Are Urban Communities in Successional Stasis? A Case Study on Epiphytic Lichen Communities

Urban areas may contain a wide range of potential habitats and environmental gradients and, given the many benefits to human health and well-being, there is a growing interest in maximizing their biodiversity potential. However, the ecological patterns and processes in urban areas are poorly understood. Using a widely applicable ecological survey method, we sampled epiphytic lichen communities, important bioindicators of atmospheric pollution, on host Quercus trees in urban parks of London, UK, to test if common patterns relating to lichen diversity are mirrored in urban green spaces. We found lichen diversity to be dependent on host species identity, and negatively related to local tree crowding. In addition, we found a strong negative effect of tree size on lichen diversity, leaving large trees as unexploited niches. A novel network analysis revealed the presence of only pioneer communities, showing the lichen communities are being held in successional stasis, likely due to the heritage effects of SO2 emissions and current nitrogen pollution and particulate emissions. Our study highlights that jointly assessing species richness, community structure and the successional stage can be key to understanding diversity patterns in urban ecosystems. Subsequently, this may help best determine the optimum conditions that will facilitate biodiversity increase within cities

The cap-snatching SFTSV endonuclease domain is an antiviral target

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne virus with 12%-30% case mortality rates and is related to the Heartland virus (HRTV) identified in the United States. Together, SFTSV and HRTV are emerging segmented, negative-sense RNA viral (sNSV) pathogens with potential global health impact. Here, we characterize the amino-terminal cap-snatching endonuclease domain of SFTSV polymerase (L) and solve a 2.4-Å X-ray crystal structure. While the overall structure is similar to those of other cap-snatching sNSV endonucleases, differences near the C terminus of the SFTSV endonuclease suggest divergence in regulation. Influenza virus endonuclease inhibitors, including the US Food and Drug Administration (FDA) approved Baloxavir (BXA), inhibit the endonuclease activity in in vitro enzymatic assays and in cell-based studies. BXA displays potent activity with a half maximal inhibitory concentration (I

Ubiquitin variants potently inhibit SARS-CoV-2 PLpro and viral replication via a novel site distal to the protease active site

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has made it clear that combating coronavirus outbreaks benefits from a combination of vaccines and therapeutics. A promising drug target common to all coronaviruses-including SARS-CoV, MERS-CoV, and SARS-CoV-2-is the papain-like protease (PLpro). PLpro cleaves part of the viral replicase polyproteins into non-structural protein subunits, which are essential to the viral replication cycle. Additionally, PLpro can cleave both ubiquitin and the ubiquitin-like protein ISG15 from host cell substrates as a mechanism to evade innate immune responses during infection. These roles make PLpro an attractive antiviral drug target. Here we demonstrate that ubiquitin variants (UbVs) can be selected from a phage-displayed library and used to specifically and potently block SARS-CoV-2 PLpro activity. A crystal structure of SARS-CoV-2 PLpro in complex with a representative UbV reveals a dimeric UbV bound to PLpro at a site distal to the catalytic site. Yet, the UbV inhibits the essential cleavage activities of the protease in vitro and in cells, and it reduces viral replication in cell culture by almost five orders of magnitude

Two geomagnetic regional models for Albania and south-east Italy from 1990 to 2010 with prediction to 2012 and comparison with IGRF-11

Here we present a revised geomagnetic reference model for the region comprising Albanian territory, south-east part of Italian Peninsula and Ionian Sea from 1990 to 2010 with prediction to 2012. This study is based on the datasets of magnetic measurements taken during different campaigns in Albania and Italy in the time of concern, together with a total intensity data set from the Ørsted and CHAMP satellite missions. The model is designed to represent the Cartesian components, X, Y, Z and the total intensity F of the main geomagnetic field (and its secular variation) for the period of interest. To develop the model, we applied a Spherical Cap Harmonic Analysis (SCHA) of the geomagnetic potential over a 16° cap with most of the observations concentrated in the central 4° half-angle. The use of a larger cap than that containing the data was made to reduce the typical problems in SV modelling over small regions. Also a new technique, called ``Radially Simplified Spherical Cap Harmonic Analysis" (RS-SCHA), was developed to improve the model especially in the radial variation of the geomagnetic field components. Both these models provide an optimal representation of the geomagnetic field in the considered region compared with the International Geomagnetic Reference Field model (IGRF-11) and can be used as reference models to reduce magnetic surveys undertaken in the area during the time of validity of the model, or to extrapolate the field till 2012

Two geomagnetic regional models for Albania and south-east Italy from 1990 to 2010 with prediction to 2012 and comparison with IGRF-11

Here we present a revised geomagnetic reference model for the region comprising Albanian territory, southeast part of Italian Peninsula and Ionian Sea from 1990 to 2010 with prediction to 2012. This study is based on the datasets of magnetic measurements taken during different campaigns in Albania and Italy in the time of concern, together with a total intensity data set from the ∅rsted and CHAMP satellite missions. The model is designed to represent the Cartesian components, X, Y, Z and the total intensity F of the main geomagnetic field (and its secular variation SV) for the period of interest. To develop the model, we applied a Spherical Cap Harmonic Analysis (SCHA) of the geomagnetic potential over a 16° cap with most of the observations concentrated in the central 4° half-angle. The use of a larger cap than that containing the data was made to reduce the typical problems in SV modelling over small regions. Also a new technique, called "Radially Simplified Spherical Cap Harmonic Analysis" (RS-SCHA), was developed to improve the model especially in the radial variation of the geomagnetic field components. Both these models provide an optimal representation of the geomagnetic field in the considered region compared with the International Geomagnetic Reference Field model (IGRF-11) and can be used as reference models to reduce magnetic surveys undertaken in the area during the time of validity of the model, or to extrapolate the field till 2012

A dynamic portal for a community-driven, continuously updated classification of Fungi and fungus-like organisms: outlineoffungi.org

The website http://outlineoffungi.org, is launched to provide a continuous up-to-date classification of the kingdom Fungi (including fossil fungi) and fungus-like taxa. This is based on recent publications and on the outline of fungi and fungus-like taxa published recently (Mycosphere 11, 1060-1456, Doi: 10.5943/mycosphere/11/1/8). The website is continuously updated according to latest classification schemes, and will present an important platform for researchers, industries, government officials and other users. Users can provide input about missing genera, new genera, and new data. They will also have the opportunity to express their opinions on classifications with notes published in the 'Notes' section of the webpage following review and editing by the curators and independent experts. The website will provide a system to stay abreast of the continuous changes in fungal classification and provide a general consensus on the systematics of fungi

A cryptic pocket in Ebola VP35 allosterically controls RNA binding

Protein-protein and protein-nucleic acid interactions are often considered difficult drug targets because the surfaces involved lack obvious druggable pockets. Cryptic pockets could present opportunities for targeting these interactions, but identifying and exploiting these pockets remains challenging. Here, we apply a general pipeline for identifying cryptic pockets to the interferon inhibitory domain (IID) of Ebola virus viral protein 35 (VP35). VP35 plays multiple essential roles in Ebola\u27s replication cycle but lacks pockets that present obvious utility for drug design. Using adaptive sampling simulations and machine learning algorithms, we predict VP35 harbors a cryptic pocket that is allosterically coupled to a key dsRNA-binding interface. Thiol labeling experiments corroborate the predicted pocket and mutating the predicted allosteric network supports our model of allostery. Finally, covalent modifications that mimic drug binding allosterically disrupt dsRNA binding that is essential for immune evasion. Based on these results, we expect this pipeline will be applicable to other proteins

Three-dimensional quantitative evaluation method of nonrigid registration algorithms for adaptive radiotherapy

Purpose: Current radiotherapy is progressing to the concept of adaptive radiotherapy, which implies the adaptation of planning along the treatment course. Nonrigid registration is an essential image processing tool for adaptive radiotherapy and image guided radiotherapy, and the three-dimensional (3D) nature of the current radiotherapy techniques requires a 3D quantification of the registration error that existing evaluation methods do not cover appropriately. The authors present a method for 3D evaluation of nonrigid registration algorithms’ performance, based on organ delineations, capable of working with near-spherical volumes even in the presence of concavities. Methods: The evaluation method is composed by a volume shape description stage, developed using a new ad hoc volume reconstruction algorithm proposed by the authors, and an error quantification stage. The evaluation method is applied to the organ delineations of prostate and seminal vesicles, obtained by an automatic segmentation method over images of prostate cancer patients treated with intensity modulated radiation therapy. Results: The volume reconstruction algorithm proposed has been shown to accurately model complex 3D surfaces by the definition of clusters of control points. The quantification method, inspired by the Haussdorf–Chebysev distance, provides a measure of the largest registration error per control direction, defining a valid metric for concave-convex volumes. Summarizing, the proposed evaluation methodology presents accurate results with a high spatial resolution in a negligible computation time in comparison with the nonrigid registration time. Conclusions: Experimental results show that the metric selected for quantifying the registration error is of utmost importance in a quantitative evaluation based on measuring distances between volumes. The accuracy of the volume reconstruction algorithm is not so relevant as long as the reconstruction is tight enough on the actual volume of the organ. The new evaluation method provides a smooth and accurate volume reconstruction for both the reference and the registered organ, and a complete 3D description of nonrigid registration algorithms’ performance, resulting in a useful tool for study and comparison of registration algorithms for adaptive radiotherapy

Structural and Energetic Mechanisms of Cooperative Autoinhibition and Activation of Vav1

SummaryVav proteins are guanine nucleotide exchange factors (GEFs) for Rho family GTPases. They control processes including T cell activation, phagocytosis, and migration of normal and transformed cells. We report the structure and biophysical and cellular analyses of the five-domain autoinhibitory element of Vav1. The catalytic Dbl homology (DH) domain of Vav1 is controlled by two energetically coupled processes. The DH active site is directly, but weakly, inhibited by a helix from the adjacent Acidic domain. This core interaction is strengthened 10-fold by contacts of the calponin homology (CH) domain with the Acidic, pleckstrin homology, and DH domains. This construction enables efficient, stepwise relief of autoinhibition: initial phosphorylation events disrupt the modulatory CH contacts, facilitating phosphorylation of the inhibitory helix and consequent GEF activation. Our findings illustrate how the opposing requirements of strong suppression of activity and rapid kinetics of activation can be achieved in multidomain systems