scholarly journals Neutrophil Involvement in Covid-19

2020 ◽  
Author(s):  
Athanasios Didangelos
Keyword(s):  
Interaction Network ◽  
Lavage Fluid ◽  
Lung Epithelial Cells ◽  
Organ Injury ◽  
Rna Seq ◽  
Protein Protein Interaction ◽  
Associated Proteins ◽  
Infected Cells ◽  
Neutrophil Response

Covid-19 is often related to hyperinflammation that drives lung or multi-organ injury. The immunopathological mechanisms that cause excessive inflammation following SARS-Cov-2 infection are under investigation while different approaches to limit hyperinflammation in affected patients are being proposed. Here, a computational protein-protein interaction network approach was used on recently available data to identify possible Covid-19 inflammatory mechanisms and bioactive genes. First, network analysis of putative SARS-Cov-2 cellular receptors and their directly associated proteins, led to the mining of a robust neutrophil response signature and multiple relevant inflammatory genes. Second, analysis of RNA-seq datasets of lung epithelial cells infected with SARS-Cov-2 revealed that infected cells specifically expressed neutrophil-attracting chemokines, further supporting the likely role of neutrophils in Covid-19 inflammation. Third, analysis of RNA-seq datasets of bronchoalveolar lavage fluid from Covid-19 patients, identified neutrophil-specific genes and chemokines. Different immunoregulatory and neutrophil-relevant molecules mined here such as, TNFR, IL8, CXCR1, CXCR2, ADAM10, GPR84, MME-neprilysin, ANPEP and LAP3 are druggable and might be therapeutic targets in efforts to limit SARS-Cov-2 inflammation in severe clinical cases. The role of neutrophils in Covid-19 needs to be studied further.

scholarly journals A Neutrophil Activation Signature in COVID-19

2020 ◽  
Author(s):  
Athanasios Didangelos
Keyword(s):  
Organ Damage ◽  
Lung Epithelial Cells ◽  
Interacting Proteins ◽  
Tnf Receptor ◽  
Rna Seq ◽  
Cellular Receptors ◽  
Lung Epithelial ◽  
Infected Cells ◽  
Neutrophil Response

Covid-19 is often related to hyperinflammation that drives lung or multi-organ damage and mortality. The immunopathological mechanisms that cause excessive inflammation following SARS-Cov-2 infection are under investigation while different approaches to limit hyperinflammation in affected patients are being proposed. Here, a computational network approach was used on recently available data to identify possible Covid-19 inflammatory mechanisms. First, network analysis of putative SARS-Cov-2 cellular receptors and their directly associated interacting proteins, led to the mining of a robust neutrophil-response signature and multiple relevant inflammatory response genes. Second, analysis of RNA-seq datasets of lung epithelial cells infected with SARS-Cov-2 found that infected cells specifically expressed neutrophil-attracting chemokines, further supporting the likely role of neutrophils in Covid-19 inflammation. The role of neutrophils in Covid-19 needs to be studied further. Different immunoregulatory molecules and pathways presented here (TNF Receptor, IL8, CXCR1, CXCR2, ADAM10, GPR84, MME-neprilysin, ANPEP, LAP3) are druggable and might be therapeutic targets in efforts to limit SARS-Cov-2 inflammation in severe clinical cases.

scholarly journals COVID-19 Hyperinflammation: What about Neutrophils?

mSphere ◽  
2020 ◽  
Vol 5 (3) ◽  
Author(s):  
Athanasios Didangelos
Keyword(s):  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Published Data ◽  
Data Sets ◽  
Rna Seq ◽  
Inflammatory Genes ◽  
Infected Cells ◽  
Neutrophil Response ◽  
Druggable Targets

ABSTRACT COVID-19 is often related to hyperinflammation that drives lung or multiorgan injury. The immunopathological mechanisms that cause excessive inflammation are under investigation and constantly updated. Here, a gene network approach was used on recently published data sets to identify possible COVID-19 inflammatory mechanisms and bioactive genes. First, network analysis of putative SARS-CoV-2 cellular receptors led to the mining of a neutrophil-response signature and relevant inflammatory genes. Second, analysis of RNA-seq data sets of lung cells infected with SARS-CoV-2 revealed that infected cells expressed neutrophil-attracting chemokines. Third, analysis of RNA-seq data sets of bronchoalveolar lavage fluid cells from COVID-19 patients identified upregulation of neutrophil genes and chemokines. Different inflammatory genes mined here, including TNFR, IL-8, CXCR1, CXCR2, ADAM10, GPR84, MME, ANPEP, and LAP3, might be druggable targets in efforts to limit SARS-CoV-2 inflammation in severe clinical cases. The possible role of neutrophils in COVID-19 inflammation needs to be studied further.

scholarly journals Evidence of a dysregulated vitamin D endocrine system in SARS-CoV-2 infected patient’s lung cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bijesh George ◽  
Revikumar Amjesh ◽  
Aswathy Mary Paul ◽  
T. R. Santhoshkumar ◽  
Madhavan Radhakrishna Pillai ◽  
...  
Keyword(s):  
Vitamin D ◽  
Endocrine System ◽  
Interaction Network ◽  
Lavage Fluid ◽  
Differentially Expressed ◽  
Cytokine Signaling ◽  
Lung Cells ◽  
Protein Protein Interaction ◽  
The Status ◽  
Infected Cells

AbstractAlthough a defective vitamin D endocrine system has been widely suspected to be associated in SARS-CoV-2 pathobiology, the status of the vitamin D endocrine system and vitamin D-modulated genes in lung cells of patients infected with SARS-CoV-2 remains unknown. To understand the significance of the vitamin D endocrine system in SARS-CoV-2 pathobiology, computational approaches were applied to transcriptomic datasets from bronchoalveolar lavage fluid (BALF) cells of such patients or healthy individuals. Levels of vitamin D receptor, retinoid X receptor, and CYP27A1 in BALF cells of patients infected with SARS-CoV-2 were found to be reduced. Additionally, 107 differentially expressed, predominantly downregulated genes, as potentially modulated by vitamin D endocrine system, were identified in transcriptomic datasets from patient’s cells. Further analysis of differentially expressed genes provided eight novel genes with a conserved motif with vitamin D-responsive elements, implying the role of both direct and indirect mechanisms of gene expression by the dysregulated vitamin D endocrine system in SARS-CoV-2-infected cells. Protein–protein interaction network of differentially expressed vitamin D-modulated genes were enriched in the immune system, NF-κB/cytokine signaling, and cell cycle regulation as top predicted pathways that might be affected in the cells of such patients. In brief, the results presented here povide computational evidence to implicate a dysregulated vitamin D endocrine system in the pathobiology of SARS-CoV-2 infection.

scholarly journals Genome-wide identification of the GATA transcription factor family and their expression patterns under temperature and salt stress in Aspergillus oryzae

AMB Express ◽  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chunmiao Jiang ◽  
Gongbo Lv ◽  
Jinxin Ge ◽  
Bin He ◽  
Zhe Zhang ◽  
...  
Keyword(s):  
Salt Stress ◽  
Expression Patterns ◽  
Interaction Network ◽  
Protein Protein Interaction ◽  
Genome Wide ◽  
Gata Transcription Factor ◽  
Starting Point ◽  
Evolutionary Features ◽  
First Time

AbstractGATA transcription factors (TFs) are involved in the regulation of growth processes and various environmental stresses. Although GATA TFs involved in abiotic stress in plants and some fungi have been analyzed, information regarding GATA TFs in Aspergillusoryzae is extremely poor. In this study, we identified and functionally characterized seven GATA proteins from A.oryzae 3.042 genome, including a novel AoSnf5 GATA TF with 20-residue between the Cys-X2-Cys motifs which was found in Aspergillus GATA TFs for the first time. Phylogenetic analysis indicated that these seven A. oryzae GATA TFs could be classified into six subgroups. Analysis of conserved motifs demonstrated that Aspergillus GATA TFs with similar motif compositions clustered in one subgroup, suggesting that they might possess similar genetic functions, further confirming the accuracy of the phylogenetic relationship. Furthermore, the expression patterns of seven A.oryzae GATA TFs under temperature and salt stresses indicated that A. oryzae GATA TFs were mainly responsive to high temperature and high salt stress. The protein–protein interaction network of A.oryzae GATA TFs revealed certain potentially interacting proteins. The comprehensive analysis of A. oryzae GATA TFs will be beneficial for understanding their biological function and evolutionary features and provide an important starting point to further understand the role of GATA TFs in the regulation of distinct environmental conditions in A.oryzae.

scholarly journals Dengue activates mTORC2 signaling to counteract apoptosis and maximize viral replication

2020 ◽  
Author(s):  
Christoph C. Carter ◽  
Jean Paul Olivier ◽  
Alexis Kaushansky ◽  
Fred D. Mast ◽  
John D. Aitchison
Keyword(s):  
Viral Replication ◽  
Cell Survival ◽  
Structural Protein ◽  
Protein Protein Interaction ◽  
Mechanistic Target Of Rapamycin ◽  
Promote Cell Survival ◽  
Important Regulator ◽  
Infected Cells ◽  
Induced Apoptosis

ABSTRACTThe mechanistic target of rapamycin (mTOR) functions in at least two distinct complexes: mTORC1, which regulates cellular anabolic-catabolic homeostasis, and mTORC2, which is an important regulator of cell survival and cytoskeletal maintenance. mTORC1 has been implicated in the pathogenesis of flaviviruses including dengue, where it contributes to the establishment of a pro-viral autophagic state. In contrast, the role of mTORC2 in viral pathogenesis is unknown. In this study, we explore the consequences of a physical protein-protein interaction between dengue non-structural protein 5 (NS5) and host cell mTOR proteins during infection. Using shRNA to differentially target mTORC1 and mTORC2 complexes, we show that mTORC2 is required for optimal dengue replication. Furthermore, we show that mTORC2 is activated during viral replication, and that mTORC2 counteracts virus-induced apoptosis, promoting the survival of infected cells. This work reveals a novel mechanism by which the dengue flavivirus can promote cell survival to maximize viral replication.

scholarly journals The diminishing role of hubs in dynamical processes on complex networks

2013 ◽  
Vol 10 (88) ◽  
pp. 20130568 ◽  
Author(s):  
Rick Quax ◽  
Andrea Apolloni ◽  
Peter M. A. Sloot
Keyword(s):  
Interaction Network ◽  
Macroscopic System ◽  
Protein Protein Interaction ◽  
Equilibrium Dynamics ◽  
Qualitative Evidence ◽  
Individual Unit ◽  
System Of Units ◽  
Protein Protein Interaction Network

It is notoriously difficult to predict the behaviour of a complex self-organizing system, where the interactions among dynamical units form a heterogeneous topology. Even if the dynamics of each microscopic unit is known, a real understanding of their contributions to the macroscopic system behaviour is still lacking. Here, we develop information-theoretical methods to distinguish the contribution of each individual unit to the collective out-of-equilibrium dynamics. We show that for a system of units connected by a network of interaction potentials with an arbitrary degree distribution, highly connected units have less impact on the system dynamics when compared with intermediately connected units. In an equilibrium setting, the hubs are often found to dictate the long-term behaviour. However, we find both analytically and experimentally that the instantaneous states of these units have a short-lasting effect on the state trajectory of the entire system. We present qualitative evidence of this phenomenon from empirical findings about a social network of product recommendations, a protein–protein interaction network and a neural network, suggesting that it might indeed be a widespread property in nature.

Construction and Analysis of Protein-Protein Interaction Network

2019 ◽  
pp. 204-220
Author(s):  
Divya Dasagrandhi ◽  
Arul Salomee Kamalabai Ravindran ◽  
Anusuyadevi Muthuswamy ◽  
Jayachandran K. S.
Keyword(s):  
Protein Interaction ◽  
Protein Interaction Network ◽  
Interaction Network ◽  
Data Sets ◽  
Protein Protein Interaction ◽  
Huge Data ◽  
Associated Proteins ◽  
High Throughput Experiments ◽  
Generation Sequencing ◽  
Protein Protein Interaction Network

Understanding the mechanisms of a disease is highly complicated due to the complex pathways involved in the disease progression. Despite several decades of research, the occurrence and prognosis of the diseases is not completely understood even with high throughput experiments like DNA microarray and next-generation sequencing. This is due to challenges in analysis of huge data sets. Systems biology is one of the major divisions of bioinformatics and has laid cutting edge techniques for the better understanding of these pathways. Construction of protein-protein interaction network (PPIN) guides the modern scientists to identify vital proteins through protein-protein interaction network, which facilitates the identification of new drug target and associated proteins. The chapter is focused on PPI databases, construction of PPINs, and its analysis.

scholarly journals Male differentiation in the marine copepod Oithona nana reveals the development of a new nervous ganglion linked to Lin12-Notch-Repeat protein-associated proteolysis

2021 ◽  
Author(s):  
Kevin Sugier ◽  
Romuald Laso-Jadart ◽  
Benoit Vacherie ◽  
Jos Kafer ◽  
Laurie Bertrand ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Protein Interaction ◽  
System Development ◽  
Interaction Network ◽  
Nervous System Development ◽  
Protein Coding ◽  
Protein Protein Interaction ◽  
Marine Copepod ◽  
Male Specific

Background: Copepods are among the most numerous animals, and play an essential role in the marine trophic web and biogeochemical cycles. The genus Oithona is described as having the highest density of copepods, and as being the most cosmopolite copepods. The Oithona male paradox describes the activity states of males, which are obliged to alternate between immobile and mobile phases for ambush feeding and mate searching, respectively, while the female is typically less mobile and often feeding. To characterize the molecular basis of this sexual dimorphism, we combined immunofluorescence, genomics, transcriptomics, and protein-protein interaction approaches. Results: Immunofluorescence of β3- and α-tubulin revealed two male-specific nervous ganglia in the lateral first segment of the Oithona nana male's prosome. In parallel, transcriptomic analysis showed male-specific enrichment for nervous system development-related transcripts. Twenty-seven Lin12-Notch Repeat domain-containing protein coding genes (LDPGs) of the 75 LDPGs identified in the genome were specifically expressed only in males. Furthermore, most of the LDPGs (27%) coded for proteins having predicted proteolytic activity, and non-LDPG proteolysis-associated transcripts showed a male-specific enrichment. Using yeast double-hybrid assays, we constructed a protein-protein interaction network involving two LDPs with proteases, extracellular matrix proteins, and neurogenesis-related proteins. Conclusions: For the first time, our study describes the lateral nervous ganglia of O. nana males, unique to copepods. We also demonstrated a role of LDPGs and their associated proteolysis in male-specific physiology, and we hypothesize a role of the LDPGs in the development of the lateral ganglia through directed lysis of the extracellular matrix for the growth of neurites and genesis of synapses.

scholarly journals Comparative Proteomic Analysis of Sweet Orange Petiole Provides Insights Into the Development of Huanglongbing Symptoms

2021 ◽  
Vol 12 ◽  
Author(s):  
Bo Li ◽  
Yi Zhang ◽  
Dewen Qiu ◽  
Frédéric Francis ◽  
Shuangchao Wang
Keyword(s):  
Proteomic Analysis ◽  
Sweet Orange ◽  
Interaction Network ◽  
Resistance Breeding ◽  
Defense Responses ◽  
Protein Accumulation ◽  
Leaf Petiole ◽  
Protein Protein Interaction ◽  
Comparative Proteomic Analysis ◽  
Associated Proteins

Huanglongbing (HLB) is the most destructive citrus disease worldwide. This is associated with the phloem-limited bacterium Candidatus Liberibacter, and the typical symptom is leaf blotchy mottle. To better understand the biological processes involved in the establishment of HLB disease symptoms, the comparative proteomic analysis was performed to reveal the global protein accumulation profiles in leaf petiole, where there are massive HLB pathogens of Ca. L. asiaticus-infected Newhall sweet orange (Citrus sinensis) plants at the asymptomatic and symptomatic stages compared to their healthy counterpart. Photosynthesis, especially the pathway involved in the photosystem I and II light reactions, was shown to be suppressed throughout the whole Ca. L. asiaticus infection cycle. Also, starch biosynthesis was induced after the symptom-free prodromal period. Many defense-associated proteins were more extensively regulated in the petiole with the symptoms than the ones from healthy plants. The change of salicylic and jasmonic acid levels in different disease stages had a positive correlation with the abundance of phytohormone biosynthesis-related proteins. Moreover, the protein–protein interaction network analysis indicated that an F-type ATPase and an alpha-1,4 glucan phosphorylase were the core nodes in the interactions of differentially accumulated proteins. Our study indicated that the infected citrus plants probably activated the non-unified and lagging enhancement of defense responses against Ca. L. asiaticus at the expense of photosynthesis and contribute to find out the key Ca. L. asiaticus-responsive genes for tolerance and resistance breeding.

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