A gene cluster for macrolide antibiotic biosynthesis in Streptomyces venezuelae: Architecture of metabolic diversity

In a survey of microbial systems capable of generating unusual metabolite structural variability, Streptomyces venezuelae ATCC 15439 is notable in its ability to produce two distinct groups of macrolide antibiotics. Methymycin and neomethymycin are derived from the 12-membered ring macrolactone 10-deoxymethynolide, whereas narbomycin and pikromycin are derived from the 14-membered ring macrolactone, narbonolide. This report describes the cloning and characterization of the biosynthetic gene cluster for these antibiotics. Central to the cluster is a polyketide synthase locus (pikA) that encodes a six-module system comprised of four multifunctional proteins, in addition to a type II thioesterase (TEII). Immediately downstream is a set of genes for desosamine biosynthesis (des) and macrolide ring hydroxylation. The study suggests that Pik TEII plays a role in forming a metabolic branch through which polyketides of different chain length are generated, and the glycosyl transferase (encoded by desVII) has the ability to catalyze glycosylation of both the 12- and 14-membered ring macrolactones. Moreover, the pikC-encoded P450 hydroxylase provides yet another layer of structural variability by introducing regiochemical diversity into the macrolide ring systems. The data support the notion that the architecture of the pik gene cluster as well as the unusual substrate specificity of particular enzymes contributes to its ability to generate four macrolide antibiotics.

SURVEY AND SUMMARY: Recent advances in the elucidation of the mechanisms of action of ribozymes

The cleavage of RNA can be accelerated by a number of factors. These factors include an acidic group (Lewis acid) or a basic group that aids in the deprotonation of the attacking nucleophile, in effect enhancing the nucleophilicity of the nucleophile; an acidic group that can neutralize and stabilize the leaving group; and any environment that can stabilize the pentavalent species that is either a transition state or a short-lived intermediate. The catalytic properties of ribozymes are due to factors that are derived from the complicated and specific structure of the ribozyme–substrate complex. It was postulated initially that nature had adopted a rather narrowly defined mechanism for the cleavage of RNA. However, recent findings have clearly demonstrated the diversity of the mechanisms of ribozyme-catalyzed reactions. Such mechanisms include the metal-independent cleavage that occurs in reactions catalyzed by hairpin ribozymes and the general double-metal-ion mechanism of catalysis in reactions catalyzed by the Tetrahymena group I ribozyme. Furthermore, the architecture of the complex between the substrate and the hepatitis delta virus ribozyme allows perturbation of the pKa of ring nitrogens of cytosine and adenine. The resultant perturbed ring nitrogens appear to be directly involved in acid/base catalysis. Moreover, while high concentrations of monovalent metal ions or polyamines can facilitate cleavage by hammerhead ribozymes, divalent metal ions are the most effective acid/base catalysts under physiological conditions.

Solution structure of the Shc SH2 domain complexed with a tyrosine-phosphorylated peptide from the T-cell receptor.

She is a widely expressed adapter protein that plays an important role in signaling via a variety of cell surface receptors and has been implicated in coupling the stimulation of growth factor, cytokine, and antigen receptors to the Ras signaling pathway. She interacts with several tyrosine-phosphorylated receptors through its C-terminal SH2 domain, and one of the mechanisms of T-cell receptor-mediated Ras activation involves the interaction of the Shc SH2 domain with the tyrosine-phosphorylated zeta chain of the T-cell receptor. Here we describe a high-resolution NMR structure of the Shc SH2 domain complexed to a phosphopeptide (GHDGLpYQGLSTATK) corresponding to a portion of the zeta chain of the T-cell receptor. Although the overall architecture of the protein is similar to other SH2 domains, distinct structural differences were observed in the smaller beta-sheet, BG loop, (pY + 3) phosphopeptide-binding site, and relative position of the bound phosphopeptide.

Symbol for a Community: The Dickens Opera House and Theaters of the American West

This paper reveals the importance of the Dickens Opera House to the local history of Longmont, Colorado. Through an exploration of pioneer history and of architectural patronage and audience accommodation, this paper illustrates how the Dickens Opera House participated in the construction of cultural identity and civic aspirations of the city of Longmont. Using the Tabor Opera House of Leadville and Wright Opera House of Ouray as framing examples to place the Dickens Opera House within its proper architectural and historical context, I approach the building’s inception, construction, and early years as a way to track the early civic identity of a community through a work of architecture. The Dickens Opera House provided a point for the citizens of Longmont to focus their hopes of success and respectability in a newly formed community. An opera house provided a high-class perception of a town that provided a projection of respectability. Such a construction was built from various sources – the architecture of the building, simply calling the building an ‘opera house’, furnishings in the latest fashions and equipment of the latest technology, and extravagant scenery and curtains. In addition to these outward projections, opera houses also provided a place for community events. It was the location in town that brought people together.

Overdeepened glacial basins as archives for the Quaternary landscape evolution of the Alps

The Alps and the Alpine foreland have been shaped by repeated glaciations during Quaternary glacial-interglacial cycles. Extent, timing and impact on landscape evolution of these glaciations are, however, poorly constrained due to the fragmentary character of terrestrial archives. In this context, the sedimentary infills of subglacially eroded, ‘overdeepened’, basins may serve as important archives to complement the Quaternary stratigraphy over several glacial-interglacial cycles. In this thesis, the infills of deep subglacial basins in the Lower Glatt valley (N Switzerland) are explored to better constrain the Middle- to Late Pleistocene environmental change. Five drill cores gave direct insight into to the up to ~200 m thick valley fill at the study site and allowed for detailed analysis of sedimentary facies, age and architecture of the basin fills. A first focus is set on the sedimentology of coarse-grained diamicts with sorted interbeds overlying bedrock in the trough center, which mark the onset of deposition in many glacial bedrock troughs. Evidence from macro- and microsedimentology suggests that these sediments are emplaced subglacially and reflect deposition, reworking and deformation in response to repeated coupling and decoupling of the ice-bed interface promoted by high basal water pressures. Overlying these subglacial sediments, large volumes of sandy glacio-deltaic, fine-grained glacio-lacustrine and lacustrine sediments document sedimentation during glacier retreat from the basins. On these thick valley fill sequences the applicability and reliability of luminescence dating is investigated in a second step on the basis of experiments with several different luminescence signals, protocols and experiments to assess the signal stability. The valley fill of the Lower Glatt valley is then grouped into nine depositional cycles (Formations A-I), which are related to the Birrfeld Glaciation (~MIS2), the Beringen Glaciation (~MIS6), and up to three earlier Middle Pleistocene glaciations, tentatively correlated to the Hagenholz, Habsburg, and Möhlin Glaciations, according to the regional glaciation history. The complex bedrock geometry and valley fill architecture are shown to be the result of multiple erosion and infilling cycles and reflect the interplay of subglacial erosion, glacial to lacustrine infilling of overdeepened basins, and fluvial down-cutting and aggradation in the non-overdeepened valley fill. Evidence suggests that in the study area deep bedrock incision, and/or partial re-excavation, occurred mainly during the Beringen and Hagenholz Glaciation, while older structures may have existed. Together with the observation of minor, ‘inlaid’ glacial basins, dynamic changes in the magnitude and focus of subglacial erosion over time are documented.

Book of the paintings, Library of Congress.

"The eighty-nine pictures here given comprise all the principal paintings of the Grand stair hall, and of the other halls of the Entrance pavilion, together with the architecture of the library building. The text contains the poems of the ʻPoetry' series, the mythological incidents of the ʻGreek Heroes, ̓the symbolism of the ʻGovernment ̓series, and other explanatory notes."

A history of the Crusades.

Bibliographical footnotes.

The history of Crowland Abbey, digested from the materials collected by Mr. Gough, and published ... 1783 and 1797; including an abstract of the observations of Mr. Essex, respecting the ancient and present state of the abbey, and the origin and use of the triangular bridge ...

"Appendix: Concerning the history of the building of our more ancient abbey churches, and the rise and progress of the pointed or English architecture; digested from the essays published by J. Taylor, on the architecture of the middle ages, by ... T. Warton, J. Bentham, and J. Milner, and Captain Grose ..." (p. [143]-182) has special half-title.

Memorials of the civil war in Cheshire and the adjacent counties,

"Both memorials are printed side by side in their entirely" (i.e. where they synchronize, Malbon is at the top of the page, Burghall at the bottom.

Direct continuities between cisternae at different levels of the Golgi complex in glucose-stimulated mouse islet beta cells

Direct continuity between the membranes of cisternae in the Golgi complex in mammalian cells rarely has been observed; when seen, its documentation has been equivocal. Here we have used dual-axis electron microscope tomography to examine the architecture of the Golgi in three dimensions at approximate to6-nm resolution in rapidly frozen, freeze-substituted murine cells that make and secrete insulin in response to glucose challenge. Our data show three types of direct connections between Golgi cisternae that are normally distinct from one another. These connections all bypass interceding cisternae. We propose that when pancreatic beta cells are stimulated to synthesize and secrete insulin rapidly in vivo, such connections provide a continuous lumen that facilitates the rapid transit of large amounts of newly made protein for secretion. The heterotypic fusion of cisternae, even transiently, raises important questions about the molecular mechanisms that (i) facilitate the fusion/fission of cisternal membranes and control the directionality and specificity of such events, and (it) retain Golgi processing enzymes at specific places within individual cisternae when two cisternae at different levels in the Golgi have fused, maintaining the sequential processing hierarchy that is a hallmark of Golgi organization.

Web services based state of the environment reporting

The Environmental Sciences Division within Queensland Environmental Protection Agency works to monitor, assess and model the condition of the environment. The Division has as a legislative responsibility to produce a whole-of-government report every four years dealing environmental conditions and trends in a ”State of the Environment report” (SoE)[1][2][3]. State of Environment Web Service Reporting System is a supplementary web service based SoE reporting tool, which aims to deliver accurate, timely and accessible information on the condition of the environment through web services via Internet [4][5]. This prototype provides a scientific assessment of environmental conditions for a set of environmental indicators. It contains text descriptions and tables, charts and maps with spatiotemporal dimensions to show the impact of certain environmental indicators on our environment. This prototype is a template based indicator system, to which the administrator may add new sql queries for new indicator services without changing the architecture and codes of this template. The benefits are brought through a service-oriented architecture which provides an online query service with seamless integration. In addition, since it uses web service architecture, each individual component within the application can be implemented by using different programming languages and in different operating systems. Although the services showed in this demo are built upon two datasets of regional ecosystem and protection area of Queensland, it will be possible to report on the condition of water, air, land, coastal zones, energy resources, biodiversity, human settlements and natural culture heritage on the fly as well. Figure 1 shows the architecture of the prototype. In the next section, I will discuss the research tasks in the prototype.

Volcanic setting of the Bajo de la Alumbrera porphyry Cu-Au deposit, Farallon Negro Volcanics, Northwest Argentina

The late Miocene Farallon Negro volcanics, comprising basaltic to rhyodacitic volcano-sedimentary rocks, host the Bajo de la Alumbrera porphyry copper-gold deposit in northwest Argentina. Early studies of the geology of the district have underpinned the general model for porphyry ore deposits where hydrothermal alteration and mineralization develop in and around porphyritic intrusions emplaced at shallow depths (2.5-3.5 km) into stratovolcanic assemblages. The Farallon Negro succession is dominated by thick sequences of volcano-sedimentary breccias, with lavas forming a minor component volumetrically. These volcaniclastic rocks conformably overlie crystalline basement-derived sedimentary rocks deposited in a developing foreland basin southeast of the Puna-Altiplano plateau. Within the Farallon Negro volcanics, volcanogenic accumulations evolved from early mafic to intermediate and silicic compositions. The younger and more silicic rocks are demonstrably coeval and comagmatic with the earliest group of mineralized porphyritic intrusions at Bajo de la Alumbrera. Our analysis of the volcanic stratigraphy and facies architecture of the Farallon Negro volcanics indicates that volcanic eruptions evolved from effusive to mixed effusive and explosive styles, as magma compositions changed to more intermediate and silicic compositions. Air early phase of mafic to intermediate voleanism was characterized by small synsedimentary intrusions with peperitic contacts, and lesser lava units scattered widely throughout the district, and interbedded with thick and extensive successions of coarse-grained sedimentary breccias. These sedimentary breccias formed from numerous debris- and hyperconcentrated flow events. A later phase of silicic volcanism included both effusive eruptions, forming several areally restricted lavas, and explosive eruptions, producing more widely dispersed (up to 5 kin) tuff units, some tip to 30-m thickness in proximal sections. Four key features of the volcanic stratigraphy suggest that the Farallon Negro volcanics need not simply record the construction of a large steep-sided polygenetic stratovolcano: (1) sheetlike, laterally continuous debris-flow and other coarse-grained sedimentary deposits are dominant, particularly in the lower sections; (2) mafic-intermediate composition lavas are volumetrically minor; (3) peperites are present throughout the sequence; and (4) fine-grained lacustrine sandstone-siltstone sequences occur in areas previously thought to be proximal to the summit region of the stratovolcano. Instead, the nature, distribution, and geometry of volcanic and volcaniclastic facies suggest that volcanism occurred as a relatively low relief, multiple-vent volcanic complex at the eastern edge of a broad, > 200-km-wide late Miocene volcanic belt and oil ail active foreland sedimentary basin to the Puna-Altiplano. Volcanism that occurred synchronously with the earliest stages of porphyry-related mineralization at Bajo de la Alumbrera apparently developed in an alluvial to ring plain setting that was distal to larger volcanic edifices.

Application of the Artificial Intelligence Algorithms for System Analysis of Multi Dimension Physiological Data for Developing Polyparametric Information System of Public Health Diagnostics

The polyparametric intelligence information system for diagnostics human functional state in medicine and public health is developed. The essence of the system consists in polyparametric describing of human functional state with the unified set of physiological parameters and using the polyparametric cognitive model developed as the tool for a system analysis of multitude data and diagnostics of a human functional state. The model is developed on the basis of general principles geometry and symmetry by algorithms of artificial intelligence systems. The architecture of the system is represented. The model allows analyzing traditional signs - absolute values of electrophysiological parameters and new signs generated by the model – relationships of ones. The classification of physiological multidimensional data is made with a transformer of the model. The results are presented to a physician in a form of visual graph – a pattern individual functional state. This graph allows performing clinical syndrome analysis. A level of human functional state is defined in the case of the developed standard (“ideal”) functional state. The complete formalization of results makes it possible to accumulate physiological data and to analyze them by mathematics methods.

A methodology for formally modeling and analyzing software architecture of mobile agent systems

A methodology for formally modeling and analyzing software architecture of mobile agent systems provides a solid basis to develop high quality mobile agent systems, and the methodology is helpful to study other distributed and concurrent systems as well. However, it is a challenge to provide the methodology because of the agent mobility in mobile agent systems.^ The methodology was defined from two essential parts of software architecture: a formalism to define the architectural models and an analysis method to formally verify system properties. The formalism is two-layer Predicate/Transition (PrT) nets extended with dynamic channels, and the analysis method is a hierarchical approach to verify models on different levels. The two-layer modeling formalism smoothly transforms physical models of mobile agent systems into their architectural models. Dynamic channels facilitate the synchronous communication between nets, and they naturally capture the dynamic architecture configuration and agent mobility of mobile agent systems. Component properties are verified based on transformed individual components, system properties are checked in a simplified system model, and interaction properties are analyzed on models composing from involved nets. Based on the formalism and the analysis method, this researcher formally modeled and analyzed a software architecture of mobile agent systems, and designed an architectural model of a medical information processing system based on mobile agents. The model checking tool SPIN was used to verify system properties such as reachability, concurrency and safety of the medical information processing system. ^ From successful modeling and analyzing the software architecture of mobile agent systems, the conclusion is that PrT nets extended with channels are a powerful tool to model mobile agent systems, and the hierarchical analysis method provides a rigorous foundation for the modeling tool. The hierarchical analysis method not only reduces the complexity of the analysis, but also expands the application scope of model checking techniques. The results of formally modeling and analyzing the software architecture of the medical information processing system show that model checking is an effective and an efficient way to verify software architecture. Moreover, this system shows a high level of flexibility, efficiency and low cost of mobile agent technologies. ^

The School and the State. Comparative Study of the Althusserian Concept of “Ideological State Apparatus”

The famous althusserian concept “The ideological State apparatus” has the inconvenient of hiding what truly should have to be discussed: The Kind of State of which it is talking about. Mostly, avoids realizing the fact that the architecture of the modern State was thought of, precisely, as antidote against ideological control. The success and failures of this political project become then, very difficult to diagnose.