Recent Molecular Evolution of Human Metapneumovirus (HMPV): Subdivision of HMPV A2b Strains

Human metapneumovirus (HMPV) is a major etiological agent of acute respiratory infections in humans. HMPV has been circulating worldwide for more than six decades and is currently divided into five agreed-upon subtypes: A1, A2a, A2b, B1, and B2. Recently, the novel HMPV subtypes A2c, A2b1, and A2b2 have been proposed. However, the phylogenetic and evolutionary relationships between these recently proposed HMPV subtypes are unclear. Here, we report a genome-wide phylogenetic and evolutionary analysis of 161 HMPV strains, including unique HMPV subtype A2b strains with a 180- or 111-nucleotide duplication in the G gene (nt-dup). Our data demonstrate that the HMPV A2b subtype contains two distinct subtypes, A2b1 and A2b2, and that the HMPV subtypes A2c and A2b2 may be different names for the same subtype. HMPV A2b strains with a nt-dup also belong to subtype A2b2. Molecular evolutionary analyses indicate that subtypes A2b1 and A2b2 diverged from subtype A2b around a decade after the subtype A2 was divided into the subtypes A2a and A2b. These data support the A2b1 and A2b2 subtypes proposed in 2012 and are essential for the unified classification of HMPV subtype A2 strains, which is important for future HMPV surveillance and epidemiological studies.

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F-Box Genes in the Wheat Genome and Expression Profiling in Wheat at Different Developmental Stages

Genes ◽

10.3390/genes11101154 ◽

2020 ◽

Vol 11 (10) ◽

pp. 1154

Author(s):

Min Jeong Hong ◽

Jin-Baek Kim ◽

Yong Weon Seo ◽

Dae Yeon Kim

Keyword(s):

Developmental Stages ◽

Brachypodium Distachyon ◽

Triticum Aestivum L ◽

Wheat Genome ◽

Post Translational Modification ◽

Genome Wide ◽

A Genome ◽

High Sequence Homology ◽

Wide Scale

Genes of the F-box family play specific roles in protein degradation by post-translational modification in several biological processes, including flowering, the regulation of circadian rhythms, photomorphogenesis, seed development, leaf senescence, and hormone signaling. F-box genes have not been previously investigated on a genome-wide scale; however, the establishment of the wheat (Triticum aestivum L.) reference genome sequence enabled a genome-based examination of the F-box genes to be conducted in the present study. In total, 1796 F-box genes were detected in the wheat genome and classified into various subgroups based on their functional C-terminal domain. The F-box genes were distributed among 21 chromosomes and most showed high sequence homology with F-box genes located on the homoeologous chromosomes because of allohexaploidy in the wheat genome. Additionally, a synteny analysis of wheat F-box genes was conducted in rice and Brachypodium distachyon. Transcriptome analysis during various wheat developmental stages and expression analysis by quantitative real-time PCR revealed that some F-box genes were specifically expressed in the vegetative and/or seed developmental stages. A genome-based examination and classification of F-box genes provide an opportunity to elucidate the biological functions of F-box genes in wheat.

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A Genome-Wide Comparative Evolutionary Analysis of Herpes Simplex Virus Type 1 and Varicella Zoster Virus

PLoS ONE ◽

10.1371/journal.pone.0022527 ◽

2011 ◽

Vol 6 (7) ◽

pp. e22527 ◽

Cited By ~ 44

Author(s):

Peter Norberg ◽

Shaun Tyler ◽

Alberto Severini ◽

Rich Whitley ◽

Jan-Åke Liljeqvist ◽

...

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

Varicella Zoster Virus ◽

Herpes Simplex Virus Type ◽

Evolutionary Analysis ◽

Varicella Zoster ◽

Genome Wide ◽

A Genome ◽

Simplex Virus

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Molecular epidemiology of human respiratory syncytial virus and human metapneumovirus in hospitalized children with acute respiratory infections in Croatia, 2014–2017

Infection Genetics and Evolution ◽

10.1016/j.meegid.2019.104039 ◽

2019 ◽

Vol 76 ◽

pp. 104039 ◽

Cited By ~ 3

Author(s):

M. Jagusic ◽

A. Slovic ◽

J. Ivancic-Jelecki ◽

S. Ljubin-Sternak ◽

T. Vilibić-Čavlek ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

Molecular Epidemiology ◽

Respiratory Infections ◽

Human Metapneumovirus ◽

Human Respiratory Syncytial Virus ◽

Hospitalized Children ◽

Acute Respiratory Infections ◽

Syncytial Virus

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Genome-wide survey and expression analysis of the SLAC/SLAH gene family in pear (Pyrus bretschneideri) and other members of the Rosaceae

10.1101/288308 ◽

2018 ◽

Author(s):

Guodong Chen ◽

Xiaolong Li ◽

Xin qiao ◽

Jiaming Li ◽

Li Wang ◽

...

Keyword(s):

Gene Family ◽

Stress Responses ◽

Prunus Persica ◽

Higher Plants ◽

Chloride Transport ◽

Structural Characteristics ◽

Evolutionary Analysis ◽

Anion Channels ◽

Genome Wide ◽

A Genome

AbstractS-type anion channels (SLAC/SLAHs), which play important roles in plant anion (such as nitrate and chloride) transport, growth and development, abiotic stress responses and hormone signaling. However, there is far less information about this family in Rosaceae species. We performed a genome-wide analysis and identified SLAC/SLAH gene family members in pear (Pyrus bretschneideri) and four other species of Rosaceae (Malus domestica, Prunus persica, Fragaria vesca and Prunus mume). A total of 21 SLAC/SLAH genes were identified from the five Rosaceae species. Based on the structural characteristics and a phylogenetic analysis of these genes, the SLAC/SLAH gene family could be classified into three main groups (I, II and III). The evolutionary analysis showed that the SLAC/SLAH gene family was comparatively conserved during the evolution of Rosaceae species. Transcriptome data demonstrated that PbrSLAC/SLAH genes were detected in all parts of the pear. However, PbrSLAC1 showed a higher expression level in leaf, while PbrSLAH2/3 was mainly expressed in roots. In addition, PbrSLAC/SLAH genes were only located on the plasma membrane in transient expression experiments in Arabidopsis protoplasts cells. These results provide valuable information that increases our understanding of the evolution, expression and functions of the SLAC/SLAH gene family in higher plants.

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A genome-wide CRISPR screen identifies interactors of the autophagy pathway as conserved coronavirus targets

10.1101/2021.02.24.432634 ◽

2021 ◽

Author(s):

Annika Kratzel ◽

Jenna N. Kelly ◽

Yannick Brueggemann ◽

Jasmine Portmann ◽

Philip V’kovski ◽

...

Keyword(s):

Host Factors ◽

The Novel ◽

Genome Wide ◽

A Genome ◽

Dependent Inhibition ◽

Crispr Screen ◽

Dose Dependent Inhibition ◽

Autophagy Pathway ◽

Approved Drugs ◽

Dose Dependent

SummaryOver the past 20 years, the emergence of three highly pathogenic coronaviruses (CoV) – SARS-CoV, MERS-CoV, and most recently SARS-CoV-2 – has shown that CoVs pose a serious risk to human health and highlighted the importance of developing effective therapies against them. Similar to other viruses, CoVs are dependent on host factors for their survival and replication. We hypothesized that evolutionarily distinct CoVs may exploit similar host factors and pathways to support their replication cycle. Here, we conducted two independent genome-wide CRISPR/Cas9 knockout screens to identify pan-CoV host factors required for the replication of both endemic and emerging CoVs, including the novel CoV SARS-CoV-2. Strikingly, we found that several autophagy-related genes, including the immunophilin FKBP8, TMEM41B, and MINAR1, were common host factors required for CoV replication. Importantly, inhibition of the immunophilin family with the compounds Tacrolimus, Cyclosporin A, and the non-immunosuppressive derivative Alisporivir, resulted in dose-dependent inhibition of CoV replication in primary human nasal epithelial cell cultures that resemble the natural site of virus replication. Overall, we identified host factors that are crucial for CoV replication and demonstrate that these factors constitute potential targets for therapeutic intervention by clinically approved drugs.

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Elucidating the genetic architecture underlying IGF1 levels and its impact on genomic instability and cancer risk

Wellcome Open Research ◽

10.12688/wellcomeopenres.16417.1 ◽

2021 ◽

Vol 6 ◽

pp. 20

Author(s):

Stasa Stankovic ◽

Felix R. Day ◽

Yajie Zhao ◽

Claudia Langenberg ◽

Nicholas J. Wareham ◽

...

Keyword(s):

Genomic Instability ◽

Genome Wide Association Study ◽

Genetic Regulation ◽

Epidemiological Studies ◽

European Ancestry ◽

Reverse Causality ◽

Lung Cancers ◽

Genome Wide ◽

A Genome ◽

The Uk

Background: Insulin-like growth factor-1 (IGF1) has been implicated in mitogenic and anti-apoptotic mechanisms that promote susceptibility to cancer development and growth. Previous epidemiological studies have described phenotypic associations between higher circulating levels of IGF1 in adults with higher risks for breast, prostate, ovarian, colorectal, melanoma and lung cancers. However, such evidence is prone to confounding and reverse causality. Furthermore, it is unclear whether IGF1 promotes only the survival and proliferation of cancerous cells, or also the malignant transformation of healthy cells. Methods: We perform a genome-wide association study in 428,525 white European ancestry individuals in the UK Biobank study (UKBB) and identify 831 independent genetic determinants of circulating IGF1 levels, double the number previously reported. Results: Collectively these signals explain ~7.5% of the variance in circulating IGF1 levels in EPIC-Norfolk, with individuals in the highest 10% of genetic risk exhibiting ~1 SD higher levels than those in the lowest 10%. Using a Mendelian randomization approach, we demonstrate that genetically higher circulating IGF1 levels are associated with greater likelihood of mosaic loss of chromosome Y in leukocytes in men in UKBB (OR per +1 SD = 1.038 (95% CI: 1.010-1.067), P=0.008) and 23andMe, Inc. (P=6.8×10-05), a biomarker of genomic instability involved in early tumorigenesis. Genetically higher IGF1 is also associated with higher risks for colorectal (OR = 1.126 (1.048-1.210), P=1.3×10-03) and breast cancer (OR= 1.075 (1.048-1.103), P=3.9×10-08), with similar effects on estrogen positive (ER+) (OR = 1.069 (1.037-1.102), P=2.3×10-05) and estrogen negative (ER-) (OR = 1.074 (1.025-1.125), P=3.9×10-08) subtypes. Conclusions: These findings give an insight into the genetic regulation of circulating IGF1 levels and support a causal role for IGF1 in early tumorigenesis and risks for breast and colorectal cancers.

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Acute respiratory infections in outpatient care in the era of the COVID-19 pandemic: the role and position of antibacterial therapy

Russian Medical Inquiry ◽

10.32364/2587-6821-2020-4-4-214-218 ◽

2020 ◽

Vol 4 (4) ◽

pp. 214-218

Author(s):

R.F. Khamitov ◽

Keyword(s):

Health Care ◽

Outpatient Care ◽

Viral Infections ◽

Respiratory Infections ◽

Respiratory Viruses ◽

Acute Respiratory Infections ◽

The Novel ◽

Coronavirus Infection ◽

Novel Coronavirus ◽

Care Costs

Acute respiratory infections of the upper and lower respiratory tract are currently the leading cause of human morbidity, mainly due to the seasonal rise of the incidence rates of viral infections. This results in the heavy burden of annual health care costs. The COVID-19 pandemic exacerbated the problem. The associations between respiratory viruses and bacteria are not always clear thus accounting for the diversity of the risks of the complicated course and fatal outcomes of various bacterial viral coinfections. Influenza virus is associated with the high rate of bacterial complications (in particular, during seasonal peaks). Meanwhile, this is less typical of the novel coronavirus infection. In addition, several studies demonstrate the competitive edge of SARS-CoV-2 when interacting with other respiratory viruses. The specificities of viral bacterial associations greatly affect the treatment whose inadequacy (in particular, the prescription of antibiotics) is the leading cause of the increasing antimicrobial resistance of contemporary germs. The novel coronavirus infection SARS-CoV-2 is no exception in terms of inappropriate antibiotic prescribing as occurred often in the seasonal rise of acute respiratory viral infections. The understanding of this issue, the optimization of treatment strategies, and a reduction in health care costs will allow for preserving antibiotics as a class of highly effective medications. KEYWORDS: acute respiratory infections, COVID-19, bacterial coinfection, outpatient care, lung damage, antimicrobial therapy. FOR CITATION: Khamitov R.F. Acute respiratory infections in outpatient care in the era of the COVID-19 pandemic: the role and position of antibacterial therapy. Russian Medical Inquiry. 2020;4(4):214–218. DOI: 10.32364/2587-6821-2020-4-4-214-218.

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Pathogenesis ofHelicobacter pylori-Related Gastroduodenal Diseases from Molecular Epidemiological Studies

Gastroenterology Research and Practice ◽

10.1155/2012/371503 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 42

Author(s):

Yoshio Yamaoka

Keyword(s):

Gastric Cancer ◽

Virulence Factors ◽

Epidemiological Studies ◽

Sequencing Technology ◽

Disease Spectrum ◽

Genome Wide ◽

A Genome ◽

High Prevalence ◽

Different Types ◽

H Pylori

Helicobacter pyloriis a major human pathogen that infects the stomach and produces inflammation that is responsible for various gastroduodenal diseases. Despite the high prevalence ofH. pyloriinfections in Africa and South Asia, the incidence of gastric cancer in these areas is much lower than in other countries. The incidence of gastric cancer also tends to decrease from north to south in East Asia. Data from molecular epidemiological studies show that this variation in different geographic areas could be explained in part by different types ofH. pylorivirulence factors, especially CagA, VacA, and OipA.H. pyloriinfection is thought to be involved in both gastric cancer and duodenal ulcer, which are at opposite ends of the disease spectrum. This discrepancy can also be explained in part by anotherH. pylorifactor, DupA, as well as by CagA typing (East Asian type versus Western type).H. pylorihas a genome of approximately 1,600 genes; therefore, there might be other novel virulence factors. Because genome wide analyses using whole-genome sequencing technology give a broad view of the genome ofH. pylori, we hope that next-generation sequencers will enable us to efficiently investigate novel virulence factors.

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