EndoNet: an information resource about regulatory networks of cell-to-cell communication†

EndoNet is an information resource about intercellular regulatory communication. It provides information about hormones, hormone receptors, the sources (i.e. cells, tissues and organs) where the hormones are synthesized and secreted, and where the respective receptors are expressed. The database focuses on the regulatory relations between them. An elementary communication is displayed as a causal link from a cell that secretes a particular hormone to those cells which express the corresponding hormone receptor and respond to the hormone. Whenever expression, synthesis and/or secretion of another hormone are part of this response, it renders the corresponding cell an internal node of the resulting network. This intercellular communication network coordinates the function of different organs. Therefore, the database covers the hierarchy of cellular organization of tissues and organs as it has been modeled in the Cytomer ontology, which has now been directly embedded into EndoNet. The user can query the database; the results can be used to visualize the intercellular information flow. A newly implemented hormone classification enables to browse the database and may be used as alternative entry point. EndoNet is accessible at: http://endonet.bioinf.med.uni-goettingen.de

Integration of gene expression data with prior knowledge for network analysis and validation

<p>Abstract</p> <p>Background</p> <p>Reconstruction of protein-protein interaction or metabolic networks based on expression data often involves in silico predictions, while on the other hand, there are unspecific networks of in vivo interactions derived from knowledge bases.</p> <p>We analyze networks designed to come as close as possible to data measured in vivo, both with respect to the set of nodes which were taken to be expressed in experiment as well as with respect to the interactions between them which were taken from manually curated databases</p> <p>Results</p> <p>A signaling network derived from the TRANSPATH database and a metabolic network derived from KEGG LIGAND are each filtered onto expression data from breast cancer (SAGE) considering different levels of restrictiveness in edge and vertex selection.</p> <p>We perform several validation steps, in particular we define pathway over-representation tests based on refined null models to recover functional modules. The prominent role of the spindle checkpoint-related pathways in breast cancer is exhibited. High-ranking key nodes cluster in functional groups retrieved from literature. Results are consistent between several functional and topological analyses and between signaling and metabolic aspects.</p> <p>Conclusions</p> <p>This construction involved as a crucial step the passage to a mammalian protein identifier format as well as to a reaction-based semantics of metabolism. This yielded good connectivity but also led to the need to perform benchmark tests to exclude loss of essential information. Such validation, albeit tedious due to limitations of existing methods, turned out to be informative, and in particular provided biological insights as well as information on the degrees of coherence of the networks despite fragmentation of experimental data.</p> <p>Key node analysis exploited the networks for potentially interesting proteins in view of drug target prediction.</p

The pairwise disconnectivity index as a new metric for the topological analysis of regulatory networks

<p>Abstract</p> <p>Background</p> <p>Currently, there is a gap between purely theoretical studies of the topology of large bioregulatory networks and the practical traditions and interests of experimentalists. While the theoretical approaches emphasize the global characterization of regulatory systems, the practical approaches focus on the role of distinct molecules and genes in regulation. To bridge the gap between these opposite approaches, one needs to combine 'general' with 'particular' properties and translate abstract topological features of large systems into testable functional characteristics of individual components. Here, we propose a new topological parameter – the pairwise disconnectivity index of a network's element – that is capable of such bridging.</p> <p>Results</p> <p>The pairwise disconnectivity index quantifies how crucial an individual element is for sustaining the communication ability between connected pairs of vertices in a network that is displayed as a directed graph. Such an element might be a vertex (i.e., molecules, genes), an edge (i.e., reactions, interactions), as well as a group of vertices and/or edges. The index can be viewed as a measure of topological redundancy of regulatory paths which connect different parts of a given network and as a measure of sensitivity (robustness) of this network to the presence (absence) of each individual element. Accordingly, we introduce the notion of a path-degree of a vertex in terms of its corresponding incoming, outgoing and mediated paths, respectively. The pairwise disconnectivity index has been applied to the analysis of several regulatory networks from various organisms. The importance of an individual vertex or edge for the coherence of the network is determined by the particular position of the given element in the whole network.</p> <p>Conclusion</p> <p>Our approach enables to evaluate the effect of removing each element (i.e., vertex, edge, or their combinations) from a network. The greatest potential value of this approach is its ability to systematically analyze the role of every element, as well as groups of elements, in a regulatory network.</p

Cation Transport and Surface Reconstruction in Lanthanum Doped Strontium Titanate at High Temperatures

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Prediction of mineral dust properties at mine sites

Predicting the properties of dust generated at mine sites is important for understanding the impact of dust dispersal to the surrounding environment. This chapter presents a new approach to predicting the mineralogical properties of the PM2.5 and PM10 dust fractions. A purpose-built dust resuspension machine was fitted with a size selective sampler to collect dust fractions. Dust particles were collected onto a polycarbonate filter, which was analyzed using a scanning electron microscope (SEM). Backscattered electron (BSE) maps of the polycarbonate surface were imaged and processed to determine dust properties. For a given population of particles, the BSE brightness distribution of the 2-5 and 5-10 µm size fractions were quantified. The mineralogical composition of the dust size fractions were inferred by the BSE brightness as biogenic particles and sulfates (30-50), silicates (60-100), iron silicates and oxides (110-190), and sulfides (>200). The method was validated by comparing laboratory-generated dust fractions with those collected from dust monitoring stations at a tailings repository site. Similar dust composition and size fractions were observed for both laboratory and field samples. Consequently, the purpose-built dust resuspension device and associated laboratory procedures allow the prediction of mineralogical properties of dust at mine sites

Assessing mineral dust properties using passive dust samplers and scanning electron microscopy

This study presents a novel method to characterize dust particles using a passive dust sampler (PDS). Six different PDS were deployed around six different metal mine sites (Tasmania, Australia) and left in the field for 1 month. Dust particles were analyzed directly on the PDS using a Field Emission Scanning Electron Microscope. Backscattered electron (BSE) images were collected with a resolution of 0.5 µm per pixel and used to characterize the size and composition of dust particles. Those particles >2 µm in diameter were classified according to the range of BSE brightness values, which correspond to mineralogical compositions. Particles were grouped according to BSE brightness and categorized as organic particles, silicates, Fe silicates and oxides, and sulfides. Dust sources with unique particle size:composition relationships were identified at particular mine site domains (e.g. rock crusher, concentrator plant, tailings dam). The documented method can be used to monitor the dispersal of mineral dust and provide information on the mineralogical composition of particle size fractions relevant to occupational health risks at metalliferous mine sites

Sr diffusion in undoped and La-doped SrTiO3 single crystals under oxidizing conditions

Strontium titanate SrTiO3(100), (110), and (111) single crystals, undoped or donor doped with up to 1 at% La, were isothermally equilibrated at temperatures between 1523 and 1773 K in synthetic air followed by two different methods of Sr tracer deposition: ion implantation of 87Sr and chemical solution deposition of a thin 86SrTiO3 layer. Subsequently, the samples were diffusion annealed under the same conditions as before. The initial and final depth profiles were measured by SIMS. For strong La-doping both tracer deposition methods yield similar Sr diffusion coefficients, whereas for weak doping the tracer seems to be immobile in the case of ion implantation. The Sr diffusivity does not depend on the crystal orientation, but shows strong dependency on the dopant concentration supporting the defect chemical model that under oxidizing conditions the donor is compensated by Sr vacancies. A comparison with literature data on Sr vacancy, Ti, and La diffusion in this system confirms the concept that all cations move via Sr vacancies. Cation diffusion is several orders of magnitude slower than oxygen diffusion. © The Owner Societies 2005

Evidence for an intrabasinal source and multiple concentration processes in the formation of the carbon leader reef, Witwatersrand Supergroup, South Africa

Laser ablation-inductively coupled plasma-mass spectrometer (LA-ICP-MS) trace element maps of pyrite and gold from the Carbon Leader Reef in the Witwatersrand basin provide new evidence that a significant proportion of the pyrite and gold was intrabasinal, derived from the West Rand Group or equivalent shales stratigraphically below this reef. Rounded detrital pyrite grains in the Carbon Leader Reef vary from compact to porous to sooty, with similar textures and composition to diagenetic pyrites reported from sedimentary rocks in the West Rand Group. Detrital porous and sooty pyrites contain 0.4 to 11.3 ppm solid-solution gold, sulfur isotope δ34S values from −17 to +16%, and high levels of As and Te, plus a wide range of other trace elements (in decreasing order: Ni, Co, Sb, Cr, Cu, U, Pb, Bi, Mo, Zn and Ag). The sooty pyrite is the most Au, Te, and Mo rich and is intergrown with alumino-silicates and organic matter. The detrital pyrite textures, S-isotopes and geochemistry resemble diagenetic pyrite developed under suboxic to anoxic bottom water conditions. The LA-ICP-MS maps also show that the detrital pyrite grains have euhedral hydrothermal pyrite overgrowths containing micro-inclusions of gold, brannerite, and Ni-As sulfides. The pyrite overgrowths are also enriched in solid-solution gold, tellurium, and other trace elements including, in decreasing order, As, Co, Ni, Cr, Cu, Mn, Pb, Bi, and Ag. Fractured and brecciated pyrite associated with brittle bedding-parallel fracture zones in the Carbon Leader Reef are also enriched in these elements due to alteration of pyrite surrounding the fractures. Laser ICP-MS Pb isotope determinations on the cores of detrital pyrite indicate an age between 2750 and 2950 Ma with hydrothermal overgrowths originating between 2100 and 2020 Ma incorporating highly radiogenic Pb. This study demonstrates that both of the two competing theories for the origin of the Witwatersrand gold reefs are likely to be correct. We suggest that the hydrothermal event was widespread (kilometer scale) and involved basinal fluids that scavenged gold, tellurium, arsenic, and trace elements (Co, Ni, Cr, Cu, Mn, Pb, Bi, Ag) from gold-bearing sedimentary units in the Central Rand Group.GeoRef Subject: clastic rocks conglomerate Africa lead mineral deposits, genesis Pb-207/Pb-204 Pb-207/Pb-206 metasomatism gold ores isotope ratios isotopes Witwatersrand Witwatersrand Supergroup metal ores metals Pb-206/Pb-204 sedimentary rocks S-34/S-32 sulfur Precambrian pyrite radioactive isotopes South Africa Southern Africa sulfides stable isotopes.Ross R. Large, Sebastien Meffre, Rob Burnett, Bradley Guy, Stuart Bull, Sarah Gilbert ... et al

Macrocrystals of Pt-Fe alloy from the Kondyor PGE placer deposit, Khabarovskiy Kray, Russia: Trace-element content, mineral inclusions and reaction assemblages

Euhedral macrocrystals of Pt-Fe alloy from the Kondyor PGE placer, Khabarovskiy Kray, eastern Siberia, Russia, have a relatively constant composition of Pt 2.4-2.6 Fe, tin and antimony contents up to 0.3 wt.%, and an unusually low content of all PGE except Pt. The millimetric crystals contain inclusions of fluorapatite, titanite, phlogopite, magnetite, ilmenite and iron-copper sulfides. The macrocrystals have a complex gold-rich rim, with four groups of gold alloy: tetra-auricupride (the most abundant gold-bearing phase), Au-Ag (98-54 wt.% Au), Au-Ag-Cu-Pd and Au-Pd-Cu alloys. The inner part of the reaction rim hosts a variety of PGE minerals, such as stannides, antimonides and tellurobismuthides of Pd and Pt. Stannides occur as copper-bearing (taimyrite-tatyanaite series) and copper-free compounds (atokite-rustenburgite series). The main antimony mineral is Sn-bearing mertieite-II. Tellurobismuthides are represented by Te-rich sobolevskite and an intermediate member of the moncheite-insizwaite solid-solution series. The reaction rim also hosts several unknown phases, such as Pd 7 Bi 3 , Pd 3 Bi, Bi 2 O 3 3H 2 O, and a phosphocarbonate of thorium. The coarse crystals occur in eluvial and alluvial placers within the Kondyor massif, a zoned clinopyroxenite-dunite intrusion of Paleozoic or Mesozoic age. The inclusion assemblage suggests that the macrocrystals of Pt-Fe alloy are associated with late apatite - magnetite - phlogopite clinopyroxenite bodies, and possibly formed in a late-magmatic pegmatitic environment. The Pt-Fe alloy crystals have undergone hydrothermal overprint by NaCl-rich solutions bearing gold - silver - palladium - copper, which produced a wide variety of intermetallic compounds as well as Pb-bearing intermetallic phases. The aqueous solutions also had a minor but characteristic bismuth - tin - antimony - tellurium component