scholarly journals MiRNA Regulatory Functions in Photoreceptors

2021 ◽  
Vol 8 ◽  
Author(s):  
Julia Sophie Pawlick ◽  
Marta Zuzic ◽  
Giovanni Pasquini ◽  
Anka Swiersy ◽  
Volker Busskamp
Keyword(s):  
Regulatory Networks ◽  
Inflammatory Responses ◽  
Genetic Manipulation ◽  
Light Sensitivity ◽  
Diagnostic Tools ◽  
Messenger Rnas ◽  
Approaches To Study ◽  
Health And Disease ◽  
Regulatory Functions ◽  
Retinal Pathologies

MicroRNAs (miRNAs) are important regulators of gene expression. These small, non-coding RNAs post-transcriptionally silence messenger RNAs (mRNAs) in a sequence-specific manner. In this way, miRNAs control important regulatory functions, also in the retina. If dysregulated, these molecules are involved in several retinal pathologies. For example, several miRNAs have been linked to essential photoreceptor functions, including light sensitivity, synaptic transmission, and modulation of inflammatory responses. Mechanistic miRNA knockout and knockdown studies further linked their functions to degenerative retinal diseases. Of note, the type and timing of genetic manipulation before, during, or after retinal development, is important when studying specific miRNA knockout effects. Within this review, we focus on miR-124 and the miR-183/96/182 cluster, which have assigned functions in photoreceptors in health and disease. As a single miRNA can regulate hundreds of mRNAs, we will also discuss the experimental validation and manipulation approaches to study complex miRNA/mRNA regulatory networks. Revealing these networks is essential to understand retinal pathologies and to harness miRNAs as precise therapeutic and diagnostic tools to stabilize the photoreceptors’ transcriptomes and, thereby, function.

scholarly journals Transcriptional noise and exaptation as sources for bacterial sRNAs

2019 ◽  
Vol 47 (2) ◽  
pp. 527-539 ◽  
Author(s):  
Bethany R. Jose ◽  
Paul P. Gardner ◽  
Lars Barquist
Keyword(s):  
Evolutionary Biology ◽  
Regulatory Networks ◽  
Genetic Manipulation ◽  
Effective Population ◽  
Transcriptional Noise ◽  
New Genes ◽  
Generation Times ◽  
Population Sizes ◽  
Rapid Generation ◽  
Regulatory Functions

Abstract Understanding how new genes originate and integrate into cellular networks is key to understanding evolution. Bacteria present unique opportunities for both the natural history and experimental study of gene origins, due to their large effective population sizes, rapid generation times, and ease of genetic manipulation. Bacterial small non-coding RNAs (sRNAs), in particular, many of which operate through a simple antisense regulatory logic, may serve as tractable models for exploring processes of gene origin and adaptation. Understanding how and on what timescales these regulatory molecules arise has important implications for understanding the evolution of bacterial regulatory networks, in particular, for the design of comparative studies of sRNA function. Here, we introduce relevant concepts from evolutionary biology and review recent work that has begun to shed light on the timescales and processes through which non-functional transcriptional noise is co-opted to provide regulatory functions. We explore possible scenarios for sRNA origin, focusing on the co-option, or exaptation, of existing genomic structures which may provide protected spaces for sRNA evolution.

Algorithmic and Stochastic Representations of Gene Regulatory Networks and Protein-Protein Interactions

2019 ◽  
Vol 19 (6) ◽  
pp. 413-425 ◽  
Author(s):  
Athanasios Alexiou ◽  
Stylianos Chatzichronis ◽  
Asma Perveen ◽  
Abdul Hafeez ◽  
Ghulam Md. Ashraf
Keyword(s):  
Protein Interactions ◽  
Biological Networks ◽  
Regulatory Networks ◽  
Review Paper ◽  
Boolean Networks ◽  
Diagnostic Tools ◽  
Complex Nature ◽  
Cellular Interactions ◽  
Protein Protein Interactions ◽  
Deterministic Models

Background:Latest studies reveal the importance of Protein-Protein interactions on physiologic functions and biological structures. Several stochastic and algorithmic methods have been published until now, for the modeling of the complex nature of the biological systems.Objective:Biological Networks computational modeling is still a challenging task. The formulation of the complex cellular interactions is a research field of great interest. In this review paper, several computational methods for the modeling of GRN and PPI are presented analytically.Methods:Several well-known GRN and PPI models are presented and discussed in this review study such as: Graphs representation, Boolean Networks, Generalized Logical Networks, Bayesian Networks, Relevance Networks, Graphical Gaussian models, Weight Matrices, Reverse Engineering Approach, Evolutionary Algorithms, Forward Modeling Approach, Deterministic models, Static models, Hybrid models, Stochastic models, Petri Nets, BioAmbients calculus and Differential Equations.Results:GRN and PPI methods have been already applied in various clinical processes with potential positive results, establishing promising diagnostic tools.Conclusion:In literature many stochastic algorithms are focused in the simulation, analysis and visualization of the various biological networks and their dynamics interactions, which are referred and described in depth in this review paper.

scholarly journals Imaging Diagnosis of Right Ventricle Involvement in Chagas Cardiomyopathy

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Minna M. D. Romano ◽  
Henrique T. Moreira ◽  
André Schmidt ◽  
Benedito Carlos Maciel ◽  
José Antônio Marin-Neto
Keyword(s):  
Right Ventricle ◽  
Tissue Characterization ◽  
Low Cost ◽  
Diagnostic Techniques ◽  
Diagnostic Tools ◽  
Deformation Analysis ◽  
Geometrical Shape ◽  
Gold Standard Method ◽  
Chagas Cardiomyopathy ◽  
Health And Disease

Right ventricle (RV) is considered a neglected chamber in cardiology and knowledge about its role in cardiac function was mostly focused on ventricular interdependence. However, progress on the understanding of myocardium diseases primarily involving the RV led to a better comprehension of its role in health and disease. In Chagas disease (CD), there is direct evidence from both basic and clinical research of profound structural RV abnormalities. However, clinical detection of these abnormalities is hindered by technical limitations of imaging diagnostic tools. Echocardiography has been a widespread and low-cost option for the study of patients with CD but, when applied to the RV assessment, faces difficulties such as the absence of a geometrical shape to represent this cavity. More recently, the technique has evolved to a focused guided RV imaging and myocardial deformation analysis. Also, cardiac magnetic resonance (CMR) has been introduced as a gold standard method to evaluate RV cavity volumes. CMR advantages include precise quantitative analyses of both LV and RV volumes and its ability to perform myocardium tissue characterization to identify areas of scar and edema. Evolution of these cardiac diagnostic techniques opened a new path to explore the pathophysiology of RV dysfunction in CD.

Genetic manipulation of 11β-hydroxysteroid dehydrogenases in mice

2005 ◽  
Vol 289 (3) ◽  
pp. R642-R652 ◽  
Author(s):  
Janice M. Paterson ◽  
Jonathan R. Seckl ◽  
John J. Mullins
Keyword(s):  
Genetic Manipulation ◽  
Receptor Activation ◽  
Regulation Of Expression ◽  
Dynamic Regulation ◽  
Temporal Regulation ◽  
Hydroxysteroid Dehydrogenases ◽  
Corticosteroid Receptor ◽  
Health And Disease ◽  
Restricted Pattern

11β-Hydroxysteroid dehydrogenases (HSDs) interconvert active 11-hydroxy glucocorticoids (cortisol, corticosterone) and their inert 11-keto derivatives (cortisone, 11-dehydrocorticosterone). 11β-HSD type 1 is a predominant reductase that regenerates active glucocorticoids in expressing cells, thus amplifying local glucocorticoid action, whereas 11β-HSD type 2 catalyzes rapid dehydrogenation, potently inactivating intracellular glucocorticoids. Both isozymes thus regulate receptor activation by substrate availability. Spatial and temporal regulation of expression are important determinants of the physiological roles of 11β-HSDs, with each isozyme exhibiting a distinct, tissue-restricted pattern together with dynamic regulation during development and in response to environmental challenges, including diet and stress. Transgenic approaches in the mouse have contributed significantly toward an understanding of the importance of these prereceptor regulatory mechanisms on corticosteroid receptor activity and have highlighted its potential relevance to human health and disease. Here we discuss current ideas of the physiological roles of 11β-HSDs, with emphasis on the key contributions made by studies of 11β-HSD gene manipulation in vivo.

scholarly journals Intracellular survival ofBurkholderia cepaciacomplex in phagocytic cells

2015 ◽  
Vol 61 (9) ◽  
pp. 607-615 ◽  
Author(s):  
Miguel A. Valvano
Keyword(s):  
Burkholderia Cepacia ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Genetic Manipulation ◽  
Intracellular Survival ◽  
Burkholderia Cenocepacia ◽  
Burkholderia Cepacia Complex ◽  
Host Responses ◽  
Current View ◽  
Phagocytic Cells

Burkholderia cepacia complex (Bcc) species are a group of Gram-negative opportunistic pathogens that infect the airways of cystic fibrosis patients, and occasionally they infect other immunocompromised patients. Bcc bacteria display high-level multidrug resistance and chronically persist in the infected host while eliciting robust inflammatory responses. Studies using macrophages, neutrophils, and dendritic cells, combined with advances in the genetic manipulation of these bacteria, have increased our understanding of the molecular mechanisms of virulence in these pathogens and the molecular details of cell-host responses triggering inflammation. This article discusses our current view of the intracellular survival of Burkholderia cenocepacia within macrophages.

scholarly journals Induction of Host Chemotactic Response by Encephalitozoon spp.

2006 ◽  
Vol 75 (4) ◽  
pp. 1619-1625 ◽  
Author(s):  
Jeffrey Fischer ◽  
Jeffrey West ◽  
Nnenaya Agochukwu ◽  
Colby Suire ◽  
Hollie Hale-Donze
Keyword(s):  
Inflammatory Responses ◽  
Kinetic Studies ◽  
Protein Profiling ◽  
Diagnostic Tools ◽  
Emerging Pathogens ◽  
Chemokine Production ◽  
Human Macrophages ◽  
Monocyte Migration

ABSTRACT Microsporidians are a group of emerging pathogens typically associated with chronic diarrhea in immunocompromised individuals. The number of reports of infections with these organisms and the disseminated pathology is growing as diagnostic tools become more readily available. However, little is known about the innate immune response induced by and generated against these parasites. Using a coculture chemotaxis system, primary human macrophages were infected with Encephalitozoon cuniculi or Encephalitozoon intestinalis, and the recruitment of naïve monocytes was monitored. Encephalitozoon spp. induced an average threefold increase in migration of naïve cells 48 h postinfection, which corresponded to optimal infection of monocyte-derived-macrophages. A limited microarray analysis of infected macrophages revealed several chemokines involved in the inflammatory responses whose expression was upregulated, including CCL1, CCL2, CCL3, CCL4, CCL7, CCL15, CCL20, CXCL1, CXCL2, CXCL3, CXCL5, and CXCL8. The levels of 6 of 11 chemokines also present in the microarray were confirmed to be elevated by protein profiling. Kinetic studies confirmed that secreted CCL2, CCL3, and CCL4 were expressed as early as 6 h postinfection, with peak expression at 12 to 24 h and expression remaining until 48 h postinfection. Neutralization of these chemokines, specifically CCL4, significantly reduced the number of migrating cells in vitro, indicating their role in the induction of monocyte migration. This mechanism of recruitment not only supports the evidence that in vivo cellular infiltration occurs but also provides new hosts for the parasites, which escape macrophages by rupturing the host cell. To our knowledge, this is the first documentation that chemokine production is induced by microsporidian infections in human macrophages.

scholarly journals Degradation rate uniformity determines success of oscillations in repressive feedback regulatory networks

2018 ◽  
Vol 15 (142) ◽  
pp. 20180157 ◽  
Author(s):  
Karen M. Page ◽  
Ruben Perez-Carrasco
Keyword(s):  
Regulatory Networks ◽  
Oscillatory Behaviour ◽  
Sustained Oscillations ◽  
Degradation Rates ◽  
Number Of Genes ◽  
Computational Exploration ◽  
The Stability ◽  
Regulatory Functions ◽  
Insight Into

Ring oscillators are biochemical circuits consisting of a ring of interactions capable of sustained oscillations. The nonlinear interactions between genes hinder the analytical insight into their function, usually requiring computational exploration. Here, we show that, despite the apparent complexity, the stability of the unique steady state in an incoherent feedback ring depends only on the degradation rates and a single parameter summarizing the feedback of the circuit. Concretely, we show that the range of regulatory parameters that yield oscillatory behaviour is maximized when the degradation rates are equal. Strikingly, this result holds independently of the regulatory functions used or number of genes. We also derive properties of the oscillations as a function of the degradation rates and number of nodes forming the ring. Finally, we explore the role of mRNA dynamics by applying the generic results to the specific case with two naturally different degradation timescales.

scholarly journals Rewiring cell signalling through chimaeric regulatory protein engineering

2013 ◽  
Vol 41 (5) ◽  
pp. 1195-1200 ◽  
Author(s):  
Baojun Wang ◽  
Mauricio Barahona ◽  
Martin Buck ◽  
Jörg Schumacher
Keyword(s):  
Regulatory Networks ◽  
Regulatory Protein ◽  
Cell Signalling ◽  
Regulatory Proteins ◽  
Signalling Pathways ◽  
Bacterial Cells ◽  
Input Signals ◽  
Sense And Respond ◽  
Regulatory Functions ◽  
Individual Input

Bacterial cells continuously sense and respond to their environment using their inherent signalling and gene regulatory networks. Cells are equipped with parallel signalling pathways, which can specifically cope with individual input signals, while interconnectivities between pathways lead to an enhanced complexity of regulatory responses that enable sophisticated adaptation. In principle, any cell signalling pathway may be rewired to respond to non-cognate signals by exchanging and recombining their underlying cognate signalling components. In the present article, we review the engineering strategies and use of chimaeric regulatory proteins in cell signalling pathways, especially the TCS (two-component signalling) system in bacteria, to achieve novel customized signalling or regulatory functions. We envisage that engineered chimaeric regulatory proteins can play an important role to aid both forward and reverse engineering of biological systems for many desired applications.

scholarly journals Noncoding RNAs: Emerging Players in Muscular Dystrophies

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Germana Falcone ◽  
Alessandra Perfetti ◽  
Beatrice Cardinali ◽  
Fabio Martelli
Keyword(s):  
Regulatory Networks ◽  
Noncoding Rnas ◽  
Skeletal Muscle Differentiation ◽  
Physiological Mechanisms ◽  
Rna Molecules ◽  
Disease Biomarkers ◽  
Cellular Processes ◽  
Sequencing Technologies ◽  
Regulatory Functions ◽  
Potential Use

The fascinating world of noncoding RNAs has recently come to light, thanks to the development of powerful sequencing technologies, revealing a variety of RNA molecules playing important regulatory functions in most, if not all, cellular processes. Many noncoding RNAs have been implicated in regulatory networks that are determinant for skeletal muscle differentiation and disease. In this review, we outline the noncoding RNAs involved in physiological mechanisms of myogenesis and those that appear dysregulated in muscle dystrophies, also discussing their potential use as disease biomarkers and therapeutic targets.

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