scholarly journals Unravelling the virome in birch: RNA-Seq reveals a complex of known and novel viruses

2019 ◽  
Author(s):  
Artemis Rumbou ◽  
Thierry Candresse ◽  
Armelle Marais ◽  
Laurence Svanella-Dumas ◽  
Maria Landgraf ◽  
...  
Keyword(s):  
High Throughput Sequencing ◽  
De Novo ◽  
Leaf Roll ◽  
Viral Population ◽  
Comprehensive Overview ◽  
Dna And Rna ◽  
Birch Trees ◽  
Viral Communities ◽  
The Impact

AbstractHigh-throughput sequencing (HTS), combined with bioinformatics for de novo discovery and assembly of plant virus or viroid genome reads, has promoted the discovery of abundant novel DNA and RNA viruses and viroids. However, the elucidation of a viral population in a single plant is rarely reported. In five birch trees of German and Finnish origin exhibiting symptoms of birch leaf-roll disease (BRLD), we identified in total five viruses, among which three are novel. The number of identified virus variants in each transcriptome ranged from one to five. The novel species are genetically - fully or partially - characterized, they belong to the genera Carlavirus, Idaeovirus and Capillovirus and they are tentatively named birch carlavirus, birch idaeovirus, and birch capillovirus, respectively. The only virus systematically detected by HTS in symptomatic trees affected by the BRLD was the recently discovered birch leafroll-associated virus. The role of the new carlavirus in BLRD etiology seems at best weak, as it was detected only in one of three symptomatic trees. Continuing studies have to clarify the impact of the carlavirus to the BLRD. The role of the Capillovirus and the Idaeovirus within the BLRD complex and whether they influence plant vitality need to be investigated. Our study reveals the viral population in single birch trees and provides a comprehensive overview for the diversities of the viral communities they harbor.

scholarly journals Contribution of retrotransposition to developmental disorders

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Eugene J. Gardner ◽  
Elena Prigmore ◽  
Giuseppe Gallone ◽  
Petr Danecek ◽  
Kaitlin E. Samocha ◽  
...  
Keyword(s):  
Developmental Disorders ◽  
De Novo ◽  
Purifying Selection ◽  
Selective Constraint ◽  
Protein Coding ◽  
Genome Wide ◽  
De Novo Gene ◽  
The Impact ◽  
Transcribed Sequences

Abstract Mobile genetic Elements (MEs) are segments of DNA which can copy themselves and other transcribed sequences through the process of retrotransposition (RT). In humans several disorders have been attributed to RT, but the role of RT in severe developmental disorders (DD) has not yet been explored. Here we identify RT-derived events in 9738 exome sequenced trios with DD-affected probands. We ascertain 9 de novo MEs, 4 of which are likely causative of the patient’s symptoms (0.04%), as well as 2 de novo gene retroduplications. Beyond identifying likely diagnostic RT events, we estimate genome-wide germline ME mutation rate and selective constraint and demonstrate that coding RT events have signatures of purifying selection equivalent to those of truncating mutations. Overall, our analysis represents a comprehensive interrogation of the impact of retrotransposition on protein coding genes and a framework for future evolutionary and disease studies.

scholarly journals Assessing Genome-Wide Diversity in European Hantaviruses through Sequence Capture from Natural Host Samples

Viruses ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 749 ◽  
Author(s):  
Melanie Hiltbrunner ◽  
Gerald Heckel
Keyword(s):  
High Throughput Sequencing ◽  
De Novo ◽  
Phylogenetic Analyses ◽  
Common Vole ◽  
Natural Host ◽  
Sequence Information ◽  
Coding Region ◽  
Sequence Capture ◽  
Genome Wide ◽  
The Impact

Research on the ecology and evolution of viruses is often hampered by the limitation of sequence information to short parts of the genomes or single genomes derived from cultures. In this study, we use hybrid sequence capture enrichment in combination with high-throughput sequencing to provide efficient access to full genomes of European hantaviruses from rodent samples obtained in the field. We applied this methodology to Tula (TULV) and Puumala (PUUV) orthohantaviruses for which analyses from natural host samples are typically restricted to partial sequences of their tri-segmented RNA genome. We assembled a total of ten novel hantavirus genomes de novo with very high coverage (on average >99%) and sequencing depth (average >247×). A comparison with partial Sanger sequences indicated an accuracy of >99.9% for the assemblies. An analysis of two common vole (Microtus arvalis) samples infected with two TULV strains each allowed for the de novo assembly of all four TULV genomes. Combining the novel sequences with all available TULV and PUUV genomes revealed very similar patterns of sequence diversity along the genomes, except for remarkably higher diversity in the non-coding region of the S-segment in PUUV. The genomic distribution of polymorphisms in the coding sequence was similar between the species, but differed between the segments with the highest sequence divergence of 0.274 for the M-segment, 0.265 for the S-segment, and 0.248 for the L-segment (overall 0.258). Phylogenetic analyses showed the clustering of genome sequences consistent with their geographic distribution within each species. Genome-wide data yielded extremely high node support values, despite the impact of strong mutational saturation that is expected for hantavirus sequences obtained over large spatial distances. We conclude that genome sequencing based on capture enrichment protocols provides an efficient means for ecological and evolutionary investigations of hantaviruses at an unprecedented completeness and depth.

Responsibility in the Supply Chain

2009 ◽  
Author(s):  
Andrew Millington
Keyword(s):  
Supply Chain ◽  
Environmental Issues ◽  
Comprehensive Overview ◽  
Legal Obligations ◽  
Stakeholder Pressure ◽  
The Subject ◽  
Social And Environmental Performance ◽  
Corporate Social ◽  
The Impact

This article provides a comprehensive overview of one of the main areas where corporate social responsibility issues have impacted upon firms across the globe, namely the supply chain. Although the legal obligations for social and environmental issues are increasingly devolved to suppliers, the role of lead firms in the development of ethical supply chain management (ESCM) has been the subject of considerable debate. This article focuses on two questions which are central to the development of ESCM. First, it looks at stakeholder pressure for ESCM and its implications for the involvement of lead firms in ESCM. Second, it considers the conditions under which lead firms will be able to influence suppliers and implement ESCM. It then reviews the impact of ESCM on social and environmental performance. Finally, it outlines the implications for the development of effective ESCM.

The Oxford Handbook of Hope

2017 ◽  
Keyword(s):  
Current Knowledge ◽  
Physical And Mental Health ◽  
Comprehensive Overview ◽  
Future Directions ◽  
Theoretical Perspectives ◽  
The Many ◽  
The Impact ◽  
Made In

The Oxford Handbook of Hope provides a comprehensive overview of current knowledge regarding the science and practice of hope. Hope has long been a topic of interest to philosophers and the general public, but it was only in recent decades that hope became a focus of psychological science. Rick Snyder defined hope as a cognitive trait that helps individuals to identify and pursue goals and consists of two components: pathways, the perceived capacity to identify strategies necessary to achieve goals, and agency, the willpower or motivation to pursue those pathways to achieve goals. Hope has become one of most robust and promising topics in the burgeoning field of positive psychology. This book reviews the progress that has been made in the past 25 years regarding the origins and influence of hope. Topics covered include current theoretical perspectives on how best to define hope and how it is distinct from related constructs, current best practices for measuring and quantifying hope, interventions and strategies for promoting hope across different settings and the lifespan, the impact that hope has on many dimensions and domains of physical and mental health, and the many ways and contexts in which hope promotes resilience and positive functioning. Experts in the field both review what is currently known about the role of hope in different domains and identify topics and questions that can help to guide the next decade of research. The handbook concludes with a collaborative vision on the future directions of the science of hope.

scholarly journals Maternal mosaicism for a missense variant in the SMS gene that causes Snyder-Robinson syndrome

2021 ◽  
pp. mcs.a006122
Author(s):  
Mohammad Marhabaie ◽  
Scott E Hickey ◽  
Katherine E Miller ◽  
Olivia Grischow ◽  
Kathleen M Schieffer ◽  
...  
Keyword(s):  
High Throughput Sequencing ◽  
De Novo ◽  
Genetic Disorders ◽  
Missense Variant ◽  
Hyperinsulinemic Hypoglycemia ◽  
Spermine Synthase ◽  
Genetic Mosaicism ◽  
The Family ◽  
Bilateral Sensorineural Hearing Loss

There is increasing recognition for the contribution of genetic mosaicism to human disease, particularly as high-throughput sequencing has enabled detection of sequence variants at very low allele frequencies. Here, we describe an infant male who presented at 9 months of age with hypotonia, dysmorphic features, congenital heart disease, hyperinsulinemic hypoglycemia, hypothyroidism, and bilateral sensorineural hearing loss. Whole-genome sequencing of the proband and the parents uncovered an apparent de novo mutation in the X-linked SMS gene. SMS encodes spermine synthase, which catalyzes the production of spermine from spermidine. Inactivation of the SMS gene disrupts the spermidine/spermine ratio, resulting in Snyder-Robinson syndrome. The variant in our patient is absent from the gnomAD and ExAC databases and causes a missense change (p.Arg130Cys) predicted to be damaging by most in silico tools. While Sanger sequencing confirmed the de novo status in our proband, PCR and deep targeted resequencing to ~84,000-175,000x depth revealed that the variant is present in blood from the unaffected mother at ~3% variant allele frequency. Our findings thus provided a long-sought diagnosis for the family while highlighting the role of parental mosaicism in severe genetic disorders.

scholarly journals Human Cytomegalovirus Genome Diversity in Longitudinally Collected Breast Milk Samples

2021 ◽  
Vol 11 ◽  
Author(s):  
Jasper Götting ◽  
Katrin Lazar ◽  
Nicolás M. Suárez ◽  
Lars Steinbrück ◽  
Tabea Rabe ◽  
...  
Keyword(s):  
Breast Milk ◽  
Human Cytomegalovirus ◽  
High Throughput Sequencing ◽  
De Novo ◽  
Severe Disease ◽  
Viral Population ◽  
Preterm Neonates ◽  
Genotype Distribution ◽  
Milk Samples ◽  
Wide Range

Reactivation and shedding of human cytomegalovirus (HCMV) in breast milk during lactation is highly frequent in HCMV-seropositive mothers. This represents a key transmission route for postnatal HCMV infection and can lead to severe disease in preterm neonates. Little is known about HCMV strain composition or longitudinal intrahost viral population dynamics in breast milk from immunocompetent women. We performed HCMV-specific target enrichment and high-throughput sequencing of 38 breast milk samples obtained in Germany between days 10 and 60 postpartum from 15 mothers with HCMV DNA lactia, and assembled HCMV consensus sequences de novo. The genotype distribution and number of HCMV strains present in each sample were determined by quantifying genotype-specific sequence motifs in 12 hypervariable viral genes, revealing a wide range of genotypes (82/109) for these genes in the cohort and a unique, longitudinally stable strain composition in each mother. Reactivation of up to three distinct HCMV strains was detected in 8/15 of mothers, indicating that a representative subset of the woman’s HCMV reservoir might be locally reactivated early during lactation. As described previously, nucleotide diversity of samples with multiple strains was much higher than that of samples with single strains. Breast milk as a main source of postnatal mother-to-infant transmission may serve as a repository for viral diversity and thus play an essential role in the natural epidemiology of HCMV.

A Complex Scenario and Underestimated Challenge: The Tumor Microenvironment, ER Stress, and Cancer Treatment

2018 ◽  
Vol 25 (21) ◽  
pp. 2465-2502 ◽  
Author(s):  
Oleg I. Chen ◽  
Yaroslav P. Bobak ◽  
Oleh V. Stasyk ◽  
Leoni A. Kunz-Schughart
Keyword(s):  
Er Stress ◽  
Stress Responses ◽  
Tumor Hypoxia ◽  
Cancer Treatments ◽  
Comprehensive Overview ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Complex Scenario ◽  
The Impact

The paradoxical role of ER stress in malignant diseases is only just being unraveled and remains incompletely understood. A particular challenge is the complex interplay between spaciotemporal and locoregional microenvironmental constraints in solid tumors and stress responses upon treatment; thus, the potential for new combinatorial therapeutic options to foster the coincidence of ER stress-related deadly events is likely to be underestimated. Without claiming this review to be complete, we present a comprehensive overview of the signaling mechanisms associated with the unfolded protein response (UPR) and the molecular link to cell survival and death mechanisms. We (i) delineate the mechanistic scenario and outcome of the UPR; (ii) discuss the role of ER stress in cancer development and progression; (iii) highlight the impact of various environmental conditions and stress stimuli, such as nutrient limitation and tumor hypoxia, in this context; and (iv) attempt to shed some light on the putative link between DNA damage, irradiation, and ER stress to emphasize the potential of therapeutic targeting of ER stress pathways for combined cancer treatments.

Impact of fire on vegetation, soil microbes and CH4 emission from a degraded tropical peatland

2020 ◽  
Author(s):  
Hasan Akhtar ◽  
Massimo Lupascu ◽  
Omkar S. Kulkarni ◽  
Aditya Bandla ◽  
Rahayu S. Sukri ◽  
...  
Keyword(s):  
Southeast Asia ◽  
Water Table ◽  
Vegetation Structure ◽  
High Throughput Sequencing ◽  
Microbial Community Composition ◽  
Tropical Peatland ◽  
Tropical Peatlands ◽  
Peat Profile ◽  
The Impact

<p>Over the past few decades, tropical peatlands in Southeast Asia have been heavily degraded for multiple land uses, mainly by employing drainage and fire. More importantly, the extent of these degraded areas, primarily covered with ferns and sedges, have increased to almost 10% of the total peatland area in Southeast Asia. In particular, the role of sedges in plant-mediated gas transport to the atmosphere has been recognized as a significant CH<sub>4</sub> pathway in northern peatlands, however, in the Tropics this is still unknown. Within this context, we adopted an integrated approach using on-site measurements (CH<sub>4</sub>, porewater physicochemical characteristics) with genomics to investigate the role of hydrology, vegetation structure, and microbiome on CH<sub>4</sub> emission from fire-degraded tropical peatland in Brunei.</p><p>          We found for the first time that in degraded tropical peatlands of Southeast Asia, sedges transported 70-80% of the total CH<sub>4</sub> emission and significantly varied with values ranging from 1.22±0.13 to 6.15±0.57 mg CH<sub>4</sub> m<sup>-2</sup> hr<sup>-1</sup>, during dry and wet period, respectively. This variation was mainly attributed to water table position along with changes in sedge cover and porewater properties, which created more optimal methanogenesis conditions. Total emissions via this process might increase in the future as the extent of degraded tropical peatlands expands due to more frequent fire episodes and flooding.</p><p>          Further, we used 16S rRNA high-throughput sequencing to investigate the microbiomes in peat profile (above and below water table) as well as rhizo-compartments (Rhizosphere, Rhizoplane, Endosphere) of sedges. We found that the peat profile as well as rhizo-compartments of sedge harboured a higher number of methanogenic archaea in the order Methanomicrobiales and Methanobacteriales, compared to non-burnt and bulk soil, which further explains our findings of higher CH<sub>4</sub> emission from degraded tropical peatland areas covered with sedges. These insights into the impact of fire on hydrology, vegetation structure, and microbial community composition on CH<sub>4</sub> emissions provide an important basis for future studies on CH<sub>4</sub> dynamics in degraded tropical peatland areas.</p>

scholarly journals Evolutionary dynamics and structural consequences of de novo beneficial mutations and mutant lineages arising in a constant environment

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Margie Kinnersley ◽  
Katja Schwartz ◽  
Dong-Dong Yang ◽  
Gavin Sherlock ◽  
Frank Rosenzweig
Keyword(s):  
High Frequency ◽  
High Throughput Sequencing ◽  
Evolutionary Dynamics ◽  
De Novo ◽  
Allelic Diversity ◽  
Microbial Evolution ◽  
De Novo Mutations ◽  
Beneficial Mutations ◽  
Adaptive Mutations ◽  
The Impact

Abstract Background Microbial evolution experiments can be used to study the tempo and dynamics of evolutionary change in asexual populations, founded from single clones and growing into large populations with multiple clonal lineages. High-throughput sequencing can be used to catalog de novo mutations as potential targets of selection, determine in which lineages they arise, and track the fates of those lineages. Here, we describe a long-term experimental evolution study to identify targets of selection and to determine when, where, and how often those targets are hit. Results We experimentally evolved replicate Escherichia coli populations that originated from a mutator/nonsense suppressor ancestor under glucose limitation for between 300 and 500 generations. Whole-genome, whole-population sequencing enabled us to catalog 3346 de novo mutations that reached > 1% frequency. We sequenced the genomes of 96 clones from each population when allelic diversity was greatest in order to establish whether mutations were in the same or different lineages and to depict lineage dynamics. Operon-specific mutations that enhance glucose uptake were the first to rise to high frequency, followed by global regulatory mutations. Mutations related to energy conservation, membrane biogenesis, and mitigating the impact of nonsense mutations, both ancestral and derived, arose later. New alleles were confined to relatively few loci, with many instances of identical mutations arising independently in multiple lineages, among and within replicate populations. However, most never exceeded 10% in frequency and were at a lower frequency at the end of the experiment than at their maxima, indicating clonal interference. Many alleles mapped to key structures within the proteins that they mutated, providing insight into their functional consequences. Conclusions Overall, we find that when mutational input is increased by an ancestral defect in DNA repair, the spectrum of high-frequency beneficial mutations in a simple, constant resource-limited environment is narrow, resulting in extreme parallelism where many adaptive mutations arise but few ever go to fixation.

scholarly journals Role of Locoregional Treatment in De Novo Stage IV Breast Cancer

2020 ◽  
Vol 14 ◽  
pp. 117955492094244
Author(s):  
Joanna S Lee ◽  
Osman Toktas ◽  
Atilla Soran
Keyword(s):  
Breast Cancer ◽  
United States ◽  
De Novo ◽  
Stage Iv ◽  
The United States ◽  
Comprehensive Overview ◽  
Primary Systemic Therapy ◽  
Locoregional Treatment ◽  
Stage Iv Breast Cancer

It is estimated that approximately 154000 women in the United States have stage IV breast cancer (BC). A subset of this group has metastatic disease at presentation, known as de novo stage IV disease. De novo stage IV BC accounts for approximately 6% of all BC diagnoses in the United States. Traditionally, stage IV BC patients are treated with primary systemic therapy with a palliative intent reserving possible locoregional treatment (LRT) as last resort. There has been a lot of interest in the role of LRT in de novo stage IV BC for the past decade with mixed conclusions. Although this review is not intended to be a comprehensive overview of all literature regarding this topic to date, we will review the recent findings in literature focusing on the studies with larger sample sizes to investigate the role of LRT in de novo stage IV BC.

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