scholarly journals Lung Disease Network Reveals the Impact of Comorbidity on SARS-CoV-2 infection

2020 ◽  
Author(s):  
Asim Bikas Das
Keyword(s):  
Lung Diseases ◽  
Small World ◽  
Disease Association ◽  
Disease Network ◽  
Functional Protein ◽  
Protein Protein Interaction ◽  
Formidable Challenge ◽  
Small World Property ◽  
Clinical Conditions ◽  
The Impact

AbstractHigher mortality of COVID19 patients with comorbidity is the formidable challenge faced by the health care system. In response to the present crisis, understanding the molecular basis of comorbidity is essential to accelerate the development of potential drugs. To address this, we have measured the genetic association between COVID19 and various lung disorders and observed a remarkable resemblance. 141 lung disorders directly or indirectly linked to COVID19 result in a high-density disease-disease association network that shows a small-world property. The clustering of many lung diseases with COVID19 demonstrates a greater complexity and severity of SARS-CoV-2 infection. Furthermore, our results show that the functional protein-protein interaction modules involved RNA and protein metabolism, substantially hijacked by SARS-CoV-2, are connected to several lung disorders. Therefore we recommend targeting the components of these modules to inhibit the viral growth and improve the clinical conditions in comorbidity.

scholarly journals Lung Disease Network Reveals the Impact of Comorbidity on SARS-CoV-2 Infection and Opportunities of Drug Repurposing

2020 ◽  
Author(s):  
ASIM BIKAS DAS
Keyword(s):  
Lung Disease ◽  
Lung Diseases ◽  
Drug Repurposing ◽  
Functional Protein ◽  
Potential Threat ◽  
Protein Protein Interaction ◽  
Molecular Features ◽  
Formidable Challenge ◽  
Clinical Conditions ◽  
The Impact

Abstract Higher mortality of COVID-19 patients with comorbidity is the formidable challenge faced by the health care system. In response to the present crisis, understanding the molecular basis of comorbidity is essential to accelerate the development of drugs. To address this, the genetic association between COVID-19 and various lung disorders was measured and notable molecular resemblance was observed. 141 lung diseases were linked to a neighborhood network of SARS-CoV-2 targets, and 59 lung diseases topologically overlapped with COVID-19 module. This demonstrates the clustering of lung diseases with COVID-19 in the same network vicinity, indicating the potential threat for lung patients upon SARS-CoV-2 infection. Pathobiological similarities between lung diseases and COVID-19, and clinical evidences suggest that shared molecular features probably the reason for comorbidity. Additionally, topological overlap with various lung disorders provides an opportunity to repurpose the drugs used for lung disease to hit the closely associated COVID-19 module. Further analysis showed that the functional protein-protein interaction modules in the lungs, substantially hijacked by SARS-CoV-2, were connected to several lung disorders. The network-based proximity measure identified the FDA approved targets in hijacked protein modules which can be hit by existing drugs to rescue these modules from viral possessions, and can lead to the improvement of clinical conditions.

Optimization Decision Promotion Model of Supply Chain Networks with Logistics Speed

2014 ◽  
Vol 644-650 ◽  
pp. 6170-6173
Author(s):  
Lang Liao ◽  
Yong Hong Huang ◽  
Chang Jiang Zhao
Keyword(s):  
Supply Chain ◽  
Decision Model ◽  
Small World ◽  
Optimal Decision ◽  
Supply Chain Networks ◽  
Product Consumption ◽  
Product Pricing ◽  
Total Profit ◽  
Small World Property ◽  
The Impact

Commercial logistics speed has the dynamic characteristics of the impact on supply chain. In order to establish the relationship between logistics speed and supply chain network decision model, accurately grasp the logistics effect on supply chain decision, an optimization decision model of supply chain networks with logistics layer weighting was proposed. The whole complex network model of hierarchical supply chain was established. The product pricing and logistics strategies and optimization decision were proposed for realizing the maximum total profit. The simulation results show that the optimal decision model is shown in small world property, and it can reflect the product consumption demand reality effectively, the total profit of the whole supply chain is significantly increased compared with the traditional method, and the network system is adaptive and robust.

scholarly journals Lung disease network reveals impact of comorbidity on SARS-CoV-2 infection and opportunities of drug repurposing

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Asim Bikas Das
Keyword(s):  
Lung Disease ◽  
Drug Targets ◽  
Lung Diseases ◽  
Drug Repurposing ◽  
Pathway Enrichment Analysis ◽  
Functional Protein ◽  
Potential Threat ◽  
Molecular Features ◽  
Formidable Challenge ◽  
Protein Modules

Abstract Background Higher mortality of COVID-19 patients with lung disease is a formidable challenge for the health care system. Genetic association between COVID-19 and various lung disorders must be understood to comprehend the molecular basis of comorbidity and accelerate drug development. Methods Lungs tissue-specific neighborhood network of human targets of SARS-CoV-2 was constructed. This network was integrated with lung diseases to build a disease–gene and disease-disease association network. Network-based toolset was used to identify the overlapping disease modules and drug targets. The functional protein modules were identified using community detection algorithms and biological processes, and pathway enrichment analysis. Results In total, 141 lung diseases were linked to a neighborhood network of SARS-CoV-2 targets, and 59 lung diseases were found to be topologically overlapped with the COVID-19 module. Topological overlap with various lung disorders allows repurposing of drugs used for these disorders to hit the closely associated COVID-19 module. Further analysis showed that functional protein–protein interaction modules in the lungs, substantially hijacked by SARS-CoV-2, are connected to several lung disorders. FDA-approved targets in the hijacked protein modules were identified and that can be hit by exiting drugs to rescue these modules from virus possession. Conclusion Lung diseases are clustered with COVID-19 in the same network vicinity, indicating the potential threat for patients with respiratory diseases after SARS-CoV-2 infection. Pathobiological similarities between lung diseases and COVID-19 and clinical evidence suggest that shared molecular features are the probable reason for comorbidity. Network-based drug repurposing approaches can be applied to improve the clinical conditions of COVID-19 patients.

scholarly journals Ageratina adenophora Inhibits Spleen Immune Function in Rats via the Loss of the FRC Network and Th1–Th2 Cell Ratio Elevation

Toxins ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 309
Author(s):  
Zhihua Ren ◽  
Pei Gao ◽  
Samuel Kumi Okyere ◽  
Yujing Cui ◽  
Juan Wen ◽  
...  
Keyword(s):  
Protein Expression ◽  
Immune Function ◽  
Tissue Sample ◽  
Th2 Cells ◽  
Sample Collection ◽  
Functional Protein ◽  
Th2 Cell ◽  
Ageratina Adenophora ◽  
Mrna And Protein Expression ◽  
The Impact

The objective of this study was to determine the impact of Ageratina adenophora (A. adenophora) on splenic immune function in a rat model. Rats were fed with 10 g/100 g normal feed and an experimental feed, which was composed of 3:7 A. adenophora powder and normal feed for 60 days. On days 14, 28, and 60, subsets of rats (n = 8 rats/group/time point) were selected for blood and spleen tissue sample collection. The results showed that the proportion of CD3+ T cells in the spleen was decreased at day 60 (vs. control). Also, mRNA and protein expression of chemokines CCL21 and CCL19 and functional protein gp38 in spleen decreased significantly versus the control at day 60. In addition, ER-TR7 antigen protein expression was also decreased at day 60. Levels of T-helper (Th)1 cells significantly increased, whereas those of Th2 cells decreased significantly versus the control at day 60 in spleen. The finding revealed that A. adenophora could affect splenic immune function in rats by altering the fibroblast reticulocyte (FRC) network, as well as by causing an imbalance in Th1/Th2 cell ratios. This research provides new insights into potential mechanisms of spleen immunotoxicity due to exposures to A. Adenophora.

scholarly journals Can recurrence networks show small-world property?

2016 ◽  
Vol 380 (35) ◽  
pp. 2718-2723 ◽  
Author(s):  
Rinku Jacob ◽  
K.P. Harikrishnan ◽  
R. Misra ◽  
G. Ambika
Keyword(s):  
Small World ◽  
Small World Property

Predictive Control and Simulation for Variable-Pitch Wind Turbines

2012 ◽  
Vol 562-564 ◽  
pp. 1012-1015
Author(s):  
S.X. Wang ◽  
Z.X. Li ◽  
D.X. Sun ◽  
X.X. Xie
Keyword(s):  
Neural Network ◽  
Predictive Control ◽  
Small World ◽  
Modeling Method ◽  
Reference Trajectory ◽  
System Delay ◽  
Variable Pitch ◽  
Electricity Grid ◽  
System Output ◽  
The Impact

In order to avoid the limitations of traditional mechanism modeling method, a neural network (NN) model of variable - pitch wind turbine is built by the NN modeling method based on field data. Then considering that from wind turbine’s startup to grid integration, the generator speed must be controlled to rise to the synchronous speed smoothly and precisely, a neural network model predictive control (NNMPC) strategy based on the small-world optimization algorithm (SWOA) is proposed. Simulation results show that the strategy can forecast the change of generator rotational speed based on the wind speed disturbance, making the controller act ahead to eliminate the impact of system delay. Furthermore, the system output can track the reference trajectory well, making sure that the system can connect the electricity grid steadily.

The state of the cardiovascular system in occupational bronchitis and chronic obstructive pulmonary disease, not associated with the impact of harmful industrial factors

2021 ◽  
pp. 55-68
Author(s):  
Vyacheslav S. Lotkov ◽  
Anton Vladimirovich Glazistov ◽  
Antonina G. Baykova ◽  
Marina Yuryevna Vostroknutova ◽  
Natalia E. Lavrentieva
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Cardiovascular System ◽  
Pulmonary Disease ◽  
Lung Diseases ◽  
Chronic Obstructive ◽  
External Respiration ◽  
Obstructive Pulmonary Disease ◽  
Occupational Lung Diseases ◽  
The Right ◽  
The Impact

The formation and progression of chronic dust bronchitis and chronic bronchitis of toxic-chemical etiology, chronic obstructive pulmonary disease is accompanied by an increase in the degree of ventilation disorders, echocardiographic signs of hypertrophy and dilatation of the right ventricle are formed, typical for chronic pulmonary heart disease. The progression of disturbances in the function of external respiration in dusty lung diseases leads to a decrease in myocardial contractility. The detection of hemodynamic disturbances at the early stages of the development of occupational lung diseases indicates the need for individual monitoring of the functional state of the cardiovascular system in the process of contact with industrial aerosols, especially in groups of workers with long-term exposure.

Selection of AmpC β-lactamase variants and metallo-β-lactamases leading to ceftolozane/tazobactam and ceftazidime/avibactam-resistance during treatment of MDR/XDR Pseudomonas aeruginosa infections

2021 ◽  
Author(s):  
Alba Ruedas-López ◽  
Isaac Alonso García ◽  
Cristina Lasarte-Monterrubio ◽  
Paula Guijarro-Sánchez ◽  
Eva Gato ◽  
...  
Keyword(s):  
3D Models ◽  
Resistance Mechanisms ◽  
Class 1 ◽  
Long Read ◽  
Cephalosporin Resistance ◽  
One Year ◽  
Clinical Conditions ◽  
Hybrid Assemblies ◽  
Chromosomal Mutations ◽  
The Impact

Infections caused by ceftolozane/tazobactam and ceftazidime/avibactam-resistant P. aeruginosa infections are an emerging concern. We aimed to analyze the underlying ceftolozane/tazobactam and ceftazidime/avibactam resistance mechanisms in all MDR/XDR P. aeruginosa isolates recovered during one year (2020) from patients with a documented P. aeruginosa infection. Fifteen isolates showing ceftolozane/tazobactam and ceftazidime/avibactam resistance were evaluated. Clinical conditions, previous positive cultures and β-lactams received in the previous month were reviewed for each patient. MICs were determined by broth microdilution. MLSTs and resistance mechanisms were determined using short- and long-read WGS. The impact of PDCs on β-lactam resistance was demonstrated by cloning into an ampC -deficient PAO1 derivative (PAOΔC) and construction of 3D models. Genetic support of acquired β-lactamases was determined in silico from high-quality hybrid assemblies. In most cases, the isolates were recovered after treatment with ceftolozane/tazobactam or ceftazidime/avibactam. Seven isolates from different STs owed their β-lactam resistance to chromosomal mutations and all displayed specific substitutions in PDC: Phe121Leu and Gly222Ser, Pro154Leu, Ala201Thr, Gly214Arg, ΔGly203-Glu219 and Glu219Lys. In the other eight isolates, the ST175 clone was overrepresented (6 isolates) and associated with IMP-28 and IMP-13, whereas two ST1284 isolates produced VIM-2. The cloned PDCs conferred enhanced cephalosporin resistance. 3D PDC models revealed rearrangements affecting residues involved in cephalosporin hydrolysis. Carbapenemases were chromosomal (VIM-2) or plasmid-borne (IMP-28, IMP-13), and associated with class-1 integrons located in Tn402-like transposition modules. Our findings highlight that cephalosporin/ß-lactamase inhibitors are potential selectors of MDR/XDR P. aeruginosa strains producing PDC variants or metallo-ß-lactamases. Judicious use of these agents is encouraged.

GEMPROT: visualization of the impact on the protein of the genetic variants found on each haplotype

2018 ◽  
Vol 35 (14) ◽  
pp. 2492-2494
Author(s):  
Tania Cuppens ◽  
Thomas E Ludwig ◽  
Pascal Trouvé ◽  
Emmanuelle Genin
Keyword(s):  
Genetic Variants ◽  
Protein Sequence ◽  
Sequence Data ◽  
Protein Sequences ◽  
Supplementary Information ◽  
Analysis Tool ◽  
Functional Protein ◽  
Key Players ◽  
On Line ◽  
The Impact

Abstract Summary When analyzing sequence data, genetic variants are considered one by one, taking no account of whether or not they are found in the same individual. However, variant combinations might be key players in some diseases as variants that are neutral on their own can become deleterious when associated together. GEMPROT is a new analysis tool that allows, from a phased vcf file, to visualize the consequences of the genetic variants on the protein. At the level of an individual, the program shows the variants on each of the two protein sequences and the Pfam functional protein domains. When data on several individuals are available, GEMPROT lists the haplotypes found in the sample and can compare the haplotype distributions between different sub-groups of individuals. By offering a global visualization of the gene with the genetic variants present, GEMPROT makes it possible to better understand the impact of combinations of genetic variants on the protein sequence. Availability and implementation GEMPROT is freely available at https://github.com/TaniaCuppens/GEMPROT. An on-line version is also available at http://med-laennec.univ-brest.fr/GEMPROT/. Supplementary information Supplementary data are available at Bioinformatics online.

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