Molecular Insights Revealing Interaction of Tim23 and Channel Subunits of Presequence Translocase

Tim23 is an essential channel-forming subunit of the presequence translocase recruiting multiple components for assembly of the core complex, thereby regulating the protein translocation process. However, understanding of the precise interaction of subunits associating with Tim23 remains largely elusive. Our findings highlight that transmembrane helix 1 (TM1) is required for homodimerization of Tim23, while, together with TM2, it is involved in preprotein binding within the channel. Based on our evidence, we predict that the TM1 and TM2 from each dimer are involved in the formation of the central translocation pore, aided by Tim17. Furthermore, TM2 is also involved in the recruitment of Tim21 and the presequence-associated motor (PAM) subcomplex to the Tim23 channel, while the matrix-exposed loop L1 generates specificity in their association with the core complex. Strikingly, our findings indicate that the C-terminal sequence of Tim23 is dispensable for growth and functions as an inhibitor for binding of Tim21. Our model conceptually explains the cooperative function between Tam41 and Pam17 subunits, while the antagonistic activity of Tim21 predominantly determines the bound and free forms of the PAM subcomplex during import.

Strong-coupling expansion for ultracold bosons in an optical lattice at finite temperatures in the presence of superfluidity

We develop a strong-coupling (t << U) expansion technique for calculating the density profile for bosonic atoms trapped in an optical lattice with an overall harmonic trap at finite temperature and finite on-site interaction in the presence of superfluid regions. Our results match well with quantum Monte Carlo simulations at finite temperature. We also show that the superfluid order parameter never vanishes in the trap due to the proximity effect. Our calculations for the scaled density in the vacuum-to-superfluid transition agree well with the experimental data for appropriate temperatures. We present calculations for the entropy per particle as a function of temperature which can be used to calibrate the temperature in experiments. We also discuss issues connected with the demonstration of universal quantum critical scaling in the experiments.

Friction Stir-Welded Dissimilar Aluminum Alloys: Microstructure, Mechanical Properties, and Physical State

A356 and 6061 aluminum alloys were joined by friction stir welding at constant tool rotational rate with different tool-traversing speeds. Thermomechanical data of welding showed that increment in tool speed reduced the pseudo heat index and temperature at weld nugget (WN). On the other hand, volume of material within extrusion zone, strain rate, and Zenner Hollomon parameter were reduced with decrease in tool speed. Optical microstructure of WN exhibited nearly uniform dispersion of Si-rich particles, fine grain size of 6061 Al alloy, and disappearance of second phase within 6061 Al alloy. With enhancement in welding speed, matrix grain size became finer, yet size of Si-rich particles did not reduce incessantly. Size of Si-rich particles was governed by interaction time between tool and substrate. Mechanical property of WN was evaluated. It has been found that the maximum joint efficiency of 116% with respect to that of 6061 alloy was obtained at an intermediate tool-traversing speed, where matrix grain size was significantly fine and those of Si-rich particles were substantially small.

Protumorigenic actions of S100A2 involve regulation of PI3/Akt signaling and functional interaction with Smad3

S100 family of calcium-binding proteins is commonly upregulated in a variety of tumor types and is often associated with tumor progression. Among several S100 members, altered expression of S100A2 is a potential diagnostic and prognostic marker in cancer. Several reports suggest a role for S100A2 in metastasis. Earlier, our studies established regulation of S100A2 by transforming growth factor- (TGF-) and its involvement in TGF--mediated cancer cell invasion and migration. However, the molecular mechanisms of S100A2 protumorigenic actions remain unexplored. In the present study, we demonstrate that overexpression of S100A2 in A549 lung cancer cells induced epithelialmesenchymal transition (EMT) followed by increased invasion, loose colony morphology in soft agar and enhanced Akt phosphorylation (Ser-473). Furthermore, overexpression of S100A2 led to increased tumor growth in immunocompromised mice. In agreement, immunohistochemical examination of resected xenograft tumors established inverse correlation between S100A2 and E-cadherin expression together with activated Akt signaling. Interestingly, our study demonstrates a strong dependence of S100A2 and Smad3 in TGF--induced Hep3B cell EMT and invasion. Most importantly, we demonstrate that these effects of S100A2 are manifested through functional interaction with Smad3, which is enhanced in the presence of high calcium and TGF-. S100A2 stabilizes Smad3 and binds to its C-terminal MH2 domain. Additionally, loss of S100A2 attenuates the transcription of TGF-/Smad3 target genes involved in tumor promotion, such as PA1-1 and vimentin. Collectively, our findings present the first mechanistic details of S100A2 protumorigenic actions and its involvement in TGF--mediated cancer cell invasion and EMT.

Shock-boundary layer interaction and transonic flutter

The transonic flutter dip of an aeroelastic system is primarily caused by compressibility of the flowing fluid. Viscous effects are not dominant in the pre-transonic dip region. In fact, an Euler solver can predict this flutter boundary with considerable accuracy. However with an increase in Mach number the shock moves towards the trailing edge causing shock induced separation. This shock-boundary layer interaction changes the flutter boundary in the transonic and post-transonic dip region significantly. We discuss the effect of viscosity in changing the flutter boundary in the post-transonic dip region using a RANS solver coupled to a two-degree of freedom model of the structural dynamics of a wing.

Transonic flutter, shocks, and parameter effects

There is a drop in the flutter boundary of an aeroelastic system placed in a transonic flow due to compressibility effects and is known as the transonic dip. Viscous effects can shift the lo-cation of the shock and depending on the shock strength the boundary layer may separate leading to changes in the flutter speed. An unsteady Euler flow solver coupled with the structural dynamic equations is used to understand the effect of shock on the transonic dip. The effect of various system parameters such as mass ratio, location of the center of mass, position of the elastic axis, ratio of uncoupled natural frequencies in heave and pitch are also studied. Steady turbulent flow results are presented to demonstrate the effect of viscosity on the location and strength of the shock.

Study on ride comfort assessment of multiple occupants using lumped parameter analysis

Growing consumer expectations continue to fuel further advancements in vehicle ride comfort analysis including development of a comprehensive tool capable of aiding the understanding of ride comfort. To date, most of the work on biodynamic responses of human body in the context of ride comfort mainly concentrates on driver or a designated occupant and therefore leaves the scope for further work on ride comfort analysis covering a larger number of occupants with detailed modeling of their body segments. In the present study, governing equations of a 13-DOF (degrees-of-freedom) lumped parameter model (LPM) of a full car with seats (7-DOF without seats) and a 7-DOF occupant model, a linear version of an earlier non-linear occupant model, are presented. One or more occupant models can be coupled with the vehicle model resulting into a maximum of 48-DOF LPM for a car with five occupants. These multi-occupant models can be formulated in a modular manner and solved efficiently using MATLAB/SIMULINK for a given transient road input. The vehicle model and the occupant model are independently verified by favorably comparing computed dynamic responses with published data. A number of cases with different dispositions of occupants in a small car are analyzed using the current modular approach thereby underscoring its potential for efficient ride quality assessment and design of suspension systems.

Evaluation of the accuracy of an impact load cell using lumped parameter modeling and analysis

The objective of the current study is to evaluate the fidelity of load cell reading during impact testing in a drop-weight impactor using lumped parameter modeling. For the most common configuration of a moving impactor-load cell system in which dynamic load is transferred from the impactor head to the load cell, a quantitative assessment is made of the possible discrepancy that can result in load cell response. A 3-DOF (degrees-of-freedom) LPM (lumped parameter model) is considered to represent a given impact testing set-up. In this model, a test specimen in the form of a steel hat section similar to front rails of cars is represented by a nonlinear spring while the load cell is assumed to behave in a linear manner due to its high stiffness. Assuming a given load-displacement response obtained in an actual test as the true behavior of the specimen, the numerical solution of the governing differential equations following an implicit time integration scheme is shown to yield an excellent reproduction of the mechanical behavior of the specimen thereby confirming the accuracy of the numerical approach. The spring representing the load cell, however,predicts a response that qualitatively matches the assumed load-displacement response of the test specimen with a perceptibly lower magnitude of load.

mu-Oxamido binuclear copper (II) complexes: Synthesis, crystal structure, DNA interaction and antibacterial studies

Four binuclear copper (II) complexes Cu(oxpn)Cu(B)](2+) (2-5) bridged by N, N'-bis3-(methylamino) propyl] oxamide (oxpn), where, B is N, N-donor heterocyclic bases (viz. 2,2'-bipyridine (bpy, 2), 1,10-phenathroline (phen, 3), dipyrido3,2-d:2',3'-f]quinoxaline (dpq, 4) and dipyrido3,2-a:2',3'-c]phenazine (dppz, 5) are synthesized, characterized by different spectroscopic and single crystal X-ray data technique. The phen (3) and dpq (4) complexes were structurally characterized by X-ray data analysis. Their DNA binding, oxidative cleavage and antibactirial activities were studied. The dpq (4) and dppz (5) complexes are avid binders to the Calf thymus DNA (CT-DNA). The phen (3), dpq (4) and dppz (5) complexes show efficient oxidative cleavage of supercoiled DNA (SC DNA) through hydroxyl radical ((OH)-O-center dot) pathway in the presence of Mercaptopropionic acid (MPA). (C) 2013 Elsevier Ltd. All rights reserved.

Synthesis, crystal structure, DNA interaction and cleavage activities of mononuclear and trinuclear copper(II) complexes

Mono- and trinuclear copper(II) complexes with 2-1-(2-dimethylamino-ethylamino)-ethyl]-phenol (HL) have been synthesized and structurally characterized. The mononuclear complex Cu(L)(H2O)(ONO2)] (1) crystallizes in monoclinic space group P2(1) /n with a square pyramidal Cu(II) center coordinated by the tridentate Schiff base (L) and a water ligand in the equatorial plane and an oxygen atom from nitrate in the axial position. The trinuclear complex (CuL)(3)(mu(3)-OH)](ClO4)(2)center dot H2O (2) crystallizes in hexagonal space group P6(3); all three copper atoms are five-coordinate with square pyramidal geometries. The interactions of these complexes with calf-thymus DNA have been investigated using absorption spectrophotometry. The mononuclear complex binds more strongly than the trinuclear complex. The DNA cleavage activity of these complexes has been studied on double-stranded pBR 322 plasmid DNA by gel electrophoresis experiments in the absence and in the presence of added oxidant (H2O2). The trinuclear complex cleaves DNA more efficiently than the mononuclear complex in the presence of H2O2.

PLIC: protein-ligand interaction clusters

Most of the biological processes are governed through specific protein-ligand interactions. Discerning different components that contribute toward a favorable protein-ligand interaction could contribute significantly toward better understanding protein function, rationalizing drug design and obtaining design principles for protein engineering. The Protein Data Bank (PDB) currently hosts the structure of similar to 68 000 protein-ligand complexes. Although several databases exist that classify proteins according to sequence and structure, a mere handful of them annotate and classify protein-ligand interactions and provide information on different attributes of molecular recognition. In this study, an exhaustive comparison of all the biologically relevant ligand-binding sites (84 846 sites) has been conducted using PocketMatch: a rapid, parallel, in-house algorithm. PocketMatch quantifies the similarity between binding sites based on structural descriptors and residue attributes. A similarity network was constructed using binding sites whose PocketMatch scores exceeded a high similarity threshold (0.80). The binding site similarity network was clustered into discrete sets of similar sites using the Markov clustering (MCL) algorithm. Furthermore, various computational tools have been used to study different attributes of interactions within the individual clusters. The attributes can be roughly divided into (i) binding site characteristics including pocket shape, nature of residues and interaction profiles with different kinds of atomic probes, (ii) atomic contacts consisting of various types of polar, hydrophobic and aromatic contacts along with binding site water molecules that could play crucial roles in protein-ligand interactions and (iii) binding energetics involved in interactions derived from scoring functions developed for docking. For each ligand-binding site in each protein in the PDB, site similarity information, clusters they belong to and description of site attributes are provided as a relational database-protein-ligand interaction clusters (PLIC).

NaOsO3: A high Neel temperature 5d oxide

The origin of a high Neel temperature in a 5d oxide, NaOsO3, has been analyzed within the mean-field limit of a multiband Hubbard model and compared with the analogous 4d oxide, SrTcO3. Our analysis shows that there are a lot of similarities in both of these oxides on the dependence of the effective exchange interaction strength (J(0)) on the electron-electron interaction strength ( U). However, the relevant value of U in each system puts them in different portions of the parameter space. Although the Neel temperature for NaOsO3 is less than that for SrTcO3, our results suggest that there could be examples among other 5d oxides that have a higher Neel temperature. We have also examined the stability of the G-type antiferromagnetic state found in NaOsO3 as a function of electron doping within GGA + U calculations and find a robust G-type antiferromagnetic metallic state stabilized. The most surprising aspect of the doped results is the rigid bandlike evolution of the electronic structure, which indicates that the magnetism in NaOsO3 is not driven by Fermi surface nesting.

Relation between the Isentropic Index and the Gruneisen Parameter for Saturated Liquids

We investigate the isentropic index along the saturated vapor line as a correlating parameter with quantities both in the saturated liquid phase and the saturated vapor phase. The relation is established via temperatures such as T-hgmax and T* where the saturated vapor enthalpy and the product of saturation temperature and saturated liquid density attain a maximum, respectively. We obtain that the saturated vapor isentropic index is correlated with these temperatures but also with the saturated liquid Gruneisen parameters at T-hgmax. and T*.

Context dependency of rewards and services in an Indian ant-plant interaction: southern sites favour the mutualism between plants and ants

Protection-based ant-plant mutualisms may vary in strength due to differences in ant rewards, abundance of protective ants and herbivory pressure. We investigated geographical and temporal variation in host plant traits and herbivory pressure at five sites spanning the distribution range of the myrmecophyte Humboldtia brunonis (Fabaceae) in the Indian Western Ghats. Southern siteshad, onaverage, 2.4 times greater abundance of domatia-bearing individuals, 1.6 times greater extrafloral nectary numbers per leaf, 1.2 times larger extrafloral nectary sizes, 2.2 times greater extrafloral nectar (EFN) volumes and a two-fold increase in total amino acid and total sugar concentrations in EFN compared with northern sites. Astrong protection-based mutualismwith ants occurred at only one southern site where herbivory was highest, suggesting that investments in attracting ants correlate with anti-herbivore benefits gained from the presence of protective ants. Our results confirm a temporally stable north-south gradient in myrmecophytic traits in this ant-plant as several of these traits were re-sampled after a 5-y interval. However, the chemical composition of EFN varied at both spatial and short-term temporal scales suggesting that only repeated measurements of rewards such as EFN can reveal the real spectrum of trait variation in an ant-plant mutualistic system.