Remnants of an ancient metabolism without phosphate

Phosphate is essential for all living systems, serving as a building block of genetic and metabolic machinery. However, it is unclear how phosphate could have assumed these central roles on primordial Earth, given its poor geochemical accessibility. We used systems biology approaches to explore the alternative hypothesis that a protometabolism could have emerged prior to the incorporation of phosphate. Surprisingly, we identified a cryptic phosphate-independent core metabolism producible from simple prebiotic compounds. This network is predicted to support the biosynthesis of a broad category of key biomolecules. Its enrichment for enzymes utilizing iron-sulfur clusters, and the fact that thermodynamic bottlenecks are more readily overcome by thioester rather than phosphate couplings, suggest that this network may constitute a "metabolic fossil" of an early phosphate-free nonenzymatic biochemistry. Our results corroborate and expand previous proposals that a putative thioester-based metabolism could have predated the incorporation of phosphate and an RNA-based genetic system. PAPERCLIP

GTPases and the origin of the ribosome

Background This paper is an attempt to trace the evolution of the ribosome through the evolution of the universal P-loop GTPases that are involved with the ribosome in translation and with the attachment of the ribosome to the membrane. The GTPases involved in translation in Bacteria/Archaea are the elongation factors EFTu/EF1, the initiation factors IF2/aeIF5b + aeIF2, and the elongation factors EFG/EF2. All of these GTPases also contain the OB fold also found in the non GTPase IF1 involved in initiation. The GTPase involved in the signal recognition particle in most Bacteria and Archaea is SRP54. Results 1) The Elongation Factors of the Archaea based on structural considerations of the domains have the following evolutionary path: EF1→ aeIF2 → EF2. The evolution of the aeIF5b was a later event; 2) the Elongation Factors of the Bacteria based on the topological considerations of the GTPase domain have a similar evolutionary path: EFTu→ IF→2→EFG. These evolutionary sequences reflect the evolution of the LSU followed by the SSU to form the ribosome; 3) the OB-fold IF1 is a mimic of an ancient tRNA minihelix. Conclusion The evolution of translational GTPases of both the Archaea and Bacteria point to the evolution of the ribosome. The elongation factors, EFTu/EF1, began as a Ras-like GTPase bringing the activated minihelix tRNA to the Large Subunit Unit. The initiation factors and elongation factor would then have evolved from the EFTu/EF1 as the small subunit was added to the evolving ribosome. The SRP has an SRP54 GTPase and a specific RNA fold in its RNA component similar to the PTC. We consider the SRP to be a remnant of an ancient form of an LSU bound to a membrane. Reviewers This article was reviewed by George Fox, Leonid Mirny and Chris Sander.National Science Foundation (U.S.) (Grant DBI-0516000

Inferring genome-scale rearrangement phylogeny and ancestral gene order: a Drosophila case study

A simple, fast, and biologically-inspired computational approach to infer genome-scale rearrangement phylogeny and ancestral gene order has been developed and applied to eight Drosophila genomes, providing insights into evolutionary chromosomal dynamics

Visible Volume: a Robust Measure for Protein Structure Characterization

We propose a new characterization of protein structure based on the natural tetrahedral geometry of the β carbon and a new geometric measure of structural similarity, called visible volume. In our model, the side-chains are replaced by an ideal tetrahedron, the orientation of which is fixed with respect to the backbone and corresponds to the preferred rotamer directions. Visible volume is a measure of the non-occluded empty space surrounding each residue position after the side-chains have been removed. It is a robust, parameter-free, locally-computed quantity that accounts for many of the spatial constraints that are of relevance to the corresponding position in the native structure. When computing visible volume, we ignore the nature of both the residue observed at each site and the ones surrounding it. We focus instead on the space that, together, these residues could occupy. By doing so, we are able to quantify a new kind of invariance beyond the apparent variations in protein families, namely, the conservation of the physical space available at structurally equivalent positions for side-chain packing. Corresponding positions in native structures are likely to be of interest in protein structure prediction, protein design, and homology modeling. Visible volume is related to the degree of exposure of a residue position and to the actual rotamers in native proteins. In this article, we discuss the properties of this new measure, namely, its robustness with respect to both crystallographic uncertainties and naturally occurring variations in atomic coordinates, and the remarkable fact that it is essentially independent of the choice of the parameters used in calculating it. We also show how visible volume can be used to align protein structures, to identify structurally equivalent positions that are conserved in a family of proteins, and to single out positions in a protein that are likely to be of biological interest. These properties qualify visible volume as a powerful tool in a variety of applications, from the detailed analysis of protein structure to homology modeling, protein structural alignment, and the definition of better scoring functions for threading purposes.National Library of Medicine (LM05205-13

The origin and evolution of the ribosome

<p>Abstract</p> <p>Background</p> <p>The origin and early evolution of the active site of the ribosome can be elucidated through an analysis of the ribosomal proteins' taxonomic block structures and their RNA interactions. Comparison between the two subunits, exploiting the detailed three-dimensional structures of the bacterial and archaeal ribosomes, is especially informative.</p> <p>Results</p> <p>The analysis of the differences between these two sites can be summarized as follows: 1) There is no self-folding RNA segment that defines the decoding site of the small subunit; 2) there is one self-folding RNA segment encompassing the entire peptidyl transfer center of the large subunit; 3) the protein contacts with the decoding site are made by a set of universal alignable sequence blocks of the ribosomal proteins; 4) the majority of those peptides contacting the peptidyl transfer center are made by bacterial or archaeal-specific sequence blocks.</p> <p>Conclusion</p> <p>These clear distinctions between the two subunit active sites support an earlier origin for the large subunit's peptidyl transferase center (PTC) with the decoding site of the small subunit being a later addition to the ribosome. The main implications are that a single self-folding RNA, in conjunction with a few short stabilizing peptides, formed the precursor of the modern ribosomal large subunit in association with a membrane.</p> <p>Reviewers</p> <p>This article was reviewed by Jerzy Jurka, W. Ford Doolittle, Eugene Shaknovich, and George E. Fox (nominated by Jerzy Jurka).</p

Phylogenetic Relationship of the Complete Rauscher Murine Leukemia Virus Genome with Other Murine Leukemia Virus Genomes

AbstractWe report the complete nucleotide sequence of the genome of Rauscher murine leukemia virus (R-MuLV), the replication-competent helper virus present in the Rauscher virus complex, and its phylogenetic relationship with other murine leukemia virus genomes. An overall sequence identity of 97.6% was found between R-MuLV and the Friend helper virus (F-MuLV), and the two viruses were closely related on the phylogenetic trees constructed from eithergag, pol,orenvsequences. Moloney murine leukemia virus (Mo-MuLV) was the next closest relative to R-MuLV and F-MuLV on all trees, followed by Akv and radiation leukemia virus (RadLV). The most distantly related helper virus was Hortulanus murine leukemia virus (Ho-MuLV). Interestingly, Cas-Br-E branched with Mo-MuLV on thegagandpoltrees, whereas on theenvtree, it revealed the highest degree of relatedness to Ho-MuLV, possibly due to an ancient recombination with an Ho-MuLV ancestor. In summary, a phylogenetic analysis involving various MuLVs has been performed, in which the postulated close relationship between R-MuLV and F-MuLV has been confirmed, consistent with the pathobiology of the two viruses

Assessing the role of contact tracing in a suspected H7N2 influenza A outbreak in humans in Wales.

BACKGROUND: The detailed analysis of an outbreak database has been undertaken to examine the role of contact tracing in controlling an outbreak of possible avian influenza in humans. The outbreak, initiating from the purchase of infected domestic poultry, occurred in North Wales during May and June 2007. During this outbreak, extensive contact tracing was carried out. Following contact tracing, cases and contacts believed to be at risk of infection were given treatment/prophylaxis. METHODS: We analyse the database of cases and their contacts identified for the purposes of contact tracing in relation to both the contact tracing burden and effectiveness. We investigate the distribution of numbers of contacts identified, and use network structure to explore the speed with which treatment/prophylaxis was made available and to estimate the risk of transmission in different settings. RESULTS: Fourteen cases of suspected H7N2 influenza A in humans were associated with a confirmed outbreak among poultry in May-June 2007. The contact tracing dataset consisted of 254 individuals (cases and contacts, of both poultry and humans) who were linked through a network of social contacts. Of these, 102 individuals were given treatment or prophylaxis. Considerable differences between individuals' contact patterns were observed. Home and workplace encounters were more likely to result in transmission than encounters in other settings. After an initial delay, while the outbreak proceeded undetected, contact tracing rapidly caught up with the cases and was effective in reducing the time between onset of symptoms and treatment/prophylaxis. CONCLUSIONS: Contact tracing was used to link together the individuals involved in this outbreak in a social network, allowing the identification of the most likely paths of transmission and the risks of different types of interactions to be assessed. The outbreak highlights the substantial time and cost involved in contact tracing, even for an outbreak affecting few individuals. However, when sufficient resources are available, contact tracing enables cases to be identified before they result in further transmission and thus possibly assists in preventing an outbreak of a novel virus.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

A Multi-Wavelength Infrared Study of NGC 891

We present a multi-wavlength infrared study of the nearby, edge-on, spiral galaxy NGC 891. We have examined 20 independent, spatially resolved IR images of this galaxy, 14 of which are newly reduced and/or previously unpublished images. These images span a wavelength regime from 1.2 microns in which the emission is dominated by cool stars, through the MIR, in which emission is dominated by PAHs, to 850 microns, in which emission is dominated by cold dust in thermal equilibrium with the radiation field. The changing morphology of the galaxy with wavelength illustrates the changing dominant components. We detect extra-planar dust emission in this galaxy, consistent with previously published results, but now show that PAH emission is also in the halo, to a vertical distance of z >= 2.5 kpc. We compare the vertical extents of various components and find that the PAHs (from 7.7 and 8 micron data) and warm dust (24 microns) extend to smaller z heights than the cool dust (450 microns). For six locations in the galaxy for which the S/N was sufficient, we present SEDs of the IR emission, including two in the halo - the first time a halo SED in an external galaxy has been presented. We have modeled these SEDs and find that the PAH fraction is similar to Galactic values (within a factor of two), with the lowest value at the galaxy's center, consistent with independent results of other galaxies. In the halo environment, the fraction of dust exposed to a colder radiation field, is of order unity, consistent with an environment in which there is no star formation. The source of excitation is likely from photons escaping from the disk.Comment: 24 pages, 17 figures, 7 tables, accepted for publication in MNRA

BASS. XXXIV. A Catalog of the Nuclear Millimeter-wave Continuum Emission Properties of AGNs Constrained on Scales ≤ 100-200 pc

We present a catalog of the millimeter-wave (mm-wave) continuum properties of 98 nearby (z &lt; 0.05) active galactic nuclei (AGNs) selected from the 70 month Swift/BAT hard-X-ray catalog that have precisely determined X-ray spectral properties and subarcsecond-resolution Atacama Large Millimeter/submillimeter Array Band 6 (211-275 GHz) observations as of 2021 April. Due to the hard-X-ray (&gt;10 keV) selection, the sample is nearly unbiased for obscured systems at least up to Compton-thick-level obscuration, and provides the largest number of AGNs with high-physical-resolution mm-wave data (less than or similar to 100-200 pc). Our catalog reports emission peak coordinates, spectral indices, and peak fluxes and luminosities at 1.3 mm (230 GHz). Additionally, high-resolution mm-wave images are provided. Using the images and creating radial surface brightness profiles of mm-wave emission, we identify emission extending from the central sources and isolated blob-like emission. Flags indicating the presence of these emission features are tabulated. Among 90 AGNs with significant detections of nuclear emission, 37 AGNs (approximate to 41%) appear to have both or one of extended or blob-like components. We, in particular, investigate AGNs that show well-resolved mm-wave components and find that these seem to have a variety of origins (i.e., a jet, radio lobes, a secondary AGN, stellar clusters, a narrow-line region, galaxy disk, active star formation regions, or AGN-driven outflows), and some components have currently unclear origins

Aerodynamic investigations of ventilated brake discs.

The heat dissipation and performance of a ventilated brake disc strongly depends on the aerodynamic characteristics of the flow through the rotor passages. The aim of this investigation was to provide an improved understanding of ventilated brake rotor flow phenomena, with a view to improving heat dissipation, as well as providing a measurement data set for validation of computational fluid dynamics methods. The flow fields at the exit of four different brake rotor geometries, rotated in free air, were measured using a five-hole pressure probe and a hot-wire anemometry system. The principal measurements were taken using two-component hot-wire techniques and were used to determine mean and unsteady flow characteristics at the exit of the brake rotors. Using phase-locked data processing, it was possible to reveal the spatial and temporal flow variation within individual rotor passages. The effects of disc geometry and rotational speed on the mean flow, passage turbulence intensity, and mass flow were determined. The rotor exit jet and wake flow were clearly observed as characterized by the passage geometry as well as definite regions of high and low turbulence. The aerodynamic flow characteristics were found to be reasonably independent of rotational speed but highly dependent upon rotor geometry