scholarly journals Regulatory Networks, Legal Federalism, and Multi-Level Regulatory Systems

Author(s):  
Wolfgang Kerber
2016 ◽  
Vol 36 (1) ◽  
Author(s):  
G. Daniel Grass ◽  
Bryan P. Toole

Matrix metalloproteinases (MMPs) comprise a family of 23 zinc-dependent enzymes involved in various pathologic and physiologic processes. In cancer, MMPs contribute to processes from tumour initiation to establishment of distant metastases. Complex signalling and protein transport networks regulate MMP synthesis, cell surface presentation and release. Earlier attempts to disrupt MMP activity in patients have proven to be intolerable and with underwhelming clinical efficacy; thus targeting ancillary proteins that regulate MMP activity may be a useful therapeutic approach. Extracellular matrix metalloproteinase inducer (EMMPRIN) was originally characterized as a factor present on lung cancer cells, which stimulated collagenase (MMP-1) production in fibroblasts. Subsequent studies demonstrated that EMMPRIN was identical with several other protein factors, including basigin (Bsg), all of which are now commonly termed CD147. CD147 modulates the synthesis and activity of soluble and membrane-bound [membrane-type MMPs (MT-MMPs)] in various contexts via homophilic/heterophilic cell interactions, vesicular shedding or cell-autonomous processes. CD147 also participates in inflammation, nutrient and drug transporter activity, microbial pathology and developmental processes. Despite the hundreds of manuscripts demonstrating CD147-mediated MMP regulation, the molecular underpinnings governing this process have not been fully elucidated. The present review summarizes our present knowledge of the complex regulatory systems influencing CD147 biology and provides a framework to understand how CD147 may influence MMP activity.


2002 ◽  
Vol 3 (6) ◽  
pp. 499-503 ◽  
Author(s):  
Thomas Schlitt ◽  
Alvis Brazma

Gene regulatory networks are a major focus of interest in molecular biology. A crucial question is how complex regulatory systems are encoded and controlled by the genome. Three recent publications have raised the question of what can be learned about gene regulatory networks from microarray experiments on gene deletion mutants. Using this indirect approach, topological features such as connectivity and modularity have been studied.


2021 ◽  
Author(s):  
Vincent Lau ◽  
Rachel Woo ◽  
Bruno Pereira ◽  
Asher Pasha ◽  
Eddi Esteban ◽  
...  

AbstractGene regulatory networks (GRNs) are complex networks that capture multi-level regulatory events between one or more regulatory macromolecules, such as transcription factors (TFs), and their target genes. Advancements in screening technologies such as enhanced yeast-one-hybrid screens have allowed for high throughput determination of GRNs. However, visualization of GRNs in Arabidopsis has been limited to ad hoc networks and are not interactive. Here, we describe the Arabidopsis GEne Network Tool (AGENT) that houses curated GRNs and provides tools to visualize and explore them. AGENT features include expression overlays, subnetwork motif scanning, and network analysis. We show how to use AGENT’s multiple built-in tools to identify key genes that are involved in flowering and seed development along with identifying temporal multi-TF control of a key transporter in nitrate signaling. AGENT can be accessed at https://bar.utoronto.ca/AGENT.


BMC Genomics ◽  
2020 ◽  
Vol 21 (S5) ◽  
Author(s):  
Sefa Kılıç ◽  
Miquel Sánchez-Osuna ◽  
Antonio Collado-Padilla ◽  
Jordi Barbé ◽  
Ivan Erill

Abstract Background Comparative genomics methods enable the reconstruction of bacterial regulatory networks using available experimental data. In spite of their potential for accelerating research into the composition and evolution of bacterial regulons, few comparative genomics suites have been developed for the automated analysis of these regulatory systems. Available solutions typically rely on precomputed databases for operon and ortholog predictions, limiting the scope of analyses to processed complete genomes, and several key issues such as the transfer of experimental information or the integration of regulatory information in a probabilistic setting remain largely unaddressed. Results Here we introduce CGB, a flexible platform for comparative genomics of prokaryotic regulons. CGB has few external dependencies and enables fully customized analyses of newly available genome data. The platform automates the merging of experimental information and uses a gene-centered, Bayesian framework to generate and integrate easily interpretable results. We demonstrate its flexibility and power by analyzing the evolution of type III secretion system regulation in pathogenic Proteobacteria and by characterizing the SOS regulon of a new bacterial phylum, the Balneolaeota. Conclusions Our results demonstrate the applicability of the CGB pipeline in multiple settings. CGB’s ability to automatically integrate experimental information from multiple sources and use complete and draft genomic data, coupled with its non-reliance on precomputed databases and its easily interpretable display of gene-centered posterior probabilities of regulation provide users with an unprecedented level of flexibility in launching comparative genomics analyses of prokaryotic transcriptional regulatory networks. The analyses of type III secretion and SOS response regulatory networks illustrate instances of convergent and divergent evolution of these regulatory systems, showcasing the power of formal ancestral state reconstruction at inferring the evolutionary history of regulatory networks.


Author(s):  
David Coen ◽  
Alexander Katsaitis ◽  
Matia Vannoni

This chapter examines business lobbying in the EU from a historical perspective. Conceptually, it discusses how the EU’s evolution has influenced interest intermediation in Brussels. In doing so, it addresses the increasing authority handed to the European Commission, the growth of European regulatory networks, and multi-level governance; and their influence on business and the strategic choices it makes. From the opposite perspective, it examines the impact that business has had on the EU’s integration, and its policy-making procedures. Empirically, the chapter draws on unique business surveys spanning from the mid-1990s up until today, and a large-N analysis of 12,000 registered organizations on the EU’s transparency register. It also provides a case study on business strategies, focused on the directive on tobacco control. Theoretically, this chapter contributes to discussions on European integration, interest group activity, business lobbying, and governance in the EU.,


2018 ◽  
Vol 20 (4) ◽  
pp. 809-826 ◽  
Author(s):  
Corina Lacatus

Regulatory networks are increasingly important actors in multi-level systems of human rights governance. Yet we know little about the role that domestic networks play as intermediaries or about the strategies they use to integrate sub-national human rights institutions to ensure compliance at the local level. We draw on the theoretical literature on orchestration to conceptualise network governance and propose a new intermediary for the human rights governance, the multi-level network, which operates inside one country. We apply this theoretical model to the case of a multi-level network operating at the domestic level in the United Kingdom – Northern Ireland Human Rights Commission, Equality and Human Rights Commission, and Scottish Human Rights Commission. We discuss how the three commissions use the tools of managerial stewardship to facilitate intra-network collaboration and how they engage in hierarchical stewardship to gain access to international networks and take on a leadership role globally and regionally.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ivan Rodrigo Wolf ◽  
Rafael Plana Simões ◽  
Guilherme Targino Valente

AbstractGene regulatory networks (GRNs) play key roles in development, phenotype plasticity, and evolution. Although graph theory has been used to explore GRNs, associations amongst topological features, transcription factors (TFs), and systems essentiality are poorly understood. Here we sought the relationship amongst the main GRN topological features that influence the control of essential and specific subsystems. We found that the Knn, page rank, and degree are the most relevant GRN features: the ones are conserved along the evolution and are also relevant in pluripotent cells. Interestingly, life-essential subsystems are governed mainly by TFs with intermediary Knn and high page rank or degree, whereas specialized subsystems are mainly regulated by TFs with low Knn. Hence, we suggest that the high probability of TFs be toured by a random signal, and the high probability of the signal propagation to target genes ensures the life-essential subsystems’ robustness. Gene/genome duplication is the main evolutionary process to rise Knn as the most relevant feature. Herein, we shed light on unexplored topological GRN features to assess how they are related to subsystems and how the duplications shaped the regulatory systems along the evolution. The classification model generated can be found here: https://github.com/ivanrwolf/NoC/.


2022 ◽  
Author(s):  
Yichen Gao ◽  
Ai-Ping Pang ◽  
Leyao Ma ◽  
Haiyan Wang ◽  
Samran Durrani ◽  
...  

Abstract Background Knowledge on regulatory networks associated with cellulase biosynthesis is prerequisite for exploitation of such regulatory systems in ehancing cellulase production with low cost. The biological functions of intron retention (IR) and nonsense-mediated mRNA decay (NMD) in filamentous fungi is lack of study, let alone their roles in cellulase biosynthesis. Result We found that major cellulase genes (cel7a, cel7b, and cel3a) exhibited concomitant decrease in IR rates and increase in their gene expression in T. reesei under cellulase-producing condition (cellulose and lactose) that was accompanied with a more active NMD pathway, as compared to non cellulase-producing condition (glucose). In the presence of the NMD pathway inhibitor that successfully repressed the NMD pathway, the mRNA levels of cellulase genes were sharply down-regulated, but the rates of IR in these genes were significantly up-regulated. Consistently, the cellulase activities were severely inhibited. In addition, the NMD pathway inhibitor caused the downregulated mRNA levels of two important genes of the target of rapamycin (TOR) pathway, trfkbp12 and trTOR1. The absence of gene trfkbp12 made the cellulase production in T. reesei more sensitive to the NMD pathway inhibitor. Conclusion All these findings suggest that the IR of cellulase genes regulates their own gene expression by coupling with the NMD pathway, which might involve the TOR pathway. Our results provide better understanding on intron retention, the NMD pathway, and cellulase production mechanism in filamentous fungi.


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