Prediction of protein-protein interactions in dengue virus coat proteins guided by low resolution cryoEM structures

Background: Dengue virus along with the other members of the flaviviridae family has reemerged as deadly human pathogens. Understanding the mechanistic details of these infections can be highly rewarding in developing effective antivirals. During maturation of the virus inside the host cell, the coat proteins E and M undergo conformational changes, altering the morphology of the viral coat. However, due to low resolution nature of the available 3-D structures of viral assemblies, the atomic details of these changes are still elusive. Results: In the present analysis, starting from C alpha positions of low resolution cryo electron microscopic structures the residue level details of protein-protein interaction interfaces of dengue virus coat proteins have been predicted. By comparing the preexisting structures of virus in different phases of life cycle, the changes taking place in these predicted protein-protein interaction interfaces were followed as a function of maturation process of the virus. Besides changing the current notion about the presence of only homodimers in the mature viral coat, the present analysis indicated presence of a proline-rich motif at the protein-protein interaction interface of the coat protein. Investigating the conservation status of these seemingly functionally crucial residues across other members of flaviviridae family enabled dissecting common mechanisms used for infections by these viruses. Conclusions: Thus, using computational approach the present analysis has provided better insights into the preexisting low resolution structures of virus assemblies, the findings of which can be made use of in designing effective antivirals against these deadly human pathogens.

Improved retrieval of aerosol size-resolved properties from moderate resolution imaging spectroradiometer over India: Role of aerosol model and surface reflectance

We have compared the total as well as fine mode aerosol optical depth (tau and tau(fine)) retrieved by Moderate Resolution Imaging Spectroradiometer (MODIS) onboard Terra and Aqua (2001-2005) with the equivalent parameters derived by Aerosol Robotic Network (AERONET) at Kanpur (26.45 degrees N, 80.35 degrees E), northern India. MODIS Collection 005 (C005)-derived tau(0.55) was found to be in good agreement with the AERONET measurements. The tau(fine) and eta (tau(fine)/tau) were, however, biased low significantly in most matched cases. A new set of retrieval with the use of absorbing aerosol model (SSA similar to 0.87) with increased visible surface reflectance provided improved tau and tau(fine) at Kanpur. The new derivation of eta also compares well qualitatively with an independent set of in situ measurements of accumulation mass fraction over much of the southern India. This suggests that though MODIS land algorithm has limited information to derive size properties of aerosols over land, more accurate parameterization of aerosol and surface properties within the existing C005 algorithm may improve the accuracy of size-resolved aerosol optical properties. The results presented in this paper indicate that there is a need to reconsider the surface parameterization and assumed aerosol properties in MODIS C005 algorithm over the Indian region in order to retrieve more accurate aerosol optical and size properties, which are essential to quantify the impact of human-made aerosols on climate.

High-resolution methyl edited GFT NMR experiments for protein resonance assignments and structure determination

Three-dimensional (3D) structure determination of proteins is benefitted by long-range distance constraints comprising the methyl groups, which constitute the hydrophobic core of proteins. However, in methyl groups (of Ala, Ile, Leu, Met, Thr and Val) there is a significant overlap of C-13 and H-1 chemical shifts. Such overlap can be resolved using the recently proposed (3,2)D HCCH-COSY, a G-matrix Fourier transform (GFT) NMR based experiment, which facilitates editing of methyl groups into distinct spectral regions by combining their C-13 chemical shifts with that of the neighboring, directly attached, C-13 nucleus. Using this principle, we present three GFT experiments: (a) (4,3)D NOESY-HCCH, (b) (4,3)D H-1-TOCSY-HCCH and (c) (4,3)D C-13-TOCSY-HCCH. These experiments provide unique 4D spectral information rapidly with high sensitivity and resolution for side-chain resonance assignments and NOE analysis of methyl groups. This is exemplified by (4,3)D NOESY-HCCH data acquired for 17.9 kDa non-deuterated cytosolic human J-protein co-chaperone, which provided crucial long-range distance constraints for its 3D structure determination.

Redundancy resolution using tractrix -- Simulations and Experiments

Hyper-redundant robots are characterized by the presence of a large number of actuated joints, many more than the number required to perform a given task. These robots have been proposed and used for many applications involving avoiding obstacles or, in general, to provide enhanced dexterity in performing tasks. Making effective use of the extra degrees of freedom or resolution of redundancy has been an extensive topic of research and several methods have been proposed in literature. In this paper, we compare three known methods and show that an algorithm based on a classical curve called the tractrix leads to a more 'natural' motion of the hyper-redundant robot, with the displacements diminishing from the end-effector to the fixed base. In addition, since the actuators nearer the base 'see' a greater inertia due to the links farther away, smaller motion of the actuators nearer the base results in better motion of the end-effector as compared to other two approaches. We present simulation and experimental results performed on a prototype eight link planar hyper-redundant manipulator.

Structure of bovine prothrombin fragment 1 refined at 2.25 Å resolution

The structure of bovine prothrombin fragment 1 has been refined at 2.25 Å resolution using high resolution measurements made with the synchrotron beam at CHESS. The synchrotron data were collected photographically by oscillation methods (R-merge = 0.08). These were combined with lower order diffractometer data for refinement purposes. The structure was refined using restrained least-squares methods with the program PROLSQ to a crystallographic R-value of 0.175. The structure includes 105 water molecules with occupancies of >0·6. The first 35 residues (Ala1-Leu35) of the N-terminal ?-carboxy glutamic acid-domain (Ala1-Cys48) of fragment 1 are disordered as are two carbohydrate chains of Mr ? 5000; the latter two combine to render 40% of the structure disordered. The folding of the kringle of fragment 1 is related to the close intramolecular contact between the inner loop disulfide groups. Half of the conserved sequence of the kringle forms an inner core surrounding these disulfide groups. The remainder of the sequence conservation is associated with the many turns of the main chain. The Pro95 residue of the kringle has a cis conformation and Tyr74 is ordered in fragment 1, although nuclear magnetic resonance studies indicate that the comparable residue of plasminogen kringle 4 has two positions. Surface accessibility calculations indicate that none of the disulfide groups of fragment 1 is accessible to solvent.

The management of large mammals in relation to male strategies and conflict with people

Many large mammals such as elephant, rhino and tiger often come into conflict with people by destroying agricultural crops and even killing people, thus providing a deterrent to conservation efforts. The males of these polygynous species have a greater variance in reproductive success than females, leading to selection pressures favouring a ‘high risk-high gain’ strategy for promoting reproductive success. This brings them into greater conflict with people. For instance, adult male elephants are far more prone than a member of a female-led family herd to raid agricultural crops and to kill people. In polygynous species, the removal of a certain proportion of ‘surplus’ adult males is not likely to affect the fertility and growth rate of the population. Hence, this could be a management tool which would effectively reduce animal-human conflict, and at the same time maintain the viability of the population. Selective removal of males would result in a skewed sex ratio. This would reduce the ‘effective population size’ (as opposed to the total population or census number), increase the rate of genetic drift and, in small populations, lead to inbreeding depression. Plans for managing destructive mammals through the culling of males will have to ensure that the appropriate minimum size in the populations is being maintained.

Sensitive high-resolution ion microprobe U-Pb dating of prograde and retrograde ultrahigh-temperature metamorphism as exemplified by Sri Lankan granulites

Ultrahigh-temperature (UHT) granulites of the central Highland Complex, Sri Lanka, underwent some of the highest known peak temperatures of crustal metamorphism. Zircon and monazite U-Pb systems in granulites near Kandy, the highest grade region (similar to 1050 degrees C; 0.9 GPa), preserve both a record of the timing of prograde and retrograde phases of UHT metamorphism and evidence for the ages of older protolith components. Zircon grains from a quartz-saturated granulite containing relics of the peak UHT assemblage have remnant detrital cores with dates of ca. 2.5-0.83 Ga. Date clusters of ca. 1.7 and 1.04-0.83 Ga record episodes of zircon growth in the source region of the protolith sediment. Two generations of overgrowths with contrasting Th/U record metamorphic zircon growth at 569 +/- 5 and 551 +/- 7 Ma, probably in the absence and presence of monazite, respectively. The age of coexisting metamorphic monazite (547 +/- 7 Ma) is indistinguishable from that of the younger, low-Th/U zircon overgrowths. Zircon from a quartz-undersaturated monazite-absent UHT granulite with a mainly retrograde assemblage is mostly metamorphic (551 +/- 5 Ma). The ca. 570 Ma zircon overgrowths in the quartz-saturated granulite probably record partial melting just before or at the metamorphic peak. The ca. 550 Ma zircon in both rocks, and the ca. 550 Ma monazite in the quartz-saturated sample, record post-peak isothermal decompression. A possible model for this pressure-temperature-time evolution is ultrahot collisional orogeny during the assembly of Gondwana, locally superheated by basaltic underplating, followed by fast extensional exhumation.

Visualisation of a 2′-5′ parallel stranded double helix at atomic resolution: crystal structure of cytidylyl-2′,5′-adenosine

X-ray crystallographlc studies on 3′–5′ ollgomers have provided a great deal of information on the stereochemistry and conformational flexibility of nucleic acids and polynucleotides. In contrast, there is very little Information available on 2′–5′ polynucleotides. We have now obtained the crystal structure of Cytidylyl-2′,5′-Adenoslne (C2′p5′A) at atomic resolution to establish the conformational differences between these two classes of polymers. The dlnucleoside phosphate crystallises in the monocllnlc space group C2, with a = 33.912(4)Å, b =16.824(4)Å, c = 12.898(2)Å and 0 = 112.35(1) with two molecules in the asymmetric unit. Spectacularly, the two independent C2′p5′A molecules in the asymmetric unit form right handed miniature parallel stranded double helices with their respective crystallographic two fold (b axis) symmetry mates. Remarkably, the two mini duplexes are almost indistinguishable. The cytosines and adenines form self-pairs with three and two hydrogen bonds respectively. The conformation of the C and A residues about the glycosyl bond is anti same as in the 3′–5′ analog but contrasts the anti and syn geometry of C and A residues in A2′p5′C. The furanose ring conformation is C3′endo, C2′endo mixed puckering as in the C3′p5′A-proflavine complex. A comparison of the backbone torsion angles with other 2′–5′ dinucleoside structures reveals that the major deviations occur in the torsion angles about the C3′–C2′ and C4′-C3′ bonds. A right-handed 2′–5′ parallel stranded double helix having eight base pairs per turn and 45° turn angle between them has been constructed using this dinucleoside phosphate as repeat unit. A discussion on 2′–5′ parallel stranded double helix and its relevance to biological systems is presented.

Dynamical Resolution of Redundancy for Robot Manipulators

A large class of work in the robot manipulator literature deals with the kinematical resolution of redundancy based on the pseudo-inverse of the manipulator Jacobian. In this paper an alternative dynamical approach to redundancy resolution is developed which utilizes the mapping between the actuator torques and the acceleration of the end-effector, at a given dynamic state of the manipulator. The potential advantages of the approach are discussed and an example of a planar 3R manipulator following a circular end-effector trajectory is used to illustrate the proposed approach as well as to compare it with the more well-known approach based on the pseudo-inverse.

Impaired conflict monitoring in Parkinson's disease patients during an oculomotor redirect task

Fallibility is inherent in human cognition and so a system that will monitor performance is indispensable. While behavioral evidence for such a system derives from the finding that subjects slow down after trials that are likely to produce errors, the neural and behavioral characterization that enables such control is incomplete. Here, we report a specific role for dopamine/basal ganglia in response conflict by accessing deficits in performance monitoring in patients with Parkinson's disease. To characterize such a deficit, we used a modification of the oculomotor countermanding task to show that slowing down of responses that generate robust response conflict, and not post-error per se, is deficient in Parkinson's disease patients. Poor performance adjustment could be either due to impaired ability to slow RT subsequent to conflicts or due to impaired response conflict recognition. If the latter hypothesis was true, then PD subjects should show evidence of impaired error detection/correction, which was found to be the case. These results make a strong case for impaired performance monitoring in Parkinson's patients.

Maximum-entropy calculation of the electron density at 4 A resolution of Pf1 filamentous bacteriophage

A 4 A electron-density map of Pf1 filamentous bacterial virus has been calculated from x-ray fiber diffraction data by using the maximum-entropy method. This method produces a map that is free of features due to noise in the data and enables incomplete isomorphous-derivative phase information to be supplemented by information about the nature of the solution. The map shows gently curved (banana-shaped) rods of density about 70 A long, oriented roughly parallel to the virion axis but slewing by about 1/6th turn while running from a radius of 28 A to one of 13 A. Within these rods, there is a helical periodicity with a pitch of 5 to 6 A. We interpret these rods to be the helical subunits of the virion. The position of strongly diffracted intensity on the x-ray fiber pattern shows that the basic helix of the virion is right handed and that neighboring nearly parallel protein helices cross one another in an unusual negative sense.

Structural refinement using high-resolution powder X-ray diffraction data of Ca0.5Ti2P3O12, a low-thermal-expansion material

The structures of Ca0.5Ti2P3O12 and Sr0.5Ti2P3O12, low-thermal-expansion materials, have been refined by the Rietveld method using high-resolution powder X-ray diffraction (XRD) data. The assignment of space group R[3 with combining macron] to NASICON-type compounds containing divalent cations is confirmed. 31P magic-angle spinning nuclear magnetic resonance (MASNMR) data are presented as supporting data. A comparison of changes in the polyhedral network resulting from the cation distribution, is made with NaTi2P3O12 and Nb2P3O12. Factors that may govern thermal expansion in this family of compounds are discussed.

Structure of Sesbania Mosaic Virus at 4·7 Å Resolution and Partial Sequence of the Coat Protein

Sesbania mosaic virus (SMV) is a plant virus infecting Sesbania grandiflora plants in Andhra Pradesh, India. Amino acid sequence of the tryptic peptides of SMV coat protein were determined using a gas phase sequenator. These sequences showed identical amino acids at 69% of the positions when aligned with the corresponding residues of southern bean mosaic virus (SBMV).Crystals diffracting to better than 3 Å resolution were obtained by precipitating the virus with ammonium sulphate. The crystals belonged to rhombohedral space group R3 with α = 291·4 Å and α = 61·9°. Three-dimensional X-ray diffraction data on these crystals were collected to a resolution of 4·7 Å, using a Siemens-Nicolet area detector system. Self-rotation function studies revealed the icosahedral symmetry of the virus particles, as well as their precise orientation in the unit cell. Cross-rotation function and modelling studies with SBMV showed that it is a valid starting model for SMV structure determination. Low resolution phases computed using a polyalanine model of SBMV were subjected to refinement and extension by real-space electron density averaging and solvent flattening. The final electron density map revealed a polypeptide fold similar to SBMV. The single disulphide bridge of SBMV coat protein is retained in SMV. Four icosahedrally independent cation binding sites have been tentatively identified. Three of these sites, related by a quasi threefold axis, are also found in SBMV. The fourth site is situated on the quasi threefold axis. Aspartic acid residues, which replace Ile218 of SBMV from the quasi threefold-related subunits are suitable ligands to the cation at this site

Resolution of conflicting views on thermodynamics of glass transition: A unified model

Classical description of thermodynamic properties during glass transition has been questioned by the entropy-loss model. The uncompensated loss of entropy at the glass transition temperature and zero residual entropy is at the heart of the controversy. Both the models are critically reviewed. A unified model is presented which incorporates features of both entropy loss and residual entropy. It implies two different types of contributions to the entropy of the supercooled liquid, one of which vanishes at the transition and the other which contributes to residual entropy. Entropy gain during spontaneous relaxation of glass, and the nature of heat capacity `hysteresis' during cooling and heating through the glass transition range support the proposed model. Experiments are outlined for differentiating between the models.

Area Optimized H.264 Intra Prediction Architecture for 1080p HD Resolution

High performance video standards use prediction techniques to achieve high picture quality at low bit rates. The type of prediction decides the bit rates and the image quality. Intra Prediction achieves high video quality with significant reduction in bit rate. This paper present an area optimized architecture for Intra prediction, for H.264 decoding at HDTV resolution with a target of achieving 60 fps. The architecture was validated on Virtex-5 FPGA based platform. The architecture achieves a frame rate of 64 fps. The architecture is based on multi-level memory hierarchy to reduce latency and ensure optimum resources utilization. It removes redundancy by reusing same functional blocks across different modes. The proposed architecture uses only 13% of the total LUTs available on the Xilinx FPGA XC5VLX50T.