scholarly journals Evolution along the parasitism-mutualism continuum determines the genetic repertoire of prophages

2020 ◽  
Vol 16 (12) ◽  
pp. e1008482
Author(s):  
Amjad Khan ◽  
Alita R. Burmeister ◽  
Lindi M. Wahl

Integrated into their bacterial hosts’ genomes, prophage sequences exhibit a wide diversity of length and gene content, from highly degraded cryptic sequences to intact, functional prophages that retain a full complement of lytic-function genes. We apply three approaches—bioinformatics, analytical modelling and computational simulation—to understand the diverse gene content of prophages. In the bioinformatics work, we examine the distributions of over 50,000 annotated prophage genes identified in 1384 prophage sequences, comparing the gene repertoires of intact and incomplete prophages. These data indicate that genes involved in the replication, packaging, and release of phage particles have been preferentially lost in incomplete prophages, while tail fiber, transposase and integrase genes are significantly enriched. Consistent with these results, our mathematical and computational approaches predict that genes involved in phage lytic function are preferentially lost, resulting in shorter prophages that often retain genes that benefit the host. Informed by these models, we offer novel hypotheses for the enrichment of integrase and transposase genes in cryptic prophages. Overall, we demonstrate that functional and cryptic prophages represent a diversity of genetic sequences that evolve along a parasitism-mutualism continuum.

2020 ◽  
Author(s):  
M. E. Johnson ◽  
A. Chen ◽  
J. R. Faeder ◽  
P. Henning ◽  
I. I. Moraru ◽  
...  

ABSTRACTMost of the fascinating phenomena studied in cell biology emerge from interactions among highly organized multi-molecular structures and rapidly propagating molecular signals embedded into complex and frequently dynamic cellular morphologies. For the exploration of such systems, computational simulation has proved to be an invaluable tool, and many researchers in this field have developed sophisticated computational models for application to specific cell biological questions. However it is often difficult to reconcile conflicting computational results that use different simulation approaches (for example partial differential equations versus particle-based stochastic methods) to describe the same phenomenon. Moreover, the details of the computational implementation of any particular algorithm may give rise to quantitatively or even qualitatively different results for the same set of starting assumptions and parameters. In an effort to address this issue systematically, we have defined a series of computational test cases ranging from very simple (bimolecular binding in solution) to moderately complex (spatial and temporal oscillations generated by proteins binding to membranes) that represent building blocks for comprehensive three-dimensional models of cellular function. Having used two or more distinct computational approaches to solve each of these test cases with consistent parameter sets, we generally find modest but measurable differences in the solutions of the same problem, and a few cases where significant deviations arise. We discuss the strengths and limitations of commonly used computational approaches for exploring cell biological questions and provide a framework for decision-making by researchers wishing to develop new models for cell biology. As computational power and speed continue to increase at a remarkable rate, the dream of a fully comprehensive computational model of a living cell may be drawing closer to reality, but our analysis demonstrates that it will be crucial to evaluate the accuracy of such models critically and systematically.


Acta Naturae ◽  
2016 ◽  
Vol 8 (2) ◽  
pp. 35-46 ◽  
Author(s):  
V. N. Novoseletsky ◽  
A. D. Volyntseva ◽  
K. V. Shaitan ◽  
M. P. Kirpichnikov ◽  
A. V. Feofanov

Modeling of the structure of voltage-gated potassium (KV) channels bound to peptide blockers aims to identify the key amino acid residues dictating affinity and provide insights into the toxin-channel interface. Computational approaches open up possibilities for in silico rational design of selective blockers, new molecular tools to study the cellular distribution and functional roles of potassium channels. It is anticipated that optimized blockers will advance the development of drugs that reduce over activation of potassium channels and attenuate the associated malfunction. Starting with an overview of the recent advances in computational simulation strategies to predict the bound state orientations of peptide pore blockers relative to KV-channels, we go on to review algorithms for the analysis of intermolecular interactions, and then take a look at the results of their application.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Theresa Zwiener ◽  
Frank Mickoleit ◽  
Marina Dziuba ◽  
Christian Rückert ◽  
Tobias Busche ◽  
...  

Abstract Background Magnetosome formation in the alphaproteobacterium Magnetospirillum gryphiswaldense is controlled by more than 30 known mam and mms genes clustered within a large genomic region, the ‘magnetosome island’ (MAI), which also harbors numerous mobile genetic elements, repeats, and genetic junk. Because of the inherent genetic instability of the MAI caused by neighboring gene content, the elimination of these regions and their substitution by a compact, minimal magnetosome expression cassette would be important for future analysis and engineering. In addition, the role of the MAI boundaries and adjacent regions are still unclear, and recent studies indicated that further auxiliary determinants for magnetosome biosynthesis are encoded outside the MAI. However, techniques for large-scale genome editing of magnetic bacteria are still limited, and the full complement of genes controlling magnetosome formation has remained uncertain. Results Here we demonstrate that an allelic replacement method based on homologous recombination can be applied for large-scale genome editing in M. gryphiswaldense. By analysis of 24 deletion mutants covering about 167 kb of non-redundant genome content, we identified genes and regions inside and outside the MAI irrelevant for magnetosome biosynthesis. A contiguous stretch of ~ 100 kb, including the scattered mam and mms6 operons, could be functionally substituted by a compact and contiguous ~ 38 kb cassette comprising all essential biosynthetic gene clusters, but devoid of interspersing irrelevant or problematic gene content. Conclusions Our results further delineate the genetic complement for magnetosome biosynthesis and will be useful for future large-scale genome editing and genetic engineering of magnetosome biosynthesis.


2005 ◽  
Vol 41 ◽  
pp. 15-30 ◽  
Author(s):  
Helen C. Ardley ◽  
Philip A. Robinson

The selectivity of the ubiquitin–26 S proteasome system (UPS) for a particular substrate protein relies on the interaction between a ubiquitin-conjugating enzyme (E2, of which a cell contains relatively few) and a ubiquitin–protein ligase (E3, of which there are possibly hundreds). Post-translational modifications of the protein substrate, such as phosphorylation or hydroxylation, are often required prior to its selection. In this way, the precise spatio-temporal targeting and degradation of a given substrate can be achieved. The E3s are a large, diverse group of proteins, characterized by one of several defining motifs. These include a HECT (homologous to E6-associated protein C-terminus), RING (really interesting new gene) or U-box (a modified RING motif without the full complement of Zn2+-binding ligands) domain. Whereas HECT E3s have a direct role in catalysis during ubiquitination, RING and U-box E3s facilitate protein ubiquitination. These latter two E3 types act as adaptor-like molecules. They bring an E2 and a substrate into sufficiently close proximity to promote the substrate's ubiquitination. Although many RING-type E3s, such as MDM2 (murine double minute clone 2 oncoprotein) and c-Cbl, can apparently act alone, others are found as components of much larger multi-protein complexes, such as the anaphase-promoting complex. Taken together, these multifaceted properties and interactions enable E3s to provide a powerful, and specific, mechanism for protein clearance within all cells of eukaryotic organisms. The importance of E3s is highlighted by the number of normal cellular processes they regulate, and the number of diseases associated with their loss of function or inappropriate targeting.


1991 ◽  
Vol 88 ◽  
pp. 2731-2731
Author(s):  
EN Trifonov
Keyword(s):  

2020 ◽  
Vol 64 (1-4) ◽  
pp. 1253-1259
Author(s):  
Minghui Wang ◽  
Hongliu Yu

Clamping devices with constant force or pressure are desired in medical device, such as hemostatic forceps and the artificial sphincter, to prevent soft tissues from injures due to overloading. It is easily obtained by stretching an SMA wire. However, studies with SMA bending round bar have seldom been reported before. This paper studied constant force characteristic of C-shaped round bar with shape memory alloys. Optimization designs of the components were carried out with computational simulation. Numerical results show that the phenomenon of constant force strongly depends on contour curve shape and geometric dimensions of the C-shaped round bar of SMA component.


2019 ◽  
pp. 53-65
Author(s):  
Renata Domingos ◽  
Emeli Guarda ◽  
Elaise Gabriel ◽  
João Sanches

In the last decades, many studies have shown ample evidence that the existence of trees and vegetation around buildings can contribute to reduce the demand for energy by cooling and heating. The use of green areas in the urban environment as an effective strategy in reducing the cooling load of buildings has attracted much attention, though there is a lack of quantitative actions to apply the general idea to a specific building or location. Due to the large-scale construction of high buildings, large amounts of solar radiation are reflected and stored in the canyons of the streets. This causes higher air temperature and surface temperature in city areas compared to the rural environment and, consequently, deteriorates the urban heat island effect. The constant high temperatures lead to more air conditioning demand time, which results in a significant increase in building energy consumption. In general, the shade of the trees reduces the building energy demand for air conditioning, reducing solar radiation on the walls and roofs. The increase of urban green spaces has been extensively accepted as effective in mitigating the effects of heat island and reducing energy use in buildings. However, by influencing temperatures, especially extreme, it is likely that trees also affect human health, an important economic variable of interest. Since human behavior has a major influence on maintaining environmental quality, today's urban problems such as air and water pollution, floods, excessive noise, cause serious damage to the physical and mental health of the population. By minimizing these problems, vegetation (especially trees) is generally known to provide a range of ecosystem services such as rainwater reduction, air pollution mitigation, noise reduction, etc. This study focuses on the functions of temperature regulation, improvement of external thermal comfort and cooling energy reduction, so it aims to evaluate the influence of trees on the energy consumption of a house in the mid-western Brazil, located at latitude 15 ° S, in the center of South America. The methodology adopted was computer simulation, analyzing two scenarios that deal with issues such as the influence of vegetation and tree shade on the energy consumption of a building. In this way, the methodological procedures were divided into three stages: climatic contextualization of the study region; definition of a basic dwelling, of the thermophysical properties; computational simulation for quantification of energy consumption for the four facade orientations. The results show that the façades orientated to north, east and south, without the insertion of arboreal shading, obtained higher values of annual energy consumption. With the adoption of shading, the facades obtained a consumption reduction of around 7,4%. It is concluded that shading vegetation can bring significant climatic contribution to the interior of built environments and, consequently, reduction in energy consumption, promoting improvements in the thermal comfort conditions of users.


Tick-borne encephalitis virus (TBEV) exists in natural foci, which are areas where TBEV is circulating among its vectors (ticks of different species and genera) and reservoir hosts (usually rodents and small mammals). Based on phylogenetic studies, four TBEV subtypes (Far-Eastern, Siberian, European, Baikalian) and two putative subtypes (Himalayan and “178-79” group) are known. Within each subtype, some genetic lineages are described. The European subtype (TBEV-EU) (formerly known also as the “Western subtype”) of TBEV is prevalent in Europe, but it was also isolated in Western and Eastern Siberia in Russia and South Korea. The Far-Eastern subtype (TBEV-FE) was preferably found in the territory of the far-eastern part of Eurasia, but some strains were isolated in other regions of Eurasia. The Siberian (TBEV-SIB) subtype is the most common and has been found in almost all TBEV habitat areas. The Baikalian subtype is prevalent around Lake Baikal and was isolated several times from ticks and rodents. In addition to the four TBEV subtypes, one single isolate of TBEV (178-79) and two genetic sequences (Himalayan) supposed to be new TBEV subtypes were described in Eastern Siberia and China. The data on TBEV seroprevalence in humans and animals can serve as an indication for the presence or absence of TBEV in studied area.


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