scholarly journals Simulation study reveals factors that affect the predominance of SARS-CoV-2 novel variant

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Yuki Furuse
Keyword(s):  
Immune Escape ◽  
Good Control ◽  
The Novel ◽  
Novel Variants ◽  
Increasing Trend ◽  
Novel Variant ◽  
Global Concern ◽  
Case Number ◽  
Large Case ◽  
Infection Spread

AbstractThe novel variants of the SARS-CoV-2 are a great global concern for the ongoing COVID-19 pandemic. However, how the novel variants predominate and replace existing strains remains elusive. In this study, I simulated the infection spread to investigate what kinds of viral, immunological, and epidemiological factors affect the predominance of SARS-CoV-2 novel variants. The results showed that the increase of the transmissibility of the novel variant substantially enhanced the predominance probability. In addition, the increasing trend of the infection spread, the large case number of the epidemic, and the ability of immune escape of the novel variant increased the predominance probability. A small number of cases and a decreasing trend of an entire epidemic, including not only the novel variant but also earlier strains, are especially important to reduce the chance of the predominance of the novel variant and delay the process. Good control of the COVID-19 epidemic could make the disease burden small and sequester the spread of the SARS-CoV-2 novel variants.

scholarly journals Clinical and Functional Characterization of Novel INSR Variants in Two Families With Severe Insulin Resistance Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Qiaoli Zhou ◽  
Jing Yu ◽  
Xuewen Yuan ◽  
Chunli Wang ◽  
Ziyang Zhu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Resistance Syndrome ◽  
Type A ◽  
Chinese Children ◽  
The Novel ◽  
Severe Insulin Resistance ◽  
Functional Assays ◽  
Novel Variants ◽  
Novel Variant

ObjectiveDefects in the insulin receptor (INSR) gene cause various severe insulin resistance conditions, including Donohue syndrome (DS), Rabson-Mendenhall syndrome (RMS) and type A insulin resistance (type A-IR). This study aimed to investigate the clinical characterization and molecular defects in three Chinese children with INSR-related insulin resistance syndrome.MethodsWe reviewed the clinical data of three Chinese children with INSR-related insulin resistance syndrome from two unrelated kindreds. Genetic analysis was performed using whole-exome sequencing and the effects of the novel variants were further assessed by in vitro functional assays.ResultsThe proband with type A-IR presented with acanthosis nigricans, hypertrichosis, and euglycemia with mild insulin resistance in early childhood. His sister presented with features typical of type A-IR and was diagnosed with diabetes mellitus with severe insulin resistance at the age of 9.8 years. The proband with DS showed typical dysmorphic characteristics, severe intrauterine growth retardation, extreme insulin resistance, fasting hypoglycemia and postprandial hyperglycemia from birth. The heterozygote variants c.[3670G>A]; c.[3614C>T] were identified in both siblings with type A-IR; and c.[749_751del]; c.[3355C>T] in the patient with DS. In vitro studies showed that the novel variant c.749_751del [p.(Thr250del)] in the α-subunit, reduced expression of the mature INSR protein and severely impaired INSR function. In contrast, the novel variant c.3670G>A [p.(Val1224Met)] in the β-subunit had no effect on total protein expression and phosphorylation of INSR and Akt, suggesting that the variant p.Val1224Met appeared to be tolerated and was not responsible for the severe insulin resistance.ConclusionOur study detailed the clinical features of three patients with type A-IR and DS, and identified two novel variants in the INSR gene. Functional assays indicated the novel variant p.Thr250del was pathogenic. In contrast, the novel variant p.Val1224Met was suggested to be tolerated by our experimental data, even though bioinformatics analyses predicted the variant as deleterious.

scholarly journals Novel variants in PDE6A and PDE6B genes and its phenotypes in patients with retinitis pigmentosa in Chinese families

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Yuyu Li ◽  
Ruyi Li ◽  
Hehua Dai ◽  
Genlin Li
Keyword(s):  
Retinitis Pigmentosa ◽  
Autosomal Recessive ◽  
Compound Heterozygous ◽  
The Novel ◽  
Specific Enzyme ◽  
Genetic Changes ◽  
Chinese Families ◽  
Novel Variants ◽  
Novel Variant ◽  
Compound Heterozygous State

Abstract Background Retinitis pigmentosa (RP) is a genetically heterogeneous disease with 89 causative genes identified to date. However, only approximately 60% of RP cases genetically solved to date, predicating that many novel disease-causing variants are yet to be identified. The purpose of this study is to identify novel variants in PDE6A and PDE6B genes and present its phenotypes in patients with retinitis pigmentosa in Chinese families. Methods Five retinitis pigmentosa patients with PDE6A variants and three with PDE6B variants were identified through a hereditary eye disease enrichment panel (HEDEP), all patients’ medical and ophthalmic histories were collected, and ophthalmological examinations were performed, followed by an analysis of the possible causative variants. Sanger sequencing was used to verify the variants. Results We identified 20 variants in eight patients: 16 of them were identified in either PDE6A or PDE6B in a compound heterozygous state. Additional four heterozygous variants were identified in the genes ADGRA3, CA4, OPTN, RHO. Two novel genetic changes in PDE6A were identified (c.1246G > A and c.1747 T > A), three novel genetic changes in PDE6B were identified (c.401 T > C, c.2293G > C and c.1610-1612del), out of the novel identified variants one was most probably non-pathogenic (c.2293G > C), all other novel variants are pathogenic. Additional variant was identified in CA4 and RHO, which can cause ADRP (c.243G > A, c.688G > A). In addition, a novel variant in ADGRA3 was identified (c.921-1G > A). Conclusions This study reveals novel and known variants in PDE6A and PDE6B genes in Chinese families with autosomal recessive RP, and expands the clinical and genetic findings of photoreceptor-specific enzyme deficiencies.

scholarly journals Diminished neutralization responses towards SARS-CoV-2 Omicron VoC after mRNA or vector-based COVID-19 vaccinations

2021 ◽  
Author(s):  
Henning Jacobsen ◽  
Monika Strengert ◽  
Henrike Maass ◽  
Mario Alberto Ynga Durand ◽  
Barbora Kessel ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Immune Escape ◽  
Significant Risk ◽  
Neutralization Assay ◽  
The Novel ◽  
Wild Type ◽  
Neutralization Activity ◽  
Novel Variant

Background: SARS-CoV-2 variants accumulating immune escape mutations provide a significant risk to vaccine-induced protection. The novel variant of concern Omicron (B.1.1.529) has to date the largest number of amino acid alterations in its Spike protein. Thus, it may efficiently escape recognition by neutralizing antibodies, allowing breakthrough infections in convalescent and vaccinated individuals. Aims: We analysed neutralization activity after vaccination with all mRNA-, vector- or heterologous immunization schemes currently available in Europe at peak response and in a longitudinal follow-up with BNT162b2 vaccinees to define immune escape potential of the Omicron VoC. Methods: We tested sera by in vitro neutralization assay towards SARS-CoV-2 B.1, Omicron, Beta and Delta pseudotypes Results: All vaccines apart from Ad26.CoV2.S showed high levels of responder rates (93.3-100%) towards SARS-CoV-2 wild-type, but some reductions in neutralizing Beta and Delta VoC pseudotypes. The novel Omicron variant had the biggest impact, both in terms of response rates and neutralization titres among responders. Only mRNA-1273 showed a 100% response rate to Omicron and induced the highest titres of neutralizing antibodies, followed by heterologous prime-boost approaches. Homologous BNT162b2 vaccination or vector-based formulations with AZD1222 or Ad26.CoV2.S performed less well with peak responder rates of 33%, 50% and 9%, respectively. However, Omicron responder rates in BNT162b2 recipients were maintained in our six month longitudinal follow-up and even slightly increased to 47%, indicating cross-protection against Omicron is maintained over time. Conclusions: Overall, our data strongly argues for urgent booster doses in individuals who were previously vaccinated with BNT162b2, or a vector-based immunization scheme.

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.

scholarly journals Analysis and Prediction of COVID-19 Using SIR, SEIQR, and Machine Learning Models: Australia, Italy, and UK Cases

Information ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 109 ◽  
Author(s):  
Iman Rahimi ◽  
Amir H. Gandomi ◽  
Panagiotis G. Asteris ◽  
Fang Chen
Keyword(s):  
Machine Learning ◽  
Logistic Function ◽  
Prediction Performance ◽  
Machine Learning Algorithms ◽  
Model Parameters ◽  
The Novel ◽  
Chinese City ◽  
Limited Memory ◽  
Increasing Trend ◽  
Novel Coronavirus

The novel coronavirus disease, also known as COVID-19, is a disease outbreak that was first identified in Wuhan, a Central Chinese city. In this report, a short analysis focusing on Australia, Italy, and UK is conducted. The analysis includes confirmed and recovered cases and deaths, the growth rate in Australia compared with that in Italy and UK, and the trend of the disease in different Australian regions. Mathematical approaches based on susceptible, infected, and recovered (SIR) cases and susceptible, exposed, infected, quarantined, and recovered (SEIQR) cases models are proposed to predict epidemiology in the above-mentioned countries. Since the performance of the classic forms of SIR and SEIQR depends on parameter settings, some optimization algorithms, namely Broyden–Fletcher–Goldfarb–Shanno (BFGS), conjugate gradients (CG), limited memory bound constrained BFGS (L-BFGS-B), and Nelder–Mead, are proposed to optimize the parameters and the predictive capabilities of the SIR and SEIQR models. The results of the optimized SIR and SEIQR models were compared with those of two well-known machine learning algorithms, i.e., the Prophet algorithm and logistic function. The results demonstrate the different behaviors of these algorithms in different countries as well as the better performance of the improved SIR and SEIQR models. Moreover, the Prophet algorithm was found to provide better prediction performance than the logistic function, as well as better prediction performance for Italy and UK cases than for Australian cases. Therefore, it seems that the Prophet algorithm is suitable for data with an increasing trend in the context of a pandemic. Optimization of SIR and SEIQR model parameters yielded a significant improvement in the prediction accuracy of the models. Despite the availability of several algorithms for trend predictions in this pandemic, there is no single algorithm that would be optimal for all cases.

scholarly journals Novel dry electrode EEG headbands for home use: Comparing performance and comfort

2020 ◽  
Vol 6 (3) ◽  
pp. 139-142
Author(s):  
Jens Haueisen ◽  
Patrique Fiedler ◽  
Anna Bernhardt ◽  
Ricardo Gonçalves ◽  
Carlos Fonseca
Keyword(s):  
Brain Activity ◽  
Skin Impedance ◽  
Signal Quality ◽  
The Novel ◽  
Application Time ◽  
Dry Electrodes ◽  
Power Spectral ◽  
Dry Electrode ◽  
Increasing Trend ◽  
Eeg Recordings

AbstractMonitoring brain activity at home using electroencephalography (EEG) is an increasing trend for both medical and non-medical applications. Gel-based electrodes are not suitable due to the gel application requiring extensive preparation and cleaning support for the patient or user. Dry electrodes can be applied without prior preparation by the patient or user. We investigate and compare two dry electrode headbands for EEG acquisition: a novel hybrid dual-textile headband comprising multipin and multiwave electrodes and a neoprene-based headband comprising hydrogel and spidershaped electrodes. We compare the headbands and electrodes in terms of electrode-skin impedance, comfort, electrode offset potential and EEG signal quality. We did not observe considerable differences in the power spectral density of EEG recordings. However, the hydrogel electrodes showed considerably increased impedances and offset potentials, limiting their compatibility with many EEG amplifiers. The hydrogel and spider-shaped electrodes required increased adduction, resulting in a lower wearing comfort throughout the application time compared to the novel headband comprising multipin and multiwave electrodes.

Characterization of novel ybjG and dacC variants in Escherichia coli

2013 ◽  
Vol 62 (11) ◽  
pp. 1728-1734 ◽  
Author(s):  
Dongguo Wang ◽  
Enping Hu ◽  
Jiayu Chen ◽  
Xiulin Tao ◽  
Katelyn Gutierrez ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Multiple Drug Resistance ◽  
Multiple Drug ◽  
The Novel ◽  
Conventional Pcr ◽  
E Coli ◽  
Novel Variants ◽  
Restriction Sites ◽  
Genetic Structures

A total of 69 strains of Escherichia coli from patients in the Taizhou Municipal Hospital, China, were isolated, and 11 strains were identified that were resistant to bacitracin, chloramphenicol, tetracycline and erythromycin. These strains were PCR positive for at least two out of three genes, ybjG, dacC and mdfA, by gene mapping with conventional PCR detection. Conjugation experiments demonstrated that these genes existed in plasmids that conferred resistance. Novel ybjG and dacC variants were isolated from E. coli strains EC2163 and EC2347, which were obtained from the sputum of intensive care unit patients. Genetic mapping showed that the genes were located on 8200 kb plasmid regions flanked by EcoRI restriction sites. Three distinct genetic structures were identified among the 11 PCR-positive strains of E. coli, and two contained the novel ybjG and dacC variants. The putative amino acid differences in the ybjG and dacC gene variants were characterized. These results provide evidence for novel variants of ybjG and dacC, and suggest that multiple drug resistance in hospital strains of E. coli depends on the synergistic function of ybjG, dacC and mdfA within three distinct genetic structures in conjugative plasmids.

scholarly journals A novel multi-word paradigm for investigating semantic context effects in language production

2019 ◽  
Author(s):  
Cornelia van Scherpenberg ◽  
Rasha Abdel Rahman ◽  
Hellmuth Obrig
Keyword(s):  
Eye Tracking ◽  
Picture Naming ◽  
Language Production ◽  
Context Effects ◽  
Semantic Context ◽  
The Novel ◽  
Target Picture ◽  
Novel Variant ◽  
Lexical Interference ◽  
Respective Category

Semantic context modulates precision and speed of language production. Using different experimental designs including the Picture-Word-Interference (PWI) paradigm, it has consistently been shown that categorically related distractor words (e.g., cat) inhibit retrieval of the target picture name (dog). Here we introduce a novel variant of the PWI paradigm in which we present 8 words prior to a to be named target picture. Within this set, the number of words categorically related was varied between 3 and 5, and the picture to be named was either related or unrelated to the respective category. To disentangle interacting effects of semantic context we combined different naming paradigms manipulating the number of competitors, and assessing the effect of repeated naming instances. Evaluating processing of the cohort by eye-tracking provided us with a metric of the (implicit) recognition of the semantic cohort. Results replicate the interference effect in that overall naming of pictures categorically related to the distractor set was slower compared to unrelated pictures. However, interference did not increase with increasing number of distractors. Tracking this effect across naming repetitions, we found that interference is prominent at the first naming instance of every picture only, whereby it is stable across distractor conditions, but dissipates across the experiment. Regarding eye-tracking our data show that participants fixated longer on semantically related items, indicating the identification of the lexico-semantic cohort. Our findings confirm the validity of the novel paradigm and indicate that besides interference during first exposure, repeated exposure to the semantic context may facilitate picture naming and counteract lexical interference.

scholarly journals Antibody Cocktail Exhibits Broad Neutralization against SARS-CoV-2 and SARS-CoV-2 variants

2021 ◽  
Author(s):  
Yuanyuan Qu ◽  
Xueyan Zhang ◽  
Meiyu Wang ◽  
Lina Sun ◽  
Yongzhong Jiang ◽  
...  
Keyword(s):  
Immune Escape ◽  
Conformational Epitope ◽  
Viral Escape ◽  
Angiotensin Converting Enzyme 2 ◽  
Neutralizing Activity ◽  
High Affinity ◽  
Phage Display Libraries ◽  
Novel Variants ◽  
Antibody Phage ◽  
Antibody Phage Display

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has precipitated multiple variants resistant to therapeutic antibodies. In this study, 12 high-affinity antibodies were generated from convalescent donors in early outbreaks using immune antibody phage display libraries. Of them, two RBD-binding antibodies (F61 and H121) showed high affinity neutralization against SARS-CoV-2, whereas three S2-target antibodies failed to neutralize SARS-CoV-2. Following structure analysis, F61 identified a linear epitope located in residues G446 - S494, which overlapped with angiotensin-converting enzyme 2 (ACE2) binding sites, while H121 recognized a conformational epitope located on the side face of RBD, outside from ACE2 binding domain. Hence the cocktail of the two antibodies achieved better performance of neutralization to SARS-CoV-2. Importantly, F61 and H121 exhibited efficient neutralizing activity against variants B.1.1.7 and B.1.351, those showed immune escape. Efficient neutralization of F61 and H121 against multiple mutations within RBD revealed a broad neutralizing activity against SARS-CoV-2 variants, which mitigated the risk of viral escape. Our findings defined the basis of therapeutic cocktails of F61 and H121 with broad neutralization and delivered a guideline for the current and future vaccine design, therapeutic antibody development, and antigen diagnosis of SARS-CoV-2 and its novel variants.

scholarly journals Limited within-host diversity and tight transmission bottlenecks limit SARS-CoV-2 evolution in acutely infected individuals

2021 ◽  
Author(s):  
Katarina Braun ◽  
Gage Kahl Moreno ◽  
Cassia Wagner ◽  
Molly A. Accola ◽  
William M Rehrauer ◽  
...  
Keyword(s):  
Immune Escape ◽  
Acute Infection ◽  
Host Diversity ◽  
Recent Emergence ◽  
Novel Variants ◽  
Efficient Selection

The recent emergence of divergent SARS-CoV-2 lineages has raised concerns about the role of selection within individual hosts in propagating novel variants. Of particular concern are variants associated with immune escape and/or enhanced transmissibility. Though growing evidence suggests that novel variants can arise during prolonged infections, most infections are acute. Understanding the extent to which variants emerge and transmit among acutely infected hosts is therefore critical for predicting the pace at which variants resistant to vaccines or conferring increased transmissibility might emerge in the majority of SARS-CoV-2 infections. To characterize how within-host diversity is generated and propagated, we combine extensive laboratory and bioinformatic controls with metrics of within- and between-host diversity to 133 SARS-CoV-2 genomes from acutely infected individuals. We find that within-host diversity during acute infection is low and transmission bottlenecks are narrow, with very few viruses founding most infections. Within-host variants are rarely transmitted, even among individuals within the same household. Accordingly, we also find that within-host variants are rarely detected along phylogenetically linked infections in the broader community. Together, these findings suggest that efficient selection and transmission of novel SARS-CoV-2 variants is unlikely during typical, acute infection.

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