Crystal structure of dimeric FabZ of Plasmodium falciparum reveals conformational switching to active hexamers by peptide flips

The crystal structure of beta-hydroxyacyl acyl carrier protein dehydratase of Plasmodium falciparum (PfFabZ) has been determined at a resolution of 2.4 angstrom. PfFabZ has been found to exist as a homodimer (d-PfFabZ) in the crystals of the present study in contrast to the reported hexameric form (h-PfFabZ) which is a trimer of dimers crystallized in a different condition. The catalytic sites of this enzyme are located in deep narrow tunnel-shaped pockets formed at the dimer interface. A histidine residue from one subunit of the dimer and a glutamate residue from the other subunit lining the tunnel form the catalytic dyad in the reported crystal structures. While the position of glutamate remains unaltered in the crystal structure of d-PffabZ compared to that in b-PfFabZ, the histidine residue takes up an entirely different conformation and moves away from the tunnel leading to a His-Phe cis-trans peptide flip at the histidine residue. In addition, a loop in the vicinity has been observed to undergo a similar flip at a Tyr-Pro peptide bond. These alterations not only prevent the formation of a hexamer but also distort the active site geometry resulting in a dimeric form of FabZ that is incapable of substrate binding. The dimeric state and an altered catalytic site architecture make d-PfFabZ distinctly different from the FabZ structures described so far. Dynamic light scattering and size exclusion chromatographic studies clearly indicate a pH-related switching of the dimers to active hexamers. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserv.

Transition to turbulence in the free convection boundary layers on an inclined heated plate

An experimental study has been made of transition to turbulence in the free convective flows on a heated plate. Observations have been made with the plate vertical and inclined at angles up to about 50° to the vertical, both above and below the plate. A fibre anemometer was used to survey the region of intermittent turbulence. Information has thus been obtained about the range of Grashof numbers over which transition takes place. Even when the plate is vertical the region of intermittent turbulence is long. When it is inclined, this region becomes still longer in the flow below the plate as a result of the stabilizing stratification, a Richardson number effect. It is possible to have a whole flow such that it should be described as transitional, not laminar or turbulent. It was noticed that in this flow and the vertical plate one, the velocity during the laminar periods could be either of two characteristic values, one of them close to zero. The behaviour above an inclined plate could be interpreted largely as a trend towards the behaviour described in a preceding paper.

Effectors of Salmonella pathogenicity island 2: An island crucial to the life of Salmonella

The tug of war between a pathogen and its host has been one of the most amazing stories in the field of microbial pathogenesis for ages. The strongest known species of all living organisms is the Homo sapiens and yet it is incredible how a pathogen of the size of few microns is smart enough to defeat this mightiest group of survivors. It is of utmost interest to understand the mechanisms behind the successful habitation of a pathogen inside the ever-resisting and complicate human body. Numerous examples of diseases caused by such pathogens exist which intrigues us to venture in the world of host-pathogen interactions.

A dynamical instability due to fluid–wall coupling lowers the transition Reynolds number in the flow through a flexible tube

A flow-induced instability in a tube with flexible walls is studied experimentally. Tubes of diameter 0.8 and 1.2 mm are cast in polydimethylsiloxane (PDMS) polymer gels, and the catalyst concentration in these gels is varied to obtain shear modulus in the range 17–550 kPa. A pressure drop between the inlet and outlet of the tube is used to drive fluid flow, and the friction factor $f$ is measured as a function of the Reynolds number $Re$. From these measurements, it is found that the laminar flow becomes unstable, and there is a transition to a more complicated flow profile, for Reynolds numbers as low as 500 for the softest gels used here. The nature of the $f$–$Re$ curves is also qualitatively different from that in the flow past rigid tubes; in contrast to the discontinuous increase in the friction factor at transition in a rigid tube, it is found that there is a continuous increase in the friction factor from the laminar value of $16\ensuremath{/} Re$ in a flexible tube. The onset of transition is also detected by a dye-stream method, where a stream of dye is injected into the centre of the tube. It is found that there is a continuous increase of the amplitude of perturbations at the onset of transition in a flexible tube, in contrast to the abrupt disruption of the dye stream at transition in a rigid tube. There are oscillations in the wall of the tube at the onset of transition, which is detected from the laser scattering off the walls of the tube. This indicates that the coupling between the fluid stresses and the elastic stresses in the wall results in an instability of the laminar flow.

A New Family of Soft Transition Converters: Design Example and Dynamic Model

The soft switching converters evolved through the resonant load, resonant switch, resonant transition and active clamp converters to eliminate switching losses in power converters. This paper briefly presents the operating principle of the new family of soft transition converters; the methodology of design of these converters is presented through an example. In the proposed family of converters, the switching transitions of both the main switch and auxiliary switch are lossless.When these converters are analysed in terms of the pole current and throw voltage, the defining equations of all converters belonging to this family become identical.Such a description allows one to define simple circuit oriented model for these converters. These circuit models help in evaluating the steady state and dynamic model of these converters. The standard dynamic performance functions of the converters are readily obtainable from this model. This paper presents these dynamic models and verifies the same through measurements on a prototype converter.

A new family of soft transition converters: Design and dynamic model

The soft switching converters evolved through the resonant load, resonant switch, resonant transition and active clamp converters to eliminate switching losses in power converters. This paper briefly presents the operating principle of the new family of soft transition converters; the methodology of design of these converters is presented through an example. In the proposed family of converters, the switching transitions of both the main switch and auxiliary switch are lossless. When these converters are analysed in terms of the pole current and throw voltage, the defining equations of all converters belonging to this family become identical.Such a description allows one to define simple circuit oriented model for these converters. These circuit models help in evaluating the steady state and dynamic model of these converters. The standard dynamic performance functions of the converters are readily obtainable from this model. This paper presents these dynamic models and verifies the same through measurements on a prototype converter.

Flocking at a distance in active granular matter

The self-organized motion of vast numbers of creatures in a single direction is a spectacular example of emergent order. Here, we recreate this phenomenon using actuated nonliving components. We report here that millimetre-sized tapered rods, rendered motile by contact with an underlying vibrated surface and interacting through a medium of spherical beads, undergo a phase transition to a state of spontaneous alignment of velocities and orientations above a threshold bead area fraction. Guided by a detailed simulation model, we construct an analytical theory of this flocking transition, with two ingredients: a moving rod drags beads; neighbouring rods reorient in the resulting flow like a weathercock in the wind. Theory and experiment agree on the structure of our phase diagram in the plane of rod and bead concentrations and power-law spatial correlations near the phase boundary. Our discovery suggests possible new mechanisms for the collective transport of particulate or cellular matter.

Fuzzy-logic-based health monitoring and residual-life prediction for composite helicopter rotor

A health-monitoring and life-estimation strategy for composite rotor blades is developed in this work. The cross-sectional stiffness reduction obtained by physics-based models is expressed as a function of the life of the structure using a recent phenomenological damage model. This stiffness reduction is further used to study the behavior of measurable system parameters such as blade deflections, loads, and strains of a composite rotor blade in static analysis and forward flight. The simulated measurements are obtained using an aeroelastic analysis of the composite rotor blade based on the finite element in space and time with physics-based damage modes that are then linked to the life consumption of the blade. The model-based measurements are contaminated with noise to simulate real data. Genetic fuzzy systems are developed for global online prediction of physical damage and life consumption using displacement- and force-based measurement deviations between damaged and undamaged conditions. Furthermore, local online prediction of physical damage and life consumption is done using strains measured along the blade length. It is observed that the life consumption in the matrix-cracking zone is about 12-15% and life consumption in debonding/delamination zone is about 45-55% of the total life of the blade. It is also observed that the success rate of the genetic fuzzy systems depends upon the number of measurements, type of measurements and training, and the testing noise level. The genetic fuzzy systems work quite well with noisy data and are recommended for online structural health monitoring of composite helicopter rotor blades.

Freezing of a colloidal liquid subject to shear flow

A nonequilibrium generalization of the density-functional theory of freezing is proposed to investigate the shear-induced first-order phase transition in colloidal suspensions. It is assumed that the main effect of a steady shear is to break the symmetry of the structure factor of the liquid and that for small shear rate, the phenomenon of a shear-induced order-disorder transition may be viewed as an equilibrium phase transition. The theory predicts that the effective density at which freezing takes place increases with shear rate. The solid (which is assumed to be a bcc lattice) formed upon freezing is distorted and specifically there is less order in one plane compared with the order in the other two perpendicular planes. It is shown that there exists a critical shear rate above which the colloidal liquid does not undergo a transition to an ordered (or partially ordered) state no matter how large the density is. Conversely, above the critical shear rate an initially formed bcc solid always melts into an amorphous or liquidlike state. Several of these predictions are in qualitative agreement with the light-scattering experiments of Ackerson and Clark. The limitations as well as possible extensions of the theory are also discussed.

Out-of-equilibrium microrheology using optical tweezers to probe directional viscoelastic properties under shear

Many wormlike micellar systems exhibit appreciable shear thinning due to shear-induced alignment. As the micelles get aligned introducing directionality in the system, the viscoelastic properties are no longer expected to be isotropic. An optical-tweezers-based active microrheology technique enables us to probe the out-of-equilibrium rheological properties of a wormlike micellar system simultaneously along two orthogonal directions-parallel to the applied shear, as well as perpendicular to it. While the displacements of a trapped bead in response to active drag force carry signature of conventional shear thinning, its spontaneous position fluctuations along the perpendicular direction manifest an orthogonal shear thickening, an effect hitherto unobserved. Copyright (C) EPLA, 2010

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).

Biomonitoring of Lotic habitats through Diatoms

Freshwater ecosystems vary in size and composition and contain a wide range of organisms which interact with each other and with the environment. These interactions are between organisms and the environment as nutrient cycling, biomass formation and transfer, maintenance of internal environment and interactions with the external environment. The range of organisms present in aquatic communities decides the generation and transfer function of biomass, which defines and characterises the system. These organisms have distinct roles as they occupy particular trophic levels, forming an interconnected system in a food chain. Availability of resources and competition would primarily determine the balance of individual species within the food web, which in turn influences the variety and proportions of the different organisms, with important implications for the overall functioning of the system. This dynamic and diverse relationship decides the physical, chemical and biological elements across spatial and temporal scales in the aquatic ecosystem, which can be recorded by regular inventorying and monitoring to maintain the integrity and conserve the ecosystem. Regular environmental monitoring, particularly water quality monitoring allows us to detect, assess and manage the overall impacts on the rivers. The appreciation of water quality is in constant flux. Water quality assessments derived through the biotic indices, i.e. assessments based on observations of the resident floral and faunal communities has gained importance in recent years. Biological evaluations provide a description of the water quality that is often not achievable from elemental analyses alone. A biological indicator (or bioindicator) is a taxon or taxa selected based on its sensitivity to a particular attribute, and then assessed to make inferences about that attribute. In other words, they are a substitute for directly measuring abiotic features or other biota. Bioindicators are evaluated through presence or absence, condition, relative abundance, reproductive success, community structure (i.e. composition and diversity), community function (i.e. trophic structure), or any combination thereof.Biological communities reflect the overall ecological integrity by integrating various stresses, thus providing a broad measure of their synergistic impacts. Aquatic communities, both plants and animals, integrate and reflect the effects of chemical and physical disturbances that occur over extended periods of time. Monitoring procedures based on the biota measure the health of a river and the ability of aquatic ecosystems to support life as opposed to simply characterising the chemical and physical components of a particular system. This is the central purpose of assessing the biological condition of aquatic communities of a river.Diatoms (Bacillariophyceae), blue green algae (Cyanophyceae), green algae (Chlorophyceae), and red algae (Rhodphyceae) are the main groups of algae in flowing water. These organisms are widely used as biological indicators of environmental health in the aquatic ecosystem because algae occupy the most basic level in the transfer of energy through natural aquatic systems. The distribution of algae in an aquatic ecosystem is directly related to the fundamental factors such as physical, chemical and biological constituents. Soft algae (all the algal groups except diatoms) have also been used as indicators of biological integrity, but they may have less efficiency than diatoms in this respect due to their highly variable morphology. The diatoms (Bacillariophyceae) comprise a ubiquitous, highly successful and distinctive group of unicellular algae with the most obvious distinguishing characteristic feature being siliceous cell walls (frustules). The photosynthetic organisms living within its photic zone are responsible for about one-half of global primary productivity. The most successful organisms are thought to be photosynthetic prokaryotes (cyanobacteria and prochlorophytes) and a class of eukaryotic unicellular algae known as diatoms. Diatoms are likely to have arisen around 240 million years ago following an endosymbiotic event between a red eukaryotic alga and a heterotrophic flagellate related to the Oomycetes.The importance of algae to riverine ecology is easily appreciated when one considers that they are primary producers that convert inorganic nutrients into biologically active organic compounds while providing physical habitat for other organisms. As primary producers, algae transform solar energy into food from which many invertebrates obtain their energy. Algae also transform inorganic nutrients, such as atmospheric nitrogen into organic forms such as ammonia and amino acids that can be used by other organisms. Algae stabilises the substrate and creates mats that form structural habitats for fish and invertebrates. Algae are a source of organic matter and provide habitat for other organisms such as non-photosynthetic bacteria, protists, invertebrates, and fish. Algae's crucial role in stream ecosystems and their excellent indicator properties make them an important component of environmental studies to assess the effects of human activities on stream health. Diatoms are used as biological indicators for a number of reasons: 1. They occur in all types of aquatic ecosystems. 2. They collectively show a broad range of tolerance along a gradient of aquatic productivity, individual species have specific water chemistry requirements. 3. They have one of the shortest generation times of all biological indicators (~2 weeks). They reproduce and respond rapidly to environmental change and provide early measures of both pollution impacts and habitat restoration. 4. It takes two to three weeks before changes are reflected to a measurable extent in the assemblage composition.

The study of pressure induced structural phase transition in spin-frustrated Yb2Ti2O7 pyrochlore

Our in situ x-ray diffraction and Raman measurements of Yb2Ti2O7 pyrochlore show that it undergoes a reversible structural phase transition from cubic pyrochlore to a monoclinic phase at similar to 28.6 GPa. Analysis of the x-ray data shows the transition to be thermodynamically first order and the high pressure phase to be substitutionally disordered. These experimental results are supported by our first principles calculations. (C) 2012 American Institute of Physics. [doi:10.1063/1.3681300]

Effective Mass-Driven Structural Transition in a Mn-Doped ZnS Nanoplatelet

Mn doping in ZnS nanoplatelets has been shown to induce a structural transition from the wurtzite to the zinc blende phase. We trace the origin of this transition to quantum confinement effects, which shift the valence band maximum of the wurtzite and zinc blende polyrnorphs of ZnS at different rates as a function of the nanocrystal size, arising from different effective hole masses in the two structures. This modifies the covalency associated with Mn incorporation and is reflected in the size-dependent binding energy difference for the two structures.