137 research outputs found
Mycobacterium tuberculosis Transcriptome In Vivo Studies – A Key to Understand the Pathogen Adaptation Mechanism
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DePolymerase Predictor (DePP): a machine learning tool for the targeted identification of phage depolymerases
No full textAbstract Biofilm production plays a clinically significant role in the pathogenicity of many bacteria, limiting our ability to apply antimicrobial agents and contributing in particular to the pathogenesis of chronic infections. Bacteriophage depolymerases, leveraged by these viruses to circumvent biofilm mediated resistance, represent a potentially powerful weapon in the fight against antibiotic resistant bacteria. Such enzymes are able to degrade the extracellular matrix that is integral to the formation of all biofilms and as such would allow complementary therapies or disinfection procedures to be successfully applied. In this manuscript, we describe the development and application of a machine learning based approach towards the identification of phage depolymerases. We demonstrate that on the basis of a relatively limited number of experimentally proven enzymes and using an amino acid derived feature vector that the development of a powerful model with an accuracy on the order of 90% is possible, showing the value of such approaches in protein functional annotation and the discovery of novel therapeutic agents
ProFlex as a linguistic bridge for decoding protein dynamics in normal mode analysis
No full textArtificial intelligence is revolutionizing structural bioinformatics, with AlphaFold arguably being the most impactful development to date. The structural atlases generated by these methods present significant opportunities for unraveling biological mysteries but also pose challenges in leveraging such massive datasets effectively. In this work, we explore the dynamic landscape of hundreds of thousands of AlphaFold-predicted structures using normal mode analysis. The resulting data serve to empirically define an alphabet summarizing relative protein flexibility, termed ProFlex. Leveraging ProFlex, we describe the flexibility information space occupied by this massive dataset. We believe leveraging the data compression offered by ProFlex-like approaches opens opportunities for understanding protein function, refining structural predictions, and rendering analyses computationally tractable
Бруно Латур и аналитическая эпистемология
Full text linkIn the article, the author examines the theory of knowledge of Bruno Latour from the perspective of analytic epistemology. Representatives of this approach-as well as Bruno Latour himself- are trying to answer the question: "What is knowledge?". The author explicates the difference between Latour's theory and the basic premises of the analytic epistemologists. In order to do this, the author highlights the theoretical foundations of Latour's theory of knowledge and demonstrates the conventions in the analysis of knowledge which this approach violates. Using the distinctions of analytic epistemology, the author classifies Latour's theory as a purist antisceptic invariantistic externalism. Such a theoretical position is one of the most common views on knowledge in this field. This classification of Latour's views makes it possible to identify the problems specific to this position. The author demonstrates that Latour's theory avoids some of these problems, that some of the problems have a solution specific to this theory, and that some of the problems are not specifically addressed within it. The advantage of Latour's theory is that it copes well with the two main challenges of analytic theories of knowledge: the Gettier problem and the prob- 117 lem of skepticism. In the conclusion, the author offers a critique specific to Latour's theory and presents possible objections to it
Formation of prerequisites for the renovationist schism among the liberal nobility and clergy of Orel guberniya in 1900–1917
No full textBased on the analysis of the periodicals of Orel guberniya of the early 20th century, as well as information on the public utterances of provincial public fi gures on the Church question in the pre-revolutionary period, the author reconstructs the process of formation of Renovationist schism among the liberal nobility and clergy of the province of Orel, trying to explain the presence of succession between the supporters of the reform of the Church in diff erent periods. The author also traces the emergence of ideas of Christian socialism in the province, which later became central to Soviet Renovationism. The study of the genesis of these ideas in the province during the period from the First Russian revolution to the February revolution makes it possible to understand the connection between religious and political factors in this dramatic period. When describing the events known to historians of the “Church revolution” of 1917 in Orel guberniya, the article draws on a unique material of personal origin, i.e. a detailed description of these events by one of the priests who was a participant and witness. The author of the article formulates his view on the processes of using the ideas of reforming the Church by various political parties from the Cadets to the Bolsheviks, finds a point of convergence of interests of those who fought for political power, and those who, being a certain stratum of the regional clergy, expressed their readiness to ensure the interests of the existing power, quickly changing their “patrons” if necessary. Moreover, attention is drawn to the facts of a rapid and radical change in the political position of certain representatives of Orel priesthood precisely during the implementation of serious revolutionary changes in the Russian state. The author was able to identify these names, specify them in the article and establish the diff erences between the schismatic element and those who really cared about the welfare of the Church
BANKING SECTOR MODERNIZATION(SPANISH RECIPE)
No full textThe aim of the research is to analyze transformation of the Spanish banking sector after the financial crisis of the year 2008. The author examines a hypothesis that banking system played an important role in the development of Spain’s economy. Spain’s banking sector was substantially transformed during the economic crisis, and now serves as a prerequisite for development of Spain’s national economy during post crisis perio
Genomic hypervariability of phage Andromeda is unique among known dsDNA viruses
No full textA new lytic bacteriophage Andromeda, specific to the economically important plant pathogen Pseudomonas syringae, was isolated and characterised. It belongs to the Podoviridae family, Autographivirinae subfamily and possesses a linear dsDNA genome of 40,008 bp with four localised nicks. Crucially, Andromeda’s genome has no less than 80 hypervariable sites (SNPs), which show genome wide distribution resulting in heterogenous populations of this phage reminiscent of those of RNA virus quasispecies. Andromeda has no nucleotide sequence homology to phage phiNFS, a member of phiKMVviruses, in which a similar phenomenon was discovered. We show that Andromeda and Andromeda-related phages form a group within the Autographivirinae, designated here as the “ExophiKMVviruses”. The “ExophiKMVviruses” were revealed to share conservation of gene order with core phiKMVviruses despite their sequence-based relationship to SP6-related phages. Our findings suggest that genomic hypervariability might be a feature that occurs among various Autographivirinae groups
Leveraging Structural Relationships as a Novel Mode of Viral Classification
No full text100 years have passed since the independent discovery of the humble bacteriophage (phage) by Frederick Twort and Felix d’Herelle in 1915 and 1917 respectively, and since then, it has become commonly accepted that phages represent the most abundant biological entities on Earth. Despite this fact, viral taxonomy lies in extremely treacherous waters, ever changing to accommodate the next series of phylogenetic mysteries.The utilisation of genes such as the terminase large sub-unit can in some cases provide a robust taxonomic marker, but this is often found to fail at higher taxonomic levels. In addition, the rapid evolutionary dynamics and highly modular nature of phages provide yet more phylogenetic roadblocks, necessitating additional and multifaceted approaches as a means of resolution.Here, we describe a novel approach towards the taxonomic classification of phage systems. Tools for accurately predicting the three dimensional structure of proteins are improving at an unprecedented rate due to the fact that the number of protein sequences far exceeds the number of experimentally determined structures. Our approach leverages these methods through a pipeline which compares models of phage marker genes in order to permit the inference of phylogenetic relationships based on cross model superimposition. We hope this method will supplement other approaches in providing a more holistic approach to viral classification
Leveraging structural relationships as a novel mode of viral classification
No full text100 years have passed since the independent discovery of the humble bacteriophage (phage) by Frederick Twort and Felix d’Herelle in 1915 and 1917 respectively, and since then, it has become commonly accepted that phages represent the most abundant biological entities on Earth. Despite this fact, viral taxonomy lies in extremely treacherous waters, ever changing to accommodate the next series of phylogenetic mysteries. The utilisation of genes such as the terminase large sub-unit can in some cases provide a robust taxonomic marker, but this is often found to fail at higher taxonomic levels. In addition, the rapid evolutionary dynamics and highly modular nature of phages provide yet more phylogenetic roadblocks, necessitating additional and multifaceted approaches as a means of resolution. Here, we describe a novel approach towards the taxonomic classification of phage systems. Tools for accurately predicting the three dimensional structure of proteins are improving at an unprecedented rate due to the fact that the number of protein sequences far exceeds the number of experimentally determined structures. Our approach leverages these methods through a pipeline which compares models of phage marker genes in order to permit the inference of phylogenetic relationships based on cross model superimposition. We hope this method will supplement other approaches in providing a more holistic approach to viral classification.<br/
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