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Guthrie, Graeme. "Regulating Infrastructure: The Impact on Risk and Investment". Journal of Economic Literature 44, n. 4 (1 novembre 2006): 925–72. http://dx.doi.org/10.1257/jel.44.4.925.
Testo completoAbstract (sommario):
The last thirty years have witnessed a fundamental change in the regulation of infrastructure industries. Whereas firms were subject to rate of return regulation and protected from entry in the past, they now face various forms of incentive regulation, competition is actively promoted by many regulators, and both regulators and the firms they regulate must often confront rapid technological progress. This paper surveys the literature on the investment implications of different regulatory schemes, highlighting the relevance of modern investment theory, which puts risk and intertemporal issues, such as the irreversibility of much infrastructure investment, center stage. It discusses the impact on regulated monopolists' investment behavior of key regulatory characteristics, namely the price flexibility allowed by the regulator, the length of the regulatory cycle, and the costs the regulator will allow the firm to recover at future regulatory hearings. It also considers the impact of competition, especially the situation where a vertically integrated firm has its operation of a bottleneck asset regulated, on investment by regulated firms and their competitors.
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Rashid, M. Mamunur, Yumi Ikawa e Seiji Tsuge. "GamR, the LysR-Type Galactose Metabolism Regulator, RegulateshrpGene Expression via Transcriptional Activation of Two KeyhrpRegulators, HrpG and HrpX, in Xanthomonas oryzae pv. oryzae". Applied and Environmental Microbiology 82, n. 13 (22 aprile 2016): 3947–58. http://dx.doi.org/10.1128/aem.00513-16.
Testo completoAbstract (sommario):
ABSTRACTXanthomonas oryzaepv. oryzae is the causal agent of bacterial leaf blight of rice. For the virulence of the bacterium, thehrpgenes, encoding components of the type III secretion system, are indispensable. The expression ofhrpgenes is regulated by two keyhrpregulators, HrpG and HrpX: HrpG regulateshrpX, and HrpX regulates otherhrpgenes. Several other regulators have been shown to be involved in the regulation ofhrpgenes. Here, we found that a LysR-type transcriptional regulator that we named GamR, encoded byXOO_2767ofX. oryzaepv. oryzae strain MAFF311018, positively regulated the transcription of bothhrpGandhrpX, which are adjacent to each other but have opposite orientations, with an intergenic upstream region in common. In a gel electrophoresis mobility shift assay, GamR bound directly to the middle of the upstream region common tohrpGandhrpX. The loss of either GamR or its binding sites decreasedhrpGandhrpXexpression. Also, GamR bound to the upstream region of either a galactose metabolism-related gene (XOO_2768) or a galactose metabolism-related operon (XOO_2768toXOO_2771) located next togamRitself and positively regulated the genes. The deletion of the regulator gene resulted in less bacterial growth in a synthetic medium with galactose as a sole sugar source. Interestingly, induction of the galactose metabolism-related gene was dependent on galactose, while that of thehrpregulator genes was galactose independent. Our results indicate that the LysR-type transcriptional regulator that regulates the galactose metabolism-related gene(s) also acts in positive regulation of two keyhrpregulators and the followinghrpgenes inX. oryzaepv. oryzae.IMPORTANCEThe expression ofhrpgenes encoding components of the type III secretion system is essential for the virulence of many plant-pathogenic bacteria, includingXanthomonas oryzaepv. oryzae. It is specifically induced during infection. Research has revealed that in this bacterium,hrpgene expression is controlled by two keyhrpregulators, HrpG and HrpX, along with several other regulators in the complex regulatory network, but the details remain unclear. Here, we found that a novel LysR-type transcriptional activator, named GamR, functions as anhrpregulator by directly activating the transcription of bothhrpGandhrpX. Interestingly, GamR also regulates a galactose metabolism-related gene (or operon) in a galactose-dependent manner, while the regulation ofhrpGandhrpXis independent of the sugar. Our finding of a novelhrpregulator that directly and simultaneously regulates two keyhrpregulators provides new insights into an important and complex regulation system ofX. oryzaepv. oryzaehrpgenes.
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Baltrus, David A., Kevin Dougherty, Beatriz Diaz e Rachel Murillo. "Evolutionary Plasticity of AmrZ Regulation in Pseudomonas". mSphere 3, n. 2 (18 aprile 2018): e00132-18. http://dx.doi.org/10.1128/msphere.00132-18.
Testo completoAbstract (sommario):
ABSTRACT amrZ encodes a master regulator protein conserved across pseudomonads, which can be either a positive or negative regulator of swimming motility depending on the species examined. To better understand plasticity in the regulatory function of AmrZ, we characterized the mode of regulation for this protein for two different motility-related phenotypes in Pseudomonas stutzeri. As in Pseudomonas syringae, AmrZ functions as a positive regulator of swimming motility within P. stutzeri, which suggests that the functions of this protein with regard to swimming motility have switched at least twice across pseudomonads. Shifts in mode of regulation cannot be explained by changes in AmrZ sequence alone. We further show that AmrZ acts as a positive regulator of colony spreading within this strain and that this regulation is at least partially independent of swimming motility. Closer investigation of mechanistic shifts in dual-function regulators like AmrZ could provide unique insights into how transcriptional pathways are rewired between closely related species. IMPORTANCE Microbes often display finely tuned patterns of gene regulation across different environments, with major regulatory changes controlled by a small group of “master” regulators within each cell. AmrZ is a master regulator of gene expression across pseudomonads and can be either a positive or negative regulator for a variety of pathways depending on the strain and genomic context. Here, we demonstrate that the phenotypic outcomes of regulation of swimming motility by AmrZ have switched at least twice independently in pseudomonads, so that AmrZ promotes increased swimming motility in P. stutzeri and P. syringae but represses this phenotype in Pseudomonas fluorescens and Pseudomonas aeruginosa. Since examples of switches in regulatory mode are relatively rare, further investigation into the mechanisms underlying shifts in regulator function for AmrZ could provide unique insights into the evolution of bacterial regulatory proteins.
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Gao, Rong, Sophie Bouillet e Ann M. Stock. "Structural Basis of Response Regulator Function". Annual Review of Microbiology 73, n. 1 (8 settembre 2019): 175–97. http://dx.doi.org/10.1146/annurev-micro-020518-115931.
Testo completoAbstract (sommario):
Response regulators function as the output components of two-component systems, which couple the sensing of environmental stimuli to adaptive responses. Response regulators typically contain conserved receiver (REC) domains that function as phosphorylation-regulated switches to control the activities of effector domains that elicit output responses. This modular design is extremely versatile, enabling different regulatory strategies tuned to the needs of individual signaling systems. This review summarizes structural features that underlie response regulator function. An abundance of atomic resolution structures and complementary biochemical data have defined the mechanisms for response regulator enzymatic activities, revealed trends in regulatory strategies utilized by response regulators of different subfamilies, and provided insights into interactions of response regulators with their cognate histidine kinases. Among the hundreds of thousands of response regulators identified, variations abound. This article provides a framework for understanding structural features that enable function of canonical response regulators and a basis for distinguishing noncanonical configurations.
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Vasil, Michael L., Urs A. Ochsner, Zaiga Johnson, Jane A. Colmer e Abdul N. Hamood. "The Fur-Regulated Gene Encoding the Alternative Sigma Factor PvdS Is Required for Iron-Dependent Expression of the LysR-Type Regulator PtxR in Pseudomonas aeruginosa". Journal of Bacteriology 180, n. 24 (15 dicembre 1998): 6784–88. http://dx.doi.org/10.1128/jb.180.24.6784-6788.1998.
Testo completoAbstract (sommario):
ABSTRACT We previously identified a novel regulator of the exotoxin A gene (toxA) in Pseudomonas aeruginosa, PtxR, that belongs to the LysR family of prokaryotic regulatory proteins. Preliminary data also suggest that PtxR affects the expression of siderophores in P. aeruginosa. Because toxAexpression and siderophore production in this organism are coordinately regulated by the ferric uptake regulator (Fur) and the Fur-regulated alternative sigma factor PvdS, regulation of ptxR itself in the context of these regulators was examined. RNase protection analyses of ptxR transcription revealed that there are two independent transcription initiation sites (T1 and T2). While transcription from the promoter of T1 is constitutive throughout the growth cycle of PAO1, transcription from the second promoter (P2) is negatively affected by iron. Transcription from the P2 promoter is constitutive in a fur mutant under microaerobic conditions but still iron regulated during aerobic growth. High concentrations (>100 nM) of the ferric uptake regulatory protein (Fur) failed to bind to either of the promoter regions of ptxR in either gel mobility shift assays or DNase I footprint experiments. These results indicate that Fur indirectly regulates the iron-dependent expression ofptxR. Iron-regulated transcription of ptxR from the P2 promoter, but not constitutive expression from the P1 promoter, was dependent on the Fur-regulated alternative sigma factor genepvdS, even under aerobic conditions. Consequently, there are two levels of iron-regulated expression of ptxR. The iron-regulated expression of ptxR under microaerobic conditions from the P2 promoter of ptxR is mediated indirectly by Fur through the iron-regulated expression ofpvdS. In contrast, pvdS-mediated iron regulation of ptxR under aerobic conditions is Fur independent.
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Hill, Robert E., e Laura A. Lettice. "Alterations to the remote control of Shh gene expression cause congenital abnormalities". Philosophical Transactions of the Royal Society B: Biological Sciences 368, n. 1620 (19 giugno 2013): 20120357. http://dx.doi.org/10.1098/rstb.2012.0357.
Testo completoAbstract (sommario):
Multi-species conserved non-coding elements occur in the vertebrate genome and are clustered in the vicinity of developmentally regulated genes. Many are known to act as cis -regulators of transcription and may reside at long distances from the genes they regulate. However, the relationship of conserved sequence to encoded regulatory information and indeed, the mechanism by which these contribute to long-range transcriptional regulation is not well understood. The ZRS, a highly conserved cis -regulator, is a paradigm for such long-range gene regulation. The ZRS acts over approximately 1 Mb to control spatio-temporal expression of Shh in the limb bud and mutations within it result in a number of limb abnormalities, including polydactyly, tibial hypoplasia and syndactyly. We describe the activity of this developmental regulator and discuss a number of mechanisms by which regulatory mutations in this enhancer function to cause congenital abnormalities.
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Artiach, Tracy, Helen Irvine, Janet Mack e Christine Ryan. "The legitimising processes of a new regulator". Accounting, Auditing & Accountability Journal 29, n. 5 (20 giugno 2016): 802–27. http://dx.doi.org/10.1108/aaaj-10-2014-1850.
Testo completoAbstract (sommario):
Purpose – The purpose of this paper is to strengthen the theoretical understanding of the processes through which a new regulator seeks to gain legitimacy within an existing regulatory space. The authors do this by investigating the case of the Australian Charities and Not-for-profit Commission (ACNC). Design/methodology/approach – Synthesising legitimacy theory with the concept of regulatory space, the authors analyse formal public discourse surrounding the establishment and operations of the ACNC. Findings – Regulation is essentially a context-bound political process in which a new regulator needs to establish legitimacy to ensure its survival. It must convince its constituents that it has developed processes to operate effectively and professionally in addressing constituents’ needs, to bargain authoritatively with other regulators in establishing its operational boundaries, and to engage politically with government and constituents. Over a relatively short time, the ACNC built legitimacy, despite the political threats to its formal regulatory authority. Research limitations/implications – The conclusions are based on the analysis of one case. There is scope for further investigations of the processes by which new regulators establish their legitimacy in different contexts. Practical implications – The potential for a political threat to the authority of a new regulator, and the difficulty of achieving regulatory reform, particularly in a federated system such as Australia, highlight the necessity for a new regulator to develop a compelling discourse of legitimacy. Originality/value – The authors synthesise regulatory space and legitimacy perspectives, contributing to an understanding of the processes of regulation.
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Luo, Jiawei, Dan Song, Cheng Liang, Guanghui Li e Buwen Cao. "Detecting Co-Regulatory Modules from Human Regulatory Network by Randomly Walking Between Regulator and Gene Modules". Journal of Computational and Theoretical Nanoscience 14, n. 1 (1 gennaio 2017): 384–88. http://dx.doi.org/10.1166/jctn.2017.6331.
Testo completoAbstract (sommario):
Gene expression is jointly regulated by microRNAs and transcriptional factors. As such, constructing a regulatory network for microRNAs and transcriptional factors and analyzing their combinatorial effects are vital to understand living organisms. Co-regulatory modules, including functional homogeneous microRNAs, transcriptional factors, and genes, provide insights into coordinate regulation. In this paper, we propose a random walk with restart between regulator and gene modules (RWRRGM) method to detect co-regulatory modules from a human regulatory network. The network integrates large, heterogeneous data, including transcriptional regulation, post-transcriptional regulation, and gene-gene interaction. RWRRGM first identifies regulator and gene modules by greedily expanding seed nodes and then walks on the identified modules randomly. Finally, functional homogeneous regulator and gene modules are integrated to form co-regulatory modules. RWRRGM-based modules exhibit higher enrichment in gene ontology terms and known pathways than modules predicted by other methods.
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Peeters, Eveline, e Daniel Charlier. "The Lrp Family of Transcription Regulators in Archaea". Archaea 2010 (2010): 1–10. http://dx.doi.org/10.1155/2010/750457.
Testo completoAbstract (sommario):
Archaea possess a eukaryotic-type basal transcription apparatus that is regulated by bacteria-like transcription regulators. A universal and abundant family of transcription regulators are the bacterial/archaeal Lrp-like regulators. The Lrp family is one of the best studied regulator families in archaea, illustrated by investigations of proteins from the archaeal model organisms:Sulfolobus,Pyrococcus,Methanocaldococcus, andHalobacterium. These regulators are extremely versatile in their DNA-binding properties, response to effector molecules, and molecular regulatory mechanisms. Besides being involved in the regulation of the amino acid metabolism, they also regulate central metabolic processes. It appears that these regulatory proteins are also involved in large regulatory networks, because of hierarchical regulations and the possible combinatorial use of different Lrp-like proteins. Here, we discuss the recent developments in our understanding of this important class of regulators.
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Wu, Irene. "Who Regulates Phones, Television, and the Internet? What Makes a Communications Regulator Independent and Why It Matters". Perspectives on Politics 6, n. 4 (13 novembre 2008): 769–83. http://dx.doi.org/10.1017/s1537592708081905.
Testo completoAbstract (sommario):
More political scientists should engage in the debates surrounding regulation of communications networks, the infrastructure on which telecom, media, and Internet services ride. In 1990 there were 14 communications regulators worldwide, by 2007 there were 148. To fulfill World Trade Organization Agreement on Basic Telecommunications commitments, many countries aim to create regulatory agencies that are “independent.” What characterizes independence? Regulators are embedded in a political context that includes three main constituencies : other government institutions, industry, and consumers. Independent regulators are able to take action autonomously from other government institutions and industry while serving as advocates for consumers. In a survey of 18 countries, several traits emerge; a leader who cannot be dismissed arbitrarily, regulatory authority clearly distinct from policymaking, independent funding, minimal staff exchange between regulator and regulated firm, and dedicated support for consumers. It is usually easier for a regulator to be independent if operators are privatized. In a study of 4 countries, independent regulators follow decision-making procedures that give the public notice about proposed rule changes, opportunities to provide comments, and final decisions with explanation. Also, independent regulators have gift, conflict of interest, and post-employment rules, which set ethical standards and expectations for staff.
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Pérez-Morales, Deyanira, Jessica Nava-Galeana, Roberto Rosales-Reyes, Paige Teehan, Helen Yakhnin, Erika I. Melchy-Pérez, Yvonne Rosenstein, Miguel A. De la Cruz, Paul Babitzke e Víctor H. Bustamante. "An incoherent feedforward loop formed by SirA/BarA, HilE and HilD is involved in controlling the growth cost of virulence factor expression by Salmonella Typhimurium". PLOS Pathogens 17, n. 5 (28 maggio 2021): e1009630. http://dx.doi.org/10.1371/journal.ppat.1009630.
Testo completoAbstract (sommario):
An intricate regulatory network controls the expression of Salmonella virulence genes. The transcriptional regulator HilD plays a central role in this network by controlling the expression of tens of genes mainly required for intestinal colonization. Accordingly, the expression/activity of HilD is highly regulated by multiple factors, such as the SirA/BarA two-component system and the Hcp-like protein HilE. SirA/BarA positively regulates translation of hilD mRNA through a regulatory cascade involving the small RNAs CsrB and CsrC, and the RNA-binding protein CsrA, whereas HilE inhibits HilD activity by protein-protein interaction. In this study, we show that SirA/BarA also positively regulates translation of hilE mRNA through the same mentioned regulatory cascade. Thus, our results reveal a paradoxical regulation exerted by SirA/BarA-Csr on HilD, which involves simultaneous opposite effects, direct positive control and indirect negative control through HilE. This kind of regulation is called an incoherent type-1 feedforward loop (I1-FFL), which is a motif present in certain regulatory networks and represents a complex biological problem to decipher. Interestingly, our results, together with those from a previous study, indicate that HilE, the repressor component of the I1-FFL reported here (I1-FFLSirA/BarA-HilE-HilD), is required to reduce the growth cost imposed by the expression of the genes regulated by HilD. Moreover, we and others found that HilE is necessary for successful intestinal colonization by Salmonella. Thus, these findings support that I1-FFLSirA/BarA-HilE-HilD cooperates to control the precise amount and activity of HilD, for an appropriate balance between the growth cost and the virulence benefit generated by the expression of the genes induced by this regulator. I1-FFLSirA/BarA-HilE-HilD represents a complex regulatory I1-FFL that involves multiple regulators acting at distinct levels of gene expression, as well as showing different connections to the rest of the regulatory network governing Salmonella virulence.
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Chubiz, Jessica E. Cott, Yekaterina A. Golubeva, Dongxia Lin, Lucas D. Miller e James M. Slauch. "FliZ Regulates Expression of the Salmonella Pathogenicity Island 1 Invasion Locus by Controlling HilD Protein Activity in Salmonella enterica Serovar Typhimurium". Journal of Bacteriology 192, n. 23 (1 ottobre 2010): 6261–70. http://dx.doi.org/10.1128/jb.00635-10.
Testo completoAbstract (sommario):
ABSTRACT A prerequisite for Salmonella enterica to cause both intestinal and systemic disease is the direct injection of effector proteins into host intestinal epithelial cells via a type three secretion system (T3SS); the T3SS genes are carried on Salmonella pathogenicity island 1 (SPI1). These effector proteins induce inflammatory diarrhea and bacterial invasion. Expression of the SPI1 T3SS is tightly regulated in response to environmental signals through a variety of global regulatory systems. We have previously shown that three AraC-like regulators, HilD, HilC, and RtsA, act in a complex feed-forward regulatory loop to control the expression of the hilA gene, which encodes the direct regulator of the SPI1 structural genes. In this work, we characterize a major positive regulator of this system, the flagellar protein FliZ. Through genetic and biochemical analyses, we show that FliZ posttranslationally controls HilD to positively regulate hilA expression. This mechanism is independent of other flagellar components and is not mediated through the negative regulator HilE or through FliZ-mediated RpoS regulation. We demonstrate that FliZ controls HilD protein activity and not stability. FliZ regulates HilD in the absence of Lon protease, previously shown to degrade HilD. Indeed, it appears that FliZ, rather than HilD, is the most relevant target of Lon as it relates to SPI1 expression. Mutants lacking FliZ are significantly attenuated in their ability to colonize the intestine but are unaffected during systemic infection. The intestinal attenuation is partially dependent on SPI1, but FliZ has additional pleiotropic effects.
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Zhou, Xue, Guoliang Qian, Yuan Chen, Liangcheng Du, Fengquan Liu e Gary Y. Yuen. "PilG is Involved in the Regulation of Twitching Motility and Antifungal Antibiotic Biosynthesis in the Biological Control Agent Lysobacter enzymogenes". Phytopathology® 105, n. 10 (ottobre 2015): 1318–24. http://dx.doi.org/10.1094/phyto-12-14-0361-r.
Testo completoAbstract (sommario):
Lysobacter enzymogenes strain C3 is a gliding bacterium which produces the antifungal secondary metabolite heat-stable antifungal factor (HSAF) and type IV pilus (T4P) as important mechanisms in biological control activity against fungal pathogens. To date, the regulators that control HSAF biosynthesis and T4P-dependent twitching motility in L. enzymogenes are poorly explored. In the present study, we addressed the role of pilG in the regulation of these two traits in L. enzymogenes. PilG of L. enzymogenes was found to be a response regulator, commonly known as a component of a two-component transduction system. Mutation of pilG in strain C3 abolished its ability to display spreading colony phenotype and cell movement at the colony margin, which is indicative of twitching motility; hence, PilG positively regulates twitching motility in L. enzymogenes. Mutation of pilG also enhanced HSAF production and the transcription of its key biosynthetic gene hsaf pks/nrps, suggesting that PilG plays a negative regulatory role in HSAF biosynthesis. This finding represents the first demonstration of the regulator PilG having a role in secondary metabolite biosynthesis in bacteria. Collectively, our results suggest that key ecological functions (HSAF production and twitching motility) in L. enzymogenes strain C3 are regulated in opposite directions by the same regulatory protein, PilG.
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Chaturongakul, Soraya, Sarita Raengpradub, M. Elizabeth Palmer, Teresa M. Bergholz, Renato H. Orsi, Yuewei Hu, Juliane Ollinger, Martin Wiedmann e Kathryn J. Boor. "Transcriptomic and Phenotypic Analyses Identify Coregulated, Overlapping Regulons among PrfA, CtsR, HrcA, and the Alternative Sigma Factors σB, σC, σH, and σLinListeria monocytogenes". Applied and Environmental Microbiology 77, n. 1 (29 ottobre 2010): 187–200. http://dx.doi.org/10.1128/aem.00952-10.
Testo completoAbstract (sommario):
ABSTRACTA set of sevenListeria monocytogenes10403S mutant strains, each bearing an in-frame null mutation in a gene encoding a key regulatory protein, was used to characterize transcriptional networks inL. monocytogenes; the seven regulatory proteins addressed include all fourL. monocytogenesalternative sigma factors (σB, σC, σH, and σL), the virulence gene regulator PrfA, and the heat shock-related negative regulators CtsR and HrcA. Whole-genome microarray analyses, used to identify regulons for each of these 7 transcriptional regulators, showed considerable overlap among regulons. Among 188 genes controlled by more than one regulator, 176 were coregulated by σB, including 92 genes regulated by both σBand σH(with 18 of these genes coregulated by σB, σH, and at least one additional regulator) and 31 genes regulated by both σBand σL(with 10 of these genes coregulated by σB, σL, and at least one additional regulator). Comparative phenotypic characterization measuring acid resistance, heat resistance, intracellular growth in J774 cells, invasion into Caco-2 epithelial cells, and virulence in the guinea pig model indicated contributions of (i) σBto acid resistance, (ii) CtsR to heat resistance, and (iii) PrfA, σB, and CtsR to virulence-associated characteristics. Loss of the remaining transcriptional regulators (i.e.,sigH,sigL, orsigC) resulted in limited phenotypic consequences associated with stress survival and virulence. Identification of overlaps among the regulons provides strong evidence supporting the existence of complex regulatory networks that appear to provide the cell with regulatory redundancies, along with the ability to fine-tune gene expression in response to rapidly changing environmental conditions.
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Kodgire, Prashant, e K. Krishnamurthy Rao. "hag expression in Bacillus subtilis is both negatively and positively regulated by ScoC". Microbiology 155, n. 1 (1 gennaio 2009): 142–49. http://dx.doi.org/10.1099/mic.0.021899-0.
Testo completoAbstract (sommario):
In Bacillus subtilis, motility and chemotaxis require the expression of hag, which encodes flagellin. This gene is transcribed by the σ D form of RNA polymerase and is regulated by a group of proteins called transition state regulators (TSRs). Our studies show that hag transcription is negatively regulated by the transition state regulator ScoC, by binding to its promoter. Furthermore, ScoC, indirectly, also positively regulates hag by increasing the availability of σ D by downregulating the levels of the anti-σ D-factor FlgM. We further show that the positive regulation by ScoC predominates over the negative regulation.
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Agarwal, Sumit, David Lucca, Amit Seru e Francesco Trebbi. "Inconsistent Regulators: Evidence from Banking *". Quarterly Journal of Economics 129, n. 2 (7 marzo 2014): 889–938. http://dx.doi.org/10.1093/qje/qju003.
Testo completoAbstract (sommario):
Abstract We find that regulators can implement identical rules inconsistently due to differences in their institutional design and incentives, and this behavior may adversely impact the effectiveness with which regulation is implemented. We study supervisory decisions of U.S. banking regulators and exploit a legally determined rotation policy that assigns federal and state supervisors to the same bank at exogenously set time intervals. Comparing federal and state regulator supervisory ratings within the same bank, we find that federal regulators are systematically tougher, downgrading supervisory ratings almost twice as frequently as do state supervisors. State regulators counteract these downgrades to some degree by upgrading more frequently. Under federal regulators, banks report worse asset quality, higher regulatory capital ratios, and lower return on assets. Leniency of state regulators relative to their federal counterparts is related to costly outcomes, such as higher failure rates and lower repayment rates of government assistance funds. The discrepancy in regulator behavior is related to different weights given by regulators to local economic conditions and, to some extent, differences in regulatory resources. We find no support for regulator self-interest, which includes “revolving doors” as a reason for leniency of state regulators.
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Wang, Dong, Haiying Xue, Yiwen Wang, Ruochun Yin, Fang Xie e Li Luo. "The Sinorhizobium melilotintrXGene Is Involved in Succinoglycan Production, Motility, and Symbiotic Nodulation on Alfalfa". Applied and Environmental Microbiology 79, n. 23 (13 settembre 2013): 7150–59. http://dx.doi.org/10.1128/aem.02225-13.
Testo completoAbstract (sommario):
ABSTRACTRhizobia establish a symbiotic relationship with their host legumes to induce the formation of nitrogen-fixing nodules. This process is regulated by many rhizobium regulators, including some two-component regulatory systems (TCSs). NtrY/NtrX, a TCS that was first identified inAzorhizobium caulinodans, is required for free-living nitrogen metabolism and symbiotic nodulation onSesbania rostrata. However, its functions in a typical rhizobium such asSinorhizobium melilotiremain unclear. Here we found that theS. melilotiresponse regulator NtrX but not the histidine kinase NtrY is involved in the regulation of exopolysaccharide production, motility, and symbiosis with alfalfa. A plasmid insertion mutant ofntrXformed mucous colonies, which overproduced succinoglycan, an exopolysaccharide, by upregulating its biosynthesis genes. This mutant also exhibited motility defects due to reduced flagella and decreased expression of flagellins and regulatory genes. The regulation is independent of the known regulatory systems of ExoR/ExoS/ChvI, EmmABC, and ExpR. Alfalfa plants inoculated with thentrXmutant were small and displayed symptoms of nitrogen starvation. Interestingly, the deletion mutant ofntrYshowed a phenotype similar to that of the parent strain. These findings demonstrate that theS. melilotiNtrX is a new regulator of succinoglycan production and motility that is not genetically coupled with NtrY.
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Takaya, Akiko, Fumiaki Tabuchi, Hiroko Tsuchiya, Emiko Isogai e Tomoko Yamamoto. "Negative Regulation of Quorum-Sensing Systems in Pseudomonas aeruginosa by ATP-Dependent Lon Protease". Journal of Bacteriology 190, n. 12 (11 aprile 2008): 4181–88. http://dx.doi.org/10.1128/jb.01873-07.
Testo completoAbstract (sommario):
ABSTRACT Lon protease, a member of the ATP-dependent protease family, regulates numerous cellular systems by degrading specific substrates. Here, we demonstrate that Lon is involved in the regulation of quorum-sensing (QS) signaling systems in Pseudomonas aeruginosa, an opportunistic human pathogen. The organism has two acyl-homoserine lactone (HSL)-mediated QS systems, LasR/LasI and RhlR/RhlI. Many reports have demonstrated that these two systems are regulated and interconnected by global regulators. We found that lon-disrupted cells overproduce pyocyanin, the biosynthesis of which depends on the RhlR/RhlI system, and show increased levels of a transcriptional regulator, RhlR. The QS systems are organized hierarchically: the RhlR/RhlI system is subordinate to LasR/LasI. To elucidate the mechanism by which Lon negatively regulates RhlR/RhlI, we examined the effect of lon disruption on the LasR/LasI system. We found that Lon represses the expression of LasR/LasI by degrading LasI, an HSL synthase, leading to negative regulation of the RhlR/RhlI system. RhlR/RhlI was also shown to be regulated by Lon independently of LasR/LasI via regulation of RhlI, an HSL synthase. In view of these findings, it is suggested that Lon protease is a powerful negative regulator of both HSL-mediated QS systems in P. aeruginosa.
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Salomon, Eve. "The Role of Broadcasting Regulation in Media Literacy". Comunicar 16, n. 32 (1 marzo 2009): 147–56. http://dx.doi.org/10.3916/c32-2009-02-013.
Testo completoAbstract (sommario):
The author presents a global perspective on the reasons why television is regulated, the mechanisms used for regulation, and what regulation covers, particularly its cultural purposes. The author concludes with suggestions about how this might change as nations move to wards a converged, digital future, including an increased role for the regulator in the promotion of media literacy. The UK’s regulator, OFCOM, is used as an example of how a regulatory authority can take a leading role in media and information literacy, adding to its existing missions of allocating and regulating spectrum, in preparation for the digital switchover. Regulation and self-regulation, to be truly effective, will need to rely on extensive media literacy. La autora presenta una perspectiva global sobre las razones por las que la televisión está regulada, los mecanismos utilizados para la regulación, y qué es lo que abarca esa regulación, particularmente en sus propósitos culturales. La autora concluye con sugerencias acerca de cómo se podría tender en las naciones hacia un futuro digital convergente, incluyendo un papel más preponderante de los consejos reguladores en la promoción de la alfabetización mediática. OFCOM, el regulador del Reino Unido es un ejemplo de cómo una autoridad reguladora puede tener un papel destacado en la alfabetización mediática y la información, agregando éstas a sus actuales objetivos de adjudicación y regulación del espectro, en preparación de la convergencia digital. La regulación y auto-regulación, para ser efectivas, tendrán que apoyarse sobre una integral educación en medios.
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Meibom, Karin L., Anna-Lena Forslund, Kerstin Kuoppa, Khaled Alkhuder, Iharilalao Dubail, Marion Dupuis, Åke Forsberg e Alain Charbit. "Hfq, a Novel Pleiotropic Regulator of Virulence-Associated Genes in Francisella tularensis". Infection and Immunity 77, n. 5 (17 febbraio 2009): 1866–80. http://dx.doi.org/10.1128/iai.01496-08.
Testo completoAbstract (sommario):
ABSTRACT Francisella tularensis is a highly infectious pathogen that infects animals and humans, causing tularemia. The ability to replicate within macrophages is central for virulence and relies on expression of genes located in the Francisella pathogenicity island (FPI), as well as expression of other genes. Regulation of FPI-encoded virulence gene expression in F. tularensis involves at least four regulatory proteins and is not fully understood. Here we studied the RNA-binding protein Hfq in F. tularensis and particularly the role that it plays as a global regulator of gene expression in stress tolerance and pathogenesis. We demonstrate that Hfq promotes resistance to several cellular stresses (including osmotic and membrane stresses). Furthermore, we show that Hfq is important for the ability of the F. tularensis vaccine strain LVS to induce disease and persist in organs of infected mice. We also demonstrate that Hfq is important for stress tolerance and full virulence in a virulent clinical isolate of F. tularensis, FSC200. Finally, microarray analyses revealed that Hfq regulates expression of numerous genes, including genes located in the FPI. Strikingly, Hfq negatively regulates only one of two divergently expressed putative operons in the FPI, in contrast to the other known regulators, which regulate the entire FPI. Hfq thus appears to be a new pleiotropic regulator of virulence in F. tularensis, acting mostly as a repressor, in contrast to the other regulators identified so far. Moreover, the results obtained suggest a novel regulatory mechanism for a subset of FPI genes.
21
Beyhan, Sinem, Kivanc Bilecen, Sofie R. Salama, Catharina Casper-Lindley e Fitnat H. Yildiz. "Regulation of Rugosity and Biofilm Formation in Vibrio cholerae: Comparison of VpsT and VpsR Regulons and Epistasis Analysis of vpsT, vpsR, and hapR". Journal of Bacteriology 189, n. 2 (15 gennaio 2007): 388–402. http://dx.doi.org/10.1128/jb.00981-06.
Testo completoAbstract (sommario):
ABSTRACT Vibrio cholerae undergoes phenotypic variation that generates two morphologically different variants, termed smooth and rugose. The transcriptional profiles of the two variants differ greatly, and many of the differentially regulated genes are controlled by a complex regulatory circuitry that includes the transcriptional regulators VpsR, VpsT, and HapR. In this study, we identified the VpsT regulon and compared the VpsT and VpsR regulons to elucidate the contribution of each positive regulator to the rugose variant transcriptional profile and associated phenotypes. We have found that although the VpsT and VpsR regulons are very similar, the magnitude of the gene regulation accomplished by each regulator is different. We also determined that cdgA, which encodes a GGDEF domain protein, is partially responsible for the altered vps gene expression between the vpsT and vpsR mutants. Analysis of epistatic relationships among hapR, vpsT, and vpsR with respect to a whole-genome expression profile, colony morphology, and biofilm formation revealed that vpsR is epistatic to hapR and vpsT. Expression of virulence genes was increased in a vpsR hapR double mutant relative to a hapR mutant, suggesting that VpsR negatively regulates virulence gene expression in the hapR mutant. These results show that a complex regulatory interplay among VpsT, VpsR, HapR, and GGDEF/EAL family proteins controls transcription of the genes required for Vibrio polysaccharide and virulence factor production in V. cholerae.
22
Gu, Dan, Huan Liu, Zhen Yang, Yuanxing Zhang e Qiyao Wang. "Chromatin Immunoprecipitation Sequencing Technology Reveals Global Regulatory Roles of Low-Cell-Density Quorum-Sensing Regulator AphA in the Pathogen Vibrio alginolyticus". Journal of Bacteriology 198, n. 21 (22 agosto 2016): 2985–99. http://dx.doi.org/10.1128/jb.00520-16.
Testo completoAbstract (sommario):
ABSTRACTQuorum sensing (QS) is an important regulatory system in virulence expression and environmental adaptation in bacteria. The master QS regulators (MQSR) LuxR and AphA reciprocally control QS gene expression in vibrios. However, the molecular basis for the regulatory functions of AphA remains undefined. In this study, we characterized its regulatory roles inVibrio alginolyticus, an important zoonotic pathogen causing diseases in marine animals as well as in humans. AphA is involved in the motility ability, biofilm formation, andin vivosurvival ofV. alginolyticus. Specifically, AphA is expressed at low-cell-density growth phases. In addition, AphA negatively regulates the expression of the main virulence factor, alkaline serine protease (Asp), through LuxR. Chromatin immunoprecipitation (ChIP) followed by high-throughput DNA sequencing (ChIP-seq) detected 49 enriched loci harboring AphA-binding peaks across theV. alginolyticusgenome. An AphA-specific binding motif was identified and further confirmed by electrophoretic mobility shift assay (EMSA) and mutagenesis analysis. A quantitative real-time PCR (qRT-PCR) assay further validated the regulation of AphA on these genes. AphA binds directly to theaphApromoter and negatively regulates its own expression. Moreover, AphA directly regulates genes encoding adenylate cyclase, anti-σD, FabR, and the small RNA CsrB, revealing versatile regulatory roles of AphA in its physiology and virulence. Furthermore, our data indicated that AphA modulates motility through the coordinated function of LuxR and CsrB. Collectively, the findings of this work contribute to better understanding of the regulatory roles of AphA in QS and non-QS genes.IMPORTANCEIn this work, we determined that AphA, the master regulator of QS at low cell density, plays essential roles in expression of genes associated with physiology and virulence inV. alginolyticus, a Gram-negative pathogen for humans and marine animals. We further uncovered that 49 genes could be directly regulated by AphA and a 19-bp consensus binding sequence was identified. Among the 49 genes, the QS and other non-QS-associated genes were identified to be regulated by AphA. Besides, the small RNA CsrB was negatively regulated by AphA, and AphA regulate motility abilities through both CsrB and LuxR. Taken together, the findings of this study improve our understanding of the complex regulation network of AphA and QS.
23
Schär, Jennifer, Albert Sickmann e Dagmar Beier. "Phosphorylation-Independent Activity of Atypical Response Regulators of Helicobacter pylori". Journal of Bacteriology 187, n. 9 (1 maggio 2005): 3100–3109. http://dx.doi.org/10.1128/jb.187.9.3100-3109.2005.
Testo completoAbstract (sommario):
ABSTRACT The genome of the gastric pathogen Helicobacter pylori harbors a remarkably low number of regulatory genes, including three and five open reading frames encoding two-component histidine kinases and response regulators, respectively, which are putatively involved in transcriptional regulation. Two of the response regulator genes, hp1043 and hp166, proved to be essential for cell growth, and inactivation of the response regulator gene hp1021 resulted in a severe growth defect, as indicated by a small-colony phenotype. The sequences of the receiver domains of response regulators HP1043 and HP1021 differ from the consensus sequence of the acidic pocket of the receiver domain which is involved in the phosphotransfer reaction from the histidine kinase to the response regulator. Using a genetic complementation system, we demonstrated that the function of response regulator HP166, which is essential for cell growth, can be provided by a mutated derivative carrying a D52N substitution at the site of phosphorylation. We found that the atypical receiver sequences of HP1043 and HP1021 are not crucial for the function of these response regulators. Phosphorylation of the receiver domains of HP1043 and HP1021 is not needed for response regulator function and may not occur at all. Thus, the phosphorylation-independent action of these regulators differs from the well-established two-component paradigm.
24
Aguilar, Victor, Jean-Sébastien Annicotte, Xavier Escote, Joan Vendrell, Dominique Langin e Lluis Fajas. "Cyclin G2 Regulates Adipogenesis through PPARγ Coactivation". Endocrinology 151, n. 11 (15 settembre 2010): 5247–54. http://dx.doi.org/10.1210/en.2010-0461.
Testo completoAbstract (sommario):
Cell cycle regulators such as cyclins, cyclin-dependent kinases, or retinoblastoma protein play important roles in the differentiation of adipocytes. In the present paper, we investigated the role of cyclin G2 as a positive regulator of adipogenesis. Cyclin G2 is an unconventional cyclin which expression is up-regulated during growth inhibition or apoptosis. Using the 3T3-F442A cell line, we observed an up-regulation of cyclin G2 expression at protein and mRNA levels throughout the process of cell differentiation, with a further induction of adipogenesis when the protein is transiently overexpressed. We show here that the positive regulatory effects of cyclin G2 in adipocyte differentiation are mediated by direct binding of cyclin G2 to peroxisome proliferator-activated receptor γ (PPARγ), the key regulator of adipocyte differentiation. The role of cyclin G2 as a novel PPARγ coactivator was further demonstrated by chromatin immunoprecipitation assays, which showed that the protein is present in the PPARγ-responsive element of the promoter of aP2, which is a PPARγ target gene. Luciferase reporter gene assays, showed that cyclin G2 positively regulates the transcriptional activity of PPARγ. The role of cyclin G2 in adipogenesis is further underscored by its increased expression in mice fed a high-fat diet. Taken together, our results demonstrate a novel role for cyclin G2 in the regulation of adipogenesis.
25
Azoulay, M., C. G. Webb e L. Sachs. "Control of hematopoietic cell growth regulators during mouse fetal development". Molecular and Cellular Biology 7, n. 9 (settembre 1987): 3361–64. http://dx.doi.org/10.1128/mcb.7.9.3361-3364.1987.
Testo completoAbstract (sommario):
Gene expression for the four different growth-regulatory proteins for cells of the myeloid hematopoietic cell lineages was analyzed in mouse fetal and extraembryonic tissues at various stages of development. The macrophage growth inducer MGI-1M (colony-stimulating factor 1) was the only myeloid hematopoietic growth regulator detected as both mRNA and bioactive protein during fetal development. This regulator was produced predominantly in extraembryonic tissues, and the production of hematopoietic growth regulators in embryogenesis was regulated by transcriptional and posttranscriptional controls.
26
Azoulay, M., C. G. Webb e L. Sachs. "Control of hematopoietic cell growth regulators during mouse fetal development." Molecular and Cellular Biology 7, n. 9 (settembre 1987): 3361–64. http://dx.doi.org/10.1128/mcb.7.9.3361.
Testo completoAbstract (sommario):
Gene expression for the four different growth-regulatory proteins for cells of the myeloid hematopoietic cell lineages was analyzed in mouse fetal and extraembryonic tissues at various stages of development. The macrophage growth inducer MGI-1M (colony-stimulating factor 1) was the only myeloid hematopoietic growth regulator detected as both mRNA and bioactive protein during fetal development. This regulator was produced predominantly in extraembryonic tissues, and the production of hematopoietic growth regulators in embryogenesis was regulated by transcriptional and posttranscriptional controls.
27
Chi, Feng, Ying Wang, Timothy K. Gallaher, Chun-Hua Wu, Ambrose Jong e Sheng-He Huang. "Identification of IbeR as a Stationary-Phase Regulator in MeningiticEscherichia coliK1 that Carries a Loss-of-Function Mutation inrpoS". Journal of Biomedicine and Biotechnology 2009 (2009): 1–13. http://dx.doi.org/10.1155/2009/520283.
Testo completoAbstract (sommario):
IbeRis a regulator present in meningiticEscherichia colistrain E44 that carries a loss-of-function mutation in the stationary-phase (SP) regulatory generpoS. In order to determine whether IbeR is an SP regulator in E44, two-dimensional gel electrophoresis and LC-MS were used to compare the proteomes of a noninvasive ibeR deletion mutant BR2 and its parent strain E44 in the SP. Four up-regulated (TufB, GapA, OmpA, AhpC) and three down-regulated (LpdA, TnaA, OpmC) proteins in BR2 were identified when compared to E44. All these proteins contribute to energy metabolism or stress resistance, which is related to SP regulation. One of the down-regulated proteins, tryptophanase (TnaA), which is regulated by RpoS in otherE. colistrains, is associated with SP regulation via production of a signal molecule indole. Our studies demonstrated that TnaA was required for E44 invasion, and that indole was able to restore the noninvasive phenotype of thetnaAmutant. The production of indole was significantly reduced in BR2, indicating thatibeRis required for the indole production viatnaA. Survival studies under different stress conditions indicated that IbeR contributed to bacteria stress resistance in the SP. Taken together, IbeR is a novel regulator contributing to the SP regulation.
28
JÄger, Sebastian, Beate Jonas, Dorothea Pfanzelt, Matthias A. Horstkotte, Holger Rohde, Dietrich Mack e Johannes K. M. Knobloch. "Regulation of Biofilm Formation by σB is a Common Mechanism in Staphylococcus Epidermidis and is not Mediated by Transcriptional Regulation of sarA". International Journal of Artificial Organs 32, n. 9 (settembre 2009): 584–91. http://dx.doi.org/10.1177/039139880903200907.
Testo completoAbstract (sommario):
Biofilm formation is a major pathogenetic factor of Staphylococcus epidermidis. In S. epidermidis the alternative sigma factor σB was identified to regulate biofilm formation in S. epidermidis 1457. In S. aureus σB dependent regulation plays a minor role, whereas sarA (Staphylococcus accessory regulator) is an essential regulator. Therefore, we investigated the impact of σB on sarA transcription and biofilm formation in three independent S. epidermidis isolates. Mutants with dysfunctional σB displayed a strongly reduced biofilm formation, whereas in mutants with constitutive σB activity bio film formation was increased. Transcriptional analysis revealed that IcaA transcription was down-regulated in all σB negative mutants while icaR transcription was up-regulated. However, transcriptional differences varied between individual strains, indicating that additional σB-dependent regulators are involved in biofilm expression. Interestingly, despite the presence of a σB promoter beside two σA promoters no differences, or only minor ones, were observed in sarA transcription, indicating that σB-dependent sarA transcript has no influence on the phenotypic changes. The data observed in independent clinical S. epidermidis isolates suggests that, in contrast to S. aureus, regulation of biofilm formation by σB is a general feature in S. epidermidis. Additionally, we were able to demonstrate that the sarA- dependent regulation is not involved in this regulatory pathway.
29
Major, Iván, e Károly Kiss. "Interconnection and incentive regulation in network industries". Acta Oeconomica 63, n. 1 (1 marzo 2013): 1–21. http://dx.doi.org/10.1556/aoecon.63.2013.1.1.
Testo completoAbstract (sommario):
The price regulation of network industries has changed tremendously all over the world recently. Theoretical contributions specifically advocate and telecommunications, energy and other market regulators in various parts of the world practice cost-based pricing for inter-firm network access services. Cost-based pricing is performed under the assumption that the regulator has perfect information regarding the costs of producing the services. We show that — under fairly general conditions — cost-based pricing creates incentives for regulated firms not to improve their efficiency. Allowing for information asymmetry between the regulator and the regulated firms, we find that incentive regulation will eliminate the adverse effect of cost-based pricing on the firms’ efficiency and on social welfare.
30
Liu, Wei, Yan Li, Xue Bai, Haiguang Wu, Lanxing Bian e Xiaoke Hu. "LuxR-Type Regulator AclR1 of Azorhizobium caulinodans Regulates Cyclic di-GMP and Numerous Phenotypes in Free-Living and Symbiotic States". Molecular Plant-Microbe Interactions® 33, n. 3 (marzo 2020): 528–38. http://dx.doi.org/10.1094/mpmi-10-19-0306-r.
Testo completoAbstract (sommario):
LuxR-type regulators play important roles in transcriptional regulation in bacteria and control various biological processes. A genome sequence analysis showed the existence of seven LuxR-type regulators in Azorhizobium caulinodans ORS571, an important nitrogen-fixing bacterium in both its free-living state and in symbiosis with its host, Sesbania rostrata. However, the functional mechanisms of these regulators remain unclear. In this study, we identified a LuxR-type regulator that contains a cheY-homologous receiver (REC) domain in its N terminus and designated it AclR1. Interestingly, phylogenetic analysis revealed that AclR1 exhibited relatively close evolutionary relationships with MalT/GerE/FixJ/NarL family proteins. Functional analysis of an aclR1 deletion mutant (ΔaclR1) in the free-living state showed that AclR1 positively regulated cell motility and flocculation but negatively regulated exopolysaccharide production, biofilm formation, and second messenger cyclic diguanylate (c-di-GMP)-related gene expression. In the symbiotic state, the ΔaclR1 mutant was defective in competitive colonization and nodulation on host plants. These results suggested that AclR1 could provide bacteria with the ability to compete effectively for symbiotic nodulation. Overall, our results show that the REC-LuxR-type regulator AclR1 regulates numerous phenotypes both in the free-living state and during host plant symbiosis.
31
Maggetti, Martino, Christian Ewert e Philipp Trein. "Not Quite the Same". ANNALS of the American Academy of Political and Social Science 670, n. 1 (marzo 2017): 152–69. http://dx.doi.org/10.1177/0002716217691240.
Testo completoAbstract (sommario):
This article compares the role of regulatory intermediaries in the governance of pharmaceuticals and medical devices in Australia and Switzerland. We argue that the creation, selection, and activation of specific intermediaries depend on the organizational capacity of the regulator and on the potential of the intermediary to be captured by the target. To limit the risk of capture of intermediaries where the regulated industries are powerful, regulators tend to keep intermediaries under their control. To do so, the regulator must be well-funded and well-staffed, or supported by its political principal. However, when the target has limited capture potential, regulators will rely more heavily on externalized intermediaries. These intermediaries typically consist of transnational organizations in charge of multiple regulatory issues in several jurisdictions, and can provide unique expertise in an efficient way. Four case studies of the Australian and Swiss regulatory regimes for therapeutic products support this argument.
32
Koppenhöfer, Sonja, e Andrew S. Lang. "Interactions among Redox Regulators and the CtrA Phosphorelay in Dinoroseobacter shibae and Rhodobacter capsulatus". Microorganisms 8, n. 4 (14 aprile 2020): 562. http://dx.doi.org/10.3390/microorganisms8040562.
Testo completoAbstract (sommario):
Bacteria employ regulatory networks to detect environmental signals and respond appropriately, often by adjusting gene expression. Some regulatory networks influence many genes, and many genes are affected by multiple regulatory networks. Here, we investigate the extent to which regulatory systems controlling aerobic–anaerobic energetics overlap with the CtrA phosphorelay, an important system that controls a variety of behavioral processes, in two metabolically versatile alphaproteobacteria, Dinoroseobacter shibae and Rhodobacter capsulatus. We analyzed ten available transcriptomic datasets from relevant regulator deletion strains and environmental changes. We found that in D. shibae, the CtrA phosphorelay represses three of the four aerobic–anaerobic Crp/Fnr superfamily regulator-encoding genes (fnrL, dnrD, and especially dnrF). At the same time, all four Crp/Fnr regulators repress all three phosphorelay genes. Loss of dnrD or dnrF resulted in activation of the entire examined CtrA regulon, regardless of oxygen tension. In R. capsulatus FnrL, in silico and ChIP-seq data also suggested regulation of the CtrA regulon, but it was only with loss of the redox regulator RegA where an actual transcriptional effect on the CtrA regulon was observed. For the first time, we show that there are complex interactions between redox regulators and the CtrA phosphorelays in these bacteria and we present several models for how these interactions might occur.
33
Yang, X. Frank, Martin S. Goldberg, Ming He, Haijun Xu, Jon S. Blevins e Michael V. Norgard. "Differential Expression of a Putative CarD-Like Transcriptional Regulator, LtpA, in Borrelia burgdorferi". Infection and Immunity 76, n. 10 (28 luglio 2008): 4439–44. http://dx.doi.org/10.1128/iai.00740-08.
Testo completoAbstract (sommario):
ABSTRACT The availability of microbial genome information has provided a fruitful opportunity for studying regulatory networks in a variety of pathogenic bacteria. In an initial effort to elucidate regulatory networks potentially involved in differential gene expression by the Lyme disease pathogen Borrelia burgdorferi, we have been investigating the functions and regulation of putative transcriptional regulatory factors predicted to be encoded within the B. burgdorferi genome. Herein we report the regulation of one of the predicted transcriptional regulators, LtpA (BB0355), which is homologous to the transcriptional regulator CarD from Myxococcus xanthus. LtpA expression was assessed in response to various environmental stimuli. Immunoblot and quantitative reverse transcription-PCR analyses revealed that unlike many well-characterized differentially regulated Borrelia genes whose expression is induced by elevated temperature, the expression of LtpA was significantly downregulated when spirochetes were grown at an elevated temperature (37°C), as well as when the bacteria were cultivated in a mammalian host-adapted environment. In contrast, LtpA was induced at a lower culture temperature (23°C). Further analyses indicated that the downregulation of LtpA was not dependent on the Rrp2-RpoN-RpoS regulatory pathway, which is involved in the downregulation of OspA when B. burgdorferi is grown in a mammalian host-adapted environment. LtpA protein levels in B. burgdorferi were unaltered in response to changes in the pH in the borrelial cultures. Multiple attempts to generate an LtpA-deficient mutant were unsuccessful, which has hampered the elucidation of its role in pathogenesis. Given that LtpA is exclusively expressed during borrelial cultivation at a lower temperature, a parameter that has been widely used as a surrogate condition to mimic B. burgdorferi in unfed (flat) ticks, and because LtpA is homologous to a known transcriptional regulator, we postulate that LtpA functions as a regulator modulating the expression of genes important to B. burgdorferi's survival within its arthropod vector.
34
Nakamura, Tsukasa, e Hidetaka Ushigome. "Myeloid-Derived Suppressor Cells as a Regulator of Immunity in Organ Transplantation". International Journal of Molecular Sciences 19, n. 8 (10 agosto 2018): 2357. http://dx.doi.org/10.3390/ijms19082357.
Testo completoAbstract (sommario):
Regulation of allo-immune responses is proposed as a topic for investigation in the current field of organ transplantation. As a regulator, regulatory T cells (Tregs) have received attention due to their ability to control allograft rejection. Concurrently, however, the independent action of Tregs is not enough to achieve tolerance status in many situations. Meanwhile, as a multi-functional regulator, myeloid-derived suppressor cells (MDSCs) can suppress effector T cells as well as induce Tregs or regulatory B cells (Bregs) in certain circumstances. Furthermore, the importance of a crosstalk between MDSCs and natural killer T cells to induce tolerance has been reported. Thus, orchestration between MDSCs, myeloid regulators, T/Bregs and other lymphoid/myeloid regulators can shed light on achieving allogeneic tolerance. Here, we review the current knowledge in terms of immunological regulatory function displayed by MDSCs in the context of organ transplantation. Ideal control of MDSCs would lead to a reduction of allograft rejection and subsequent long-term allograft acceptance.
35
Willsey, Graham G., e Matthew J. Wargo. "Sarcosine Catabolism in Pseudomonas aeruginosa Is Transcriptionally Regulated by SouR". Journal of Bacteriology 198, n. 2 (26 ottobre 2015): 301–10. http://dx.doi.org/10.1128/jb.00739-15.
Testo completoAbstract (sommario):
ABSTRACTSarcosine (N-methylglycine) is present in many environments inhabited by pseudomonads and is likely most often encountered as an intermediate in the metabolism of choline, carnitine, creatine, and glyphosate. While the enzymology of sarcosine metabolism has been relatively well studied in bacteria, the regulatory mechanisms governing catabolism have remained largely unknown. We previously determined that the sarcosine-catabolic (sox) operon ofPseudomonas aeruginosais induced by the AraC family regulator GbdR in response to glycine betaine and dimethylglycine. However, induction of these genes was still observed in response to sarcosine in agbdRdeletion mutant, indicating that an independent sarcosine-responsive transcription factor also acted at this locus. Our goal in this study was to identify and characterize this regulator. Using a transposon-based genetic screen, we identified PA4184, or SouR (sarcosineoxidation andutilizationregulator), as the sarcosine-responsive regulator of thesoxoperon, with tight induction specificity for sarcosine. ThesouRgene is required for appreciable growth on sarcosine as a carbon and nitrogen source. We also characterized the transcriptome response to sarcosine governed by SouR using microarray analyses and performed electrophoretic mobility shift assays to identify promoters directly regulated by the transcription factor. Finally, we characterized PA3630, or GfnR (glutathione-dependentformaldehydeneutralizationregulator), as the regulator of the glutathione-dependent formaldehyde detoxification system inP. aeruginosathat is expressed in response to formaldehyde released during the catabolism of sarcosine. This study expands our understanding of sarcosine metabolic regulation in bacteria through the identification and characterization of the first known sarcosine-responsive transcriptional regulator.IMPORTANCEThePseudomonas aeruginosagenome encodes many diverse metabolic pathways, yet the specific transcription regulators controlling their expression remain mostly unknown. Here, we used a genetic screen to identify the sarcosine-specific regulator of the sarcosine oxidase operon, which we have named SouR. SouR is the first bacterial regulator shown to respond to sarcosine, and it is required for growth on sarcosine. Sarcosine is found in its free form and is also an intermediate in the catabolic pathways of glycine betaine, carnitine, creatine, and glyphosate. The similarity of SouR to the regulators of carnitine and glycine betaine catabolism suggests evolutionary diversification within this regulatory family to allow response to structurally similar but physiologically distinct ligands.
36
Chan, Pan F., e Simon J. Foster. "Role of SarA in Virulence Determinant Production and Environmental Signal Transduction in Staphylococcus aureus". Journal of Bacteriology 180, n. 23 (1 dicembre 1998): 6232–41. http://dx.doi.org/10.1128/jb.180.23.6232-6241.1998.
Testo completoAbstract (sommario):
ABSTRACT The staphylococcal accessory regulator (encoded bysarA) is an important global regulator of virulence factor biosynthesis in Staphylococcus aureus. To further characterize its role in virulence determinant production, ansarA knockout mutant was created by insertion of a kanamycin antibiotic resistance cassette into the sarAgene. N-terminal sequencing of exoproteins down-regulated bysarA identified several putative proteases, including a V8 serine protease and a novel metalloprotease, as the major extracellular proteins repressed by sarA. In kinetic studies, thesarA mutation delays the onset of α-hemolysin (encoded byhla) expression and reduces levels of hla to approximately 40% of the parent strain level. Furthermore, SarA plays a role in signal transduction in response to microaerobic growth since levels of hla were much lower in a microaerobic environment than after aerobic growth in the sarA mutant. An exoprotein exhibiting hemolysin activity on sheep blood, and up-regulated bysarA independently of the accessory gene regulator (encoded by agr), was specifically induced microaerobically. Transcriptional gene fusion and Western analysis revealed thatsarA up-regulates both toxic shock syndrome toxin 1 gene (tst) expression and staphylococcal enterotoxin B production, respectively. This study demonstrates the role ofsarA as a signal transduction regulatory component in response to aeration stimuli and suggests that sarAfunctions as a major repressor of protease activity. The possible role of proteases as regulators of virulence determinant stability is discussed.
37
Ellermeier, Jeremy R., e James M. Slauch. "Fur Regulates Expression of the Salmonella Pathogenicity Island 1 Type III Secretion System through HilD". Journal of Bacteriology 190, n. 2 (9 novembre 2007): 476–86. http://dx.doi.org/10.1128/jb.00926-07.
Testo completoAbstract (sommario):
ABSTRACT The invasion of intestinal epithelial cells by Salmonella enterica serovar Typhimurium is mediated by a type III secretion system (T3SS) encoded on Salmonella pathogenicity island 1 (SPI1). Expression of the SPI1 T3SS is tightly regulated by the combined action of HilC, HilD, and RtsA, three AraC family members that can independently activate hilA, which encodes the direct regulator of the SPI1 structural genes. Expression of hilC, hilD, and rtsA is controlled by a number of regulators that respond to a variety of environmental signals. In this work, we show that one such signal is iron mediated by Fur (ferric uptake regulator). Fur activates hilA transcription in a HilD-dependent manner. Fur regulation of HilD does not appear to be simply at the transcriptional or translational level but rather requires the presence of the HilD protein. Fur activation of SPI1 is not mediated through the Fur-regulated small RNAs RfrA and RfrB, which are the Salmonella ortholog and paralog of RyhB that control expression of sodB. Fur regulation of HilD is also not mediated through the known SPI1 repressor HilE or the CsrABC system. Although understanding the direct mechanism of Fur action on HilD requires further analysis, this work is an important step toward elucidating how various global regulatory systems control SPI1.
38
Jung, Ji Hoon, Hyemin Lee, Shelya X. Zeng e Hua Lu. "RBM10, a New Regulator of p53". Cells 9, n. 9 (16 settembre 2020): 2107. http://dx.doi.org/10.3390/cells9092107.
Testo completoAbstract (sommario):
The tumor suppressor p53 acts as a transcription factor that regulates the expression of a number of genes responsible for DNA repair, cell cycle arrest, metabolism, cell migration, angiogenesis, ferroptosis, senescence, and apoptosis. It is the most commonly silenced or mutated gene in cancer, as approximately 50% of all types of human cancers harbor TP53 mutations. Activation of p53 is detrimental to normal cells, thus it is tightly regulated via multiple mechanisms. One of the recently identified regulators of p53 is RNA-binding motif protein 10 (RBM10). RBM10 is an RNA-binding protein frequently deleted or mutated in cancer cells. Its loss of function results in various deformities, such as cleft palate and malformation of the heart, and diseases such as lung adenocarcinoma. In addition, RBM10 mutations are frequently observed in lung adenocarcinomas, colorectal carcinomas, and pancreatic ductal adenocarcinomas. RBM10 plays a regulatory role in alternative splicing. Several recent studies not only linked this splicing regulation of RBM10 to cancer development, but also bridged RBM10′s anticancer function to the p53 pathway. This review will focus on the current progress in our understanding of RBM10 regulation of p53, and its role in p53-dependent cancer prevention.
39
Lei, Mei G., e Chia Y. Lee. "MgrA Activates Staphylococcal Capsule via SigA-Dependent Promoter". Journal of Bacteriology 203, n. 2 (19 ottobre 2020): e00495-20. http://dx.doi.org/10.1128/jb.00495-20.
Testo completoAbstract (sommario):
ABSTRACTStaphylococcus aureus capsule polysaccharide is an important antiphagocytic virulence factor. The cap genes are regulated at the promoter element (Pcap) upstream of the cap operon. Pcap, which consists of a dominant SigB-dependent promoter and a weaker upstream SigA-dependent promoter, is activated by global regulator MgrA. How MgrA activates capsule is unclear. Here, we showed that MgrA directly bound to the Pcap region and affected the SigA-dependent promoter. Interestingly, an electrophoretic mobility shift assay showed that MgrA bound to a large region of Pcap, mainly downstream of the SigA-dependent promoter. We further showed that the ArlRS two-component system and the Agr quorum sensing system activated capsule primarily through MgrA in the early growth phases.IMPORTANCE The virulence of Staphylococcus aureus depends on the expression of various virulence factors, which is governed by a complex regulatory network. We have been using capsule as a model virulence factor to study virulence gene regulation in S. aureus. MgrA is one of the regulators of capsule and has a major effect on capsule production. However, how MgrA regulates capsule genes is not understood. In this study, we were able to define the mechanism involving MgrA regulation of capsule. In addition, we also delineated the role of MgrA in capsule regulatory pathways involving the key virulence regulators Agr and Arl. This study further advances our understanding of virulence gene regulation in S. aureus, an important human pathogen.
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O’Sullivan, Patrick John. "Regulatory relationships and incentives: from Riggs Bank to HSBC". International Journal of Law and Management 59, n. 5 (11 settembre 2017): 729–39. http://dx.doi.org/10.1108/ijlma-04-2016-0041.
Testo completoAbstract (sommario):
Purpose The aim of the paper is to examine what type of relationship existed between the Office of the Comptroller of the Currency (OCC) and Riggs Bank in respect of anti-money laundering (AML) compliance. Different commentators have established certain trends in the interaction between a regulator and a regulated entity, and this paper seeks to apply these findings to the relationship between the OCC and Riggs Bank and ascertain where this example lies in the wider domain of regulatory relationships. The paper then examines whether the relationship between the OCC and HSBC United States was similar to the one between the OCC and Riggs Bank or did the regulator adopt a more aggressive supervisory stance. Throughout this work, there is also a focus on the underlying incentives which may adversely affect how a financial institution interacts with a financial regulator and possible solutions to this problem proposed. Design/methodology/approach Research undertaken by commentators was assessed and their findings as the different regulatory relationships that may develop between a regulator and a regulated entity were applied to the interactions between the OCC and two different financial institutions, namely, Riggs Bank and HSBC United States. Examples from the Senate Subcommittee Reports into the AML failings into these financial institutions were examined through the prism of pre-existing regulatory relationship categories. Findings The paper ultimately concludes that the OCC was far too passive in its interactions with both Riggs Bank and HSBC United States and that the primary underlying motivations for both institutions were profit- rather than compliance-led. Research limitations/implications One of the main limitations to this research was the absence of direct input from either personnel from the banking sector in the USA or of regulators from the same jurisdiction. Practical implications This paper proposes a number of practical solutions to recast the relationship between financial regulators and regulated institutions away from the former deferring to the latter to one where the former dictates to the latter. Originality/value This paper seeks to examine an actual regulatory relationship between a financial regulator and two different institutions that is reported in the public domain by applying pre-existing academic research on question of regulatory relationships and see how the practice differs or corresponds with the theory.
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Hernández-Lucas, I., A. L. Gallego-Hernández, S. Encarnación, M. Fernández-Mora, A. G. Martínez-Batallar, H. Salgado, R. Oropeza e E. Calva. "The LysR-Type Transcriptional Regulator LeuO Controls Expression of Several Genes in Salmonella enterica Serovar Typhi". Journal of Bacteriology 190, n. 5 (21 dicembre 2007): 1658–70. http://dx.doi.org/10.1128/jb.01649-07.
Testo completoAbstract (sommario):
ABSTRACT LeuO is a LysR-type transcriptional regulator that has been implicated in the bacterial stringent response and in the virulence of Salmonella. A genomic analysis with Salmonella enterica serovar Typhi revealed that LeuO is a positive regulator of OmpS1, OmpS2, AssT, and STY3070. In contrast, LeuO down-regulated the expression of OmpX, Tpx, and STY1978. Transcriptional fusions supported the positive and negative LeuO regulation. Expression of ompS1, assT, and STY3070 was induced in an hns mutant, consistent with the notion that H-NS represses these genes; transcriptional activity was lower for tpx and STY1978 in an hns background, suggesting that this global regulatory protein has a positive effect. In contrast, ompS2 and ompX expression appeared to be H-NS independent. LeuO specifically bound to the 5′ intergenic regions of ompS2, assT, STY3070, ompX, and tpx, while it was not observed to bind to the promoter region of STY1978, suggesting that LeuO regulates in direct and indirect ways. In this work, a novel set of genes belonging to the LeuO regulon are described; interestingly, these genes are involved in a variety of biological processes, suggesting that LeuO is a global regulator in Salmonella.
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Lu, Hsu-Feng, Yu-Chieh Tsai, Li-Hua Li, Yi-Tsung Lin e Tsuey-Ching Yang. "Role of AzoR, a LysR-type transcriptional regulator, in SmeVWX pump-mediated antibiotic resistance in Stenotrophomonas maltophilia". Journal of Antimicrobial Chemotherapy 76, n. 9 (21 giugno 2021): 2285–93. http://dx.doi.org/10.1093/jac/dkab203.
Testo completoAbstract (sommario):
Abstract Background The SmeVWX efflux pump of Stenotrophomonas maltophilia contributes to menadione (MD) tolerance and resistance to chloramphenicol, quinolones and tetracycline. The components of the SmeVWX efflux pump are encoded by a five-gene operon, smeU1VWU2X. We have previously demonstrated that the smeU1VWU2X operon is intrinsically unexpressed and inducibly expressed by MD via a SoxR- and SmeRv-involved regulatory circuit in S. maltophilia KJ. We also inferred that there should be other regulator(s) involved in MD-mediated smeU1VWU2X expression in addition to SoxR and SmeRv. Objectives To identify novel regulator(s) involved in the regulation of MD-mediated smeU1VWU2X expression and elucidate the regulatory circuit. Methods A possible regulator candidate involved in the regulation of MD-mediated smeU1VWU2X expression was identified by a homologue search using the helix-turn-helix domain of SmeRv as a query. Gene expression was assessed using the promoter-xylE transcriptional fusion assay and quantitative RT–PCR. The impact of the regulator on SmeVWX pump-mediated functions was investigated via mutant construction and functional tests (antibiotic susceptibility and MD tolerance). Results AzoR (Smlt3089), a LysR-type transcriptional regulator, was investigated. In unstressed logarithmically grown cells, AzoR was abundantly expressed and functioned as a repressor, inhibiting the expression of the smeU1VWU2X operon. MD challenge attenuated azoR expression, thus derepressing the expression of the smeU1VWU2X operon in S. maltophilia KJ. AzoR down-regulation-mediated smeU1VWU2X expression was observed in quinolone-resistant and SmeVWX-overexpressing S. maltophilia clinical isolates. Conclusions AzoR negatively regulates the expression of the smeU1VWU2X operon and SmeVWX pump-mediated antibiotic resistance in S. maltophilia.
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Tronnet, Sophie, Christophe Garcie, Nadine Rehm, Ulrich Dobrindt, Eric Oswald e Patricia Martin. "Iron Homeostasis Regulates the Genotoxicity of Escherichia coli That Produces Colibactin". Infection and Immunity 84, n. 12 (12 settembre 2016): 3358–68. http://dx.doi.org/10.1128/iai.00659-16.
Testo completoAbstract (sommario):
The genotoxin colibactin is a secondary metabolite produced by a variety of pathogenic enterobacteria. Its biosynthesis requires the enzymatic activity of the phosphopantetheinyl transferase (PPTase) ClbA. We previously showed that ClbA can also contribute to the production of siderophores. Because the biosynthesis of siderophores is regulated by iron availability, we hypothesized that iron could also modulate the production of colibactin through the transcriptional regulation of clbA . This study revealed an increased transcription of clbA under iron-limiting conditions and a decrease of clbA expression in iron-rich media. We demonstrate that clbA transcription is regulated by both the ferric uptake regulator (Fur) and the small regulatory noncoding RNA RyhB. We evidenced that the regulation of the transcription of clbA by Fur and RyhB leads to the regulation of colibactin production. This work highlights the complex mechanism of regulation of an important virulence factor by the two major regulators of bacterial iron homeostasis, making iron a key environmental factor contributing to bacterial virulence and carcinogenesis.
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Munson, George P., e June R. Scott. "Binding Site Recognition by Rns, a Virulence Regulator in the AraC Family". Journal of Bacteriology 181, n. 7 (1 aprile 1999): 2110–17. http://dx.doi.org/10.1128/jb.181.7.2110-2117.1999.
Testo completoAbstract (sommario):
ABSTRACT The expression of CS1 pili by enterotoxigenic strains ofEscherichia coli is regulated at the transcriptional level and requires the virulence regulator Rns, a member of the AraC family of regulatory proteins. Rns binds at two separate sites upstream of Pcoo (the promoter of CS1 pilin genes), which were identified in vitro with an MBP::Rns fusion protein in gel mobility and DNase I footprinting assays. At each site, Rns recognizes asymmetric nucleotide sequences in two regions of the major groove and binds along one face of the DNA helix. Both binding sites are required for activation of Pcoo in vivo, because mutagenesis of either site significantly reduced the level of expression from this promoter. Thus, Rns regulates the expression of CS1 pilin genes directly, not via a regulatory cascade. Analysis of Rns-nucleotide interactions at each site suggests that binding sites for Rns and related virulence regulators are not easily identified because they do not bind palindromic or repeated sequences. A strategy to identify asymmetric binding sites is presented and applied to locate potential binding sites upstream of other genes that Rns can activate, including those encoding the CS2 and CFA/I pili of enterotoxigenic E. coli and the global regulator virB of Shigella flexneri.
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Austin, Crystal M., Ge Wang e Robert J. Maier. "Aconitase Functions as a Pleiotropic Posttranscriptional Regulator in Helicobacter pylori". Journal of Bacteriology 197, n. 19 (13 luglio 2015): 3076–86. http://dx.doi.org/10.1128/jb.00529-15.
Testo completoAbstract (sommario):
ABSTRACTPosttranscriptional regulation in bacteria has increasingly become recognized as playing a major role in response to environmental stimuli. Aconitase is a bifunctional protein that not only acts enzymatically but also can be a posttranscriptional regulator. To investigate protein expression regulated byHelicobacter pyloriAcnB in response to oxidative stress, a global proteomics study was conducted wherein the ΔacnBstrain was compared to the parent strain when both strains were O2stressed. Many proteins, including some involved in urease activity, in combating oxidative stress, and in motility, were expressed at a significantly lower level in the ΔacnBstrain. A bioinformatics prediction tool was used to identify putative targets for aconitase-mediated regulation, and electrophoretic mobility shift assays demonstrated that apo-AcnB is able to bind to RNA transcripts ofhpn(encoding a nickel-sequestering protein),ahpC(encoding alkyl hydroperoxide reductase), andflgR(encoding flagellum response regulator). Compared to the wild type (WT), the ΔacnBstrain had decreased activities of the nickel-containing enzymes urease and hydrogenase, and this could be correlated with lower total nickel levels within ΔacnBcells. Binding of apo-AcnB to thehpn5′ untranslated region (UTR) may inhibit the expression of Hpn. In agreement with the finding that AcnB regulates the expression of antioxidant proteins such as AhpC, ΔacnBcells displayed oxidative-stress-sensitive phenotypes. The ΔacnBstrain has a lesser motility ability than the WT strain, which can likely be explained by the functions of AcnB on the FlgRS-RpoN-FlgE regulatory cascade. Collectively, our results suggest a global role for aconitase as a posttranscriptional regulator in this gastric pathogen.IMPORTANCEBacterial survival depends on the ability of the cell to sense and respond to a variety of environmental changes. ForHelicobacter pylori, responding to environmental stimuli within the gastric niche is essential for persistence and host colonization. However, there is much to be learned about the regulatory mechanisms thatH. pyloriemploys to orchestrate its response to different stimuli. In this study, we explore the role of aconitase, a bifunctional protein that has been found to act as a posttranscriptional regulator in several other bacteria. Our results shed light on the magnitude of aconitase-mediated regulation inH. pylori, and we propose that aconitase acts as a global regulator of key genes involved in virulence.
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Coen, David, e John-Paul Salter. "Multilevel regulatory governance: Establishing bank-regulator relationships at the European Banking Authority". Business and Politics 22, n. 1 (10 ottobre 2019): 113–34. http://dx.doi.org/10.1017/bap.2019.21.
Testo completoAbstract (sommario):
AbstractFollowing the 2007–9 financial crisis, the EU strengthened its institutional apparatus for bank regulation, creating a trio of sectoral bodies, including the European Banking Authority (EBA). Various aspects of this new system have been studied, but to date, little is known about how banks engage with their new supranational regulator. We argue that such engagement fosters an interdependence between banks and regulators, thus contributing to the efficiency and robustness of the overall regulatory regime; but also that it is contingent on the regulator exhibiting the qualities of credibility, legitimacy, and transparency. These qualities are grounded in the domestic regulatory governance literature, but we suggest that they are rendered problematic by the complexities of the EU's multilevel system and, in particular, the overlap in competences between the EBA and the European Central Bank. We examine the EBA in the light of these criteria and find that banks’ engagement remains pitched towards established national regulators and the EU's legislative arena. This poses concerns for the efficacy of agency governance in the EU's regulatory regime for banking.
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Vihinen, Mauno. "Generic model for biological regulation". F1000Research 11 (26 agosto 2022): 419. http://dx.doi.org/10.12688/f1000research.110944.2.
Testo completoAbstract (sommario):
A substantial portion of molecules in an organism are involved in regulation of a wide spectrum of biological processes. Several models have been presented for various forms of biological regulation, including gene expression regulation and physiological regulation; however, a generic model is missing. Recently a new unifying theory in biology, poikilosis, was presented. Poikilosis indicates that all systems display intrinsic heterogeneity. The concept of poikilosis allowed development of a model for biological regulation applicable to all types of regulated systems. The perturbation-lagom-TATAR countermeasures-regulator (PLTR) model combines the effects of perturbation and lagom (allowed and sufficient extent of heterogeneity) in a system with tolerance, avoidance, repair, attenuation and resistance (TARAR) countermeasures, and possible regulators. There are three modes of regulation, two of which are lagom-related. In the first scenario, lagom is maintained, both intrinsic (passive) and active TARAR countermeasures can be involved. In the second mode, there is a shift from one lagom to another. In the third mode, reguland regulation, the regulated entity is the target of a regulatory shift, which is often irreversible or requires action of another regulator to return to original state. After the shift, the system enters to lagom maintenance mode, but at new lagom extent. The model is described and elaborated with examples and applications, including medicine and systems biology. Consequences of non-lagom extent of heterogeneity are introduced, along with a novel idea for therapy by reconstituting biological processes to lagom extent, even when the primary effect cannot be treated.
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Vihinen, Mauno. "Generic model for biological regulation". F1000Research 11 (13 aprile 2022): 419. http://dx.doi.org/10.12688/f1000research.110944.1.
Testo completoAbstract (sommario):
A substantial portion of molecules in an organism are involved in regulation of a wide spectrum of biological processes. Several models have been presented for various forms of biological regulation, including gene expression regulation and physiological regulation; however, a generic model is missing. Recently a new unifying theory in biology, poikilosis, was presented. Poikilosis indicates that all systems display intrinsic heterogeneity, which is a normal state. The concept of poikilosis allowed development of a model for biological regulation applicable to all types of regulated systems. The perturbation-lagom-TATAR countermeasures-regulator (PLTR) model combines the effects of perturbation and lagom (allowed and sufficient extent of heterogeneity) in a system with tolerance, avoidance, repair, attenuation and resistance (TARAR) countermeasures, and possible regulators. There are three modes of regulation, two of which are lagom-related. In the first scenario, lagom is maintained, both intrinsic (passive) and active TARAR countermeasures can be involved. In the second mode, there is a shift from one lagom to another. In the third mode, reguland regulation, the regulated entity is the target of a regulatory shift, which is often irreversible or requires action of another regulator to return to original state. After the shift, the system enters to lagom maintenance mode, but at new lagom extent. The model is described and elaborated with examples and applications, including medicine and systems biology. Consequences of non-lagom extent of heterogeneity are introduced, along with a novel idea for therapy by reconstituting biological processes to lagom extent, even when the primary effect cannot be treated.
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Alvarez, Clara Luz. "Regulatory State and Judicial Decisions in Telecommunications in Mexico". Law, State and Telecommunications Review 10, n. 1 (14 maggio 2018): 15–36. http://dx.doi.org/10.26512/lstr.v10i1.21498.
Testo completoAbstract (sommario):
Purpose – To assess the role of the judiciary in defining the Regulatory State and in regulating telecommunications in Mexico after almost 5 years of the creation of an independent regulator for telecommunications and broadcasting (Instituto Federal de Telecomunicaciones) with authority in antitrust matters.
Methodology/approach/design – To identify the most relevant judicial decisions in telecommunications and antitrust matters, research upon the context in which they were adopted, analyze the content of the decisions and identify the impact of such judicial decisions in the construction of the Mexican Regulatory State, and in the law, in regulation/acts of the regulator.
Findings – The main findings are that: (1) the Mexican Regulatory State is a reality now, even if it is in its beginnings; (2) Congress is receptive to Judiciary´s decisions; and (3) deference by judiciary to the regulator is not a blank check, even if there are complex technical issues and a discretionary decision.
Practical implications – The identification of a Regulatory State in Mexico evidences that there are deep changes in the traditional relationship between Congress and regulators. Also, the deference granted by the courts to regulators must be considered as a consequence of such Regulatory State. Nonetheless and despite the deference to regulators, Judiciary´s role in building the telecommunications and broadcasting sector is paramount, because judicial decisions ultimately define it.
Originality/value – Major changes to telecommunications and broadcasting have taken place in Mexico in the last years. Therefore, there has been scarce research and analysis about the new role of regulators, legislators, and judges, in the so called Regulatory State in Mexico. Moreover, the experience of Mexico may be valuable for other scholars which are assessing public policy in their own Latin American countries or in countries with similarities to them.
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Bendris, Nawal, Abdelhalim Loukil, Caroline Cheung, Nikola Arsic, Cosette Rebouissou, Robert Hipskind, Marion Peter, Bénédicte Lemmers e Jean Marie Blanchard. "Cyclin A2: a genuine cell cycle regulator?" BioMolecular Concepts 3, n. 6 (1 dicembre 2012): 535–43. http://dx.doi.org/10.1515/bmc-2012-0027.
Testo completoAbstract (sommario):
AbstractCyclin A2 belongs to the core cell cycle regulators and participates in the control of both S phase and mitosis. However, several observations suggest that it is also endowed with other functions, and our recent data shed light on its involvement in cytoskeleton dynamic and cell motility. From the transcription of its gene to its posttranslational modifications, cyclin A2 regulation reveals the complexity of the regulatory network shaping cell cycle progression. We summarize our current knowledge on this cell cycle regulator and discuss recent findings raising the possibility that cyclin A2 might play a much broader role in epithelial tissues homeostasis.