scholarly journals Antiviral RNAi in Insects and Mammals: Parallels and Differences

Viruses ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 448 ◽  
Author(s):  
Susan Schuster ◽  
Pascal Miesen ◽  
Ronald P. van Rij
Keyword(s):  
Defense Mechanism ◽  
Rnai Pathway ◽  
Future Research ◽  
Type I ◽  
Antiviral Defense ◽  
First Line ◽  
Differentiated Cells ◽  
Open Questions ◽  
Interferon System ◽  
Viral Suppressors

The RNA interference (RNAi) pathway is a potent antiviral defense mechanism in plants and invertebrates, in response to which viruses evolved suppressors of RNAi. In mammals, the first line of defense is mediated by the type I interferon system (IFN); however, the degree to which RNAi contributes to antiviral defense is still not completely understood. Recent work suggests that antiviral RNAi is active in undifferentiated stem cells and that antiviral RNAi can be uncovered in differentiated cells in which the IFN system is inactive or in infections with viruses lacking putative viral suppressors of RNAi. In this review, we describe the mechanism of RNAi and its antiviral functions in insects and mammals. We draw parallels and highlight differences between (antiviral) RNAi in these classes of animals and discuss open questions for future research.

scholarly journals Leveraging the antiviral type I interferon system as a first line of defense against SARS-CoV-2 pathogenicity

Immunity ◽  
2021 ◽  
Author(s):  
Daisy A. Hoagland ◽  
Rasmus Møller ◽  
Skyler A. Uhl ◽  
Kohei Oishi ◽  
Justin Frere ◽  
...  
Keyword(s):  
Type I Interferon ◽  
Type I ◽  
First Line ◽  
Interferon System

scholarly journals Terminal uridylyltransferases target RNA viruses as part of the innate immune system in animals

2017 ◽  
Author(s):  
Jérémie Le Pen ◽  
Hongbing Jiang ◽  
Tomás Di Domenico ◽  
Emma Kneuss ◽  
Joanna Kosałka ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Influenza A ◽  
Large Scale ◽  
Defense Mechanism ◽  
Rna Viruses ◽  
Interferon Response ◽  
Rnai Pathway ◽  
Antiviral Defense ◽  
C Elegans ◽  
Protein Levels

RNA viruses are a major threat to animals and plants. RNA interference (RNAi) and the interferon response provide innate antiviral defense against RNA viruses. Here we performed a large-scale screen using C. elegans and its natural pathogen, the Orsay virus (OrV), and identified cde-1 as important for antiviral defense. CDE-1 is a homologue of the mammalian TUT4/7 terminal uridylyltransferases; its catalytic activity is required for its antiviral function. CDE-1 uridylates the 3′ end of the OrV RNA genome and promotes its degradation, independently of the RNAi pathway. Likewise, TUT4/7 uridylate influenza A virus (IAV) mRNAs in mammalian cells. Deletion of TUT4/7 leads to increased IAV mRNA and protein levels. We have defined 3′ terminal uridylation of viral RNAs as a conserved antiviral defense mechanism.

Stem Cell-Based Therapies: A New Ray of Hope for Diabetic Patients

2019 ◽  
Vol 14 (2) ◽  
pp. 146-151 ◽  
Author(s):  
Junaid Khan ◽  
Amit Alexander ◽  
Mukta Agrawal ◽  
Ajazuddin ◽  
Sunil Kumar Dubey ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Drug Therapy ◽  
Type I Diabetes ◽  
Embryonic Stem ◽  
Health Concern ◽  
Future Research ◽  
Diabetic Patients ◽  
Successful Implementation ◽  
Type I

Diabetes and its complications are a significant health concern throughout the globe. There are physiological differences in the mechanism of type-I and type-II diabetes and the conventional drug therapy as well as insulin administration seem to be insufficient to address the problem at large successfully. Hypoglycemic swings, frequent dose adjustments and resistance to the drug are major problems associated with drug therapy. Cellular approaches through stem cell based therapeutic interventions offer a promising solution to the problem. The need for pancreatic transplants in case of Type- I diabetes can also be by-passed/reduced due to the formation of insulin producing β cells via stem cells. Embryonic Stem Cells (ESCs) and induced Pluripotent Stem Cells (iPSCs), successfully used for generating insulin producing β cells. Although many experiments have shown promising results with stem cells in vitro, their clinical testing still needs more exploration. The review attempts to bring into light the clinical studies favoring the transplantation of stem cells in diabetic patients with an objective of improving insulin secretion and improving degeneration of different tissues in response to diabetes. It also focuses on the problems associated with successful implementation of the technique and possible directions for future research.

Further investigations on Fujimoto type strong uniqueness polynomials

Filomat ◽  
2017 ◽  
Vol 31 (16) ◽  
pp. 5203-5216
Author(s):  
Abhijit Banerjee ◽  
Bikash Chakraborty ◽  
Sanjay Mallick
Keyword(s):  
Meromorphic Functions ◽  
Future Research ◽  
Strong Uniqueness ◽  
Open Questions

Taking the question posed by the first author in [1] into background, we further exhaust-ably investigate existing Fujimoto type Strong Uniqueness Polynomial for Meromorphic functions (SUPM). We also introduce a new kind of SUPM named Restricted SUPM and exhibit some results which will give us a new direction to discuss the characteristics of a SUPM. Moreover, throughout the paper, we pose a number of open questions for future research.

scholarly journals Hepatic stellate cells: current state and open questions

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Claus Kordes ◽  
Hans H. Bock ◽  
Doreen Reichert ◽  
Petra May ◽  
Dieter Häussinger
Keyword(s):  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Essential Elements ◽  
Future Research ◽  
Heinrich Heine ◽  
Current State ◽  
Open Questions ◽  
Sinusoidal Endothelium ◽  
Cell Niche ◽  
Space Of Disse

Abstract This review article summarizes 20 years of our research on hepatic stellate cells within the framework of two collaborative research centers CRC575 and CRC974 at the Heinrich Heine University. Over this period, stellate cells were identified for the first time as mesenchymal stem cells of the liver, and important functions of these cells in the context of liver regeneration were discovered. Furthermore, it was determined that the space of Disse – bounded by the sinusoidal endothelium and hepatocytes – functions as a stem cell niche for stellate cells. Essential elements of this niche that control the maintenance of hepatic stellate cells have been identified alongside their impairment with age. This article aims to highlight previous studies on stellate cells and critically examine and identify open questions and future research directions.

scholarly journals Nuclear cGAS: sequestration and beyond

2021 ◽  
Author(s):  
Juli Bai ◽  
Feng Liu
Keyword(s):  
Innate Immune ◽  
Complex Nature ◽  
Type I ◽  
Replication Forks ◽  
The Novel ◽  
Nuclear Function ◽  
Double Stranded Dna ◽  
Open Questions ◽  
Established Role ◽  
Dependent Signaling Pathway

AbstractThe cyclic GMP-AMP (cGAMP) synthase (cGAS) has been identified as a cytosolic double stranded DNA sensor that plays a pivotal role in the type I interferon and inflammation responses via the STING-dependent signaling pathway. In the past several years, a growing body of evidence has revealed that cGAS is also localized in the nucleus where it is associated with distinct nuclear substructures such as nucleosomes, DNA replication forks, the double-stranded breaks, and centromeres, suggesting that cGAS may have other functions in addition to its role in DNA sensing. However, while the innate immune function of cGAS is well established, the non-canonical nuclear function of cGAS remains poorly understood. Here, we review our current understanding of the complex nature of nuclear cGAS and point to open questions on the novel roles and the mechanisms of action of this protein as a key regulator of cell nuclear function, beyond its well-established role in dsDNA sensing and innate immune response.

The DEAH helicase DHX36 and its role in G-quadruplex-dependent processes

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Philipp Schult ◽  
Katrin Paeschke
Keyword(s):  
Current Knowledge ◽  
Future Research ◽  
Transcriptional Level ◽  
Cellular Functions ◽  
Multiple Functions ◽  
Open Questions ◽  
G Quadruplex ◽  
Cellular Pathways ◽  
Nucleic Acid Structures ◽  
Dependent Processes

AbstractDHX36 is a member of the DExD/H box helicase family, which comprises a large number of proteins involved in various cellular functions. Recently, the function of DHX36 in the regulation of G-quadruplexes (G4s) was demonstrated. G4s are alternative nucleic acid structures, which influence many cellular pathways on a transcriptional and post-transcriptional level. In this review we provide an overview of the current knowledge about DHX36 structure, substrate specificity, and mechanism of action based on the available models and crystal structures. Moreover, we outline its multiple functions in cellular homeostasis, immunity, and disease. Finally, we discuss the open questions and provide potential directions for future research.

xtgeebcv: A command for bias-corrected sandwich variance estimation for GEE analyses of cluster randomized trials

2020 ◽  
Vol 20 (2) ◽  
pp. 363-381 ◽  
Author(s):  
John A. Gallis ◽  
Fan Li ◽  
Elizabeth L. Turner
Keyword(s):  
Randomized Trials ◽  
Variance Estimation ◽  
Public Health Education ◽  
Standard Errors ◽  
Future Research ◽  
Type I ◽  
Cluster Randomized Trials ◽  
Finite Sample ◽  
Individual Level ◽  
Cluster Randomized

Cluster randomized trials, where clusters (for example, schools or clinics) are randomized to comparison arms but measurements are taken on individuals, are commonly used to evaluate interventions in public health, education, and the social sciences. Analysis is often conducted on individual-level outcomes, and such analysis methods must consider that outcomes for members of the same cluster tend to be more similar than outcomes for members of other clusters. A popular individual-level analysis technique is generalized estimating equations (GEE). However, it is common to randomize a small number of clusters (for example, 30 or fewer), and in this case, the GEE standard errors obtained from the sandwich variance estimator will be biased, leading to inflated type I errors. Some bias-corrected standard errors have been proposed and studied to account for this finite-sample bias, but none has yet been implemented in Stata. In this article, we describe several popular bias corrections to the robust sandwich variance. We then introduce our newly created command, xtgeebcv, which will allow Stata users to easily apply finite-sample corrections to standard errors obtained from GEE models. We then provide examples to demonstrate the use of xtgeebcv. Finally, we discuss suggestions about which finite-sample corrections to use in which situations and consider areas of future research that may improve xtgeebcv.

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