scholarly journals Within-patient genetic diversity of SARS-CoV-2

2020 ◽  
Author(s):  
Jack Kuipers ◽  
Aashil A Batavia ◽  
Kim Philipp Jablonski ◽  
Fritz Bayer ◽  
Nico Borgsmüller ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Genetic Variants ◽  
Large Scale ◽  
Virus Genome ◽  
Spike Gene ◽  
Medical Interventions ◽  
Consensus Sequences ◽  
The Public ◽  
Number Of Patients ◽  
The Impact

AbstractSARS-CoV-2, the virus responsible for the current COVID-19 pandemic, is evolving into different genetic variants by accumulating mutations as it spreads globally. In addition to this diversity of consensus genomes across patients, RNA viruses can also display genetic diversity within individual hosts, and co-existing viral variants may affect disease progression and the success of medical interventions. To systematically examine the intra-patient genetic diversity of SARS-CoV-2, we processed a large cohort of 3939 publicly-available deeply sequenced genomes with specialised bioinformatics software, along with 749 recently sequenced samples from Switzerland. We found that the distribution of diversity across patients and across genomic loci is very unbalanced with a minority of hosts and positions accounting for much of the diversity. For example, the D614G variant in the Spike gene, which is present in the consensus sequences of 67.4% of patients, is also highly diverse within hosts, with 29.7% of the public cohort being affected by this coexistence and exhibiting different variants. We also investigated the impact of several technical and epidemiological parameters on genetic heterogeneity and found that age, which is known to be correlated with poor disease outcomes, is a significant predictor of viral genetic diversity.Author SummarySince it arose in late 2019, the new coronavirus (SARS-CoV-2) behind the COVID-19 pandemic has mutated and evolved during its global spread. Individual patients may host different versions, or variants, of the virus, hallmarked by different mutations. We examine the diversity of genetic variants coexisting within patients across a cohort of 3939 publicly accessible samples and 749 recently sequenced samples from Switzerland. We find that a small number of patients carry most of the diversity, and that patients with more diversity tend to be older. We also find that most of the diversity is concentrated in certain regions and positions of the virus genome. In particular, we find that a variant reported to increase infectivity is among the most diverse positions. Our study provides a large-scale survey of within-patient diversity of the SARS-CoV-2 genome.

scholarly journals Genetic Diversity and Evolution of the Biological Features of the Pandemic SARS-CoV-2

Acta Naturae ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 77-89
Author(s):  
Aleksandra A. Nikonova ◽  
Eugene B. Faizuloev ◽  
Anastasia V. Gracheva ◽  
Igor Yu. Isakov ◽  
Vitaly V. Zverev
Keyword(s):  
Genetic Diversity ◽  
Genetic Variants ◽  
Large Scale ◽  
Biological Properties ◽  
Viral Genomes ◽  
Biological Features ◽  
Health Measures ◽  
Common Genetic Variants ◽  
Coronavirus Infection ◽  
The Relationship

The new coronavirus infection (COVID-19) represents a challenge for global health. Since the outbreak began, the number of confirmed cases has exceeded 117 million, with more than 2.6 million deaths worldwide. With public health measures aimed at containing the spread of the disease, several countries have faced a crisis in the availability of intensive care units. Currently, a large-scale effort is underway to identify the nucleotide sequences of the SARS-CoV-2 coronavirus that is an etiological agent of COVID-19. Global sequencing of thousands of viral genomes has revealed many common genetic variants, which enables the monitoring of the evolution of SARS-CoV-2 and the tracking of its spread over time. Understanding the current evolution of SARS-CoV-2 is necessary not only for a retrospective analysis of the new coronavirus infection spread, but also for the development of approaches to the therapy and prophylaxis of COVID-19. In this review, we have focused on the general characteristics of SARS-CoV-2 and COVID-19. Also, we have analyzed available publications on the genetic diversity of the virus and the relationship between the diversity and the biological properties of SARS-CoV-2, such as virulence and contagiousness.

Gender inequities in the online dissemination of scholars’ work

2021 ◽  
Vol 118 (39) ◽  
pp. e2102945118
Author(s):  
Orsolya Vásárhelyi ◽  
Igor Zakhlebin ◽  
Staša Milojević ◽  
Emőke-Ágnes Horvát
Keyword(s):  
Gender Gap ◽  
Large Scale ◽  
Gender Disparities ◽  
Female Representation ◽  
Scientific Impact ◽  
The Public ◽  
Research Areas ◽  
Coauthorship Networks ◽  
The Impact ◽  
The Relationship

Unbiased science dissemination has the potential to alleviate some of the known gender disparities in academia by exposing female scholars’ work to other scientists and the public. And yet, we lack comprehensive understanding of the relationship between gender and science dissemination online. Our large-scale analyses, encompassing half a million scholars, revealed that female scholars’ work is mentioned less frequently than male scholars’ work in all research areas. When exploring the characteristics associated with online success, we found that the impact of prior work, social capital, and gendered tie formation in coauthorship networks are linked with online success for men, but not for women—even in the areas with the highest female representation. These results suggest that while men’s scientific impact and collaboration networks are associated with higher visibility online, there are no universally identifiable facets associated with success for women. Our comprehensive empirical evidence indicates that the gender gap in online science dissemination is coupled with a lack of understanding the characteristics that are linked with female scholars’ success, which might hinder efforts to close the gender gap in visibility.

Design of Microplastics Citizen Science Kit

2020 ◽  
Author(s):  
Rachael Hughson-Gill
Keyword(s):  
Data Collection ◽  
Citizen Science ◽  
Large Scale ◽  
Positive Impact ◽  
Research Process ◽  
Freshwater Ecosystems ◽  
Freshwater Systems ◽  
The Public ◽  
Plastic Bags ◽  
The Impact

<p>Microplastics are an ever-increasing problem. Every river that was tested in a recent study found the presence of microplastics, with 80% of all plastic in the ocean coming from upstream. Despite this, there is little understanding into the abundance of plastic, its characteristics and the full impact that is it having on marine, freshwater ecosystems and wider ecological systems.</p><p> </p><p>Current fresh water monitoring does not consider the fluid dynamics of rivers, is difficult to use and is inaccessible to the wider public. My project will focus on creating a product that allows for the large-scale data collection of microplastic through citizen science. Allowing groups of people to analyse their local natural environment for the presence and abundance of microplastics within the water. This method of data collection could provide information on a scale that is not possible with traditional methods and would allow for the comparison between freshwater systems. This comparison is fundamental to begin to fill the knowledge gaps around the understanding of microplastics.</p><p> </p><p>Inaccessibility of monitoring to the public is not just through tools but also through the current communication of data with research rarely breaking into the public domain. Citizen science offers not just an improvement in understanding but also offers an opportunity for engagement with the public body. Increasing awareness of the impact of habits round plastic through the sharing of monitoring data can generate the much-needed change on both an individual and policy level to address the problem from the source. This method of change through public opinion can be seen to have an effect on freshwater systems through microbeads ban, plastic bags, plastic straws and industrial pollution regulation.</p><p> </p><p>Through the creation of this product a multidisciplinary approach that blends engineering and design practices is implemented. The wholistic approach to creation is something that is fundamental in the success of tools and therefore the success of the research that is implemented through them. A tool such as this whose function is within the public engagement of its use - increased awareness, as well as the outcome of its use - microplastics data, is required to have an engaging user experience as well as data integrity implemented through engineering design.</p><p> </p><p>This project offers an opportunity to show the importance of the design process within research tools to aid the research process and the positive impact that can come from it.</p>

scholarly journals A Source Like Any Other? Field and Survey Experiment Evidence on How Interest Groups Shape Public Opinion

2021 ◽  
Author(s):  
Andreas Jungherr ◽  
Alexander Wuttke ◽  
Matthias Mader ◽  
Harald Schoen
Keyword(s):  
Interest Groups ◽  
Interest Group ◽  
Large Scale ◽  
Group Communication ◽  
Survey Experiment ◽  
Moderating Effects ◽  
The Public ◽  
High Profile ◽  
Low Profile ◽  
The Impact

Abstract Interest groups increasingly communicate with the public, yet we know little about how effective they are in shaping opinions. Since interest groups differ from other public communicators, we propose a theory of interest group persuasion. Interest groups typically have a low public profile, and so most people are unlikely to have strong attitudes regarding them. Source-related predispositions, such as credibility assessments, are therefore less relevant in moderating effects of persuasive appeals by interest groups than those of high-profile communicators. We test this argument in multiple large-scale studies. A parallel survey and field experiment (N = 4,659) establishes the persuasive potential of low-profile interest groups in both controlled and realistic settings. An observational study (N = 700) shows that substantial portions of the public are unable to assess interest group credibility. A survey experiment (N = 8,245) demonstrates that credibility assessments moderate the impact of party but not interest group communication.

scholarly journals Effectiveness of Large-Scale Social Restrictions (PSBB) toward the New Normal Era during COVID-19 Outbreak: a Mini Policy Review

2020 ◽  
Vol 5 (2) ◽  
Author(s):  
Helen Andriani, S.Si, Apt, M.Sc, Ph.D
Keyword(s):  
Large Scale ◽  
Preventive Measure ◽  
State Of Emergency ◽  
New Normal ◽  
Small Communities ◽  
The Public ◽  
Better Regulation ◽  
The Government ◽  
The Impact

Abstract. The government of Indonesia has not used lockdown or quarantine as an option to tackle the spread of Coronavirus, as the impact of lockdown on small communities in the informal sector that lives from daily income will be severe. Alternatively, the government is enforcing Large-Scale Social Restrictions (Pembatasan Sosial Berskala Besar or "PSBB") to respond to the state of emergency in public health. Starting in June 2020, the government has implemented transitional PSBB in some red zone areas, including the capital Jakarta and East Java province, despite the surge in case numbers. This paper aims to investigate the effectiveness of the PSBB policy applied in Indonesia during the COVID-19 outbreak and the readiness to embrace the new normal, between April and June 2020, based on rapid literature analysis in a search on Medline(-Pubmed), government speeches and reports, social and mass media platforms. Implementation of PSBB is a preventive measure to combat Coronavirus’ spread in some Indonesian areas. Indonesia should not be in a “new normal” situation. The transitional PSBB phase serves as an early chapter of a new normal that would apply only to strategic sectors with manageable risks combined with better regulation and compliance by the public. Abstrak. Pemerintah Indonesia tidak menggunakan lockdown atau karantina sebagai opsi untuk mengatasi penyebaran Coronavirus, karena dampak lockdown pada komunitas kecil di sektor informal yang hidup dari pendapatan harian akan memburuk. Pemerintah menegakkan Pembatasan Sosial Berskala Besar (PSBB) sebagai respons terhadap keadaan darurat dalam kesehatan masyarakat. Sejak bulan Juni 2020, pemerintah telah menerapkan transisi PSBB di beberapa daerah zona merah, termasuk di provinsi DKI Jakarta dan Jawa Timur, meskipun ada peningkatan jumlah kasus. Artikel ini bertujuan untuk menyelidiki efektivitas kebijakan PSBB yang diterapkan di Indonesia selama wabah COVID-19 dan kesiapan untuk memasuki Adaptasi Kebiasaan Baru (AKB), antara bulan April dan Juni 2020, berdasarkan analisis literatur cepat dalam pencarian Medline (-Pubmed), pidato dan laporan pemerintah, platform media sosial dan media massa. Implementasi PSBB adalah langkah pencegahan untuk memerangi penyebaran Coronavirus di beberapa wilayah Indonesia. Indonesia seharusnya tidak berada dalam situasi AKB. Fase PSBB transisi berfungsi sebagai bab awal dari AKB yang hanya akan berlaku pada sektor strategis dengan risiko yang dapat dikelola bersamaan dengan regulasi dan kepatuhan public yang lebih baik.

scholarly journals Emerging Use of Public-Private Partnerships in Public Radiotherapy Facilities in Nigeria

2021 ◽  
pp. 1260-1269
Author(s):  
Chidinma P. Anakwenze Akinfenwa ◽  
Abiola Ibraheem ◽  
Kenneth Nwankwo ◽  
Nwamaka Lasebikan ◽  
Musa Ali-Gombe ◽  
...  
Keyword(s):  
Public Hospitals ◽  
Public Private Partnerships ◽  
External Beam Radiation ◽  
Linear Accelerators ◽  
Beam Radiation ◽  
Maintenance And Repair ◽  
The Public ◽  
Number Of Patients ◽  
The Impact ◽  
Maintenance Plan

PURPOSE Radiotherapy (RT) treatment at public hospitals in Nigeria is often interrupted by prolonged periods of machine breakdown because of insufficient funds for maintenance and repair. These delays have prompted the uptake of public-private partnerships (PPPs) to acquire and maintain RT equipment. This study aimed to understand Nigeria's current RT capacity and the impact of PPPs on RT availability and cost. METHODS Eleven radiation oncologists, each representing one of the 11 RT centers in Nigeria (eight public and three private), were invited to complete a survey on the type, status, acquisition, and maintenance plan of existing RT equipment, cost incurred by patients for external-beam radiation (EBRT) and brachytherapy treatment, and number of patients treated per year on each machine. Type and status of equipment at nonresponding facilities were obtained through literature review and confirmed with the facility. RESULTS A total of eight (81%) respondents completed the survey, all representing public centers, three of which reported PPP use. They reported 11 megavoltage units in total (seven linear accelerators [LINACs] and four Cobalt-60s) and 10 brachytherapy afterloaders. Of those, 57% (4/7) of the LINACs, 100% (4/4) of the Cobalt-60s, and 63% (7/11) of the afterloaders were in clinical use. All commissioned equipment supported by PPPs (three LINACs and one afterloader) were in operation. The public EBRT equipment were nonfunctional 35% of the year (resulting in 60% fewer patients treated per year). The PPP EBRT and afterloaders did not experience any periods of breakdown, but PPP costs were 338% higher than public equipment. CONCLUSION This study characterizes the use of PPP as a more reliable method of RT delivery in Nigeria, albeit at higher costs.

scholarly journals Destabilization of chromosome structure by histone H3 lysine 27 methylation

2018 ◽  
Author(s):  
Mareike Möller ◽  
Klaas Schotanus ◽  
Jessica Soyer ◽  
Janine Haueisen ◽  
Kathrin Happ ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Normal Cell ◽  
Genome Stability ◽  
Large Scale ◽  
Chromosome Structure ◽  
Cell Function ◽  
Pathogenic Fungus ◽  
The Impact ◽  
Accessory Chromosomes

AbstractChromosome and genome stability are important for normal cell function as instability often correlates with disease and dysfunction of DNA repair mechanisms. Many organisms maintain supernumerary or accessory chromosomes that deviate from standard chromosomes. The pathogenic fungus Zymoseptoria tritici has as many as eight accessory chromosomes, which are highly unstable during meiosis and mitosis, transcriptionally repressed, show enrichment of repetitive elements, and enrichment with heterochromatic histone methylation marks, e.g., trimethylation of H3 lysine 9 or lysine 27 (H3K9me3, H3K27me3). To elucidate the role of heterochromatin on genome stability in Z. tritici, we deleted the genes encoding the methyltransferases responsible for H3K9me3 and H3K27me3, kmt1 and kmt6, respectively, and generated a double mutant. We combined experimental evolution and genomic analyses to determine the impact of these deletions on chromosome and genome stability, both in vitro and in planta. We used whole genome sequencing, ChIP-seq, and RNA-seq to compare changes in genome and chromatin structure, and differences in gene expression between mutant and wildtype strains. Analyses of genome and ChIP-seq data in H3K9me3-deficient strains revealed dramatic chromatin reorganization, where H3K27me3 is mostly relocalized into regions that are enriched with H3K9me3 in wild type. Many genome rearrangements and formation of new chromosomes were found in the absence of H3K9me3, accompanied by activation of transposable elements. In stark contrast, loss of H3K27me3 actually increased the stability of accessory chromosomes under normal growth conditions in vitro, even without large scale changes in gene activity. We conclude that H3K9me3 is important for the maintenance of genome stability because it disallows H3K27me3 in these regions. In this system, H3K27me3 reduces the overall stability of accessory chromosomes, generating a “metastable” state for these quasi-essential regions of the genome.Author SummaryGenome and chromosome stability are essential to maintain normal cell function and viability. However, differences in genome and chromosome structure are frequently found in organisms that undergo rapid adaptation to changing environmental conditions, and in humans are often found in cancer cells. We study genome instability in a fungal pathogen that exhibits a high degree of genetic diversity. Regions that show extraordinary diversity in this pathogen are the transposon-rich accessory chromosomes, which contain few genes that are of unknown benefit to the organism but maintained in the population and thus considered “quasi essential”. Accessory chromosomes in all fungi studied so far are enriched with markers for heterochromatin, namely trimethylation of H3 lysine 9 and 27 (H3K9me3, H3K27me3). We show that loss of these heterochromatin marks has strong but opposing effects on genome stability. While loss of the transposon-associated mark H3K9me3 destabilizes the entire genome, presence of H3K27me3 favors instability of accessory chromosomes. Our study provides insight into the relationship between chromatin and genome stability and why some regions are more susceptible to genetic diversity than others.

scholarly journals RAPID DATA COLLECTION FOR THE AUDIT OF MONUMENTS & MEMORIALS IN SOUTH AFRICA

2021 ◽  
Vol XLVI-M-1-2021 ◽  
pp. 313-320
Author(s):  
C. Jackson ◽  
M. Nkhasi-Lesaoana ◽  
L. Mofutsanyana
Keyword(s):  
South Africa ◽  
Public Space ◽  
Large Scale ◽  
National Audit ◽  
The Public ◽  
Funding Mechanism ◽  
History Of ◽  
Monuments And Memorials ◽  
The Impact ◽  
Roll Out

Abstract. The tradition of memorialising people and events through physical constructions such as statues and monuments like in many countries, has shaped the public space of a modern South Africa. Considering the colonial and apartheid history of South Africa, these physical markers, often uncontextualized, continue to maintain positions of prominence within the modern streetscape.Since the turn of the democratic era in South Africa, a pressing need has existed to assess the impact of the markers on the heritage landscape of the country. An endeavour made more difficult by a lack of a comprehensive inventory of these resources across the country.The National Audit of Monuments and Memorials (NAMM) was designed to address this gap through a full national survey of monuments and memorials, conducted under the auspices of a job creation stimulus package designed to create short term employment in the wake of the economic fallout from the Covid-19 pandemic. Undertaking this project under this funding mechanism required that all phases of the project be undertaken within a six-month period.The compressed timeframes associated with this project required an approach that could support a level of fluidity to address the challenges of undertaking a project of this nature, whilst ensuring that the data collected by field surveyors can be monitored and included in the inventory of the national estate in an effective manner.The aim of this paper is to discuss and showcase the tools and workflows used to roll out and manage the large-scale national audit of monuments and memorials across South Africa.

A User-Centric Approach in E-Government Policies

2010 ◽  
pp. 20-36
Author(s):  
Pieter Verdegem ◽  
Laurence Hauttekeete
Keyword(s):  
Large Scale ◽  
Government Policies ◽  
Theoretical Discussion ◽  
The Public ◽  
Government Services ◽  
Electronic Service ◽  
User Centric ◽  
To Come ◽  
The Impact ◽  
Theoretical Considerations

E-government is given a central role in the modernization debate of the public sector. Despite large-scale investments the electronic public services do not (yet) seem to come up to the promising expectations. As a result, consensus seems to exist that e-government policies require a rethinking. In this chapter the origins and objectives of the electronic service delivery are discussed. The authors state that the development of e-government suffers from deterministic conceptions. Consequently, the user seems to be neglected and minor attention is given to the impact of the electronic services on the customer. As a contribution to the theoretical discussion of e-government, the authors explain why a two-fold paradigm shift is needed. The user-oriented rethinking comprises both the development of e-government services as the evaluation of its policies. At the end of this chapter, the theoretical considerations are linked to daily-based activities by presenting briefly some Belgian e-government practices.

GWAS Indicates the Presence of Rare Immunogenetic Polymorphisms as Possible Predisposition Factors in Aplastic Anemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1093-1093
Author(s):  
Bartlomiej P Przychodzen ◽  
Monika Jasek ◽  
Sandra P Smieszek ◽  
Ron Paquette ◽  
Rainer Richter ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Genetic Variants ◽  
Large Scale ◽  
Disease Risk ◽  
Conflicts Of Interest ◽  
New Paradigm ◽  
Genetic Traits ◽  
Network Analyses ◽  
Low Prevalence ◽  
The Impact

Abstract Abstract 1093 Poster Board I-115 While immune mechanisms are involved in the pathogenesis of idiopathic aplastic anemia (AA), due to the impact of exogenous factors and the low prevalence of AA, this disease is not easily amenable to genetic studies. With the advent of whole genome scanning (WGS) technologies such as single nucleotide polymorphism arrays (SNP-A), large scale investigations in various disorders have been conducted. A systems level understanding of particular disease can allows for identification of candidate genetic variants as prognostic and diagnostic markers. We have applied 6.0 SNP-A containing 924644 SNP probes to conduct a comprehensive GWAS in AA with the aim of identifying low prevalence genetic variants that contribute to the pathogenesis of this condition and contribute to individual disease risk. We studied 124 AA patients and significant cohort of 2230 controls that increase detection power using SNP-A. After exclusion of SNP's with call rate of <95% and those with violation of Hardy Weinberg equilibrium (p<.01), 809.802 SNPs (87.5% of initial set) were passed for further investigation. Single allele χ2 statistics for all autosomal markers were performed. 1935 SNP's pointing towards genes with minor allele frequency (MAF) <10% and p<.001 after Bonferroni correction (more stringent than False Discovery Rate) were selected. Of great interest was the top scoring non synonymous SNP (1/38) rs1028180 located in BLZF1 (OR 6.62) involved in cell proliferation and growth. It was represented by singular marker (p<1×10–4) occurring at a heterozygous frequency of 15% vs. 3.5% in controls, and a homozygous frequency of 3.7% vs. 0% in controls. A total of 1 non-synonymous and 3 strongest intronic SNPs were prioritized for final investigation. These included rs9566991, rs1773557 and rs1495963 and directed to informative genes TNFSF11 (OR 6.24), CD247 (OR 3.52) and IL12RB2 (OR 7.04), respectively. Remarkably, several informative LD blocks were identified represented by multiple markers pointing to the presence of informative polymorphisms in the corresponding regions. TNFSF1 gene was represented by marker rs9566991 (p<1×10–3) occurring at the heterozygous frequency of 15.4% vs. 2.7% in controls. The corresponding MAF was 7.6% vs. 1.3%. A second potential locus identified in our study (CD247) was represented by rs1773557 marker (p<1×10–20) occurring at a heterozygous frequency of 19.6% vs. 5.9% in controls, and in homozygous frequency of 0% vs. 0% in controls. Other SNPs including rs1737501, rs1737502 pointed to the same locus. IL12RB2 was represented by a singular marker rs1495963 (p<1×10–6) occurring at the heterozygous frequency of 24% vs. allelic frequency of 3.2% in controls. MAF were 12% versus 1.9%. Another potential loci marked by rs17131583 was TGFBR3. Analysis targeting individual SNP has been the primary focus of GWAS but such an approach offers only limited understanding of the complex diseases as not an individual SNP, and rather a joint action of several SNPs results in particular outcomes. Consequently, in study of AA, we applied the network gene association analysis as a new paradigm incorporating both “operator OR” and “operator AND” thereby allowing for dependence and independence testing. Consequently, the proposed paradigm may lead to identification of meaningful pathways. We performed a simulation study, where genotypes were randomly drawn including homozygous reference, heterozygous and homozygous variant for each SNP Si = 1, 50 where the MAF of SNP is chosen uniformly at random. Of great interest was a pair consisting of rs1737501 CD247 and rs1495963 IL12RB2 both in heterozygous variant, involving operator AND at p<1×10–23. It was reported with occurrence of 12.2% in patients and 0.005% in controls giving a specificity score of 99.995%. In addition to the described pair, SNP in strong LD within CD247 (rs1737502) was scored again together with rs1495963. Functionally, both genes are involved in regulation response. Another pair rs16908086 and rs1773557 that pointed together to CD247 and MRVI2 created a pair with occurrence 21% versus and 3% in controls. In sum, our study constituted the first network analyses of predisposing factors and complex genetic traits enriched in informative loci in immunoregulatory genes. Rare polymorphic variants of these genes may constitute risk factors for development of AA. Disclosures No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document