scholarly journals Zinc and Copper Ions Differentially Regulate Prion-Like Phase Separation Dynamics of Pan-Virus Nucleocapsid Biomolecular Condensates

Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1179 ◽  
Author(s):  
Anne Monette ◽  
Andrew J. Mouland
Keyword(s):  
Phase Separation ◽  
Metal Ion ◽  
Rna Binding ◽  
Copper Ions ◽  
Virus Assembly ◽  
Neurological Diseases ◽  
Meta Analysis ◽  
Metal Homeostasis ◽  
Virus Infections ◽  
As Stress

Liquid-liquid phase separation (LLPS) is a rapidly growing research focus due to numerous demonstrations that many cellular proteins phase-separate to form biomolecular condensates (BMCs) that nucleate membraneless organelles (MLOs). A growing repertoire of mechanisms supporting BMC formation, composition, dynamics, and functions are becoming elucidated. BMCs are now appreciated as required for several steps of gene regulation, while their deregulation promotes pathological aggregates, such as stress granules (SGs) and insoluble irreversible plaques that are hallmarks of neurodegenerative diseases. Treatment of BMC-related diseases will greatly benefit from identification of therapeutics preventing pathological aggregates while sparing BMCs required for cellular functions. Numerous viruses that block SG assembly also utilize or engineer BMCs for their replication. While BMC formation first depends on prion-like disordered protein domains (PrLDs), metal ion-controlled RNA-binding domains (RBDs) also orchestrate their formation. Virus replication and viral genomic RNA (vRNA) packaging dynamics involving nucleocapsid (NC) proteins and their orthologs rely on Zinc (Zn) availability, while virus morphology and infectivity are negatively influenced by excess Copper (Cu). While virus infections modify physiological metal homeostasis towards an increased copper to zinc ratio (Cu/Zn), how and why they do this remains elusive. Following our recent finding that pan-retroviruses employ Zn for NC-mediated LLPS for virus assembly, we present a pan-virus bioinformatics and literature meta-analysis study identifying metal-based mechanisms linking virus-induced BMCs to neurodegenerative disease processes. We discover that conserved degree and placement of PrLDs juxtaposing metal-regulated RBDs are associated with disease-causing prion-like proteins and are common features of viral proteins responsible for virus capsid assembly and structure. Virus infections both modulate gene expression of metalloproteins and interfere with metal homeostasis, representing an additional virus strategy impeding physiological and cellular antiviral responses. Our analyses reveal that metal-coordinated virus NC protein PrLDs initiate LLPS that nucleate pan-virus assembly and contribute to their persistence as cell-free infectious aerosol droplets. Virus aerosol droplets and insoluble neurological disease aggregates should be eliminated by physiological or environmental metals that outcompete PrLD-bound metals. While environmental metals can control virus spreading via aerosol droplets, therapeutic interference with metals or metalloproteins represent additional attractive avenues against pan-virus infection and virus-exacerbated neurological diseases.

scholarly journals Proteomics Analysis Unravels the Functional Repertoire of Coronavirus Nonstructural Protein 3

2008 ◽  
Vol 82 (11) ◽  
pp. 5279-5294 ◽  
Author(s):  
Benjamin W. Neuman ◽  
Jeremiah S. Joseph ◽  
Kumar S. Saikatendu ◽  
Pedro Serrano ◽  
Amarnath Chatterjee ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Metal Ion ◽  
Rna Binding ◽  
Virus Assembly ◽  
Nonstructural Protein ◽  
Domain Architecture ◽  
Complete Characterization ◽  
Functional Domain ◽  
Metal Ion Binding ◽  
Nonstructural Protein 3

ABSTRACT Severe acute respiratory syndrome (SARS) coronavirus infection and growth are dependent on initiating signaling and enzyme actions upon viral entry into the host cell. Proteins packaged during virus assembly may subsequently form the first line of attack and host manipulation upon infection. A complete characterization of virion components is therefore important to understanding the dynamics of early stages of infection. Mass spectrometry and kinase profiling techniques identified nearly 200 incorporated host and viral proteins. We used published interaction data to identify hubs of connectivity with potential significance for virion formation. Surprisingly, the hub with the most potential connections was not the viral M protein but the nonstructural protein 3 (nsp3), which is one of the novel virion components identified by mass spectrometry. Based on new experimental data and a bioinformatics analysis across the Coronaviridae, we propose a higher-resolution functional domain architecture for nsp3 that determines the interaction capacity of this protein. Using recombinant protein domains expressed in Escherichia coli, we identified two additional RNA-binding domains of nsp3. One of these domains is located within the previously described SARS-unique domain, and there is a nucleic acid chaperone-like domain located immediately downstream of the papain-like proteinase domain. We also identified a novel cysteine-coordinated metal ion-binding domain. Analyses of interdomain interactions and provisional functional annotation of the remaining, so-far-uncharacterized domains are presented. Overall, the ensemble of data surveyed here paint a more complete picture of nsp3 as a conserved component of the viral protein processing machinery, which is intimately associated with viral RNA in its role as a virion component.

scholarly journals Non-autoimmune diabetes mellitus and the risk of virus infections: a systematic review and meta-analysis of case-control and cohort studies

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Eric Lontchi-Yimagou ◽  
Charly Feutseu ◽  
Sebastien Kenmoe ◽  
Alexandra Lindsey Djomkam Zune ◽  
Solange Fai Kinyuy Ekali ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Systematic Review ◽  
Cohort Studies ◽  
H1n1 Virus ◽  
Autoimmune Diabetes ◽  
Meta Analysis ◽  
Case Control ◽  
Cochrane Central Register ◽  
Virus Infections ◽  
Autoimmune Diabetes Mellitus

AbstractA significant number of studies invoked diabetes as a risk factor for virus infections, but the issue remains controversial. We aimed to examine whether non-autoimmune diabetes mellitus enhances the risk of virus infections compared with the risk in healthy individuals without non-autoimmune diabetes mellitus. In this systematic review and meta-analysis, we assessed case-control and cohort studies on the association between non-autoimmune diabetes and viruses. We searched PubMed, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and Web of Science with no language restriction, to identify articles published until February 15, 2021. The main outcome assessment was the risk of virus infection in individuals with non-autoimmune diabetes. We used a random-effects model to pool individual studies and assessed heterogeneity (I2) using the χ2 test on Cochrane’s Q statistic. This study is registered with PROSPERO, number CRD42019134142. Out of 3136 articles identified, we included 68 articles (90 studies, as the number of virus and or diabetes phenotype varied between included articles). The summary OR between non-autoimmune diabetes and virus infections risk were, 10.8(95% CI: 10.3–11.4; 1-study) for SARS-CoV-2; 3.6(95%CI: 2.7–4.9, I2 = 91.7%; 43-studies) for HCV; 2.7(95% CI: 1.3–5.4, I2 = 89.9%, 8-studies;) for HHV8; 2.1(95% CI: 1.7–2.5; 1-study) for H1N1 virus; 1.6(95% CI: 1.2–2.13, I2 = 98.3%, 27-studies) for HBV; 1.5(95% CI: 1.1–2.0; 1-study) for HSV1; 3.5(95% CI: 0.6–18.3 , I2 = 83.9%, 5-studies) for CMV; 2.9(95% CI: 1–8.7, 1-study) for TTV; 2.6(95% CI: 0.7–9.1, 1-study) for Parvovirus B19; 0.7(95% CI: 0.3–1.5 , 1-study) for coxsackie B virus; and 0.2(95% CI: 0–6.2; 1-study) for HGV. Our findings suggest that, non-autoimmune diabetes is associated with increased susceptibility to viruses especially SARS-CoV-2, HCV, HHV8, H1N1 virus, HBV and HSV1. Thus, these viruses deserve more attention from diabetes health-care providers, researchers, policy makers, and stakeholders for improved detection, overall proper management, and efficient control of viruses in people with non-autoimmune diabetes.

scholarly journals The SARS-CoV-2 nucleocapsid phosphoprotein forms mutually exclusive condensates with RNA and the membrane-associated M protein

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shan Lu ◽  
Qiaozhen Ye ◽  
Digvijay Singh ◽  
Yong Cao ◽  
Jolene K. Diedrich ◽  
...  
Keyword(s):  
Phase Separation ◽  
Potential Role ◽  
Rna Binding ◽  
Stress Granule ◽  
M Protein ◽  
Rich Region ◽  
Virion Assembly ◽  
N Protein ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions

AbstractThe multifunctional nucleocapsid (N) protein in SARS-CoV-2 binds the ~30 kb viral RNA genome to aid its packaging into the 80–90 nm membrane-enveloped virion. The N protein is composed of N-terminal RNA-binding and C-terminal dimerization domains that are flanked by three intrinsically disordered regions. Here we demonstrate that the N protein’s central disordered domain drives phase separation with RNA, and that phosphorylation of an adjacent serine/arginine rich region modulates the physical properties of the resulting condensates. In cells, N forms condensates that recruit the stress granule protein G3BP1, highlighting a potential role for N in G3BP1 sequestration and stress granule inhibition. The SARS-CoV-2 membrane (M) protein independently induces N protein phase separation, and three-component mixtures of N + M + RNA form condensates with mutually exclusive compartments containing N + M or N + RNA, including annular structures in which the M protein coats the outside of an N + RNA condensate. These findings support a model in which phase separation of the SARS-CoV-2 N protein contributes both to suppression of the G3BP1-dependent host immune response and to packaging genomic RNA during virion assembly.

scholarly journals The effectiveness of Bacopa monnieri (Linn.) Wettst. as a nootropic, neuroprotective, or antidepressant supplement: analysis of the available clinical data

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
James M. Brimson ◽  
Sirikalaya Brimson ◽  
Mani Iyer Prasanth ◽  
Premrutai Thitilertdecha ◽  
Dicson Sheeja Malar ◽  
...  
Keyword(s):  
Plant Extracts ◽  
Neurological Diseases ◽  
Digit Span ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Verbal Learning ◽  
Memory Loss ◽  
Learning Task ◽  
Inspection Time ◽  
Neuroprotective Effects

AbstractBacopamonnieri (Linn.) Wettst. has been used in traditional medicine as a drug to enhance and improve memory. In this regard, this study aims to provide B. monnieri's efficacy as a neuroprotective drug and as a nootropic against various neurological diseases. Literatures were collected, following Prisma guidelines, from databases, including Scopus, PubMed, Google Scholar, and Science Direct and were scrutinized using a quality scoring system. Means, standard deviations and ‘n’ numbers were extracted from the metrics and analyzed. Jamovi computer software for Mac was used to carry out the meta-analysis. The selected studies suggested that the plant extracts were able to show some improvements in healthy subjects which were determined in Auditory Verbal Learning Task, digit span-reverse test, inspection time task and working memory, even though it was not significant, as no two studies found statistically significant changes in the same two tests. B. monnieri was able to express modest improvements in subjects with memory loss, wherein only a few of the neuropsychological tests showed statistical significance. B. monnieri in a cocktail with other plant extracts were able to significantly reduce the effects of Alzheimer’s disease, and depression which cannot be solely credited as the effect of B. monnieri. Although in one study B. monnieri was able to potentiate the beneficial effects of citalopram; on the whole, currently, there are only limited studies to establish the memory-enhancing and neuroprotective effects of B. monnieri. More studies have to be done in the future by comparing the effect with standard drugs, in order to establish these effects clinically in the plant and corroborate the preclinical data.

scholarly journals A Personal Journey across Fluorescent Sensing and Logic Associated with Polymers of Various Kinds

Polymers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1351 ◽  
Author(s):  
Chao-Yi Yao ◽  
Seiichi Uchiyama ◽  
A. Prasanna de Silva
Keyword(s):  
Phase Separation ◽  
Metal Ion ◽  
Chemical Species ◽  
Polymer Science ◽  
Molecular Sensing ◽  
Fluorescent Sensing ◽  
Molecular Logic ◽  
Fluorescent Molecular Sensing ◽  
Molecular Scale ◽  
Identification Tags

Our experiences concerning fluorescent molecular sensing and logic devices and their intersections with polymer science are the foci of this brief review. Proton-, metal ion- and polarity-responsive cases of these devices are placed in polymeric micro- or nano-environments, some of which involve phase separation. This leads to mapping of chemical species on the nanoscale. These devices also take advantage of thermal properties of some polymers in water in order to reincarnate themselves as thermometers. When the phase separation leads to particles, the latter can be labelled with identification tags based on molecular logic. Such particles also give rise to reusable sensors, although molecular-scale resolution is sacrificed in the process. Polymeric nano-environments also help to organize rather complex molecular logic systems from their simple components. Overall, our little experiences suggest that researchers in sensing and logic would benefit if they assimilate polymer concepts.

scholarly journals Hepatitis C virus infections in oral lichen planus: a systematic review and meta-analysis

2016 ◽  
Vol 61 (3) ◽  
pp. 282-287 ◽  
Author(s):  
NA Alaizari ◽  
SA Al-Maweri ◽  
HM Al-Shamiri ◽  
B Tarakji ◽  
B Shugaa-Addin
Keyword(s):  
Systematic Review ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Lichen Planus ◽  
Oral Lichen Planus ◽  
Meta Analysis ◽  
Virus Infections ◽  
Oral Lichen

Phase separation of RNA-binding protein promotes polymerase binding and transcription

2021 ◽  
Author(s):  
Wen Shao ◽  
Xianju Bi ◽  
Yixuan Pan ◽  
Boyang Gao ◽  
Jun Wu ◽  
...  
Keyword(s):  
Phase Separation ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Polymerase Binding

scholarly journals The prevalence of sleep disturbances among physicians and nurses facing the COVID-19 patients: a systematic review and meta-analysis

2020 ◽  
Vol 16 (1) ◽  
Author(s):  
Nader Salari ◽  
Habibolah Khazaie ◽  
Amin Hosseinian-Far ◽  
Hooman Ghasemi ◽  
Masoud Mohammadi ◽  
...  
Keyword(s):  
Systematic Review ◽  
Sample Size ◽  
Medical Staff ◽  
Sleep Disturbances ◽  
Meta Analysis ◽  
Workplace Stress ◽  
Cross Sectional ◽  
Significance Level ◽  
Nurses And Physicians ◽  
As Stress

Abstract Background In all epidemics, healthcare staff are at the centre of risks and damages caused by pathogens. Today, nurses and physicians are faced with unprecedented work pressures in the face of the COVID-19 pandemic, resulting in several psychological disorders such as stress, anxiety and sleep disturbances. The aim of this study is to investigate the prevalence of sleep disturbances in hospital nurses and physicians facing the COVID-19 patients. Method A systematic review and metanalysis was conducted in accordance with the PRISMA criteria. The PubMed, Scopus, Science direct, Web of science, CINHAL, Medline, and Google Scholar databases were searched with no lower time-limt and until 24 June 2020. The heterogeneity of the studies was measured using I2 test and the publication bias was assessed by the Egger’s test at the significance level of 0.05. Results The I2 test was used to evaluate the heterogeneity of the selected studies, based on the results of I2 test, the prevalence of sleep disturbances in nurses and physicians is I2: 97.4% and I2: 97.3% respectively. After following the systematic review processes, 7 cross-sectional studies were selected for meta-analysis. Six studies with the sample size of 3745 nurses were examined in and the prevalence of sleep disturbances was approximated to be 34.8% (95% CI: 24.8-46.4%). The prevalence of sleep disturbances in physicians was also measured in 5 studies with the sample size of 2123 physicians. According to the results, the prevalence of sleep disturbances in physicians caring for the COVID-19 patients was reported to be 41.6% (95% CI: 27.7-57%). Conclusion Healthcare workers, as the front line of the fight against COVID-19, are more vulnerable to the harmful effects of this disease than other groups in society. Increasing workplace stress increases sleep disturbances in the medical staff, especially nurses and physicians. In other words, increased stress due to the exposure to COVID-19 increases the prevalence of sleep disturbances in nurses and physicians. Therefore, it is important for health policymakers to provide solutions and interventions to reduce the workplace stress and pressures on medical staff.

scholarly journals Identification of Key Deregulated RNA-Binding Proteins in Pancreatic Cancer by Meta-Analysis and Prediction of Their Role as Modulators of Oncogenesis

2021 ◽  
Vol 9 ◽  
Author(s):  
Moumita Mukherjee ◽  
Srikanta Goswami
Keyword(s):  
Pancreatic Cancer ◽  
Cell Migration ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Meta Analysis ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Ppi Network ◽  
Pathway Enrichment

RNA-binding proteins (RBPs) play a significant role in multiple cellular processes with their deregulations strongly associated with cancer. However, there are not adequate evidences regarding global alteration and functions of RBPs in pancreatic cancer, interrogated in a systematic manner. In this study, we have prepared an exhaustive list of RBPs from multiple sources, downloaded gene expression microarray data from a total of 241 pancreatic tumors and 124 normal pancreatic tissues, performed a meta-analysis, and obtained differentially expressed RBPs (DE-RBPs) using the Limma package of R Bioconductor. The results were validated in microarray datasets and the Cancer Genome Atlas (TCGA) RNA sequencing dataset for pancreatic adenocarcinoma (PAAD). Pathway enrichment analysis was performed using DE-RBPs, and we also constructed the protein–protein interaction (PPI) network to detect key modules and hub-RBPs. Coding and noncoding targets for top altered and hub RBPs were identified, and altered pathways modulated by these targets were also investigated. Our meta-analysis identified 45 upregulated and 15 downregulated RBPs as differentially expressed in pancreatic cancer, and pathway enrichment analysis demonstrated their important contribution in tumor development. As a result of PPI network analysis, 26 hub RBPs were detected and coding and noncoding targets for all these RBPs were categorized. Functional exploration characterized the pathways related to epithelial-to-mesenchymal transition (EMT), cell migration, and metastasis to emerge as major pathways interfered by the targets of these RBPs. Our study identified a unique meta-signature of 26 hub-RBPs to primarily modulate pancreatic tumor cell migration and metastasis in pancreatic cancer. IGF2BP3, ISG20, NIP7, PRDX1, RCC2, RUVBL1, SNRPD1, PAIP2B, and SIDT2 were found to play the most prominent role in the regulation of EMT in the process. The findings not only contribute to understand the biology of RBPs in pancreatic cancer but also to evaluate their candidature as possible therapeutic targets.

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