scholarly journals Extensive C->U transition biases in the genomes of a wide range of mammalian RNA viruses; potential associations with transcriptional mutations, damage- or host-mediated editing of viral RNA

2021 ◽  
Vol 17 (6) ◽  
pp. e1009596
Author(s):  
Peter Simmonds ◽  
M. Azim Ansari
Keyword(s):  
Rna Structure ◽  
Rna Viruses ◽  
Multivariable Analysis ◽  
Rapid Evolution ◽  
Structural Parameter ◽  
Coding Region ◽  
Association Index ◽  
Diverse Range ◽  
Wide Range ◽  
Genome Scale

The rapid evolution of RNA viruses has been long considered to result from a combination of high copying error frequencies during RNA replication, short generation times and the consequent extensive fixation of neutral or adaptive changes over short periods. While both the identities and sites of mutations are typically modelled as being random, recent investigations of sequence diversity of SARS coronavirus 2 (SARS-CoV-2) have identified a preponderance of C->U transitions, proposed to be driven by an APOBEC-like RNA editing process. The current study investigated whether this phenomenon could be observed in datasets of other RNA viruses. Using a 5% divergence filter to infer directionality, 18 from 36 datasets of aligned coding region sequences from a diverse range of mammalian RNA viruses (including Picornaviridae, Flaviviridae, Matonaviridae, Caliciviridae and Coronaviridae) showed a >2-fold base composition normalised excess of C->U transitions compared to U->C (range 2.1x–7.5x), with a consistently observed favoured 5’ U upstream context. The presence of genome scale RNA secondary structure (GORS) was the only other genomic or structural parameter significantly associated with C->U/U->C transition asymmetries by multivariable analysis (ANOVA), potentially reflecting RNA structure dependence of sites targeted for C->U mutations. Using the association index metric, C->U changes were specifically over-represented at phylogenetically uninformative sites, potentially paralleling extensive homoplasy of this transition reported in SARS-CoV-2. Although mechanisms remain to be functionally characterised, excess C->U substitutions accounted for 11–14% of standing sequence variability of structured viruses and may therefore represent a potent driver of their sequence diversification and longer-term evolution.

scholarly journals Mutation bias implicates RNA editing in a wide range of mammalian RNA viruses

2021 ◽  
Author(s):  
Peter Simmonds ◽  
M. Azim Ansari
Keyword(s):  
Rna Editing ◽  
Rna Viruses ◽  
Rna Virus ◽  
Structural Parameters ◽  
Rapid Evolution ◽  
Sequence Variability ◽  
Diverse Range ◽  
Mouth Disease Virus ◽  
Wide Range ◽  
Virus Sequence

ABSTRACTThe rapid evolution of RNA viruses has been long considered to result from a combination of high copying error frequencies during RNA replication, short generation times and the consequent extensive fixation of neutral or adaptive changes over short periods. While both the identities and sites of mutations are typically modelled as being random, recent investigations of sequence diversity of SARS coronavirus 2 (SARS-CoV-2) have identified a preponderance of C->U transitions, potentially driven by an APOBEC-like RNA editing process. The current study investigated whether this phenomenon could be observed in the more genetically diverse datasets of other RNA viruses. Using a 5% divergence filter to infer directionality, 18 from 32 datasets of aligned coding region sequences from a diverse range of mammalian RNA viruses (including Picornaviridae, Flaviviridae, Matonaviridae, Caliciviridae and Coronaviridae) showed a >2-fold base composition normalised excess of C->U transitions compared to U->C (range 2.1x–7.5x). C->U transitions showed a favoured 5’ U upstream context consistent with previous analyses of APOBEC-mediated RNA targeting. Amongst several genomic compositional and structural parameters, the presence of genome scale RNA secondary structure (GORS) was associated with C->U/U->C transition asymmetries (p < 0.001), potentially reflecting the documented structure dependence of APOBEC-mediated RNA editing. Using the association index metric, C->U changes were specifically over-represented at phylogenetically uninformative sites, consistent with extensive homoplasy documented in SARS-CoV-2. Excess C->U substitutions accounted for 15-20% of standing sequence variability of HCV and other RNA viruses; RNA editing may therefore represent a potent driver of RNA virus sequence diversification and longer term evolution.Author SummaryThe rapid evolution of RNA viruses is thought to arise from high mutation frequencies during replication and the rapid accumulation of genetic changes over time in response to its changing environments. This study describes an additional potent factor that contributes to the evolution of RNA infecting mammals, the deliberate mutation of the viral genome by host antiviral pathways active within the cell when it becomes infected. This so called “genome editing” by one or more APOBEC enzymes leads to characteristic C->U mutations that damage the virus’s ability to replicate. While this pathway is well characterised as an antiviral defence against HIV and other retroviruses, this study provides evidence for its activity against a wide range of human and veterinary viruses, including HCV and foot and mouth disease virus. APOBEC-driven mutations accounted for 15-20% of standing sequence variability of RNA virus groups, representing a potent driver of RNA virus sequence diversification.

scholarly journals Bioinformatic and Physical Characterizations of Genome-Scale Ordered RNA Structure in Mammalian RNA Viruses

2008 ◽  
Vol 82 (23) ◽  
pp. 11824-11836 ◽  
Author(s):  
Matthew Davis ◽  
Selena M. Sagan ◽  
John P. Pezacki ◽  
David J. Evans ◽  
Peter Simmonds
Keyword(s):  
Secondary Structure ◽  
Rna Structure ◽  
Rna Secondary Structure ◽  
Large Scale ◽  
Rna Viruses ◽  
Plant Viruses ◽  
Large Set ◽  
Conserved Sequence ◽  
Evolutionarily Conserved ◽  
Genome Scale

ABSTRACT By the analysis of thermodynamic RNA secondary structure predictions, we previously obtained evidence for evolutionarily conserved large-scale ordering of RNA virus genomes (P. Simmonds, A. Tuplin, and D. J. Evans, RNA 10:1337-1351, 2004). Genome-scale ordered RNA structure (GORS) was widely distributed in many animal and plant viruses, much greater in extent than RNA structures required for viral translation or replication, but in mammalian viruses was associated with host persistence. To substantiate the existence of large-scale RNA structure differences between viruses, a large set of alignments of mammalian RNA viruses and rRNA sequences as controls were examined by thermodynamic methods (to calculate minimum free energy differences) and by algorithmically independent RNAz and Pfold methods. These methods produced generally concordant results and identified substantial differences in the degrees of evolutionarily conserved, sequence order-dependent RNA secondary structure between virus genera and groups. A probe hybridization accessibility assay was used to investigate the physical nature of GORS. Transcripts of hepatitis C virus (HCV), hepatitis G virus/GB virus-C (HGV/GBV-C), and murine norovirus, which are predicted to be structured, were largely inaccessible to hybridization in solution, in contrast to the almost universal binding of probes to a range of unstructured virus transcripts irrespective of G+C content. Using atomic force microscopy, HCV and HGV/GBV-C RNA was visualized as tightly compacted prolate spheroids, while under the same experimental conditions the predicted unstructured poliovirus and rubella virus RNA were pleomorphic and had extensively single-stranded RNA on deposition. Bioinformatic and physical characterization methods both identified fundamental differences in the configurations of viral genomic RNA that may modify their interactions with host cell defenses and their ability to persist.

scholarly journals Negative-sense RNA viruses: An underexplored platform for examining virus–host lipid interactions

2021 ◽  
Vol 32 (20) ◽  
pp. pe1
Author(s):  
Monica L. Husby ◽  
Robert V. Stahelin
Keyword(s):  
Host Cell ◽  
Rna Viruses ◽  
Life Cycles ◽  
Diverse Range ◽  
Membrane Biology ◽  
Wide Range ◽  
Range Of Functions ◽  
Pathogenic Viruses ◽  
Pathogenic Agents ◽  
Negative Sense

Viruses are pathogenic agents that can infect all varieties of organisms, including plants, animals, and humans. These microscopic particles are genetically simple as they encode a limited number of proteins that undertake a wide range of functions. While structurally distinct, viruses often share common characteristics that have evolved to aid in their infectious life cycles. A commonly underappreciated characteristic of many deadly viruses is a lipid envelope that surrounds their protein and genetic contents. Notably, the lipid envelope is formed from the host cell the virus infects. Lipid-enveloped viruses comprise a diverse range of pathogenic viruses, which often lead to high fatality rates and many lack effective therapeutics and/or vaccines. This perspective primarily focuses on the negative-sense RNA viruses from the order Mononegavirales, which obtain their lipid envelope from the host plasma membrane. Specifically, the perspective highlights the common themes of host cell lipid and membrane biology necessary for virus replication, assembly, and budding.

Early Generation Pipeline Girth Welding Practices and Their Implications for Integrity Management of North American Pipelines

2010 ◽  
Author(s):  
Bill Amend
Keyword(s):  
Brittle Fracture ◽  
Rapid Evolution ◽  
Charpy Impact ◽  
Mechanical Tests ◽  
Impact Testing ◽  
Early Generation ◽  
Diverse Range ◽  
Integrity Assessment ◽  
Wide Range ◽  
Girth Welds

The characteristics of early generation pipelines (i.e., “vintage pipelines”) reflect the rapid evolution of pipeline materials, welding, and inspection practices that occurred during the first half of the twentieth century. The diverse range of welding and inspection practices and the unique characteristics of early generation pipeline welds can influence pipeline segment risk ranking and integrity assessment. This paper summarizes some of the key findings regarding girth weld fabrication, performance and integrity assessment determined during the course of a literature review performed as part of a recently completed PRCI project. Some of the key findings include: 1. The failure rate of early generation girth welds is low, particularly for welds made by arc welding and for welds made after 1930. This is especially true when considering the rate of catastrophic failures (ruptures or nearly full circumference breaks). Welds are typically reported to be responsible for no more than about 6% of significant pipeline failures. 2. Pipeline girth welds are unlikely to fail unless subjected to axial strains that far exceed the strains related to internal pressure alone. Girth welds containing significant workmanship flaws are likely to be resistant to failure at stresses less than the pipe yield strength unless the welds are undermatched and/or are susceptible to brittle fracture initiation. Common mechanical tests, such as Charpy impact testing or CTOD tests may result in grossly conservative indications of the likelihood of brittle fracture occurring in vintage girth welds. 3. A diverse range of early generation girth weld joint designs exist, some of which hamper effective inspection using ILI or represent challenges to effective assessment using conventional fitness-for-service or engineering critical assessment methods (ECA). Effective probabilistic ECA is further hampered by wide variations in workmanship and difficulty in determining mechanical property distributions. 4. Pipeline vintage is a poor indicator of girth weld integrity. Pipeline girth weld integrity is more likely related to project-specific inspection and testing practices than to pipeline age. Welding and inspection practices evolved very quickly in the 1920s through the 1940s and a wide range of practices were used on different pipelines that were constructed in the same time period. Girth weld integrity is typically highest for post 1930s pipelines that were subjected to radiographic inspection.

Nine Centuries of Man

2017 ◽  
Keyword(s):  
Twentieth Century ◽  
Diverse Range ◽  
Gender Expectations ◽  
Court Records ◽  
The Past ◽  
Wide Range ◽  
Police Reports ◽  
Late Twentieth ◽  
Scottish History ◽  
Late Twentieth Century

What did it mean to be a man in Scotland over the past nine centuries? Scotland, with its stereotypes of the kilted warrior and the industrial ‘hard man’, has long been characterised in masculine terms, but there has been little historical exploration of masculinity in a wider context. This interdisciplinary collection examines a diverse range of the multiple and changing forms of masculinities from the late eleventh to the late twentieth century, exploring the ways in which Scottish society through the ages defined expectations for men and their behaviour. How men reacted to those expectations is examined through sources such as documentary materials, medieval seals, romances, poetry, begging letters, police reports and court records, charity records, oral histories and personal correspondence. Focusing upon the wide range of activities and roles undertaken by men – work, fatherhood and play, violence and war, sex and commerce – the book also illustrates the range of masculinities that affected or were internalised by men. Together, the chapters illustrate some of the ways Scotland’s gender expectations have changed over the centuries and how, more generally, masculinities have informed the path of Scottish history

Diversity and Integration in Private International Law

2019 ◽  
Keyword(s):  
South America ◽  
International Law ◽  
Value Systems ◽  
Private International Law ◽  
Diverse Range ◽  
Cross Border ◽  
Wide Range ◽  
Depth Analysis ◽  
And Shifts ◽  
Substantive Law

This book opens a cross-regional dialogue and shifts the Eurocentric discussion on diversity and integration to a more inclusive engagement with South America in private international law issues. It promotes a contemporary vision of private international law as a discipline enabling legal interconnectivity, with the potential to transcend its disciplinary boundaries to further promote the reality of cross-border integration, with its focus on the ever-increasing cross-border mobility of individuals. Private international law embraces legal diversity and pluralism. Different legal traditions continue to meet, interact and integrate in different forms, at the national, regional and international levels. Different systems of substantive law couple with divergent systems of private international law (designed to accommodate the former in cross-border situations). This complex legal landscape impacts individuals and families in cross-border scenarios, and international commerce broadly conceived. Private international law methodologies and techniques offer means for the coordination of this constellation of legal orders and value systems in cross-border situations. Bringing together world-renowned academics and experienced private international lawyers from a wide range of jurisdictions in Europe and South America, this edited collection focuses on the connective capabilities of private international law in bridging and balancing legal diversity as a corollary for the development of integration. The book provides in-depth analysis of the role of private international law in dealing with legal diversity across a diverse range of topics and jurisdictions.

Cultural Accommodation of Internet-Based Interventions for Substance Use and Related Disorders: A Proposed Comprehensive Framework (Preprint)

2019 ◽  
Author(s):  
Keren Gueta ◽  
Yossi Harel-Fisch ◽  
Sophie D. Walsh
Keyword(s):  
Substance Use ◽  
Ecological Validity ◽  
Limited Attention ◽  
Diverse Range ◽  
Four Dimensions ◽  
Service Engagement ◽  
Wide Range ◽  
Cultural Accommodation ◽  
Abuse Treatment ◽  
Comprehensive Framework

BACKGROUND Despite the low utilization rates of substance use and related disorders services, and the ability of internet-based interventions for substance use and related disorders (IBIS) to address challenges related to service engagement, limited attention has been placed on the processes for the accommodation of these interventions to diverse cultural settings. OBJECTIVE The purpose of this study was to develop a conceptual framework for the cultural accommodation of IBIS across populations, settings, and countries. METHODS A pilot study of cultural accommodation of an existing internet intervention for alcohol use (Down Your Drink (DYD)), focus groups and daily online surveys of prospective consumers (N=24) and interviews with experts (N=7) in the substance abuse treatment field were conducted. RESULTS Thematic analysis revealed a wide range of themes identified as needing to be addressed in the process of DYD accommodation. It also emphasized that accommodation needs to incorporate both technical and contents themes, shaped by both the general Israeli cultural as well as by the specific Israeli drinking subculture. A combined mixed emic–etic theoretical approach incorporating the pilot findings together with a scoping literature review was employed to develop a framework for cultural accommodation of IBIS. A comprehensive framework for cultural accommodation of IBIS is introduced consisting of five chronological stages of IBIS accommodation and four dimensions of accommodation. CONCLUSIONS The proposed framework can serve as a guide for the cultural accommodation of existing IBIS across a diverse range of cultural and geographical settings thus augmenting the ecological validity of IBIS and reducing health disparities worldwide.

scholarly journals A Slot-Die Technique for the Preparation of Continuous, High-Area, Chitosan-Based Thin Films

Polymers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1566
Author(s):  
Oliver J. Pemble ◽  
Maria Bardosova ◽  
Ian M. Povey ◽  
Martyn E. Pemble
Keyword(s):  
Thin Films ◽  
Mechanical Properties ◽  
High Volume ◽  
Mechanical Anisotropy ◽  
Diverse Range ◽  
Direction Parallel ◽  
High Area ◽  
Wide Range ◽  
Slot Die ◽  
Potential Applications

Chitosan-based films have a diverse range of potential applications but are currently limited in terms of commercial use due to a lack of methods specifically designed to produce thin films in high volumes. To address this limitation directly, hydrogels prepared from chitosan, chitosan-tetraethoxy silane, also known as tetraethyl orthosilicate (TEOS) and chitosan-glutaraldehyde have been used to prepare continuous thin films using a slot-die technique which is described in detail. By way of preliminary analysis of the resulting films for comparison purposes with films made by other methods, the mechanical strength of the films produced was assessed. It was found that as expected, the hybrid films made with TEOS and glutaraldehyde both show a higher yield strength than the films made with chitosan alone. In all cases, the mechanical properties of the films were found to compare very favorably with similar measurements reported in the literature. In order to assess the possible influence of the direction in which the hydrogel passes through the slot-die on the mechanical properties of the films, testing was performed on plain chitosan samples cut in a direction parallel to the direction of travel and perpendicular to this direction. It was found that there was no evidence of any mechanical anisotropy induced by the slot die process. The examples presented here serve to illustrate how the slot-die approach may be used to create high-volume, high-area chitosan-based films cheaply and rapidly. It is suggested that an approach of the type described here may facilitate the use of chitosan-based films for a wide range of important applications.

scholarly journals Assessing evidence for adaptive evolution in two hearing-related genes important for high-frequency hearing in echolocating mammals

2021 ◽  
Author(s):  
Hui Wang ◽  
Hanbo Zhao ◽  
Yujia Chu ◽  
Jiang Feng ◽  
Keping Sun
Keyword(s):  
Adaptive Evolution ◽  
Hair Cells ◽  
High Frequency ◽  
Phylogenetic Trees ◽  
Outer Hair Cells ◽  
Functional Domain ◽  
Coding Region ◽  
Selective Pressures ◽  
Wide Range ◽  
Different Parts

Abstract High-frequency hearing is particularly important for echolocating bats and toothed whales. Previously, studies of the hearing-related genes Prestin, KCNQ4, and TMC1 documented that adaptive evolution of high-frequency hearing has taken place in echolocating bats and toothed whales. In this study, we present two additional candidate hearing-related genes, Shh and SK2, that may also have contributed to the evolution of echolocation in mammals. Shh is a member of the vertebrate Hedgehog gene family and is required in the specification of the mammalian cochlea. SK2 is expressed in both inner and outer hair cells, and it plays an important role in the auditory system. The coding region sequences of Shh and SK2 were obtained from a wide range of mammals with and without echolocating ability. The topologies of phylogenetic trees constructed using Shh and SK2 were different; however, multiple molecular evolutionary analyses showed that those two genes experienced different selective pressures in echolocating bats and toothed whales compared to non-echolocating mammals. In addition, several nominally significant positively selected sites were detected in the non-functional domain of the SK2 gene, indicating that different selective pressures were acting on different parts of the SK2 gene. This study has expanded our knowledge of the adaptive evolution of high-frequency hearing in echolocating mammals.

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