Th structure of the P-II-ATP complex

P-II is a signal transduction protein that is part of the cellular machinery used by many bacteria to regulate the activity of glutamine synthetase and the transcription of its gene. The structure of P-II was solved using a hexagonal crystal form (form I). The more physiologically relevant form of P-II is a complex with small molecule effecters. We describe the structure of P-II with ATP obtained by analysis of two different crystal forms (forms II and III) that were obtained by co-crystallization of P-II with ATP. Both structures have a disordered recognition (T) loop and show differences at their C termini. Comparison of these structures with the form I protein reveals changes that occur on binding ATP. Surprisingly, the structure of the P-II/ATP complex differs with that of GlnK, a functional homologue. The two proteins bind the base and sugar of ATP in a similar manner but show differences in the way that they interact with the phosphates. The differences in structure could account for the differences in their activities, and these have been attributed to a difference in sequence at position 82. It has been demonstrated recently that P-II and GlnK form functional heterotrimers in vivo. We construct models of the heterotrimers and examine the junction between the subunits.

Crystal structure of a heptameric Sm-like protein complex from archaea: Implications for the structure and evolution of snRNPs

The Sm/Lsm proteins associate with small nuclear RNA to form the core of small nuclear ribonucleoproteins, required for processes as diverse as pre-mRNA splicing, mRNA degradation and telomere formation. The Lsm proteins from archaea are likely to represent the ancestral Sm/Lsm domain. Here, we present the crystal structure of the Lsm alpha protein from the thermophilic archaeon Methanobacterium thermoautrophicum at 2.0 Angstrom resolution. The Lsm alpha protein crystallizes as a heptameric ring comprised of seven identical subunits interacting via beta -strand pairing and hydrophobic interactions. The heptamer can be viewed as a propeller-like structure in which each blade consists of a seven-stranded antiparallel beta -sheet formed from neighbouring subunits. There are seven slots on the inner surface of the heptamer ring, each of which is lined by Asp, Asn and Arg residues that are highly conserved in the Sm/Lsm sequences. These conserved slots are likely to form the RNA-binding site. In archaea, the gene encoding Lsm alpha is located next to the L37e ribosomal protein gene in a putative operon, suggesting a role for the Lsm alpha complex in ribosome function or biogenesis. (C) 2001 Academic Press.

Jordan-Wigner fermionization of the one-dimensional Bariev model of three coupled XY chains

The Jordan-Wigner fermionization for the one-dimensional Bariev model of three coupled XY chains is formulated. The L-matrix in terms of fermion operators and the R-matrix are presented explicitly. Furthermore, the graded reflection equations and their solutions are discussed.

Evaluating design proposals for complex systems with work domain analysis

In this paper we propose a new framework for evaluating designs based on work domain analysis, the first phase of cognitive work analysis. We develop a rationale for a new approach to evaluation by describing the unique characteristics of complex systems and by showing that systems engineering techniques only partially accommodate these characteristics. We then present work domain analysis as a complementary framework for evaluation. We explain this technique by example by showing how the Australian Defence Force used work domain analysis to evaluate design proposals for a new system called Airborne Early Warning and Control. This case study also demonstrates that work domain analysis is a useful and feasible approach that complements standard techniques for evaluation and that promotes a central role for human factors professionals early in the system design and development process. Actual or potential applications of this research include the evaluation of designs for complex systems.

Computer simulations of coupled problems in geological and geochemical systems

The finite element method is used to simulate coupled problems, which describe the related physical and chemical processes of ore body formation and mineralization, in geological and geochemical systems. The main purpose of this paper is to illustrate some simulation results for different types of modelling problems in pore-fluid saturated rock masses. The aims of the simulation results presented in this paper are: (1) getting a better understanding of the processes and mechanisms of ore body formation and mineralization in the upper crust of the Earth; (2) demonstrating the usefulness and applicability of the finite element method in dealing with a wide range of coupled problems in geological and geochemical systems; (3) qualitatively establishing a set of showcase problems, against which any numerical method and computer package can be reasonably validated. (C) 2002 Published by Elsevier Science B.V.

Analytical solution for tidal propagation in a coupled semi-confined/phreatic coastal aquifer

An analytical solution is derived for tidal fluctuations in a coupled coastal aquifer system consisting of a semi-confined aquifer, a thin semi-permeable layer and a phreatic aquifer. Based on the solution, we study the interactions (via leakage) between the confined and unconfined aquifers in response to tides. The results show that, under certain conditions, leakage from the confined aquifer can affect considerably the tidal water table fluctuation in the phreatic aquifer and vice versa. Ignoring these effects could lead to errors in estimating aquifer properties based on tidal signals. (C) 2002 Elsevier Science Ltd. All rights reserved.

The sit-up: complex kinematics and muscle activity in voluntary axial movement

This paper describes the kinematics and muscle activity associated with the standard sit-up, as a first step in the investigation of complex motor coordination. Eight normal human subjects lay on a force table and performed at least 15 sit-ups, with the arms across the chest and the legs straight and unconstrained. Several subjects also performed sit-ups with an additional weight added to the head. Support surface forces were recorded to calculate the location of the center of pressure and center of gravity; conventional motion analysis was used to measure segmental positions; and surface EMG was recorded from eight muscles. While the sit-up consists of two serial components, 'trunk curling' and 'footward pelvic rotation', it can be further subdivided into five phases, based on the kinematics. Phases I and II comprise trunk curling. Phase I consists of neck and upper trunk flexion, and phase II consists of lumbar trunk lifting. Phase II corresponds to the point of peak muscle contraction and maximum postural instability, the 'critical point' of the sit-up. Phases III-V comprise footward pelvic rotation. Phase III begins with pelvic rotation towards the feet. phase W with leg lowering, and phase V with contact between the legs and the support surface. The overall pattern of muscle activity was complex with times of EMG onset, peak activity, offset, and duration differing for different muscles. This complex pattern changed qualitatively from one phase to the next, suggesting that the roles of different muscles and, as a consequence, the overall form of coordination, change during the sit-up. (C) 2003 Elsevier Science Ltd. All rights reserved.

Homomeric ring assemblies of eukaryotic Sm proteins have affinity for both RNA and DNA - Crystal structure of an oligomeric complex of yeast SmF

Sm and Sm-like proteins are key components of small ribonucleoproteins involved in many RNA and DNA processing pathways. In eukaryotes, these complexes contain seven unique Sm or Sm-like (Lsm) proteins assembled as hetero-heptameric rings, whereas in Archaea and bacteria six or seven-membered rings are made from only a single polypeptide chain. Here we show that single Sm and Lsm proteins from yeast also have the capacity to assemble into homo-oligomeric rings. Formation of homo-oligomers by the spliceosomal small nuclear ribonucleoprotein components SmE and SmF preclude hetero-interactions vital to formation of functional small nuclear RNP complexes in vivo. To better understand these unusual complexes, we have determined the crystal structure of the homomeric assembly of the spliceosomal protein SmF. Like its archaeal/bacterial homologs, the SmF complex forms a homomeric ring but in an entirely novel arrangement whereby two heptameric rings form a co-axially stacked dimer via interactions mediated by the variable loops of the individual SmF protein chains. Furthermore, we demonstrate that the homomeric assemblies of yeast Sm and Lsm proteins are capable of binding not only to oligo(U) RNA but, in the case of SmF, also to oligo(dT) single-stranded DNA.

Longevity and stability of cratonic lithosphere: Insights from numerical simulations of coupled mantle convection and continental tectonics

[1] The physical conditions required to provide for the tectonic stability of cratonic crust and for the relative longevity of deep cratonic lithosphere within a dynamic, convecting mantle are explored through a suite of numerical simulations. The simulations allow chemically distinct continents to reside within the upper thermal boundary layer of a thermally convecting mantle layer. A rheologic formulation, which models both brittle and ductile behavior, is incorporated to allow for plate-like behavior and the associated subduction of oceanic lithosphere. Several mechanisms that may stabilize cratons are considered. The two most often invoked mechanisms, chemical buoyancy and/or high viscosity of cratonic root material, are found to be relatively ineffective if cratons come into contact with subduction zones. High root viscosity can provide for stability and longevity but only within a thick root limit in which the thickness of chemically distinct, high-viscosity cratonic lithosphere exceeds the thickness of old oceanic lithosphere by at least a factor of 2. This end-member implies a very thick mechanical lithosphere for cratons. A high brittle yield stress for cratonic lithosphere as a whole, relative to oceanic lithosphere, is found to be an effective and robust means for providing stability and lithospheric longevity. This mode does not require exceedingly deep strength within cratons. A high yield stress for only the crustal or mantle component of the cratonic lithosphere is found to be less effective as detachment zones can then form at the crust-mantle interface which decreases the longevity potential of cratonic roots. The degree of yield stress variations between cratonic and oceanic lithosphere required for stability and longevity can be decreased if cratons are bordered by continental lithosphere that has a relatively low yield stress, i.e., mobile belts. Simulations that combine all the mechanisms can lead to crustal stability and deep root longevity for model cratons over several mantle overturn times, but the dominant stabilizing factor remains a relatively high brittle yield stress for cratonic lithosphere.

The amygdaloid complex: Anatomy and physiology

A converging body of literature over the last 50 years has implicated the amygdala in assigning emotional significance or value to sensory information. In particular, the amygdala has been shown to be an essential component of the circuitry underlying fear-related responses. Disorders in the processing of fear-related information are likely to be the underlying cause of some anxiety disorders in humans such as posttraumatic stress. The amygdaloid complex is a group of more than 10 nuclei that are located in the midtemporal lobe. These nuclei can be distinguished both on cytoarchitectonic and connectional grounds. Anatomical tract tracing studies have shown that these nuclei have extensive intranuclear and internuclear connections. The afferent and efferent connections of the amygdala have also been mapped in detail, showing that the amygdaloid complex has extensive connections with cortical and subcortical regions. Analysis of fear conditioning in rats has suggested that long-term synaptic plasticity of inputs to the amygdala underlies the acquisition and perhaps storage of the fear memory. In agreement with this proposal, synaptic plasticity has been demonstrated at synapses in the amygdala in both in vitro and in vivo studies. In this review, we examine the anatomical and physiological substrates proposed to underlie amygdala function.

Can metal complexes serve as hypoxia activated prodrugs? Investigations of a Co(III) complex of the MMP inhibitor marimastat

For many years proof that the hypoxic nature of malignant tumours can be used to selectively target anticancer drugs has been sought. Several classes of potential redox activated anticancer drugs have been developed to take advantage of the reducing environment resulting from the hypoxia. Drug complexes with redox active metal centres as carriers have been investigated, but have largely been employed with cytotoxic drugs that require release of the drug intracellularly, complicating the design of such complexes. MMP inhibitors, a new class of anticancer drug, conversely act in the extracellular environment and we have investigated inhibitor complexes with several redox active transition metals. Marimastat is an MMP inhibitor with potent in-vitro antimetastatic activity and was recently in Phase III clinical trials for a variety of cancer types. We have synthesised a Co(II1) complex of marimastat incorporating the tetradentate ligand tpa (tris(2-methylpyridyl)amine) as a carrier ligand. The complex was structurally characterised in the solid state by single crystal X-ray diffraction, the first example of a crystal structure containing marimastat. 2D COSY and NOESY NMR spectra showed that the complex exists in two isomeric forms in solution, corresponding to the cis and trans isomers yet only crystallises in one of these forms. Biological testing of the complex in mice with 4T1.2 tumours showed interesting and unexpected outcomes. Initial results of the tumour growth inhibition study showed that a significant inhibition of growth was exhibited by the complex over the free inhibitor and the control. However, the metastatic potential of both free marimastat and the complex were higher than the control indicating likely problems with the experimental protocol. Further experiments are needed to determine the potential of such complexes as hypoxia activated prodrugs but there appears at least to be some promise.

Designing teams for first-of-a-kind, complex systems using the initial phases of cognitive work analysis: Case study

We present a technique for team design based on cognitive work analysis (CWA). We first develop a rationale for this technique by discussing the limitations of conventional approaches for team design in light of the special characteristics of first-of-a-kind, complex systems. We then introduce the CWA-based technique for team design and provide a case study of how we used this technique to design a team for a first-of-a-kind, complex military system during the early stages of its development. In addition to illustrating the CWA-based technique by example, the case study allows us to evaluate the technique. This case study demonstrates that the CWA-based technique for team design is both feasible and useful, although empirical validation of the technique is still necessary. Applications of this work include the design of teams for first-of-a-kind, complex systems in military, medical, and industrial domains.

Does Petrolisthes armatus (Anomura, Porcellanidae) form a Species Complex or Are We Dealing with Just One Widely Distributed Species?

Fernando L. Mantelatto, Leonardo G. Pileggi, Ivana Miranda, and Ingo S. Wehrtmann (2011) Does Petrolisthes armatus (Anomura, Porcellanidae) form a species complex or are we dealing with just one widely distributed species? Zoological Studies 50(3): 372-384. Petrolisthes armatus has the widest distribution known among members of the family Porcellanidae and is one of the most ubiquitous and locally abundant intertidal decapods along the Atlantic coast of the Americas. Considering its geographical distribution and morphological plasticity, several authors postulated the existence of a P. armatus species complex. In the present study we used genetic data from the mitochondrial 16S ribosomal gene to determine the genetic variability of P. armatus from selected locations within its eastern tropical Pacific and western Atlantic distributions. Our phylogenic analysis included 49 specimens represented by 26 species of the genus Petrolisthes and 16 specimens from 10 species and 4 related genera. Genetic distances estimated among the analyzed Petrolisthes species ranged from 2.6%-22.0%; varied between 0%-5.7% for 16S. Additionally, the revision of P. armatus specimens from Pacific Costa Rica and Brazilian Waters showed no geographically significant morphological variations among the analyzed specimens. Therefore, our morphological and genetic data do not support the hypothesis of a P. armatus complex within the specimens studied herein from the Americas, but convincingly confirm the monophyly and non-separateness of the members assigned as P. armatus. http://zoolstud.sinica.edu.tw/Journals/50.3/372.pdf