An automated stochastic approach to the identification of the protein specificity determinants and functional subfamilies

<p>Abstract</p> <p>Background</p> <p>Recent progress in sequencing and 3 D structure determination techniques stimulated development of approaches aimed at more precise annotation of proteins, that is, prediction of exact specificity to a ligand or, more broadly, to a binding partner of any kind.</p> <p>Results</p> <p>We present a method, SDPclust, for identification of protein functional subfamilies coupled with prediction of specificity-determining positions (SDPs). SDPclust predicts specificity in a phylogeny-independent stochastic manner, which allows for the correct identification of the specificity for proteins that are separated on a phylogenetic tree, but still bind the same ligand. SDPclust is implemented as a Web-server <url>http://bioinf.fbb.msu.ru/SDPfoxWeb/</url> and a stand-alone Java application available from the website.</p> <p>Conclusions</p> <p>SDPclust performs a simultaneous identification of specificity determinants and specificity groups in a statistically robust and phylogeny-independent manner.</p

The fungal literature-based occurrence database in southern West Siberia (Russia)

The abstract presents the initiative to develop the Fungal Literature-based Occurrence Database for Southern West Siberia (FuSWS), which mobilizes occurrences of fungi from published literature (literature-based occurrences, Darwin Core MaterialCitation). The FuSWS database includes 28 fields describing species name, publication source, herbarium number (if exists), date of sampling or observation, locality information, vegetation, substrate, and others. The initiative on digitization of literature-based occurrence data started in the northern part of Western Siberia two years ago (Filippova et al. 2021a). The present project extends the initiative to the south and includes eight administrative regions (Sverdlovsk, Omsk, Kurgan, Tomsk, Novosibirsk, Kemerovo, Altay, and Gorny Altay). The area occupies the central to southern part of the West Siberian Plain. It extends for about 1.5 thousand km from the west to the east from the eastern slopes of the Ural Mountains to Yenisey River, and from north to south—about 1.3 thousand km. The total area equals about 1.2 million km2.Currently, the project is actively growing in spatial, collaboration and data accumulation terms. The working group of about 30 mycologists from 16 organizations dedicated to the digitization initiative was created as part of the Siberian Mycological Society (informal organization since 2019). They have created the most complete bibliographic list of mycology-related papers for the Southern West Siberia, including over 800 publications for the last two centuries (the earliest dated 1800). At abstract submission, the database had been populated with a total of about 10K records from about 100 sources. The dataset is uploaded to GBIF, where it is available for online search of species occurrences and/or download (Filippova et al. 2021b) Fig. 1. The project's page with the introduction, templates, bibliography list, video-presentations and written instructions is available at the website of the Siberian Mycological Society (https://sibmyco.org/literaturedatabase).The following protocol describes the digitization workflow in detail:The bibliography of related publications is compiled using Zotero bibliographic manager. Only published works (peer-reviewed papers, conference proceedings, PhD theses, monographs or book chapters) are selected. If possible, the sources are digitized and added to the library as PDF files. The template of the FuSWS database is made with Google Sheets, which allows simultaneous use by several specialists, in a common data format provided. The simple Microsoft Excel template is also available for the offline databasing. The Darwin Core standard is applied to the database field structure to accommodate the relevant information extracted from the publications.From the available bibliography of publications related to the region, only works with species occurrences are selected for the databasing purpose. The main source of occurrences is annotated species lists with exact localities of the records. However, different sorts of other species citations are also extracted, provided that they had the connection to any geography. All occurrences are georeferenced, either from the coordinates provided in the paper, or from the verbatim description of the field work locality. The georeferencing of the verbatim descriptions is made using Yandex or Google map services. Depending on the quality of georeference provided in publications, the uncertainty is estimated as follows: 1) the coordinate of a fruiting structure or a plot provided in the publication gives the uncertainty about 3-30 meters; 2) the coordinate of the field work locality provided in publication gives the uncertainty about 500 m to 5 km; 3) the report of the species presence in a particular region gives the centroid of the area with the uncertainty radius to include its borders.The locality names reported in Russian are translated to English and written in the «locality» field. Russian descriptions are reserved in the field «verbatimLocality» for accuracy.When possible, the «eventDate» is extracted from the annotation data. Whenever this information is absent, the date of the publication is used instead with the remarks in the «verbatimEventDate» field.The ecological features, habitat and substrate preferences are written in the «habitat» field and reserved in Russian.The original scientific names reported in publications are filled in the «originalNameUsage» field. Correction of spelling errors is made using the GBIF Species Matching tool. This tool is also used to create the additional fields of taxonomic hierarchy from species to kingdom, to fill in the «taxonRank» field and to synonymize according to the GBIF Backbone Taxonomy.To track the digitization process, a worksheet is maintained. Each bibliographic record has a series of fields to describe the digitization process and its results: the total number of extracted occurrence records, general description of the occurrence quality, presence of the observation date, details of georeferencing and the name of a person responsible for the digitization

The fungal literature-based occurrence database for southern West Siberia (Russia)

The paper presents the initiative on literature-based occurrence data mobilisation of fungi and fungi-related organisms (literature-based occurrences, Darwin Core MaterialCitation) to develop the Fungal literature-based occurrence database for the southern West Siberia (FuSWS). The initiative on mobilisation of literature-based occurrence data started in the northern part of West Siberia in 2016. The present project extends the initiative to the southern regions and includes ten administrative territories (Tyumen Region, Sverdlovsk Region, Chelyabinsk Region, Omsk Region, Kurgan Region, Tomsk Region, Novosibirsk Region, Kemerovo Region, Altai Territory and Republic of Altai). The area occupies the central to southern part of the West Siberian Plain and extends for about 1.5 K km from the west to the east from the eastern slopes of the Ural Mountains to Yenisey River and from north to south—about 1.3 K km. The total area equals about 1.4 million km . The initiative is actively growing in spatial, collaboration and data accumulation terms. The working group of about 30 mycologists from eight organisations dedicated to the data mobilisation was created as part of the Siberian Mycological Society (informal organisation since 2019). They have compiled the almost complete bibliographic list of mycology-related papers for the southern West Siberia, including over 900 publications for the last two centuries (the earliest dated 1800). All literature sources were digitised and an online library was created to integrate bibliography metadata and digitised papers using Zotero bibliography manager. The analysis of published sources showed that about two-thirds of works contain occurrences of fungi for the scope of mobilisation. At the time of the paper submission, the database had been populated with a total of about 8 K records from 93 sources. The dataset is uploaded to GBIF, where it is available for online search of species occurrences and/or download. The project's page with the introduction, templates, bibliography list, video-presentations and written instructions is available (in Russian) at the web site of the Siberian Mycological Society. The initiative will be continued in the following years to extract the records from all published sources. New information The paper presents the first project with the aim of literature-based occurrence data mobilisation of fungi and fungi-related organisms in the southern West Siberia. The full bibliography and a digital library of all regional mycological publications created for the first time includes about 900 published works. By the time of paper submission, nearly 8 K occurrence records were extracted from about 90 literature sources and integrated into the FuSWS database published in GBIF

Automated selection of positions determining functional specificity of proteins by comparative analysis of orthologous groups in protein families

The increasing volume of genomic data opens new possibilities for analysis of protein function. We introduce a method for automated selection of residues that determine the functional specificity of proteins with a common general function (the specificity-determining positions [SDP] prediction method). Such residues are assumed to be conserved within groups of orthologs (that may be assumed to have the same specificity) and to vary between paralogs. Thus, considering a multiple sequence alignment of a protein family divided into orthologous groups, one can select positions where the distribution of amino acids correlates with this division. Unlike previously published techniques, the introduced method directly takes into account nonuniformity of amino acid substitution frequencies. In addition, it does not require setting arbitrary thresholds. Instead, a formal procedure for threshold selection using the Bernoulli estimator is implemented. We tested the SDP prediction method on the LacI family of bacterial transcription factors and a sample of bacterial water and glycerol transporters belonging to the major intrinsic protein (MIP) family. In both cases, the comparison with available experimental and structural data strongly supported our predictions

Synthesis of 1,1,3,3,5,5-Hexamethyl-7,7-diorganocyclotetrasiloxanes and Its Copolymers

This paper reports a method for the synthesis of 1,1,3,3,5,5-hexamethyl-7,7-diorganocyclotetrasiloxanes by the interaction of 1,5-disodiumoxyhexamethylsiloxane with dichlorodiorganosilanes such as methyl-, methylvinyl-, methylphenyl-, diphenyl- and diethyl dichlorosilanes. Depending on the reaction conditions, the preparative yield of the target cyclotetrasiloxanes is 55–75%. Along with mixed cyclotetrasiloxanes, the proposed method leads to the formation of polymers with regular alternation of diorganosylil and dimethylsylil units. For example, in the case of dichlorodiethylsilane, 70% content of linear poly(diethyl)dimethylsiloxanes with regular alternation of units can be achieved in the reaction product. Using 7,7-diethyl-1,1,3,3,5,5-hexamethylcyclotetrasiloxane as an example, the prospects of the mixed cycle in copolymer preparation in comparison with the copolymerization of octamethyl- and octaethylcyclotetrasiloxanes are shown

New Principles of Polymer Composite Preparation. MQ Copolymers as an Active Molecular Filler for Polydimethylsiloxane Rubbers

Colorless transparent vulcanizates of silicone elastomers were prepared by mixing the components in a common solvent followed by solvent removal. We studied the correlation between the mechanical behavior of polydimethylsiloxane (PDMS)-rubber compositions prepared using MQ (mono-(M) and tetra-(Q) functional siloxane) copolymers with different ratios of M and Q parts as a molecular filler. The composition and molecular structure of the original rubber, MQ copolymers, and carboxyl-containing PDMS oligomers were also investigated. The simplicity of the preparation of the compositions, high strength and elongation at break, and their variability within a wide range allows us to consider silicone elastomers as a promising alternative to silicone materials prepared by traditional methods

True Molecular Composites: Unusual Structure and Properties of PDMS-MQ Resin Blends

Poly(dimethyl siloxane)-MQ rubber molecular composites are easy to prepare, as it does not require a heterophase mixing of ingredients. They are characterized by perfect homogeneity, so they are very promising as rubber materials with controllable functional characteristics. The manuscript reveals that MQ resin particles can significantly, more than by two orders of magnitude, enhance the mechanical properties of poly(dimethyl siloxane), and, as fillers, they are not inferior to aerosils. In the produced materials, MQ particles play a role of the molecular entanglements, so rubber molecular weight and MQ filler concentration are the parameters determining the structure and properties of such composites. Moreover, a need for a saturation of the reactive groups and minimization of the surface energy of MQ particles also determine the size and distribution of the filler at different filler rates. An unusual correlation of the concentration of MQ component and the interparticle spacing was revealed. Based on the extraordinary mechanical properties and structure features, a model of the structure poly(dimethyl siloxane)-rubber molecular composites and of its evolution in the process of stretching, was proposed

Current practice in the management of ocular toxoplasmosis

Background Ocular toxoplasmosis is common across all regions of the world. Understanding of the epidemiology and approach to diagnosis and treatment have evolved recently. In November 2020, an international group of uveitis-specialised ophthalmologists formed the International Ocular Toxoplasmosis Study Group to define current practice. Methods 192 Study Group members from 48 countries completed a 36-item survey on clinical features, use of investigations, indications for treatment, systemic and intravitreal treatment with antiparasitic drugs and corticosteroids, and approach to follow-up and preventive therapy. Results For 77.1% of members, unilateral retinochoroiditis adjacent to a pigmented scar accounted for over 60% of presentations, but diverse atypical presentations were also reported. Common complications included persistent vitreous opacities, epiretinal membrane, cataract, and ocular hypertension or glaucoma. Most members used clinical examination with (56.8%) or without (35.9%) serology to diagnose typical disease but relied on intraocular fluid testing-usually PCR-in atypical cases (68.8%). 66.1% of members treated all non-pregnant patients, while 33.9% treated selected patients. Oral trimethoprim-sulfamethoxazole was first-line therapy for 66.7% of members, and 60.9% had experience using intravitreal clindamycin. Corticosteroid drugs were administered systemically by 97.4%; 24.7% also injected corticosteroid intravitreally, almost always in combination with an antimicrobial drug (72.3%). The majority of members followed up all (60.4%) or selected (35.9%) patients after resolution of acute disease, and prophylaxis against recurrence with trimethoprim-sulfamethoxazole was prescribed to selected patients by 69.8%. Conclusion Our report presents a current management approach for ocular toxoplasmosis, as practised by a large international group of uveitis-specialised ophthalmologists