Regulatory State Research Articles (Page 1)

Cardiac contractility is driven by shortening of ∼2-μm-long, macromolecular assemblies known as sarcomeres. During contraction, the motor protein myosin binds to, and exerts force upon actin filaments, utilizing energy from the hydrolysis of ATP. When not actively contracting, myosin partition into two subpopulations, distinguished by their basal rates of ATP hydrolysis, known as the "Disordered Relaxed" (DRX) and "Super Relaxed" (SRX) states. Additionally, the slower hydrolyzing SRX state has been proposed as a sequestered or "reserve pool" of myosin that do not contribute to contraction but can be recruited for enhanced contractility in response to external stimuli. Thus, the fraction of myosin in the SRX state is thought to reflect the overall regulatory state of the myosin population. In this volume of the Journal of General Physiology, a study by Pilagov et al. explores how the SRX state is regulated by phosphorylation or haploinsufficiency of a key regulatory protein, Myosin Binding Protein-C (MyBP-C). Surprisingly, they found that perturbations of MyBP-C led to a negligible change in the overall abundance of SRX. Instead, they found a rearrangement of SRX myosin throughout the sarcomere - specifically a decrease in SRX in regions of the sarcomere that contain MyBP-C and a compensatory increase in SRX in regions lacking MyBP-C. Their findings suggest that the influence of MyBP-C extends beyond its immediate vicinity and can simultaneously exert both positive and negative effects in a location-specific manner.

This essay examines the growing prevalence of junk fees, including mandatory back-end fees and hidden add-on charges, which obscure the true cost of goods and services. Drawing on examples from event tickets, hotels, cable bills, restaurants, and financial services, I show how these pricing practices increase search costs and equilibrium prices, distort consumer choices, and divert innovation toward exploitative rather than value-enhancing strategies. Economic theory and evidence suggest that competition and disclosure alone are often insufficient to discipline junk fees. I review recent regulatory responses, including federal and state rules that require all-in-one upfront pricing, and discuss their implications for consumer welfare and market efficiency. The rapid evolution of junk fee policies provides economists with rich opportunities to study their intended and unintended consequences. At its core, the case for regulating junk fees rests not on paternalism but on enhancing market functioning.

The article explores the transformation of theoretical approaches to understanding the categories of "risk" and "uncertainty" in economics, focusing on their interpretation in the works published in the 20th and 21st centuries by leading financiers and representatives of other economic disciplines. Special attention is paid to the differentiation of these concepts proposed by F. Knight, and the subsequent evolution of the researchers' views. The changes in the methodological foundations of risk assessment are analyzed. Based on a comparison of the regulatory framework and state standards (including Russian and international regulatory documents), a gradual convergence of practical approaches to risk management with theoretical concepts is being identified.

Expression pattern of the HIFα-family in equine chorioallantois during pregnancy and placental pathology.

Regulatory state capacity for accelerating net-zero transitions: Lessons learned from governing electricity storage in Germany

Cellular development and differentiation in Eukaryotes depends upon sequential gene regulatory decisions that allow a single genome to encode many hundreds of distinct cellular phenotypes. Decisions are stored in the regulatory state of each cell, an important part of which is the epi-genome-the collection of proteins, RNA and their specific associations with the genome. Additionally, further cellular responses are, in part, determined by this regulatory state. To date, models of regulatory state have failed to include the contingency of incoming regulatory signals on the current epi-genetic state and none have done so at the whole-genome level. Here we introduce GenomicLayers, a new R package to run rules-based simulations of epigenetic state changes genome-wide in Eukaryotes. Simulations model the accumulation of changes to genome-wide layers by user-specified binding factors. As a first exemplar, we show two versions of a simple model of the recruitment and spreading of epigenetic marks near telomeres in the yeast Saccharomyces cerevisiae. By combining the output from 100 runs of the simulation, we generate whole genome predictions of epigenetic state at 1bp resolution. The example yeast models are included within a 'vignette' with the GenomicLayers package, which is available at https://github.com/davetgerrard/GenomicLayers . To demonstrate the use of GenomicLayers on the full human reference genome (hg38), we show the results from parameter refinement on a simplistic model of the action of pluripotency factors against a self-spreading repressor seeded at CpG islands. The human genome model is included in supplementary information as an R script. GenomicLayers enables scientists working on diverse eukaryotic organisms to test models of gene regulation in silico. Applications include epigenetic silencing, activation by combinatorial binding of transcription factors and the sink effects caused by down-regulation of components of epigenetic regulators. The software is intended to be used to parameterise, refine and combine models and thereby capitalise on data from the thousands of studies of Eukaryotic epigenomes.

ABSTRACT This paper situates the 2020 creation of the Recovery and Resilience Facility (RRF) and subsequent developments in the context of the evolution of EU finances since the establishment of the European Coal and Steel Community (ECSC) in 1952 and examines the dynamic pressures on EU finances in the 21st century. A budgetary and finance lens offers us a corrective on the idea that the EU is solely a regulatory state, and that integration thorough law is the dominant, even sole instrument of European public power. Moreover, EU public finance is at an important juncture as the demands for EU capacity building grow in response to new challenges and the financial liabilities of the EU increase. Historical Institutionalism (HI) provides the theoretical framework for the analysis.

Rapid proliferation of artificial intelligence (AI) in key domains such as healthcare, education, public services, and digital economies has heightened global commitment to developing strong ethical and governance standards. This systematic review, based on the PRISMA approach, synthesizes evidence from 22 peer-reviewed journal articles, white papers, and policy documents between 2020 and 2025. It examines governance frameworks, ethical concepts, regulatory approaches, sectoral application, and common challenges in operationalizing AI ethics internationally. The review sees wide confluence on core ethical values of fairness, transparency, accountability, explainability, and sustainability. There remains, however, wide variability in the application and institutionalization of these values across jurisdictions. The European Union’s AI Act provides a binding three-tiered risk system with centralized monitoring, whereas global institutions such as the World Health Organization (WHO) and the United Nations advocate high-level ethical frameworks but without statutory implementation. Regional efforts by ASEAN, Hong Kong SAR, and China reflect different states of maturity in the application of lifecycle audit and sector-level policy tools. Five recurring challenges are identified throughout literature: algorithmic bias, privacy risks of the data, patchwork of regulatory environments, corporate and state incumbents, and risks of labor market dislocation. Institutional models by the Alan Turing Institute and corporate players such as NTT DATA stress the value of building ethics from the outset of the life of AI. Educational and civil society voices add further calls for inclusive and collaborative governance frameworks. This paper concludes by advocating for the creation of an internationally coordinated AI regulation agency, cross-border certification schemes, ethics-by-design design methodologies, and adaptive governance mechanisms for the safe, equitable, and transparent application of AI technology.

This article explores the authoritarian entrepreneurial approach to urban governance and its transformative influence on community dynamics in Istanbul’s Fikirtepe Urban Regeneration Project. As a large-scale urban redevelopment initiative, Fikirtepe has become a contested ground of competing interests, where strict regulations coexist with flexible planning practices, forming a complex governance model that turns community actors into quasi-developers. We argue that a governance framework characterised by a fusion of authoritarian and entrepreneurial traits, through mechanisms like the Disaster Law No. 6306 and the 2/3 majority rule, embeds profit-seeking behaviours within regulatory practices and state–market alliances, sidelining local authorities, marginalising stakeholders and intensifying conflicts. Unlike typical capitalist frameworks, this model compels both developers and residents to adopt opportunistic, profit-driven strategies, a phenomenon termed ‘entrepreneurial citizenship’. This redefines the roles of urban actors and disrupts traditional planning processes. In connection with this convergence of governance extremes, negotiation-orientated approaches to planning emerge, where all stakeholders, from residents to property developers to policy networks, engage in competitive adaptation. By illustrating the distinctive challenges unique to Fikirtepe, we conclude by evidencing an imperative trend in urban governance, subject to both progressively authoritarian and entrepreneurial turns, and issue an urgent call to examine its broader implications for urban studies.

ABSTRACTThe UK is often viewed as a centralised entity that has pursued neoliberal policies. Yet its political system features devolved parliaments whose governments deploy responsibilities including those linked to employment relations. This article explores the Welsh Government's role within employment relations to argue that it has shaped pathways to substate variation by (1) defining the procedural status of other actors through creating social partnership structures (2) deploying its role as employer, funder, and procurer to influence employer behaviour, and (3) making some statutory regulation. We conclude that the Welsh Government is part of an increasingly fragmented regulatory state within the UK that offers some opportunities for subnational actors to create divergences within its national system of employment relations.

ABSTRACT Regulatory governance concerns the delivery of evidence-based responses to societal risks, including health, environmental, economic, technological, and security threats. This body of scholarship assumes rationality in citizen-regulator interactions, where independent regulators address emerging risks through rigorous assessments, expecting citizens to make informed decisions based on expert advice. While these foundational assumptions have been challenged, they have received limited attention in relation to the core rationale for insulating regulators from citizens – namely, their vulnerability to emotional judgment and behaviour. To address this gap, this research agenda article focuses on the role of emotions in regulators' formulation of, and citizens' reception of, regulatory responses. It argues that accounting for emotion in regulatory politics enables novel inquiries into regulatory decision-making, advances our understanding of citizens' emotions in the regulatory state context, and accounts for the role of emotions on citizens' judgments of, and behaviour towards, regulatory rules and the regulators themselves. This approach broadens the research agenda to include not only the rational and cognitive aspects of regulation but also an affective layer in the traditional understanding of regulatory politics – explicitly addressing the role of emotions in shaping regulatory rules and governance, as well as corresponding citizens' judgments and behaviours.

ABSTRACTPublic service delivery has increasingly involved mixed markets, with for‐profit, not‐for‐profit, and government‐delivered programs. In such contexts, regulation can protect the public interest by enhancing safety, expanding consumer choice, or improving the quality of goods or services. In this article, we explore how citizens experience varying regulated markets, and whether regulatory stringency shapes citizen perceptions of service quality in the context of early childhood education and care (ECEC) services in the United States. We rely on automated textual analysis of online Google reviews of ECEC alongside a dataset of state policy stringency that tracks whether states allow for unlicensed care environments. Using a regression discontinuity design to test the impact of regulatory systems on reviews of care, we find evidence that parents in states with less stringent regulations are more likely to post negative reviews and express anger and anxiety, relative to parents in states with robust regulatory regimes.

SUMMARYAntibody responses are determined by activated B cells bifurcating into plasmablasts (PBs) and germinal center B cells (GCBCs). Gene regulatory networks (GRNs) underlying human B cell fate choice remain uncharted. Temporally resolved single-cell multi-omics, computational modeling and CRISPR-based perturbations were used to assemble, simulate and test high-resolution GRNs underlying PB and GC fates. The results converged with orthogonal predictions of transcription factor (TF) action at single-nucleotide resolution, revealing dominant and reciprocal actions of IRF4 and its binding partners at simple and composite IRF motifs. Single-cell perturbation analysis of these TFs demonstrated multiple reciprocal negative feedback loops controlling the bifurcation. Additionally, IRF4 and BLIMP1, co-repressed the cell cycle regulators MYC and CCND2. G0/G1 lengthening accelerated the switching of cells to an IRF4hiBLIMP1hi regulatory state and enhanced the probability of PB specification, thereby uncovering a self-reinforcing regulatory module that couples cell cycle dynamics to B cell fate choice.

ABSTRACTWhile recent research has studied the coping behaviors of street‐level bureaucrats (SLBs), less attention has been paid to the institutional antecedents of these coping behaviors. This paper examines how macro‐level institutional factors—specifically, competing institutional logics—shape SLBs' meso‐level organizational conflicts and micro‐level coping behaviors. We use semi‐structured interviews and archival data to investigate environmental policy implementation in China, where developmental state logic and regulatory state logic coexist and compete. We found that regulatory state logic increases SLBs' workloads and accountability, while developmental state logic limits their power and resources. These competing institutional logics result in unclear responsibilities, expanding the number of tasks but constraining resources, creating pressure for enforcement officials while providing few rewards. In response, SLBs engage in active and passive coping behaviors. Our study contributes to public administration and institutional theory research by introducing a multi‐level framework that links competing logics to organizational conflicts and individual coping.

ABSTRACT The Single Supervisory Mechanism (SSM), comprising the European Central Bank (ECB) and national competent authorities, transformed the supervision of banks in participating countries. Theoretical perspectives interpret the ECB in the SSM as either a primary driver of integration, a self-empowering agent, or identify the SSM as a form of experimentalist governance. This article argues in contrast that the regulatory state theory provides a more comprehensive account, by assessing not only the ECB but also the exogenous institutional framework and contingent judicial review. The regulatory state theory is thereby newly conceptualised as constituted by four necessary components. Applied to bank regulation and supervision in the SSM, it reveals a strengthening across all four components which fostered the maturing of the European regulatory state and consolidation of the legal order. The article concludes on implications for assessing the nature and functioning of the EU and entertains further applications of the regulatory state theory.

Kinases regulate cellular processes and are essential for understanding cellular function and disease. To investigate the regulatory state of a kinase, numerous methods have been developed to infer kinase activities from phosphoproteomics data using kinase-substrate libraries. However, few phosphorylation sites can be attributed to an upstream kinase in these libraries, limiting the scope of kinase activity inference. Moreover, inferred activities vary across methods, necessitating evaluation for accurate interpretation. Here, we present benchmarKIN, an R package enabling comprehensive evaluation of kinase activity inference methods. Alongside classical perturbation experiments, benchmarKIN introduces a tumor-based benchmarking approach utilizing multi-omics data to identify highly active or inactive kinases. We used benchmarKIN to evaluate kinase-substrate libraries, inference algorithms and the potential of adding predicted kinase-substrate interactions to overcome the coverage limitations. Our evaluation shows most computational methods perform similarly, but the choice of library impacts the inferred activities with a combination of manually curated libraries demonstrating superior performance in recapitulating kinase activities. Additionally, in the tumor-based evaluation, adding predicted targets from NetworKIN further boosts the performance. We then demonstrate how kinase activity inference aids characterize kinase inhibitor responses in cell lines. Overall, benchmarKIN helps researchers to select reliable methods for identifying deregulated kinases.

This project uses a variety of lenses – the state as spender, producer, employer, investor and steward – to assess how the size and shape of the state has changed. We explore the conventional wisdom that New Zealand’s ‘neoliberal’ reforms of the 1980s and early 1990s resulted in a dramatic reduction in the size of the state. We find – with two notable exceptions – that the shrinking of the state over this period of reform is an urban myth. Indeed, relative to GDP, spending on real resources to support public production and investment in non-market outputs has been stable or has increased slightly since the 1990s, while the Crown’s balance sheet has steadily strengthened. We include an additional lens to explore the proposition that ‘deregulation’ in 1980s and 1990s led to a reduction in the regulatory state. We find the opposite: that the number of words used in the New Zealand statutes has grown steadily since 1908, but dramatically from the 1960s. In the last decade, under the Ardern–Hipkins Labour administration, government current spending on collective consumption grew rapidly to reach record levels, even after allowing for Covid-19-related spending programmes. The fiscal adjustment proposed by the National–Act–New Zealand First administration in the 2024 Budget involves winding much of this increase back.

In Australia, Human Research Ethics Committees (HRECs) play a ubiquitous role reviewing human subjects research, as do Institutional Review Boards in the US and elsewhere. While HRECs were established as peer review bodies, we argue they should now be characterised a ‘devolved regulator’ within the broader context of the regulatory state. We evidence HRECs’ regulatory role through three examples of current responsibilities. By categorising HRECs as a regulator, we are able to assess their role through a regulatory lens. Drawing on Reeve and Magnusson’s ‘regulatory scaffolding’ approach, we suggest key ways in which the role provided by HRECs could be improved. These include setting clear roles and responsibilities HREC review; ensuring HREC accountability for the substantive aspects of their decision making; and accountability for trial sponsors who seek review of trials under the Clinical Trials Notification Scheme. Deficits in the above must incur a credible expectation of escalation and review.

ABSTRACTThe contemporary literature on regulation and development has emphasised the importance of low discretion devices for achieving desired policy objectives. At the same time, there has been a growing recognition that state capacity in general, and regulatory capacity more specifically, are essential for achieving development goals in a world of uncertainty. However, as with most concepts in public administration, while everyone may agree on the significance of regulatory capacity, there is less agreement as to what regulatory capacity actually means. In this article, we explore different doctrines on ‘how to’ organise for regulatory capacity, pointing to the contemporary dominance of the ‘low discretion’ strain of doctrines. We also highlight the sources of policy disappointment and emerging calls for a more discretionary understanding of regulatory capacity. This argument is explored in the context of Brazil, a large emerging economy with a track record of regulatory reforms over the past decades.

BackgroundImmunotherapy has revolutionized cancer treatment but has yet to be translated into brain tumors. Studies in other solid tumors suggest a central role of B-cell immunity in driving immune checkpoint blockade efficacy. In glioblastoma (GBM), tumor B cells are driven into a regulatory B-cell state that suppresses immune activation and T-cell function.MethodsWe used spatially resolved transcriptomics and multiplex immunofluorescence to characterize B-cell neighborhoods within GBM and identify enhanced TGFβ-signaling between myeloid and B cells. We generated conditional knockouts to investigate the effects of TGFβ signaling on B-cell function and survival in vivo. Additionally, we combined TGFβ blockade with PD-1 inhibition to evaluate their combined anti-glioma efficacy.ResultsOur findings reveal that myeloid cells are the primary interactors with B cells in GBM through the TGFβ pathway. Pharmacological or genetic TGFβ blockade expanded intratumoral B cells and synergized with PD-1 inhibition to enhance survival (60% tumor eradication in dual-treated mice). Therapeutic efficacy critically depended on B cells, as their depletion abolished survival benefits. Dual αVβ8/PD-1 blockade reduced B-cell-mediated suppression of CD8⁺ T-cell cytotoxicity and increased plasmablast differentiation, while partial efficacy in RagKO mice implicated ancillary roles for innate immunity.ConclusionTargeting TGFβ signaling using an anti-αVβ8 blocker can impact anti-tumor immunity through different possible mechanisms, of which we highlight the rescuing of B-cell function through synergy with PD-1 checkpoint blockade therapy. Our work underscores the critical role of intratumoral B-cell immunity in enhancing immunotherapy against brain tumors.