The role of glycodelin as an immune-modulating agent at the feto-maternal interface

Glycodelin A is a progesterone-induced endometrial glycoprotein which has been amply documented to play a role in down-modulation of the maternal immune response to fetal allo-antigens and to be indispensable for the maintenance and progression of pregnancy. Earlier studies from our laboratory have focused on the effect of glycodelin on T cells, key regulators of both the antibody and cell-mediated arms of the acquired immune system. Glycodelin-induced apoptosis inactivated T cells occurs through a caspase-dependant intrinsic mitochondrial pathway. Interestingly, glycodelin inhibited the proliferation of B cells but did not induce apoptosis. More recently, we have studied the effect of glycodelin on the cells of the innate immune system, namely monocytes and NK cells. We have found that glycodelin induced apoptosis in monocytic cells before their differentiation to macrophages, via the mitochondrial pathway, but did not affect their phagocytic capacity after differentiation. Glycodelin induced apoptosis in NK cells but this activity was independent of caspases. In conclusion, glycodelin is observed to affect many cells of the immune system, although the nature of the effect and signaling mechanisms involved in each cell type may be distinct.

Recognition of Interaction Interface Residues in Low-Resolution Structures of Protein Assemblies Solely from the Positions of C alpha Atoms

Background: The number of available structures of large multi-protein assemblies is quite small. Such structures provide phenomenal insights on the organization, mechanism of formation and functional properties of the assembly. Hence detailed analysis of such structures is highly rewarding. However, the common problem in such analyses is the low resolution of these structures. In the recent times a number of attempts that combine low resolution cryo-EM data with higher resolution structures determined using X-ray analysis or NMR or generated using comparative modeling have been reported. Even in such attempts the best result one arrives at is the very course idea about the assembly structure in terms of trace of the C alpha atoms which are modeled with modest accuracy. Methodology/Principal Findings: In this paper first we present an objective approach to identify potentially solvent exposed and buried residues solely from the position of C alpha atoms and amino acid sequence using residue type-dependent thresholds for accessible surface areas of C alpha. We extend the method further to recognize potential protein-protein interface residues. Conclusion/Significance: Our approach to identify buried and exposed residues solely from the positions of C alpha atoms resulted in an accuracy of 84%, sensitivity of 83-89% and specificity of 67-94% while recognition of interfacial residues corresponded to an accuracy of 94%, sensitivity of 70-96% and specificity of 58-94%. Interestingly, detailed analysis of cases of mismatch between recognition of interface residues from C alpha positions and all-atom models suggested that, recognition of interfacial residues using C alpha atoms only correspond better with intuitive notion of what is an interfacial residue. Our method should be useful in the objective analysis of structures of protein assemblies when positions of only C alpha positions are available as, for example, in the cases of integration of cryo-EM data and high resolution structures of the components of the assembly.

Assessing vulnerability at the urban interface

House loss during unplanned bushfires is a complex phenomenon where design, configuration, material and siting, can significantly influence the loss. In collaboration with the Bushfire Cooperative Research Centre the CSIRO has developed a tool to assess the vulnerability of a specific house at the urban interface. The tool is based on a spatial profiling of urban assets including their design, material, surrounding objects and their relationship amongst one another. The analysis incorporates both probabilistic and deterministic parameters, and is based on the impact of radiant heat, flame and embers on the surrounding elements and the structure itself. It provides a breakdown of the attributes and design parameters that contribute to the vulnerability level. This paper describes the tool which allows the user to explore the vulnerability of a house to varying levels of bushfire attacks. The tool is aimed at government agencies interested in building design, town planning and community education for bushfire risk mitigation.

Allostery and conformational free energy changes in human tryptophanyl-tRNA synthetase from essential dynamics and structure networks

The interdependence of the concept of allostery and enzymatic catalysis, and they being guided by conformational mobility is gaining increased prominence. However, to gain a molecular level understanding of llostery and hence of enzymatic catalysis, it is of utter importance that the networks of amino acids participating in allostery be deciphered. Our lab has been exploring the methods of network analysis combined with molecular dynamics simulations to understand allostery at molecular level. Earlier we had outlined methods to obtain communication paths and then to map the rigid/flexible regions of proteins through network parameters like the shortest correlated paths, cliques, and communities. In this article, we advance the methodology to estimate the conformational populations in terms of cliques/communities formed by interactions including the side-chains and then to compute the ligand-induced population shift. Finally, we obtain the free-energy landscape of the protein in equilibrium, characterizing the free-energy minima accessed by the protein complexes. We have chosen human tryptophanyl-tRNA synthetase (hTrpRS), a protein esponsible for charging tryptophan to its cognate tRNA during protein biosynthesis for this investigation. This is a multidomain protein exhibiting excellent allosteric communication. Our approach has provided valuable structural as well as functional insights into the protein. The methodology adopted here is highly generalized to illuminate the linkage between protein structure networks and conformational mobility involved in the allosteric mechanism in any protein with known structure.

Free and ATP-bound structures of Ap(4)A hydrolase from Aquifex aeolicus V5

Asymmetric diadenosine tetraphosphate (Ap(4)A) hydrolases degrade the metabolite Ap(4)A back into ATP and AMP. The three-dimensional crystal structure of Ap(4)A hydrolase (16 kDa) from Aquifex aeolicus has been determined in free and ATP-bound forms at 1.8 and 1.95 angstrom resolution, respectively. The overall three-dimensional crystal structure of the enzyme shows an alpha beta alpha-sandwich architecture with a characteristic loop adjacent to the catalytic site of the protein molecule. The ATP molecule is bound in the primary active site and the adenine moiety of the nucleotide binds in a ring-stacking arrangement equivalent to that observed in the X-ray structure of Ap(4)A hydrolase from Caenorhabditis elegans. Binding of ATP in the active site induces local conformational changes which may have important implications in the mechanism of substrate recognition in this class of enzymes. Furthermore, two invariant water molecules have been identified and their possible structural and/or functional roles are discussed. In addition, modelling of the substrate molecule at the primary active site of the enzyme suggests a possible path for entry and/or exit of the substrate and/or product molecule.

Force-free equilibria of magnetized jets

Force-free equilibrium configurations of magnetic-pressure-dominated magnetized supersonic jets confined by slowly varying external pressure are investigated analytically. For the case where internal dissipation mechanisms are active, the lowest-energy field configuration is found to be the superposition of an axisymmetric mode and a helical mode with a wavelength equal to 5 times the jet radius, and the pressure below which the nonaxisymmetric mode becomes energetically favorable is given as 2700 times the product of the 4th power of the magnetic helicity per unit length and the -6th power of the magnetic flux. A model of the total and polarized emission of such a configuration is developed and applied to the extended well-collimated astronomically resolved jet NGC 6251. The model is shown to reproduce significant features such as transverse oscillations of the ridge line, width oscillations and emission knots, the projected magnetic-field configuration, oscillations of the degree of polarization, and the distribution of the Faraday rotation measure.

Magnetic energy dissipation in force-free jets

It is shown that a magnetic-pressure-dominated, supersonic jet which expands (or contracts) in response to variations in the confining external pressure can dissipate magnetic energy through field-line reconnection as it relaxes to a minimum-energy configuration. In order for a continuous dissipation to take place, the effective reconnection time must be a fraction ɛ ⪉ 1 of the expansion time. The amount of energy dissipation is calculated, and it is concluded that magnetic energy dissipation could, in principle, power the observed synchrotron emission in extragalactic radio jets such as NGC 6251. However, this mechanism is only viable if the reconnection time is substantially shorter than the nominal resistive tearing time in the jet.

Mechanism of failure in a free-standing Pt-aluminide bond coat during tensile testing at room temperature

The room temperature (RT) tensile behaviour of a free-standing high activity Pt-aluminide bond coat has been evaluated by microtensile testing technique. The coating had a typical three-layer microstructure. The stress-strain plot for the free-standing coating was linear, indicating the coating to be brittle at RT. Different fracture features were observed across the coating layers, namely quasi-cleavage in the outer layer and inner interdiffusion zone, and cleavage in the intermediate layer. By employing interrupted tensile test and observing the cross-sectional microstructure of the tested specimens, it was determined that failure of the microtensile samples occurred by the initiation of a single crack in the intermediate layer of the coating and its subsequent inside-out propagation. Such a mechanism of failure has been explained in terms of the fracture features observed across the sample thickness. This mechanism of failure is consistent with fracture toughness values of the individual coating layers. (C) 2009 Elsevier B.V. All rights reserved.

A germanium/single-walled carbon nanotube composite paper as a free-standing anode for lithium-ion batteries

Paper-like free-standing germanium (Ge) and single-walled carbon nanotube (SWCNT) composite anodes were synthesized by the vacuum filtration of Ge/SWCNT composites, which were prepared by a facile aqueous-based method. The samples were characterized by X-ray diffraction, field emission scanning electron microscopy, and transmission electron microscopy. Electrochemical measurements demonstrate that the Ge/SWCNT composite paper anode with the weight percentage of 32% Ge delivered a specific discharge capacity of 417 mA h g-1 after 40 cycles at a current density of 25 mA g-1, 117% higher than the pure SWCNT paper anode. The SWCNTs not only function as a flexible mechanical support for strain release, but also provide excellent electrically conducting channels, while the nanosized Ge particles contribute to improving the discharge capacity of the paper anode.

3D hierarchical rutile TiO2 and metal-free organic sensitizer producing dye-sensitized solar cells 8.6% conversion efficiency

Three-dimensional (3D) hierarchical nanoscale architectures comprised of building blocks, with specifically engineered morphologies, are expected to play important roles in the fabrication of 'next generation' microelectronic and optoelectronic devices due to their high surface-to-volume ratio as well as opto-electronic properties. Herein, a series of well-defined 3D hierarchical rutile TiO2 architectures (HRT) were successfully prepared using a facile hydrothermal method without any surfactant or template, simply by changing the concentration of hydrochloric acid used in the synthesis. The production of these materials provides, to the best of our knowledge, the first identified example of a ledgewise growth mechanism in a rutile TiO2 structure. Also for the first time, a Dye-sensitized Solar Cell (DSC) combining a HRT is reported in conjunction with a high-extinction-coefficient metal-free organic sensitizer (D149), achieving a conversion efficiency of 5.5%, which is superior to ones employing P25 (4.5%), comparable to state-of-the-art commercial transparent titania anatase paste (5.8%). Further to this, an overall conversion efficiency 8.6% was achieved when HRT was used as the light scattering layer, a considerable improvement over the commercial transparent/reflector titania anatase paste (7.6%), a significantly smaller gap in performance than has been seen previously.

Organic–inorganic bismuth (III)-based material: A lead-free, air-stable and solution-processable light-absorber beyond organolead perovskites

Methylammonium bismuth (III) iodide single crystals and films have been developed and investigated. We have further presented the first demonstration of using this organic–inorganic bismuth-based material to replace lead/tin-based perovskite materials in solution-processable solar cells. The organic–inorganic bismuth-based material has advantages of non-toxicity, ambient stability, and low-temperature solution-processability, which provides a promising solution to address the toxicity and stability challenges in organolead- and organotin-based perovskite solar cells. We also demonstrated that trivalent metal cation-based organic–inorganic hybrid materials can exhibit photovoltaic effect, which may inspire more research work on developing and applying organic-inorganic hybrid materials beyond divalent metal cations (Pb (II) and Sn (II)) for solar energy applications.

Computation of Thermal Stress Intensity Factors for Bimaterial Interface Cracks Using Domain Integral Method

The concept of domain integral used extensively for J integral has been applied in this work for the formulation of J(2) integral for linear elastic bimaterial body containing a crack at the interface and subjected to thermal loading. It is shown that, in the presence of thermal stresses, the J(k) domain integral over a closed path, which does not enclose singularities, is a function of temperature and body force. A method is proposed to compute the stress intensity factors for bimaterial interface crack subjected to thermal loading by combining this domain integral with the J(k) integral. The proposed method is validated by solving standard problems with known solutions.

Behaviour of Bi-material interface cracks in the presence of material nonlinearity of adherends

The well known features of crack face interpenetration/contact at the tip of an interface crack is re-examined using finite element analysis and assuming material nonlinear properties for the adherends. It was assumed in literature that the crack tips are fully open at all load levels in the presence of material nonlinearity of the adherends. Analysis for the case of remote tension shows that even in the presence of material nonlinearity, crack tip closes at small load levels and opens above a certain load level. Mixed-mode fracture parameters are evaluated for the situation when the crack tips are fully open. Due to the presence of nonlinearity, the mixed-mode fracture parameters are measured with the symmetric and anti-symmetric components of J-integral. The present analysis explains the sequence of events at the interface crack tip with progressively increasing remote tension load for the case of adherends with material nonlinear behaviour.