropic and orthotropic shells. Finally, we present natural frequency expressions in finite shells (isotropic and orthotropic) for the axisymmetric mode and compare them with numerical and ANSYS results. Here also, the comparison is found to be good. (C) 2011 Elsevier Ltd. All rights reserved.

Andaman Postseismic Deformation Observations: Still Slipping after All These Years?

More than six years after the great (M-w 9.2) Sumatra-Andaman earthquake, postevent processes responsible for relaxation of the coseismic stress change remain controversial. Modeling of Andaman Islands Global Positioning System (GPS) displacements indicated early near-field motions were dominated by slip down-dip of the rupture, but various researchers ascribe elements of relaxation to dominantly poroelastic, dominantly viscoelastic, and dominantly fault slip processes, depending primarily on their measurement sampling and modeling tools used. After subtracting a pre-2004 interseismic velocity, significant transient motion during the 2008.5-2010.5 epoch confirms that postseismic relaxation processes continue in Andaman. Modeling three-component velocities as viscoelastic flow yields a weighted root-mean-square (wrms) misfit that always exceeds the wrms of the measured signal (26.3 mm/yr). The best-fitting models are those that yield negligible deformation, indicating the model parameters have no real physical meaning. GPS velocities are well fit (wrms 4.0 mm/yr) by combining a viscoelastic flow model that best fits the horizontal velocities with similar to 50 cm/yr thrust slip down-dip of the coseismic rupture. Both deep slip and flow respond to stress changes, and each can significantly change stress in the realm of the other; it therefore is reasonable to expect that both transient deep slip and viscoelastic flow will influence surface deformation long after a great earthquake.

Smart polymer mediated purification and recovery of active proteins from inclusion bodies

Obtaining correctly folded proteins from inclusion bodies of recombinant proteins expressed in bacterial hosts requires solubilization with denaturants and a refolding step. Aggregation competes with the second step. Refolding of eight different proteins was carried out by precipitation with smart polymers. These proteins have different molecular weights, different number of disulfide bridges and some of these are known to be highly prone to aggregation. A high throughput refolding screen based upon fluorescence emission maximum around 340 nm (for correctly folded proteins) was developed to identify the suitable smart polymer. The proteins could be dissociated and recovered after the refolding step. The refolding could be scaled up and high refolding yields in the range of 8 mg L-1 (for CD4D12, the first two domains of human CD4) to 58 mg L-1 (for malETrx, thioredoxin fused with signal peptide of maltose binding protein) were obtained. Dynamic light scattering (DLS) showed that polymer if chosen correctly acted as a pseuclochaperonin and bound to the proteins. It also showed that the time for maximum binding was about 50 min which coincided with the time required for incubation (with the polymer) before precipitation for maximum recovery of folded proteins. The refolded proteins were characterized by fluorescence emission spectra, circular dichroism (CD) spectroscopy, melting temperature (T-m), and surface hydrophobicity measurement by ANS (8-anilinol-naphthalene sulfonic acid) fluorescence. Biological activity assay for thioredoxin and fluorescence based assay in case of maltose binding protein (MBP) were also carried out to confirm correct refolding. (C) 2012 Elsevier B.V. All rights reserved.

Synthesis of Cholic Acid Oligomer-Taurine Conjugates: A Study of Their Aggregation and Cholesterol Solubilization

Taurine conjugates of two cholic acid derived oligomers with different spacers between the cholic acid units were synthesized. These molecules self-assemble in aqueous media. The critical micelle concentration (CMC) values were measured by using fluorescence spectroscopic analysis and the aggregates were characterized by dynamic light scattering and electron microscopy. The cooperativity of the cholic acid units in these tetramers to solubilize cholesterol was investigated. The ability of these molecules to act as nanocarriers for liphophilic dyes was also studied.

Selective colorimetric detection of nanomolar Cr (VI) in aqueous solutions using unmodified silver nanoparticles

In this study we present a colorimetric detection method for Cr (VI) in aqueous solution based on as synthesized silver nanoparticles (Ag NPs) without surface functionalization. The method principle involves reduction of Cr (VI) to Cr (III) by excess reductant present in as synthesized Ag NP dispersion, and subsequent aggregation of Ag NPs by Cr (III) leading to red-shift of the surface plasmon resonance (SPR) peak. The UV-vis absorption spectra. Zeta potentials, dynamic light scattering measurements, and scanning electron microscopy (SEM) confirmed the aggregation of the Ag NPs. Under the optimized conditions, a good linear relationship (correlation coefficient r=0.981) was obtained between the ratio of the absorbance at 550 nm to that at 390 nm (A(550/390)) and the concentration of Cr (VI) over the range of 10(-3)-10(-9) M 50 mg/L to 50 ng/L]. The reported probe has a limit of detection down to 1 nM, which, to the best of our knowledge, is the lowest ever reported for the colorimetric detection of Cr (VI). Furthermore, a remarkable feature of this method is that it involves a simple technique exhibiting high selectivity to Cr (VI) over other tested heavy metal ions. (C) 2012 Elsevier BM. All rights reserved.

Synthesis and characterization of high molecular weight polyaniline for organic electronic applications

High molecular weight polyaniline (PANI) was synthesized by a combined procedure incorporating various synthesis methods. Temperature and open circuit potential of the reaction mixture were collected to monitor the reaction progress. The polymer is characterized by various techniques including gel permeation chromatography, dynamic light scattering, infrared spectroscopy, solid-state nuclear magnetic resonance, and differential scanning calorimetry for elucidating the molecular architecture obtained by this method. As-synthesized PANI was found to possess high molecular weight, reduced branching, reduced cross-linking, and to predominantly consist of linear polymer chains. This polymer was also found to be more stable in solution form. JV characteristics of as-synthesized PANI films indicate a high current density which is due to increased free pathways and less traps for the charge transport to occur in PANI films. POLYM. ENG. SCI., 2012. (C) 2012 Society of Plastics Engineers

The hazard potential of the western segment of the Makran subduction zone, northern Arabian Sea

Evaluating the hazard potential of the Makran subduction zone requires understanding the previous records of the large earthquakes and tsunamis. We address this problem by searching for earthquake and tectonic proxies along the Makran Coast and linking those observations with the available constraints on historical seismicity and the tell-tale characteristics of sea floor morphology. The earthquake of Mw 8.1 of 1945 and the consequent tsunami that originated on the eastern part of the Makran are the only historically known hazardous events in this region. The seismic status of the western part of the subduction zone outside the rupture area of the 1945 earthquake remains an enigma. The near-shore shallow stratigraphy of the central part of Makran near Chabahar shows evidence of seismically induced liquefaction that we attribute to the distant effects of the 1945 earthquake. The coastal sites further westward around Jask are remarkable for the absence of liquefaction features, at least at the shallow level. Although a negative evidence, this possibly implies that the western part of Makran Coast region may not have been impacted by near-field large earthquakes in the recent past-a fact also supported by the analysis of historical data. On the other hand, the elevated marine terraces on the western Makran and their uplift rates are indicative of comparable degree of long-term tectonic activity, at least around Chabahar. The offshore data suggest occurrences of recently active submarine slumps on the eastern part of the Makran, reflective of shaking events, owing to the great 1945 earthquake. The ocean floor morphologic features on the western segment, on the contrary, are much subdued and the prograding delta lobes on the shelf edge also remain intact. The coast on the western Makran, in general, shows indications of progradation and uplift. The various lines of evidence thus suggest that although the western segment is potentially seismogenic, large earthquakes have not occurred there in the recent past, at least during the last 600 years. The recurrence period of earthquakes may range up to 1,000 years or more, an assessment based on the age of the youngest dated coastal ridge. The long elapsed time points to the fact that the western segment may have accumulated sufficient slip to produce a major earthquake.

Wheeler-Feynman absorber revisited: a useful technique to calculate decay rates and lifetimes in small scale optical systems

The Wheeler-Feynman (WF) absorber theory of radiation though no more of interest in explaining self interaction of an electron, can be very useful in today's research in small scale optical systems. The significance of the WF absorber is the use of time-symmetrical solution of Maxwell's equations as opposed to only the retarded solution. The radiative coupling of emitters to nano wires in the near field and change in their lifetimes due to small mode volume enclosures have been elucidated with the retarded solutions before. These solutions have also been shown to agree with quantum electrodynamics, thus allowing for classical electromagnetic approaches in such problems. It is here assumed that the radiative coupling of the emitter with a body is in proportion to its contribution to the classical force of radiative reaction as derived in the WF absorber theory. Representing such nano structures as a partial WF absorber acting on the emitter makes the computations considerably easier than conventional electromagnetic solutions for full boundary conditions.

Basic features of current induced/shared by cables mounted on down conductors/towers during stroke interception

The telecommunication, broadcasting and other instrumented towers carry power and/or signal cables from their ground end to their upper regions. During a direct hit to the tower, significant induction can occur to these mounted cables. In order to provide adequate protection to the equipments connected to them, protection schemes have been evolved in the literature. Development of more effective protection schemes requires a quantitative knowledge on various parameters. However, such quantitative knowledge is difficult to find at present. Amongst several of these aspects, the present work aims to investigate on the two important aspects: (i) what would be the nature of the induced currents and (ii) what will be the current sharing if as per the practice, the sheath of the cable is connected to the down conductor/tower. These aspects will be useful in design of protection schemes and also in analyzing the field structure around instrumented towers.