SARS-CoV-2 structural coverage map reveals viral protein assembly, mimicry, and hijacking mechanisms

Abstract We modeled 3D structures of all SARS‐CoV‐2 proteins, generating 2,060 models that span 69% of the viral proteome and provide details not available elsewhere. We found that ˜6% of the proteome mimicked human proteins, while ˜7% was implicated in hijacking mechanisms that reverse post‐translational modifications, block host translation, and disable host defenses; a further ˜29% self‐assembled into heteromeric states that provided insight into how the viral replication and translation complex forms. To make these 3D models more accessible, we devised a structural coverage map, a novel visualization method to show what is—and is not—known about the 3D structure of the viral proteome. We integrated the coverage map into an accompanying online resource (https://aquaria.ws/covid) that can be used to find and explore models corresponding to the 79 structural states identified in this work. The resulting Aquaria‐COVID resource helps scientists use emerging structural data to understand the mechanisms underlying coronavirus infection and draws attention to the 31% of the viral proteome that remains structurally unknown or dark

Identification of novel Cyclooxygenase-2-dependent genes in Helicobacter pylori infection in vivo

<p>Abstract</p> <p>Background</p> <p><it>Helicobacter pylori </it>is a crucial determining factor in the pathogenesis of benign and neoplastic gastric diseases. Cyclooxygenase-2 (Cox-2) is the inducible key enzyme of arachidonic acid metabolism and is a central mediator in inflammation and cancer. Expression of the <it>Cox-2 </it>gene is up-regulated in the gastric mucosa during <it>H. pylori </it>infection but the pathobiological consequences of this enhanced Cox-2 expression are not yet characterized. The aim of this study was to identify novel genes down-stream of Cox-2 in an <it>in vivo </it>model, thereby identifying potential targets for the study of the role of Cox- 2 in <it>H. pylori </it>pathogenesis and the initiation of pre- cancerous changes.</p> <p>Results</p> <p>Gene expression profiles in the gastric mucosa of mice treated with a specific Cox-2 inhibitor (NS398) or vehicle were analysed at different time points (6, 13 and 19 wk) after <it>H. pylori </it>infection. <it>H. pylori </it>infection affected the expression of 385 genes over the experimental period, including regulators of gastric physiology, proliferation, apoptosis and mucosal defence. Under conditions of Cox-2 inhibition, 160 target genes were regulated as a result of <it>H. pylori </it>infection. The Cox-2 dependent subset included those influencing gastric physiology (<it>Gastrin, Galr1</it>), epithelial barrier function (<it>Tjp1, connexin45, Aqp5</it>), inflammation (<it>Icam1</it>), apoptosis (<it>Clu</it>) and proliferation (<it>Gdf3, Igf2</it>). Treatment with NS398 alone caused differential expression of 140 genes, 97 of which were unique, indicating that these genes are regulated under conditions of basal Cox-2 expression.</p> <p>Conclusion</p> <p>This study has identified a panel of novel Cox-2 dependent genes influenced under both normal and the inflammatory conditions induced by <it>H. pylori </it>infection. These data provide important new links between Cox-2 and inflammatory processes, epithelial repair and integrity.</p

Independent large scale duplications in multiple M. tuberculosis lineages overlapping the same genomic region

Mycobacterium tuberculosis, the causative agent of most human tuberculosis, infects one third of the world's population and kills an estimated 1.7 million people a year. With the world-wide emergence of drug resistance, and the finding of more functional genetic diversity than previously expected, there is a renewed interest in understanding the forces driving genome evolution of this important pathogen. Genetic diversity in M. tuberculosis is dominated by single nucleotide polymorphisms and small scale gene deletion, with little or no evidence for large scale genome rearrangements seen in other bacteria. Recently, a single report described a large scale genome duplication that was suggested to be specific to the Beijing lineage. We report here multiple independent large-scale duplications of the same genomic region of M. tuberculosis detected through whole-genome sequencing. The duplications occur in strains belonging to both M. tuberculosis lineage 2 and 4, and are thus not limited to Beijing strains. The duplications occur in both drug-resistant and drug susceptible strains. The duplicated regions also have substantially different boundaries in different strains, indicating different originating duplication events. We further identify a smaller segmental duplication of a different genomic region of a lab strain of H37Rv. The presence of multiple independent duplications of the same genomic region suggests either instability in this region, a selective advantage conferred by the duplication, or both. The identified duplications suggest that large-scale gene duplication may be more common in M. tuberculosis than previously considere

COMPARTMENTS: unification and visualization of protein subcellular localization evidence.

Information on protein subcellular localization is important to understand the cellular functions of proteins. Currently, such information is manually curated from the literature, obtained from high-throughput microscopy-based screens and predicted from primary sequence. To get a comprehensive view of the localization of a protein, it is thus necessary to consult multiple databases and prediction tools. To address this, we present the COMPARTMENTS resource, which integrates all sources listed above as well as the results of automatic text mining. The resource is automatically kept up to date with source databases, and all localization evidence is mapped onto common protein identifiers and Gene Ontology terms. We further assign confidence scores to the localization evidence to facilitate comparison of different types and sources of evidence. To further improve the comparability, we assign confidence scores based on the type and source of the localization evidence. Finally, we visualize the unified localization evidence for a protein on a schematic cell to provide a simple overview. Database URL: http://compartments.jensenlab.org

Comparative analysis of mycobacterium and related actinomycetes yields insight into the evolution of mycobacterium tuberculosis pathogenesis

<p>Abstract</p> <p>Background</p> <p>The sequence of the pathogen <it>Mycobacterium tuberculosis </it>(<it>Mtb</it>) strain <it>H37Rv </it>has been available for over a decade, but the biology of the pathogen remains poorly understood. Genome sequences from other <it>Mtb </it>strains and closely related bacteria present an opportunity to apply the power of comparative genomics to understand the evolution of <it>Mtb </it>pathogenesis. We conducted a comparative analysis using 31 genomes from the Tuberculosis Database (TBDB.org), including 8 strains of <it>Mtb </it>and <it>M. bovis</it>, 11 additional Mycobacteria, 4 Corynebacteria, 2 Streptomyces, <it>Rhodococcus jostii RHA1, Nocardia farcinia, Acidothermus cellulolyticus, Rhodobacter sphaeroides, Propionibacterium acnes</it>, and <it>Bifidobacterium longum</it>.</p> <p>Results</p> <p>Our results highlight the functional importance of lipid metabolism and its regulation, and reveal variation between the evolutionary profiles of genes implicated in saturated and unsaturated fatty acid metabolism. It also suggests that DNA repair and molybdopterin cofactors are important in pathogenic Mycobacteria. By analyzing sequence conservation and gene expression data, we identify nearly 400 conserved noncoding regions. These include 37 predicted promoter regulatory motifs, of which 14 correspond to previously validated motifs, as well as 50 potential noncoding RNAs, of which we experimentally confirm the expression of four.</p> <p>Conclusions</p> <p>Our analysis of protein evolution highlights gene families that are associated with the adaptation of environmental Mycobacteria to obligate pathogenesis. These families include fatty acid metabolism, DNA repair, and molybdopterin biosynthesis. Our analysis reinforces recent findings suggesting that small noncoding RNAs are more common in Mycobacteria than previously expected. Our data provide a foundation for understanding the genome and biology of <it>Mtb </it>in a comparative context, and are available online and through TBDB.org.</p

Measuring, modelling and managing gully erosion at large scales: A state of the art

Soil erosion is generally recognized as the dominant process of land degradation. The formation and expansion of gullies is often a highly significant process of soil erosion. However, our ability to assess and simulate gully erosion and its impacts remains very limited. This is especially so at regional to continental scales. As a result, gullying is often overlooked in policies and land and catchment management strategies. Nevertheless, significant progress has been made over the past decades. Based on a review of >590 scientific articles and policy documents, we provide a state-of-the-art on our ability to monitor, model and manage gully erosion at regional to continental scales. In this review we discuss the relevance and need of assessing gully erosion at regional to continental scales (Section 1); current methods to monitor gully erosion as well as pitfalls and opportunities to apply them at larger scales (section 2); field-based gully erosion research conducted in Europe and European Russia (section 3); model approaches to simulate gully erosion and its contribution to catchment sediment yields at large scales (section 4); data products that can be used for such simulations (section 5); and currently existing policy tools and needs to address the problem of gully erosion (section 6). Section 7 formulates a series of recommendations for further research and policy development, based on this review. While several of these sections have a strong focus on Europe, most of our findings and recommendations are of global significance.info:eu-repo/semantics/publishedVersio

Detection of massive tidal tails around the globular cluster Pal 5 with SDSS commissioning data

We report the discovery of two well-defined tidal tails emerging from the sparse remote globular cluster Palomar 5. These tails stretch out symmetrically to both sides of the cluster in the direction of constant Galactic latitude and subtend an angle of 2.6 degrees on the sky. The tails have been detected in commissioning data of the Sloan Digital Sky Survey (SDSS), providing deep five-color photometry in a 2.5 degrees wide band along the equator. The stars in the tails make up a substantial part (~1/3) of the current total population of cluster stars in the magnitude interval 19.5 < i* < 22.0. This reveals that the cluster is subject to heavy mass loss. The orientation of the tails provides an important key for the determination of the cluster's Galactic orbit.Comment: 7 pages, 3 postscript figures, accepted for publication in ApJ Letter

Modeling the seasonal autochthonous sources of dissolved organic carbon and nitrogen in the upper Chesapeake Bay

In this paper we investigate the seasonal autochthonous sources of dissolved organic carbon (DOC) and nitrogen (DON) in the euphotic zone at a station in the upper Chesapeake Bay using a new mass-based ecosystem model. Important features of the model are: (1) carbon and nitrogen are incorporated by means of a set of fixed and varying C:N ratios; (2) dissolved organic matter (DOM) is separated into labile, semi-labile, and refractory pools for both C and N; (3) the production and consumption of DOM is treated in detail; and (4) seasonal observations of light, temperature, nutrients, and surface layer circulation are used to physically force the model. The model reasonably reproduces the mean observed seasonal concentrations of nutrients, DOM, plankton biomass, and chlorophyll a. The results suggest that estuarine DOM production is intricately tied to the biomass concentration, ratio, and productivity of phytoplankton, zooplankton, viruses, and bacteria. During peak spring productivity phytoplankton exudation and zooplankton sloppy feeding are the most important autochthonous sources of DOM. In the summer when productivity peaks again, autochthonous sources of DOM are more diverse and, in addition to phytoplankton exudation, important ones include viral lysis and the decay of detritus. The potential importance of viral decay as a source of bioavailable DOM from within the bulk DOM pool is also discussed. The results also highlight the importance of some poorly constrained processes and parameters. Some potential improvements and remedies are suggested. Sensitivity studies on selected parameters are also reported and discussed