scholarly journals Identification of HLA-A*24:02-restricted CTL candidate epitopes derived from the non-structural polyprotein 1a of SARS-CoV-2 and analysis of their conservation using the mutation database of SARS-CoV-2 variants

2021 ◽  
Author(s):  
Akira Takagi ◽  
Masanori Matsui
Keyword(s):  
Neutralizing Antibodies ◽  
Viral Evolution ◽  
Critical Role ◽  
Amino Acid Sequences ◽  
Viral Control ◽  
Mutation Database ◽  
Wide Range ◽  
Novel Variants ◽  
Near Future ◽  
Original Virus

COVID-19 vaccines are currently being administrated worldwide and playing a critical role in controlling the pandemic. They have been designed to elicit neutralizing antibodies against Spike protein of the original SARS-CoV-2, and hence they are less effective against SARS-CoV-2 variants with mutated Spike than the original virus. It is possible that novel variants with abilities of enhanced transmissibility and/or immunoevasion will appear in the near future and perfectly escape from vaccine-elicited immunity. Therefore, the current vaccines may need to be improved to compensate for the viral evolution. For this purpose, it may be beneficial to take advantage of CD8+ cytotoxic T lymphocytes (CTLs). Several lines of evidence suggest the contribution of CTLs on the viral control in COVID-19, and CTLs target a wide range of proteins involving comparatively conserved non-structural proteins. Here, we identified twenty-two HLA-A*24:02-restricted CTL candidate epitopes derived from the non-structural polyprotein 1a (pp1a) of SARS-CoV-2 using computational algorithms, HLA-A*24:02 transgenic mice and the peptide-encapsulated liposomes. We focused on pp1a and HLA-A*24:02 because pp1a is relatively conserved and HLA-A*24:02 is predominant in East Asians such as Japanese. The conservation analysis revealed that the amino acid sequences of 7 out of the 22 epitopes were hardly affected by a number of mutations in the Sequence Read Archive database of SARS-CoV-2 variants. The information of such conserved epitopes might be useful for designing the next-generation COVID-19 vaccine that is universally effective against any SARS-CoV-2 variants by the induction of both anti-Spike neutralizing antibodies and CTLs specific for conserved epitopes.

scholarly journals Consensus proposals for classification of the family Hepeviridae

2014 ◽  
Vol 95 (10) ◽  
pp. 2223-2232 ◽  
Author(s):  
Donald B. Smith ◽  
Peter Simmonds ◽  
Shahid Jameel ◽  
Suzanne U. Emerson ◽  
Tim J. Harrison ◽  
...  
Keyword(s):  
Mammalian Species ◽  
Cutthroat Trout ◽  
Hepatitis E ◽  
Amino Acid Sequences ◽  
Sequence Information ◽  
Virus Species ◽  
Wide Range ◽  
The Family ◽  
Novel Variants

The family Hepeviridae consists of positive-stranded RNA viruses that infect a wide range of mammalian species, as well as chickens and trout. A subset of these viruses infects humans and can cause a self-limiting acute hepatitis that may become chronic in immunosuppressed individuals. Current published descriptions of the taxonomical divisions within the family Hepeviridae are contradictory in relation to the assignment of species and genotypes. Through analysis of existing sequence information, we propose a taxonomic scheme in which the family is divided into the genera Orthohepevirus (all mammalian and avian hepatitis E virus (HEV) isolates) and Piscihepevirus (cutthroat trout virus). Species within the genus Orthohepevirus are designated Orthohepevirus A (isolates from human, pig, wild boar, deer, mongoose, rabbit and camel), Orthohepevirus B (isolates from chicken), Orthohepevirus C (isolates from rat, greater bandicoot, Asian musk shrew, ferret and mink) and Orthohepevirus D (isolates from bat). Proposals are also made for the designation of genotypes within the human and rat HEVs. This hierarchical system is congruent with hepevirus phylogeny, and the three classification levels (genus, species and genotype) are consistent with, and reflect discontinuities in the ranges of pairwise distances between amino acid sequences. Adoption of this system would include the avoidance of host names in taxonomic identifiers and provide a logical framework for the assignment of novel variants.

scholarly journals Identification of HLA-A*24:02-Restricted CTL Candidate Epitopes Derived from the Nonstructural Polyprotein 1a of SARS-CoV-2 and Analysis of Their Conservation Using the Mutation Database of SARS-CoV-2 Variants

2021 ◽  
Vol 9 (3) ◽  
Author(s):  
Akira Takagi ◽  
Masanori Matsui
Keyword(s):  
Neutralizing Antibodies ◽  
Spike Protein ◽  
Mutation Database ◽  
Novel Variants

COVID-19 vaccines have been designed to elicit neutralizing antibodies against the Spike protein of the original SARS-CoV-2, and hence they are less effective against variants. It is possible that novel variants will appear and escape from vaccine-elicited immunity.

scholarly journals The chevkinite group: underestimated accessory phases from a wide range of parageneses

Mineralogia ◽  
2013 ◽  
Vol 44 (3-4) ◽  
pp. 99-114 ◽  
Author(s):  
Bogusław Bagiński ◽  
Ray Macdonald
Keyword(s):  
Critical Role ◽  
Geochemical Modelling ◽  
Accessory Mineral ◽  
Compositional Variation ◽  
Optical Techniques ◽  
Wide Range ◽  
Mineral Assemblages ◽  
Coherent Pairs ◽  
Near Future

AbstractChevkinite-group minerals are widespread in a very wide range of igneous and metamorphic parageneses, forming important components of accessory mineral assemblages. Their presence in a rock may be difficult to establish by standard optical techniques, which has contributed to their importance being underestimated; a combination of SEM and EMPA is recommended here. Currently, there are eleven IMAapproved members of the group but undoubtedly several more will be described in the near future. There is considerable compositional variation in the group, which can be expressed as: REE + M2+C + M3+C = Ca2+ A + Sr + Ti4+C + Zr4+C where A and C are structural sites. Chevkinite-group minerals strongly fractionate geochemically coherent pairs, such as LREE-HREE, Nb-Ta, Zr-Hf and Th-U, and thus play a critical role in geochemical modelling.

Application of the Innovative and Non-Invasive Technique, Molecular Music Therapy (MMT), Bio-Frequency Therapy, for the Treatment of a Wide Range of Disorders and Pathologies, with Consequent Verification of Molecular Parameters by Using Bi-Digital O-Ring Test (BDORT)

2020 ◽  
Vol 44 (3) ◽  
pp. 177-189
Author(s):  
Momir Dunjic ◽  
Stefano Turini ◽  
Dejan Krstic ◽  
Katarina Dunjic ◽  
Marija Dunjic ◽  
...  
Keyword(s):  
Amino Acid ◽  
Music Therapy ◽  
Amino Acid Sequences ◽  
Sirtuin 1 ◽  
Ring Test ◽  
Invasive Technique ◽  
Specific Gene ◽  
Radiofrequency Therapy ◽  
Wide Range ◽  
Clinical Pictures

Radiofrequency therapy is an unconventional method, already applied for some time, with numerous results in numerous clinical pictures. Our group has developed a software, later called SONGENPROT-SOLARIS, capable of directly converting nucleotide sequences (DNA and/or RNA) and amino acid sequences (polypeptides and proteins) into musical sequences, based on mathematic matrices, designed by the French physicist and musician Joel Sternheimer, which allows to associate a musical note with a nucleotide or an amino acid. Innovation in our software is that, in the algorithm that defines it, a variant is directly implemented that allows the reproduction of sounds, phase-shifted by 30 Hz, between one ear and another reproducing the phenomenon of Binaural Tones, capable of induce a specific brain activity and also the release of particles called solitons. Thanks to this software we have developed a technique called MMT (Molecular Music Therapy) and currently, we are in the phase of applying the technique on a cohort of 91 patients, with a high spectrum of clinical pictures, examining the same, using the technique Bi-Digital-ORing-Test (BDORT), before and after treatment with MMT. Aim of project is to stimulate the expression of a specific gene (the same genetic sequence that the patient listens to, translated into music), only through the use of sound sequences. We have concentrated our attention on three main molecules: Sirtuin-1, Telomers and TP-53. The results obtained with BDORT, after treatment with MMT, showed a significant increase in the values of the three molecules, on all the examined patients, demonstrating the operative efficacy of the technique and the its applicability to numerous diseases. In order to confirm the data obtained by BDORT, we propose, with the help of an accredited laboratory, to perform epigenetic tests on the three parameters listed above, paving the way to understanding how frequencies can influence gene expression.

The chemistry of 4-(dicyanomethylene)-3-methyl-l-phenyl-2-pyrazoline-5- ones as a privileged scaffold in synthesis of heterocycles

2020 ◽  
Vol 17 ◽  
Author(s):  
Mohsen A.-M. Gomaa ◽  
Huda A. Ali
Keyword(s):  
Building Block ◽  
Heterocyclic Compounds ◽  
Recent Progress ◽  
Reaction Conditions ◽  
Azacrown Ethers ◽  
Wide Range ◽  
Privileged Scaffold ◽  
Number Of Publications ◽  
Near Future

Background : The reactivity of 4-(dicyanomethylene)-3-methyl-l-phenyl-2-pyrazoline-5-one DCNP 1 and its derivatives makes it valuable as a building block for the synthesis of heterocyclic compounds like pyrazolo-imidazoles, - thiazoles, spiropyridines, spiropyrroles, spiropyrans and others. As a number of publications have reported on the reactivity of DCNP and its derivatives, we compiled some features of this interesting molecule. Objective: This article aims to review the preparation of DCNP, its reactivity and application in heterocyclic and dyes synthesis. Conclusion: In this review we have provided an overview of recent progress in the chemistry of DCNP and its significance in synthesis of various classes of heterocyclic compounds and dyes. The unique reactivity of DCNP offers unprecedentedly mild reaction conditions for the generation of versatile cynomethylene dyes from a wide range of precursors including amines, α-aminocarboxylic acids, their esters, phenols, malononitriles and azacrown ethers. We anticipate that more innovative transformations involving DCNP will continue to emerge in the near future.

Shooting a Tiger

2018 ◽  
Author(s):  
Vijaya Ramadas Mandala
Keyword(s):  
Critical Role ◽  
Late Nineteenth Century ◽  
Way Of Life ◽  
Colonial India ◽  
British Raj ◽  
Early Colonial ◽  
Wide Range ◽  
Forest Legislation ◽  
Imperial Governance ◽  
North And South

The main contention of Shooting a Tiger is that hunting during the colonial period was not merely a recreational activity, but a practice intimately connected with imperial governance. The book positions shikar or hunting at the heart of colonial rule by demonstrating that, for the British in India, it served as a political, practical, and symbolic apparatus in the consolidation of power and rule during the nineteenth and early twentieth centuries. The book analyses early colonial hunting during the Company period, and then surveys different aspects of hunting during the high imperial decades in the later nineteenth and early twentieth centuries. The book draws upon an impressive array of archival material and uses a wide range of evidence to support its contentions. It examines hunting at a variety of social and ethnic levels—military, administrative, elite, princely India, Indian professional hunters, and in terms of Indian auxiliaries and (sometimes) resisters. It also deals with different geographical contexts—the plains, the mountains, north and south India. The exclusive privilege of hunting exercised by the ruling classes, following colonial forest legislation, continued to be extended to the Indian princes who played a critical role in sustaining the lavish hunts that became the hallmark of the late nineteenth-century British Raj. Hunting was also a way of life in colonial India, undertaken by officials and soldiers alike alongside their everyday duties, necessary for their mental sustenance and vital for the smooth operation of the colonial administration. There are also two final chapters on conservation, particularly the last chapter focusing on two British hunter-turned-conservationists, Jim Corbett and Colonel Richard Burton.

scholarly journals Unique structural solution from a VH3-30 antibody targeting the hemagglutinin stem of influenza A viruses

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wayne D. Harshbarger ◽  
Derrick Deming ◽  
Gordon J. Lockbaum ◽  
Nattapol Attatippaholkun ◽  
Maliwan Kamkaew ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Influenza A ◽  
Critical Role ◽  
Binding Activity ◽  
Human Antibody ◽  
Broadly Neutralizing Antibodies ◽  
Influenza A Viruses ◽  
Universal Vaccine ◽  
Structural Details ◽  
Structural Solution

AbstractBroadly neutralizing antibodies (bnAbs) targeting conserved influenza A virus (IAV) hemagglutinin (HA) epitopes can provide valuable information for accelerating universal vaccine designs. Here, we report structural details for heterosubtypic recognition of HA from circulating and emerging IAVs by the human antibody 3I14. Somatic hypermutations play a critical role in shaping the HCDR3, which alone and uniquely among VH3-30 derived antibodies, forms contacts with five sub-pockets within the HA-stem hydrophobic groove. 3I14 light-chain interactions are also key for binding HA and contribute a large buried surface area spanning two HA protomers. Comparison of 3I14 to bnAbs from several defined classes provide insights to the bias selection of VH3-30 antibodies and reveals that 3I14 represents a novel structural solution within the VH3-30 repertoire. The structures reported here improve our understanding of cross-group heterosubtypic binding activity, providing the basis for advancing immunogen designs aimed at eliciting a broadly protective response to IAV.

scholarly journals SARS-CoV-2 specific antibody and neutralization assays reveal the wide range of the humoral immune response to virus

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Mikail Dogan ◽  
Lina Kozhaya ◽  
Lindsey Placek ◽  
Courtney Gunter ◽  
Mesut Yigit ◽  
...  
Keyword(s):  
Specific Antibody ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
High Specificity ◽  
Spike Protein ◽  
Humoral Immune ◽  
Specificity And Sensitivity ◽  
Wide Range ◽  
Specific Igg ◽  
Negative Controls

AbstractDevelopment of antibody protection during SARS-CoV-2 infection is a pressing question for public health and for vaccine development. We developed highly sensitive SARS-CoV-2-specific antibody and neutralization assays. SARS-CoV-2 Spike protein or Nucleocapsid protein specific IgG antibodies at titers more than 1:100,000 were detectable in all PCR+ subjects (n = 115) and were absent in the negative controls. Other isotype antibodies (IgA, IgG1-4) were also detected. SARS-CoV-2 neutralization was determined in COVID-19 and convalescent plasma at up to 10,000-fold dilution, using Spike protein pseudotyped lentiviruses, which were also blocked by neutralizing antibodies (NAbs). Hospitalized patients had up to 3000-fold higher antibody and neutralization titers compared to outpatients or convalescent plasma donors. Interestingly, some COVID-19 patients also possessed NAbs against SARS-CoV Spike protein pseudovirus. Together these results demonstrate the high specificity and sensitivity of our assays, which may impact understanding the quality or duration of the antibody response during COVID-19 and in determining the effectiveness of potential vaccines.

scholarly journals Using Satellite Data for CBRN (Chemical, Biological, Radiological, and Nuclear) Threat Detection, Monitoring, and Modelling

2021 ◽  
Author(s):  
Gary Sutlieff ◽  
Lucy Berthoud ◽  
Mark Stinchcombe
Keyword(s):  
Satellite Data ◽  
Meteorological Data ◽  
Atmospheric Composition ◽  
Chemical Detection ◽  
List Type ◽  
Data Types ◽  
Wide Range ◽  
Future Technologies ◽  
The Impact ◽  
Near Future

Abstract CBRN (Chemical, Biological, Radiological, and Nuclear) threats are becoming more prevalent, as more entities gain access to modern weapons and industrial technologies and chemicals. This has produced a need for improvements to modelling, detection, and monitoring of these events. While there are currently no dedicated satellites for CBRN purposes, there are a wide range of possibilities for satellite data to contribute to this field, from atmospheric composition and chemical detection to cloud cover, land mapping, and surface property measurements. This study looks at currently available satellite data, including meteorological data such as wind and cloud profiles, surface properties like temperature and humidity, chemical detection, and sounding. Results of this survey revealed several gaps in the available data, particularly concerning biological and radiological detection. The results also suggest that publicly available satellite data largely does not meet the requirements of spatial resolution, coverage, and latency that CBRN detection requires, outside of providing terrain use and building height data for constructing models. Lastly, the study evaluates upcoming instruments, platforms, and satellite technologies to gauge the impact these developments will have in the near future. Improvements in spatial and temporal resolution as well as latency are already becoming possible, and new instruments will fill in the gaps in detection by imaging a wider range of chemicals and other agents and by collecting new data types. This study shows that with developments coming within the next decade, satellites should begin to provide valuable augmentations to CBRN event detection and monitoring. Article Highlights There is a wide range of existing satellite data in fields that are of interest to CBRN detection and monitoring. The data is mostly of insufficient quality (resolution or latency) for the demanding requirements of CBRN modelling for incident control. Future technologies and platforms will improve resolution and latency, making satellite data more viable in the CBRN management field

scholarly journals Whole-Genome Sequence Analysis of Pseudorabies Virus Clinical Isolates from Pigs in China between 2012 and 2017 in China

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1322
Author(s):  
Ruiming Hu ◽  
Leyi Wang ◽  
Qingyun Liu ◽  
Lin Hua ◽  
Xi Huang ◽  
...  
Keyword(s):  
Selection Pressure ◽  
Pseudorabies Virus ◽  
Viral Evolution ◽  
Infectious Agent ◽  
Genomic Diversity ◽  
Whole Genome Sequence ◽  
Evolutionary Constraint ◽  
The Novel ◽  
Novel Variants ◽  
Pressure Analysis

Pseudorabies virus (PRV) is an economically significant swine infectious agent. A PRV outbreak took place in China in 2011 with novel virulent variants. Although the association of viral genomic variability with pathogenicity is not fully confirmed, the knowledge concerning PRV genomic diversity and evolution is still limited. Here, we sequenced 54 genomes of novel PRV variants isolated in China from 2012 to 2017. Phylogenetic analysis revealed that China strains and US/Europe strains were classified into two separate genotypes. PRV strains isolated from 2012 to 2017 in China are highly related to each other and genetically close to classic China strains such as Ea, Fa, and SC. RDP analysis revealed 23 recombination events within novel PRV variants, indicating that recombination contributes significantly to the viral evolution. The selection pressure analysis indicated that most ORFs were under evolutionary constraint, and 19 amino acid residue sites in 15 ORFs were identified under positive selection. Additionally, 37 unique mutations were identified in 19 ORFs, which distinguish the novel variants from classic strains. Overall, our study suggested that novel PRV variants might evolve from classical PRV strains through point mutation and recombination mechanisms.

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