PROPHET, a national computing resource for life science research.

PROPHET is a national computing resource tailored to meet the data management and analysis needs of life scientists working in a wide variety of disciplines, ranging from pharmacology to molecular biology. The PROPHET system offers a fully integrated graphics-oriented environment designed to aid research scientists in the manipulation and analysis of scientific spreadsheets of data, graphs, molecular structures, biological simulation models, and protein and nucleic acid sequences, and it includes access to a range of molecular structure and sequence databases. This paper briefly describes the PROPHET system, some of its current capabilities, and plans for a new fully distributed version of the system now under development.     

PROPHET--a national computing resource for life science research

PROPHET is a national computing resource tailored to meet the data management and analysis needs of life scientists working in a wide variety of disciplines, ranging from pharmacology to molecular biology. The PROPHET system offers a fully integrated graphics-oriented environment designed for the manipulation and analysis of tabular data, graphs, molecular structures, biological simulation models, and protein and nucleic acid sequences, and it includes access to molecular structure and sequence databases.     

Protein structure alignment using environmental profiles

A new protein structure alignment procedure is described. An initial alignment is made by comparing a one-dimensional list of primary, secondary and tertiary structural features (profiles) of two proteins, without explicitly considering the three-dimensional geometry of the structures. The alignment is then iteratively refined in the second step, in which new alignments are found by three-dimensional superposition of the structures based on the current alignment. This new procedure is fast enough to do all-against-all structural comparisons routinely. The procedure sometimes finds an alignment that suggests an evolutionary relationship and which is not normally obtained if only geometry is considered. All pair-wise comparisons were made among 3539 protein structural domains that represent all known protein structures. The resulting 3539 z-scores were used to cluster the proteins. The number of main clusters increased continuously as the z-cutoff was raised, but the number of multiple-member clusters showed a maximum at z-cutoff values of 5.0 and 5.5. When a z-cutoff value of 5.0 was used, the total number of main clusters was 2043, of which only 336 clusters had more than one member.     

Collapsing a Perfect Superposition to a Chosen Quantum State without Measurement

Given a perfect superposition of states on a quantum system of qubits. We propose a fast quantum algorithm for collapsing the perfect superposition to a chosen quantum state without applying any measurements. The basic idea is to use a phase destruction mechanism. Two operators are used, the first operator applies a phase shift and a temporary entanglement to mark in the superposition, and the second operator applies selective phase shifts on the states in the superposition according to their Hamming distance with . The generated state can be used as an excellent input state for testing quantum memories and linear optics quantum computers. We make no assumptions about the used operators and applied quantum gates, but our result implies that for this purpose the number of qubits in the quantum register offers no advantage, in principle, over the obvious measurement-based feedback protocol.     

A finite-element model for the mechanical analysis of skeletal muscles

In the present paper, a finite-element model for simulating muscle mechanics is described. Based on nonlinear continuum mechanics an algorithm is proposed that includes the contractile active and passive properties of skeletal muscle. Stress in the muscle is assumed to result from the superposition of a passive and an active part. The passive properties are described by a hyperelastic constitutive material law whereas the active part depends on the fibre length, shortening velocity and an activation function. The constraint of approximate incompressibility of the muscle element is satisfied as a property of the constitutive equations. Because of the nonlinear behaviour of the material and the highly dynamical performance an incremental procedure including iterative methods is used. The advantage of the model over previous formulations is the possibility to integrate the element into an engineering standard finite-element programme ANSYS using advanced numerical tools. The model allows simulations of muscle recruitment, calculations of stress and strain distributions and predictions of muscle shape. Other possible applications are studies of the muscle architecture, the effect of inertia and impacts. First, simple examples are presented.     

Ungulate carcass transport strategies at the Middle Palaeolithic site of Abric Romaní (Capellades,Spain)

We evaluated the skeletal profiles from several levels of the Neanderthal site of Abric Romaní, focusing on the methodology proposed by Faith and Gordon (2007): differences in the skeletal distribution of animals in accordance with their size and weight; the statistical correlation between the skeletal profiles and standard food utility index; and the anatomical diversity of size-weight categories. Results indicate an unconstrained transport strategy in all levels and all size-weight categories. However, we also found differences in the skeletal distribution of medium-sized and large animals, which may be due to different transport strategies. These characteristics suggest that the superposition of transport and occupation events could be responsible for our results. In addition, we applied the same analysis to Hadza assemblages, which revealed similar results to those found at Abric Romaní. The most striking feature of the Hadza assemblages examined is the superposition of transport events as a result of successive occupation/deposition events. This suggests that the transport strategies used by Neanderthals at Abric Romaní are also characterized by a high degree of diversity in transport decisions.     

Radioimmunoassay of urinary oxytocin in man]

A radioimmunoassay (RIA) for oxytocin (OT) in urine is described. 125I-OT was prepared, and antibodies were raised in rabbits against OT coupled to bovine serumalbumine. This allowed us to set up of RIA for OT which limit of detection is 1.25 pg/tube (0.6 microU). The use of an extraction procedure using CG50 Amberlite is essential. The recovery after extraction reaches 70.5%. pH 5 is the optimum pH were urine samples must be stored. The superposition of the elution peak of endogenous OT on that of exogenous hormone is an argument in favour of the validity of such an extraction procedure. Daily urinary excretion of OT reaches 9.58 mU +/- 3.48 in 18 healthy young men.     

The superposition of a temporally incoherent magnetic field inhibits 60 Hz-induced changes in the ODC activity of developing chick embryos

Previously, we have shown that the application of a weak (4 μT) 60 Hz magnetic field (MF) can alter the magnitudes of the ornithine decarboxylase (ODC) activity peaks which occur during gastrulation and neurulation of chick embryos. We report here the ODC activity of chick embryos which were exposed to the superposition of a weak noise MF over a 60 Hz MF of equal (rms strength). In contrast to the results we obtain with a 60 Hz field alone, the activity of ODC in embryos exposed to the superposition of the incoherent and 60 Hz fields was indistinguishable from the control activity during both gastrulation and neurulation. This result adds to the body of experimental evidence which demonstrates that the superposition of an incoherent field inhibits the response of biological systems to a coherent MF. The observation that a noise field inhibits ODC activity changes is consistent with our speculation that MF-induced ODC activity changes during early development may be related to MF-induced neural tube defects at slightly later stages (which are also inhibited by the superposition of a noise field). Bioelectromagnetics 19:53–56, 1998. © 1998 Wiley-Liss, Inc.     

北京萤火虫复眼的光学成像*

本文利用光学成像方法,研究了不同适应状态下的北京萤火虫phrococelia Pekininsis复眼所成的光学重叠像以及复眼的视场角。不同适应状态的晶体柱都能在距离复眼表面300-350μm之处形成光学重叠像。经过暗适应的晶体柱可以对不同物距的目标形成清晰的正重叠像,像的大小随物距的增大而减小;经明适应的晶体柱,成像物距范围变小,重叠像的像面亮度降低;经过漂白处理的晶体柱只能对一定的物距成像,像面亮度最低。 不同数目的晶体柱都能形成一重叠像,并随着其数目的增加,像面亮度也逐渐增强。根据对局部复眼视场范围的观察和其结构特征的了解,认为萤火虫单个复眼的视场角大于180度。     

How Ala-->Gly mutations in different helices affect the stability of the apomyoglobin molten globule

The apomyoglobin molten globule has a complex, partly folded structure with a folded A[B]GH subdomain; the factors determining its stability are not yet known in detail. Ala-->Gly mutations, made at solvent-exposed positions, are used to probe the role of helix propensity of individual helices in stabilizing the molten globule. Molten globule stability is measured by reversible urea unfolding, monitored both by circular dichroism and by tryptophan fluorescence. Two-state unfolding is tested by superposition of these two unfolding curves, and stability data are reported only for variants which satisfy the superposition test. Results for sites Q8 in the A helix and E109 in the G helix confirm that the helix propensities of the A and G helices both strongly affect molten globule stability, in contrast to results for the G65A/G73A double mutant which show that changing the helix propensity of the E-helix sequence has no significant stabilizing effect. Changing the helix propensity of the B-helix sequence with the G23A/G25A double mutant affects molten globule stability to an intermediate extent, confirming an earlier report that this mutant has increased stability. These results are consistent with the bipartite structure for the molten globule in which the A, G, and H helices are stably folded, while the long E helix is unfolded and the B helix has intermediate stability. Some differences are found in the shapes of the unfolding curves of different mutants even though they satisfy the superposition test for two-state unfolding, and possible explanations are discussed.     

An effective sequence-alignment-free superpositioning of pairwise or multiple structures with missing data

Background

Superpositioning is an important problem in structural biology. Determining an optimal superposition requires a one-to-one correspondence between the atoms of two proteins structures. However, in practice, some atoms are missing from their original structures. Current superposition implementations address the missing data crudely by ignoring such atoms from their structures.

Results

In this paper, we propose an effective method for superpositioning pairwise and multiple structures without sequence alignment. It is a two-stage procedure including data reduction and data registration.

Conclusions

Numerical experiments demonstrated that our method is effective and efficient. The code package of protein structure superposition method for addressing the cases with missing data is implemented by MATLAB, and it is freely available from: http://sourceforge.net/projects/pssm123/files/?source=navbar

     

Determining and visualizing flexibility in protein structures

How to compare the structures of an ensemble of protein conformations is a fundamental problem in structural biology. As has been previously observed, the widely used RMSD measure due to Kabsch, in which a rigid‐body superposition minimizing the least‐squares positional deviations is performed, has its drawbacks when comparing and visualizing a set of flexible protein structures. Here, we develop a method, fleximatch, of protein structure comparison that takes flexibility into account. Based on a distance matrix measure of flexibility, a weighted superposition of distance matrices rather than of atomic coordinates is performed. Subsequently, this allows a consistent determination of (a) a superposition of structures for visualization, (b) a partitioning of the protein structure into rigid molecular components (core atoms), and (c) an atomic mobility measure. The method is suitable for highlighting both particularly flexible and rigid parts of a protein from structures derived from NMR, X‐ray diffraction or molecular simulation. Proteins 2015; 83:820–826. © 2015 Wiley Periodicals, Inc.     

The ultrastructure of the compound eye of Munida rugosa (Crustacea: Anomura) and pigment migration during light and dark adaptation

The galatheid squat lobster, Munida rugosa, has compound eyes of the reflecting superposition type in which a distal cone cell layer and a proximal rhabdom layer are separated by an extensive clear zone. The eye is shown to have certain unique features. In all other reflecting superposition eyes, the clear zone is traversed by crystalline tracts formed by the cone cells. In M. rugosa a thin distal rhabdom thread, formed by the eighth retinula cell, connects the cones to the proximal fusiform rhabdoms. The cytoplasm of the other retinula cells also crosses the clear zone in a complex pattern. Fully light-adapted ommatidia are optically isolated by limited migrations of distal shielding pigments. A reflecting pigment multilayer lines each cone to facilitate the formation of a superposition image. This also shows a light-induced change which may limit the acceptance angle of the eye during light adaptation.     

Adsorbate-surface interaction studied by second-harmonic generation in total reflection

We have studied the coherent superposition of nonlinear optical signals due to the substrate background and an organic surface layer deposited on this substrate by second-harmonic generation (SHG). The increased sensitivity of the total reflection geometry used permits identification of subtle details of this superposition; for example partial cancellation of the phase-reversed SH-signals or the observation of a coverage-density-dependent tilt angle of the organic chromophores. The second-harmonic signals from the Langmuir-Blodgett-type monolayers exceed the SH-response of the adsorbates prepared by simple wetting with chloroform solutions of the same amphiphilic dyes by two orders of magnitude under identical coverage-density conditions.     

An iterative refinement algorithm for consistency based multiple structural alignment methods

MOTIVATION: Multiple STructural Alignment (MSTA) provides valuable information for solving problems such as fold recognition. The consistency-based approach tries to find conflict-free subsets of alignments from a pre-computed all-to-all Pairwise Alignment Library (PAL). If large proportions of conflicts exist in the library, consistency can be hard to get. On the other hand, multiple structural superposition has been used in many MSTA methods to refine alignments. However, multiple structural superposition is dependent on alignments, and a superposition generated based on erroneous alignments is not guaranteed to be the optimal superposition. Correcting errors after making errors is not as good as avoiding errors from the beginning. Hence it is important to refine the pairwise library to reduce the number of conflicts before any consistency-based assembly. RESULTS: We present an algorithm, Iterative Refinement of Induced Structural alignment (IRIS), to refine the PAL. A new measurement for the consistency of a library is also proposed. Experiments show that our algorithm can greatly improve T-COFFEE performance for less consistent pairwise alignment libraries. The final multiple alignment outperforms most state-of-the-art MSTA algorithms at assembling 15 transglycosidases. Results on three other benchmarks showed that the algorithm consistently improves multiple alignment performance. AVAILABILITY: The C++ code of the algorithm is available upon request.     

Technical note: CT-guided biopsy: A new diagnostic method for paleopathological research

The aim of this paper was to demonstrate the application of computerized tomographic (CT)-guided biopsy in a paleopathological examination. Researchers dealing with such special tasks should be aware of this method. We performed a CT-guided percutaneous biopsy of an ancient Egyptian child mummy, which allowed us to revise its initial diagnosis. Based on this experience, extended preinterventional planning and the choice of equipment (needle type) preferred by performing radiologists are strongly recommended, since they will influence diagnostic outcome. Easy documentation, suitable approaches according to the object's condition, and a reliable anatomical orientation without superposition effects during the procedure are some of the advantages of this method. It its already widely established in clinical practice. This technique is recommended for future tissue-sampling of human paleopathologic remains like mummies that are still wrapped within their original bandages, or any small bone lesion of unclear etiology.     

Spare parts for helix-helix interaction.

About 6000 contact regions (patches) of helix-to-helix packing from 300 well-resolved non-homologous protein structures were considered. The patches were defined by the spatial helical neighbors and were estimated in atomic detail using a variable distance criterion. The following questions are addressed. (1) Are the amino acid preferences and atomic composition of distinct types of helical patches indicative for the type of their neighbor? Distributions of size, atomic composition and packing density are compared for different types of helical interfaces. Thereby contact preferences are derived for parts of secondary structures adjoining each other or pointing towards the solvent. (2) Is it possible to cluster helical patches according to their structural similarity? For these purposes the patches were classified with an automatic sequence-independent superposition procedure which yields a distinctively reduced set of representative interfaces. On this basis, the methodology for finding exchangeable patches in different proteins is demonstrated.     

Studies of calcium influx into squid giant axons with aequorin

Calcium-influx associated with the action potential was studied in squid giant axons using an EDTA-free preparation of aequorin as a probe. Associated with an individual action potential there was a transient increase in aequorin luminescence and the time course of this increase was examined on a kinetic basis. The luminescent response associated with a train of action potentials was compared with that expected on the basis of superposition of individual responses. The analyses of luminescence curves produced by long trains of action potentials were complicated by failure of superposition. A long pulse of inward current was found to produce a very large enhancement of luminescence.