scholarly journals Mutational Analysis of SARS-CoV-2 Genome in African Population

2020 ◽  
Author(s):  
Olabode E. Omotoso ◽  
Ayoade D. Babalola ◽  
Amira Matareek
Keyword(s):  
Global Economy ◽  
Mutational Analysis ◽  
Evolutionary Genetics ◽  
Human Interaction ◽  
African Population ◽  
Multiple Sequence ◽  
Genome Variability ◽  
Pathogenic Virus ◽  
Mutational Hotspots ◽  
Protein Membrane

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a highly infectious and pathogenic virus has claimed lot of lives globally since its outbreak in December 2019 posing dire threat on public health, global economy, social and human interaction. At moderate rate, mutations in the SARS-CoV-2 genome are evolving which might have contributed to viral genome variability, transmission, replication efficiency and virulence in different regions of the world. The present study elucidated the mutational landscape in SARS-CoV-2 genome among the African population, which may have contributed to the virulence, pathogenicity and transmission observed in the region. Multiple sequence alignment of the SARS-CoV-2 genome (356 viral protein sequences) was performed using ClustalX version 2.1 and phylogenetic tree was built using Molecular Evolutionary Genetics Analysis (MEGA) X software. ORF1ab polyprotein, spike glycoprotein, ORF3, ORF8 and nucleocapsid phosphoprotein were observed as mutational hotspots in the African population and may be of keen interest in the adaptability of SARS-CoV-2 to the human host. While, there is conservation in the envelope protein, membrane glycoprotein, ORF6, ORF7a, ORF7b and ORF10. The accumulation of moderate mutations (though slowly) in the SARS-CoV-2 genome as revealed in our study, could be a promising strategy to develop drugs or vaccines with respect to the viral conserved domains and host cellular proteins and/or receptors involved in viral invasion and replication to avoid a new viral wave due to drug resistance and vaccine evasion.

scholarly journals Mutational hotspots and conserved domains of SARS-CoV-2 genome in African population

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Olabode E. Omotoso ◽  
Ayoade D. Babalola ◽  
Amira Matareek
Keyword(s):  
Global Economy ◽  
African Population ◽  
The Novel ◽  
Conserved Domains ◽  
Nucleocapsid Proteins ◽  
Genome Variability ◽  
Promising Strategy ◽  
Mutational Hotspots ◽  
Novel Coronavirus ◽  
Complete Protein

Abstract Background Since outbreak in December 2019, the highly infectious and pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused over a million deaths globally. With increasing burden, the novel coronavirus has posed a dire threat to public health, social interaction, and global economy. Mutations in the SARS-CoV-2 genome are moderately evolving which might have contributed to its genome variability, transmission, replication efficiency, and virulence in different regions of the world. Results The present study elucidated the mutational landscape in the SARS-CoV-2 genome among the African populace, which may have contributed to the virulence, spread, and pathogenicity observed in the region. A total of 3045 SARS-CoV-2 complete protein sequences with the reference viral sequence (EPI_ISL_402124) were mined and analyzed. SARS-CoV-2 ORF1ab, spike, ORF3, ORF8, and nucleocapsid proteins were observed as mutational hotspots in the African population and may be of keen interest in understanding the viral host relationship, while there is conservation in the ORF6, ORF7a, ORF7b, ORF10, envelope, and membrane proteins. Conclusions The accumulation of moderate mutations (though slowly), in the SARS-CoV-2 genome as seen in this present study, could be a promising strategy to develop antiviral drugs or vaccines. These antiviral interventions should target viral conserved domains and host cellular proteins and/or receptors involved in viral invasion and replication to avoid a new viral wave due to drug resistance and vaccine evasion.

scholarly journals Contributory role of SARS-CoV-2 genomic variations and life expectancy in COVID-19 transmission and low fatality rate in Africa

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Olabode E. Omotoso
Keyword(s):  
Mutational Analysis ◽  
Health Care Systems ◽  
Selective Advantage ◽  
African Population ◽  
Young Generation ◽  
Regulatory Policies ◽  
Recurrent Mutations ◽  
Mutational Hotspots ◽  
Care Systems ◽  
Novel Coronavirus

Abstract Background The novel coronavirus disease (COVID-19) has claimed lots of lives, posing a dire threat to global health. It was predicted that the coronavirus outbreak in the African population would be very lethal and result to economic devastation owing to the prevalence of immune-compromised population, poverty, low lifespan, fragile health care systems, poor economy, and lifestyle factors. Accumulation of mutations gives virus selective advantage for host invasion and adaptation, higher transmissibility of more virulent strains, and drug resistance. The present study determined the severe acute respiratory syndrome-2 (SARS-CoV-2) genomic variability and the contributory factors to the low COVID-19 fatality in Africa. To assess the SARS-CoV-2 mutational landscape, 924 viral sequences from the Africa region with their sociobiological characteristics mined from the Global Initiative on Sharing All Influenza Data (GISAID) database were analyzed. Results Mutational analysis of the SARS-CoV-2 sequences revealed highly recurrent mutations in the SARS-CoV-2 spike glycoprotein D614G (97.2%), concurrent R203K, and G204R (65.2%) in the nucleocapsid phosphoprotein, and P4715L (97.2%) in the RNA-dependent RNA polymerase flagging these regions as SARS-CoV-2 mutational hotspots in the African population. COVID-19 is more severe in older people (> 65 years); Africa has a low percentage of people within this age group (4.36%). The average age of the infected patients observed in this study is 46 years with only 47 infected patients (5.1%) above 65 years in Africa in comparison to 13.12% in countries in other continents with the highest prevalence of COVID-19. Conclusions Africa’s young generation, the late incidence of the disease, and adherence to public health guidelines are important indicators that may have contributed to the observed low COVID-19 deaths in Africa. However, with the easing of lockdown and regulatory policies, daily increasing incidence in most countries, and low testing and sequencing rate, the epidemiology and the true impact of the pandemic in Africa remain to be unraveled.

scholarly journals Myelodysplastic Syndrome with Excess Blasts and Secondary Acute Myeloid Leukemia: Same Disease with Different Blast Count

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2692-2692
Author(s):  
Xueyan Chen ◽  
Megan Othus ◽  
Brent L Wood ◽  
Roland B. Walter ◽  
Pamela S. Becker ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Mutational Analysis ◽  
World Health ◽  
Secondary Aml ◽  
Data Safety ◽  
Monitoring Committee ◽  
Mutational Hotspots ◽  
Acute Myeloid

Introduction: The World Health Organization (WHO) diagnoses acute myeloid leukemia (AML) if ≥20% myeloid blasts are present in peripheral blood or bone marrow. Consequently a patient with even 19% blasts is often ineligible for an "AML study". A less arbitrary means to define "AML" and myelodysplastic syndromes ("MDS") emphasizes biologic features. Here, focusing on patients with WHO-defined MDS with excess (5-19%) blasts (MDS-EB) or AML with myelodysplasia-related changes (AML-MRC) or therapy-related (t-AML) (WHO defined secondary AML), we compared morphologic blast percentage (MBP) with the frequency of mutations in genes belonging to different functional groups, and with the variant allele frequency (VAF) for individually mutated genes. Methods: 328 adults with WHO-defined AML (de novo and secondary; n=149) or MDS (n=179) and with mutational analysis by next-generation sequencing (NGS) performed at the University of Washington Hematopathology Laboratory between 2015-2017 were included. Of these, 86 had MDS-EB and 49 had secondary AML. Mutational analysis was performed using a customized, amplicon-based assay, TruSeq Custom Amplicon (Illumina, San Diego, CA). Custom oligonucleotide probes targeted specific mutational hotspots in ASXL1, CBL, CEBPA, CSF3R, EZH2, FBXW7, FGFR1, FLT3, GATA1, GATA2, HRAS, IDH1, IDH2, JAK2, KIT, KMT2A, KRAS, MAP2K1, MPL, NOTCH1, NPM1, NRAS, PDGFRA, PHF6, PTEN, RB1, RUNX1, SF3B1, SRSF2, STAG2, STAT3, TET2, TP53, U2AF1, WT1, and ZRSR2. VAF ≥5% was required to identify point mutations. Spearman's correlation coefficient was used to examine the relation between VAF of individually mutated genes and MBP. The Mann Whitney test served to compare the distribution of VAF in AML (≥20% blasts) vs. MDS (<20% blasts), before and after exclusion of subgroups as described below. Fisher's exact test was used to compare incidence of mutations. Results: 96% of cases had ≥one mutation in the 36 genes tested using NGS. Considering all 328 patients, mutations in tumor suppressor and cohesin complex genes were similarly frequent in MDS and AML, whereas spliceosomal genes, in particular SF3B1 and SRSF2, were more frequently mutated in MDS than in AML (46% vs. 26%, p<0.001). Mutations in epigenetic modifiers were more common in AML than MDS (54% vs. 42%, p= 0.035) as were transcription factor mutations (52% vs. 28%, p<0.001). However comparisons limited to MDS-EB vs. AML-MRC/t-AML, indicated the differences observed when comparing all MDS and all AML were less apparent, both statistically and more perhaps importantly with respect to observed frequencies. For example, spliceosomal gene mutations were found in 35% in MDS-EB and 27% in AML-MRC/t-AML (p=0.34) vs. 46% and 26% in all MDS and all AML. NPM1 mutations were detected in only 8% of AML-MRC/t-AML vs. 3% in MDS-EB but 29% for all AML. Results were analogous with FLT3 ITD, FLT3 TKD, and JAK2 mutations. Examining 20 individually mutated genes detected in ≥ 10 patients only with SRSF2 (p=0.04), did distribution of VAF differ statistically according to whether blast percentage was <20% versus ≥20%. Conclusions: The similar prevalence of mutations in different functional categories in MDS-EB and AML-MRC/t-AML suggests these entities are two manifestations of the same disease. We believe it appropriate to combine these WHO entities allowing patients in each to be eligible for both AML and MDS trials. Disclosures Othus: Glycomimetics: Other: Data Safety and Monitoring Committee; Celgene: Other: Data Safety and Monitoring Committee. Walter:Amgen: Consultancy; Boston Biomedical: Consultancy; Agios: Consultancy; Argenx BVBA: Consultancy; Astellas: Consultancy; BioLineRx: Consultancy; BiVictriX: Consultancy; Covagen: Consultancy; Daiichi Sankyo: Consultancy; Jazz Pharmaceuticals: Consultancy; Kite Pharma: Consultancy; New Link Genetics: Consultancy; Pfizer: Consultancy, Research Funding; Race Oncology: Consultancy; Seattle Genetics: Research Funding; Amphivena Therapeutics: Consultancy, Equity Ownership; Boehringer Ingelheim: Consultancy; Aptevo Therapeutics: Consultancy, Research Funding. Becker:Accordant Health Services/Caremark: Consultancy; AbbVie, Amgen, Bristol-Myers Squibb, Glycomimetics, Invivoscribe, JW Pharmaceuticals, Novartis, Trovagene: Research Funding; The France Foundation: Honoraria.

Global Networks and Local Societies: Cities in the Information Age

2004 ◽  
Author(s):  
Manuel Castells
Keyword(s):  
Communication Networks ◽  
Communication Systems ◽  
Global Economy ◽  
Social Systems ◽  
Information Age ◽  
Human Interaction ◽  
Spatial Proximity ◽  
Global Networks ◽  
Metropolitan Regions ◽  
The One

Cities are a major source of intellectual creativity and political engagement. We have not finished, and we will never finish, understanding the transformation of cities and the impact of this transformation on society and culture at large. The focus for this chapter is what I would call the great twenty-first century urban paradox—an urban world without cities. Let me try to explain first, and then go into the details of the analysis. I would say that cities have been throughout history sources of cultural creativity, technological innovation, material progress and political democratization. By bringing together people of multicultural origins and by establishing communication channels and systems of cooperation, cities have induced synergy from diversity, dynamic stability from competition, order from chaos. However, with the coming of the information age cities as specific social systems seem to be challenged by the related processes of globalization and informationalization. New communication technologies appear to supersede the functional need for spatial proximity as the basis for economic efficiency and personal interaction. The emergence of a global economy and of global communication systems subdue the local to the global, blurring social meaning and hampering political control traditionally exercised from and by localities. Flows seem to overwhelm places as human interaction increasingly relies on electronic communication networks. Therefore, cities as specific forms of social organization and cultural expression, materially rooted in spatially concentrated human settlements, could be made obsolete in the new technological environment. Yet, the paradox is that with the coming of the techno-economic system, urbanization— simply understood as spatial concentration—is in fact accelerated. We are reaching a predominantly urban world, which before 2005 will include for the first time in history at least 50 per cent of the planet’s population in cities. Core activities and a growing proportion of people are and will be concentrated in multimillion metropolitan regions. This pattern of social–spatial evolution could lead to what I call urbanization without cities. As, on the one hand, people concentrate in spatial settlements, at the same time suburban sprawl defuses people and activities in a very wide metropolitan span.

Comparative Insilco physiochemical and phylogenetic analysis of Insulin like growth factor 1 receptor (IGF-1R) in domestic animals

2018 ◽  
Author(s):  
P R. Sahoo ◽  
G. Sahoo ◽  
P. C. Behera
Keyword(s):  
Phylogenetic Analysis ◽  
Growth Factor ◽  
Evolutionary Genetics ◽  
Domestic Animals ◽  
Amino Acid Sequences ◽  
Insulin Like Growth Factor ◽  
Multiple Sequence ◽  
Lung Cancers ◽  
Physiochemical Parameters ◽  
Time Of Divergence

Insulin like growth factor 1receptors (IGF-1R) are the proteins which are expressed on the cell surface of almost all tissues in human as well as domestic animals with major involvement in growth, cancer, aging, production and in early embryonic development. Due to above importance, this protein needs to be characterized both in physiochemical and phylogenetically for further exploration in livestock research. In this study, the IGF1R amino acid sequences of selected domestic animals are retrieved from UniProt database and various physiochemical parameters were compared through ProtParam insilco tool. The multiple sequence alignment (MSA) and phylogenetic analysis was performed through Clustal omega and Molecular evolutionary genetics analysis (MEGA) application platform respectively. It was found that this protein is an unstable, hydrophilic in all domestic animals with amino acids varied from 1307 to 1412 in number. The phylogenetic analysis showed that highest time of divergence occurs in killer whale and rabbit, but least time of divergence occurs between goat and bovine. So this study will provide a better platform for the development of suitable anticancer therapeutics in domestic animals in nearest future as IGF-1R is implicated in several cancers, including breast, prostate, and lung cancers.

Delivering professional projects

2010 ◽  
Vol 4 (1) ◽  
pp. 73-94 ◽  
Author(s):  
Shauneen Furlong ◽  
Wafi Al‐Karaghouli
Keyword(s):  
Information Technology ◽  
Project Management ◽  
Global Economy ◽  
Management Practice ◽  
Transformation Process ◽  
Human Interaction ◽  
Ongoing Research ◽  
Content Type ◽  
Initiation Phase ◽  
The World

PurposeOwing to inadequate implementations of project management (PM) procedures and processes, many large information technology systems (ITS) projects failed to deliver its promises. Also, many of the failures in the implementation of large ITS projects around the world have been attributed to inadequate PM action. This criticism encompasses e‐government project initiatives which have attempted ambitious program change, major innovations, large transformations, enterprise wide solutions, collaboration across organisations, governments and private sectors, and the implementation of unprecedented (or ambitious) solutions. The purpose of this paper is to examine these issues.Design/methodology/approachThis paper forms part of an ongoing research of a PhD degree to describe, critically evaluate and examine the underlying barriers and challenges in large e‐government initiatives. Also, this paper examines change in organisations due to the change in the global economy and global information society as new technology is changing the nature of work. It identifies and examines the current and foreseeing problems with large e‐government projects and describes how a sociotechnical approach which takes into account, technical, business, citizen, economic needs in the creation of a sociotechnical ITS for future citizens. In addition, the paper offers a technology‐enabled enhancement to the project‐initiation phase, the area identified as being particularly weak and inadequate in addressing initial requirements of e‐government initiatives.FindingsThe paper proposes that technology can be incorporated into the professional practice of PM. It can also be a part of a passable solution as opposed to being distinct and separate from it. The PM supporting tools, as opposed to merely reporting actual versus plans have to increase the novelty (art and science) of PM through human interaction, empower the project manager and in aiding his capacity in delivering the expected outcomes.Social implicationsThe paper demonstrates the value of effective project managers within the wider context of PM in transformational e‐government initiatives. It believes that this research will have an impact on three important areas, namely project management practice (PMC), e‐government projects and the transformation process of large projects in the public sector. This paper is about changing culture and practice of PMC in handling and managing large projects when different parties involve including outsourcing. This paper investigates and addresses, not only the transformation process of e‐government projects, but also, the transformation of PM professional culture (i.e. PMC) that delivers and works.Originality/valueThis research paper contributes to the existing literature of PM of large e‐government transformational processes. The paper addresses a number of e‐government challenges, by critically analysing and summarising a list of e‐government challenges and barriers arising from an e‐government survey administered on behalf of the World Information Technology and Services Alliance which represents the national technology associations in 70 countries. It compares these challenges to the project management body of knowledge (PMBOK), which is the North American standard in PM methodology. Also, it highlights the weaknesses in PMBOK to address these challenges and offers a technology‐enabled enhancement to the project‐initiation phase. This is the strength of this paper.

scholarly journals Hybrid-Quantum approach for the optimal lockdown to stop the SARS-CoV-2 community spread subject to maximizing nation economy globally

2021 ◽  
Author(s):  
Sahil Zaman ◽  
Alex Khan ◽  
Arindam Sadhu ◽  
Dr Kunal Das ◽  
Faisal Shah Khan
Keyword(s):  
Disease Transmission ◽  
Global Economy ◽  
Human Life ◽  
Economic Factor ◽  
Human Interaction ◽  
National Economic ◽  
Full State ◽  
Quantum Approach ◽  
Respiratory Coronavirus ◽  
Essential Problem

Owing to the SARS-CoV-2 epidemic (severe acute respiratory coronavirus 2 syndromes), the global situation has changed drastically. Several countries, including India, Europe, U.S.A., introduced a full state/nation lockdown to minimize the disease transmission through human interaction after the virus entered the population and to minimize the loss of human life. Millions of people have gone unemployed due to lockdown implementation, resulting in business and industry closure and leading to a national economic slowdown. Therefore, preventing the spread of the COVID-19 virus in the world while also preserving the global economy is an essential problem requiring an effective and immediate solution. Using the compartmental epidemiology S, E, I, R or D (Susceptible, Exposed, Infectious, Recovery or Death) model extended to multiple population regions we predict the evolution of the SARS-CoV-2 disease and construct an optimally scheduled lockdown calendar to execute lockdown over phases, using the well-known Knapsack problem. A comparative analysis of both classical and quantum models shows that our model decreases SARS-CoV-2 active cases while retaining the average global economic factor, GDP, in contrast to the scenario with no lockdown.

Mutational analysis of conserved glycines 42 and 256 in Cephalosporium acremonium isopenicillin N synthase

2001 ◽  
Vol 47 (10) ◽  
pp. 961-964 ◽  
Author(s):  
Paxton Loke ◽  
Tiow-Suan Sim
Keyword(s):  
Mutational Analysis ◽  
Soluble Expression ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Cephalosporium Acremonium ◽  
Multiple Sequence ◽  
Local Protein Structure ◽  
Reduced Temperature ◽  
Isopenicillin N ◽  
Local Protein

Isopenicillin N synthase (IPNS) is critical for the catalytic conversion of δ -(L-α-aminoadipoyl)-L-cysteinyl-D-valine to isopenicillin N in the penicillin and cephalosporin biosynthetic pathway. Two conserved glycine residues in Cephalosporium acremonium IPNS (cIPNS), namely glycine-42 and glycine-256, were identified by multiple sequence alignment and investigated by site-directed mutagenesis to study the effect of the substitution on catalysis. Our study showed that both the mutations from glycine to alanine or to serine reduced the catalytic activity of cIPNS and affected its soluble expression in a heterologous host at 37°C. Soluble expression was restored at a reduced temperature of 25°C, and thus, it is possible that these glycine residues may have a role in maintaining the local protein structure and are critical for the soluble expression of cIPNS.Key words: isopenicillin N synthase, site-directed mutagenesis, glycine, Cephalosporium acremonium.

Mutational analysis of putative phosphate- and proton-binding sites in the Saccharomyces cerevisiae Pho84 phosphate:H+ transceptor and its effect on signalling to the PKA and PHO pathways

2012 ◽  
Vol 445 (3) ◽  
pp. 413-422 ◽  
Author(s):  
Dieter R. Samyn ◽  
Lorena Ruiz-Pávon ◽  
Michael R. Andersson ◽  
Yulia Popova ◽  
Johan M. Thevelein ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Mutational Analysis ◽  
Three Dimensional ◽  
Physiological Role ◽  
Binding Pocket ◽  
Amino Acid Residues ◽  
Three Dimensional Model ◽  
Sequence Alignments ◽  
Multiple Sequence ◽  
Proton Binding

In Saccharomyces cerevisiae, the Pho84 phosphate transporter acts as the main provider of phosphate to the cell using a proton symport mechanism, but also mediates rapid activation of the PKA (protein kinase A) pathway. These two features led to recognition of Pho84 as a transceptor. Although the physiological role of Pho84 has been studied in depth, the mechanisms underlying the transport and sensor functions are unclear. To obtain more insight into the structure–function relationships of Pho84, we have rationally designed and analysed site-directed mutants. Using a three-dimensional model of Pho84 created on the basis of the GlpT permease, complemented with multiple sequence alignments, we selected Arg168 and Lys492, and Asp178, Asp358 and Glu473 as residues potentially involved in phosphate or proton binding respectively, during transport. We found that Asp358 (helix 7) and Lys492 (helix 11) are critical for the transport function, and might be part of the putative substrate-binding pocket of Pho84. Moreover, we show that alleles mutated in the putative proton-binding site Asp358 are still capable of strongly activating PKA pathway targets, despite their severely reduced transport activity. This indicates that signalling does not require transport and suggests that mutagenesis of amino acid residues involved in binding of the co-transported ion may constitute a promising general approach to separate the transport and signalling functions in transceptors.

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