33 research outputs found
Örtliche Konservierung von Informationsmustern in Sequenzen
No full textInvariants (conservation laws) have served as the ultimate cornerstones of
mathematical and physical theories from the early days of science to modern
times. For example, the initial name of Einstein's theory was
“Invariantentheorie”, and Klein in the “Erlanger Programm” saw geometry as the
study of invariants under a group of transformations. However, in molecular
evolution theories, the widely observed phenotype invariance, i.e. its
preservation through generations, is not matched with any genomic sequence
invariants. On the contrary, the genomic sequences are perceived to be quite
fluid, evolving rapidly and opportunistically, frequently “neutrally”. The
classical models of molecular evolution were elaborated more than 40 years ago
with an extreme paucity of data. The consequent development of molecular
evolution theory was primarily haphazard and superficial: minor ad hoc
assumptions were introduced to fit newly obtained data but the core of these
models remained unchanged. The concepts were expanded upon with more details
and assumptions, becoming cumbersome and losing the ability of making
verifiable predictions or explanations of observable phenomena. This lack of
general fundamental principles has led to the crisis of molecular evolution
theory. Current technologies supply us with an enormous amount of molecular
data, allowing a deeper look into genome functionality, and demand a more
profound understanding of genomic functionality. This work introduces a novel
paradigm into molecular evolution theory by proposing an invariant property of
the genomic sequence, which does not vary at all or only slowly from
generation to generation, while allowing the underlying sequences to change
rapidly. The introduction of the invariant leads to more a “physical” and less
opportunistic view on sequence evolution and provides testable predictions.
The well-developed apparatus of Shannon’s informational theory is used as a
mathematical framework of the model. A functional site is regarded as a
positional probabilistic pattern, where each position of the pattern is a
four-vector of nucleotide probabilities in the equilibrium population (i.e.
abstract infinite population that has evolved for an infinite time without any
disruptive events). Introducing the invariant allows us to simulate the
genetic information dynamics and to apply basic physical principles such as
the optimal efficiency and channel capacity. The model demonstrates a
fundamental possibility of error-free information storage in sequences
possessing arbitrarily low conservation. I show that the rate of beneficial
mutations can be high in general—the lower the sequence conservation the
higher the frequency of beneficial mutations. Experimental data demonstrates
the tendency of real functional sites to optimization according to the
proposed optimality criterion. The model allows a fresh look at the well-known
phenomena (e.g. it demonstrates that the “Molecular clock” and “Drake’s rule”
possibly emerge out of common underlying process). It is also able to provide
reasonable explanations for some paradoxes (e.g. “Paradox of Variation”) which
are lacking a clear interpretation in the framework of classical theories.
Therefore I believe that further development of the model will facilitate a
deeper understanding of molecular evolution and population genetics processes.Invarianten (Erhaltungssätze) dienten mathematischen und physikalischen
Theorien als grundlegende Eckpfeiler, von der Frühzeit der Wissenschaft bis in
die Neuzeit. So war beispielsweise die erste Bezeichnung für Einsteins Theorie
„Invariantentheorie“ und Klein erachtete die Geometrie in seinem „Erlanger
Programm“ als das Studium von Invarianten unter einer Transformationsgruppe.
In den Theorien der molekularen Evolution hingegen wird die vielfach
beobachtete Invarianz des Phänotyps, d. h. sein Erhalt über Generationen
hinweg, nicht mit invarianten Genomsequenzen gleichgesetzt. Im Gegenteil, die
Genomsequenzen werden als recht veränderlich betrachtet; sie entwickeln sich
schnell und opportunistisch, oftmals „neutral“. Die klassischen Modelle der
molekularen Evolution wurden vor mehr als 40 Jahren entwickelt, wobei damals
keine umfassenden Datenmengen zur Verfügung standen. Die folgende Entwicklung
der Theorie der molekularen Evolution war zunächst willkürlich und
oberflächlich: unwesentliche Ad-hoc-Annahmen wurden eingeführt, um neu
gewonnenen Daten zu entsprechen. Der Kern dieser Modelle blieb jedoch
unverändert. Die Konzepte wurden mit mehr Details und Annahmen weiter
ausgeführt, wodurch sie kompliziert wurden und die Fähigkeit verloren,
nachweisbare Vorhersagen oder Erklärungen zu beobachtbaren Phänomenen
abzugeben. Das Fehlen allgemeiner Grundprinzipien führte zur Krise der Theorie
der molekularen Evolution. Heutige Technologien versorgen uns mit einer
Unmenge an molekularen Daten, was einen tieferen Einblick in die
Funktionsweise von Genomen ermöglicht und ein tiefgehenderes Verständnis der
Funktionsweise von Genomen erfordert. Diese Arbeit führt ein neues Paradigma
in die Theorie der molekularen Evolution ein, indem eine invariante
Eigenschaft der Genomsequenz eingebracht wird, die sich nicht oder nur langsam
von Generation zu Generation ändert, während sich die Grundsequenzen schnell
ändern können. Die Einführung der Invariante führt zu einer eher
„physikalischen“ und weniger opportunistischen Sicht auf die Sequenzevolution
und liefert prüfbare Vorhersagen. Das weit entwickelte System aus Shannons
Informationstheorie wird als mathematischer Rahmen des Modells verwendet. Ein
funktioneller Ort wird als ein positionell wahrscheinliches „Pattern“
betrachtet, wo jede Position des „Patterns“ einen Vierervektor von
Nukleotidwahrscheinlichkeiten in der Gleichgewichtspopulation (d. h. abstrakte
unendliche Population, die sich über einen unbegrenzten Zeitraum ohne störende
Ereignisse entwickelt hat) darstellt. Die Einführung der Invariante ermöglicht
uns die Simulation der Geninformationsdynamiken und die Anwendung
grundlegender physikalischer Prinzipien, wie die optimale Effizienz und
Kanalkapazität. Das Modell beweist die grundsätzliche Möglichkeit einer
fehlerfreien Informationsspeicherung in Sequenzen, deren Erhaltung willkürlich
gering ist. Ich beweise, dass die Rate vorteilhafter Mutationen im Allgemeinen
hoch sein kann. Je geringer die Sequenzerhaltung, desto höher die Frequenz der
vorteilhaften Mutationen. Die Versuchsergebnisse zeigen die Tendenz wirklich
funktioneller Orte zur Optimierung, in Übereinstimmung mit dem eingebrachten
Optimalitätskriterium. Das Modell ermöglicht einen frischen Blick auf das
wohlbekannte Phänomen (es zeigt beispielsweise, dass die „Molekulare Uhr“ und
„Drake’s Rule“ möglicherweise aus einem gemeinsamen Prozess heraus entstehen).
Es kann ebenfalls sinnvolle Erklärungen für einige Paradoxa (z. B. „Paradox of
Variation“) liefern, denen es im Rahmen klassischer Theorien an einer
eindeutigen Interpretation mangelt. Daher glaube ich, dass die
Weiterentwicklung des Modells ein tieferes Verständnis der molekularen
Evolution und populationsgenetischer Prozesse vermitteln wird
Novel Bacillus-Infecting Bacteriophage B13—The Founding Member of the Proposed New Genus Bunatrivirus
No full textIn this work, we describe a novel temperate bacteriophage, Bacillus phage B13. Bacillus-infecting phages are widespread and abundant, though often overlooked including because of their temperate lifestyle. B13 was isolated from its bacterial host via mitomycin C induction. Its host range was determined, and its pH and thermal stability were evaluated. The whole genome of B13 was sequenced and annotated. The genome is 36,864 bp long and contains 53 genes. The tail genes of B13 suggest that the phage has a siphovirus morphotype. It was found both in vitro and in silico that the phage uses the 3′-cos DNA packaging strategy, and the phage genome termini were located. Comparative analyses revealed that B13 has no close relatives and should therefore be assigned to a new viral genus, for which we propose the name Bunatrivirus
Diversity of Endolysin Domain Architectures in Bacteriophages Infecting Bacilli
No full textThe increasing number of antibiotic-resistant bacterial pathogens is a serious problem in medicine. Endolysins are bacteriolytic enzymes of bacteriophages, and a promising group of enzymes with antibacterial properties. Endolysins of bacteriophages infecting Gram-positive bacteria have a modular domain organization. This feature can be used to design enzymes with new or improved properties by modifying or shuffling individual domains. This work is a detailed analysis 1of the diversity of endolysin domains found in bacteriophages infecting bacilli. During the course of the work, a database of endolysins of such bacteriophages was created, and their domain structures were analyzed using the NCBI database, RASTtk, BLASTp, HHpred, and InterPro programs. A phylogenetic analysis of endolysins was performed using MEGA X. In 438 phage genomes, 454 genes of endolysins were found. In the endolysin sequences found, eight different types of catalytic domains and seven types of cell wall binding domains were identified. The analysis showed that many types of endolysin domains have not yet been characterized experimentally. Studies of the properties of such domains will help to reveal the potential of endolysins for the creation of new antibacterial agents
Hardware/Software Solution for Low Power Evaluation of Tsunami Danger
No full textCarbon footprint reduction issues have been drawing more and more attention these days. Reducing the energy consumption is among the basic directions along this line. In the paper, a low-energy approach to tsunami danger evaluation is concerned. After several disaster tsunamis of the XXIst century, the question arises whether is it possible to evaluate in a couple of minutes the tsunami wave parameters, expected at the particular geo location. The point is that it takes around 20 min for the wave to approach the nearest coast after a seismic event offshore of Japan. Currently, the main tool for studying tsunamis is computer modeling. In particular, the expected tsunami height near the coastline, when a major underwater earthquake is detected, can be estimated by a series of numerical experiments of various scenarios of generation and the following wave propagation. Reducing the calculation time of such scenarios and the necessary energy consumption for this is the scope of this study. Moreover, in case of the major earthquake, the electric power shutdown is possible (e.g., the accident at the Fukushima nuclear power station in Japan on 11 May 2011), so the solution should be of low energy-consuming, preferably based at regular personal computers (PCs) or laptops. The way to achieve the requested performance of numerical modeling at the PC platform is a combination of efficient algorithms and their hardware acceleration. Following this strategy, a solution for the fast numerical simulation of tsunami wave propagation has been proposed. Most of tsunami researchers use the shallow-water approximation to simulate tsunami wave propagation at deep water areas. For software implementation, the MacCormack finite-difference scheme has been chosen, as it is suitable for pipelining. For hardware code acceleration, a special processor, that is, the calculator, has been designed at a field-programmable gate array (FPGA) platform. This combination was tested in terms of precision by comparison with the reference code and with the exact solutions (known for some special cases of the bottom profile). The achieved performance made it possible to calculate the wave propagation over a 1000 × 500 km water area in 1 min (the mesh size was compared to 250 m). It was nearly 300 times faster compared to that of a regular PC and 10 times faster compared to the use of a central processing unit (CPU). This result, being implemented into tsunami warning systems, will make it possible to reduce human casualties and economy losses for the so-called near-field tsunamis. The presented paper discussed the new aspect of such implementation, namely low energy consumption. The corresponding measurements for three platforms (PC and two types of FPGA) have been performed, and a comparison of the obtained results of energy consumption was given. As the numerical simulation of numerous tsunami propagation scenarios from different sources are needed for the purpose of coastal tsunami zoning, the integrated amount of the saving energy is expected to be really valuable. For the time being, tsunami researchers have not used the FPGA-based acceleration of computer code execution. Perhaps, the energy-saving aspect is able to promote the use of FPGAs in tsunami researches. The approach to designing special FPGA-based processors for the fast solution of various engineering problems using a PC could be extended to other areas, such as bioinformatics (motif search in DNA sequences and other algorithms of genome analysis and molecular dynamics) and seismic data processing (three-dimensional (3D) wave package decomposition, data compression, noise suppression, etc.)
Characteristics of the Enterococcus Phage vB_EfS_SE, and the Properties of Its Chimeric Endolysins Harboring a PlySE-Carbohydrate-Binding Domain and a Synthetic Enzymatic Domain
No full textBackground/Objectives: The World Health Organization has selected enterococci as one of the priority multidrug-resistant microorganisms for the development of new antibacterial drugs. Bacteriophages are promising antibacterial agents, but the biology of bacteriophages requires deeper understanding. Methods: The vB_EfS_SE phage which is capable of infecting four species of the genus Enterococci was isolated from sewage plant. The complete genome of the vB_EfS_SE phage was sequenced using illumina technology. The endolysin gene was cloned into pBAD18 expression vector. Two chimeric endolysins were engineered using the vB_EfS_SE carbohydrate-binding domain (CBD) and replacing its enzymatically active domain (EAD). Results: The bacteriophage exhibits promising lytic properties and persists at temperatures of 40 °C and below, and under pH conditions ranging from 5 to 11. The genome sequence is 57,904 bp in length. The vB_EfS_SE endolysin PlySE and chimeric endolysins PlyIME-SE and PlySheep-SE were found to have the same range of specificity, but different thermostability properties and a different pH range for enzyme activity. Conclusions: Taking together the results obtained in this work and other published studies, we can highly appreciate the potential of Saphexavirus phages and their endolysins as novel antibacterial compounds
Bacteriolytic Potential of Enterococcus Phage iF6 Isolated from “Sextaphag®” Therapeutic Phage Cocktail and Properties of Its Endolysins, Gp82 and Gp84
No full textThe number of infections caused by antibiotic-resistant strains of bacteria is growing by the year. The pathogenic bacterial species Enterococcus faecalis and Enterococcus faecium are among the high priority candidate targets for the development of new therapeutic antibacterial agents. One of the most promising antibacterial agents are bacteriophages. According to the WHO, two phage-based therapeutic cocktails and two medical drugs based on phage endolysins are currently undergoing clinical trials. In this paper, we describe the virulent bacteriophage iF6 and the properties of two of its endolysins. The chromosome of the iF6 phage is 156,592 bp long and contains two direct terminal repeats, each 2108 bp long. Phylogenetically, iF6 belongs to the Schiekvirus genus, whose representatives are described as phages with a high therapeutic potential. The phage demonstrated a high adsorption rate; about 90% of iF6 virions attached to the host cells within one minute after the phage was added. Two iF6 endolysins were able to lyse enterococci cultures in both logarithmic and stationary growth phases. Especially promising is the HU-Gp84 endolysin; it was active against 77% of enterococci strains tested and remained active even after 1 h incubation at 60 °C. Thus, iF6-like enterococci phages appear to be a promising platform for the selection and development of new candidates for phage therapy
Bacillus Phage vB_BtS_B83 Previously Designated as a Plasmid May Represent a New Siphoviridae Genus
No full textThe Bacillus cereus group of bacteria includes, inter alia, the species known to be associated with human diseases and food poisoning. Here, we describe the Bacillus phage vB_BtS_B83 (abbreviated as B83) infecting the species of this group. Transmission electron microscopy (TEM) micrographs indicate that B83 belongs to the Siphoviridae family. B83 is a temperate phage using an arbitrium system for the regulation of the lysis–lysogeny switch, and is probably capable of forming a circular plasmid prophage. Comparative analysis shows that it has been previously sequenced, but was mistaken for a plasmid. B83 shares common genome organization and >46% of proteins with other the Bacillus phage, BMBtp14. Phylograms constructed using large terminase subunits and a pan-genome presence–absence matrix show that these phages form a clade distinct from the closest viruses. Based on the above, we propose the creation of a new genus named Bembunaquatrovirus that includes B83 and BMBtp14
A Genomic Analysis of the Bacillus Bacteriophage Kirovirus kirovense Kirov and Its Ability to Preserve Milk
No full textBacteriophages are widely recognized as alternatives to traditional antibiotics commonly used in the treatment of bacterial infection diseases and in the food industry, as phages offer a potential solution in combating multidrug-resistant bacterial pathogens. In this study, we describe a novel bacteriophage, Kirovirus kirovense Kirov, which infects members of the Bacillus cereus group. Kirovirus kirovense Kirov is a broad-host-range phage belonging to the Caudoviricetes class. Its chromosome is a linear 165,667 bp double-stranded DNA molecule that contains two short, direct terminal repeats, each 284 bp long. According to bioinformatics predictions, the genomic DNA contains 275 protein-coding genes and 5 tRNA genes. A comparative genomic analysis suggests that Kirovirus kirovense Kirov is a novel species within the Kirovirus genus, belonging to the Andregratiavirinae subfamily. Kirovirus kirovense Kirov demonstrates the ability to preserve and decontaminate B. cereus from cow milk when present in milk at a concentration of 104 PFU/mL. After 4 h of incubation with the phage, the bacterial titer drops from 105 to less than 102 CFU/mL
Shaping Arctic’s Tomorrow through Indigenous Knowledge Engagement and Knowledge Co-Production
No full textThis perspective presents a statement of the 10th International Congress of Arctic Social Sciences Indigenous Knowledge and knowledge co-production panel and discussion group, 20 July 2021. The statement is designed to serve as a characterization of the state-of-the-art and guidance for further advancement of Indigenous Knowledge and knowledge co-production in the Arctic. It identifies existing challenges and provides specific recommendations for researchers, Indigenous communities, and funding agencies on meaningful recognition and engagement of Indigenous Knowledge systems
Synthesis of 2-((3-(ethoxycarbonyl)-4,5,6,7-tetrahydrobenzo [b] thiophen-2-yl)amino)-4-(4-methoxyphenyl)-4-oxobut-2-enoate
No full text2-((3-(Ethoxycarbonyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)amino)-4-(4-methoxyphenyl)-4-oxobut-2-enoate has been synthesized by the reaction of ethyl (E)-2-((5-(4-methoxyphenyl)-2-oxofuran-3(2H)-ylidene)amino)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate or 2-((3-(ethoxycarbonyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)amino)-4-(4-methoxyphenyl)-4-oxobut-2-enoate with potassium tert-butoxide. © 2022 Author(s).The work was done with the financial support of the Russian Foundation for Basic Research (project no. 19-43-590023)
