Genomic Control Process explores the biological phenomena around genomic regulatory systems that control and shape animal development processes, and which determine the nature of evolutionary ...processes that affect body plan. Unifying and simplifying the descriptions of development and evolution by focusing on the causality in these processes, it provides a comprehensive method of considering genomic control across diverse biological processes. This book is essential for graduate researchers in genomics, systems biology and molecular biology seeking to understand deep biological processes which regulate the structure of animals during development. * Covers a vast area of current biological research to produce a genome oriented regulatory bioscience of animal life * Places gene regulation, embryonic and postembryonic development, and evolution of the body plan in a unified conceptual framework * Provides the conceptual keys to interpret a broad developmental and evolutionary landscape with precise experimental illustrations drawn from contemporary literature * Includes a range of material, from developmental phenomenology to quantitative and logic models, from phylogenetics to the molecular biology of gene regulation, from animal models of all kinds to evidence of every relevant type * Demonstrates the causal power of system-level understanding of genomic control process * Conceptually organizes a constellation of complex and diverse biological phenomena * Investigates fundamental developmental control system logic in diverse circumstances and expresses these in conceptual models * Explores mechanistic evolutionary processes, illuminating the evolutionary consequences of developmental control systems as they are encoded in the genome
Homology-a similar trait shared by different species and derived from common ancestry, such as a seal's fin and a bird's wing-is one of the most fundamental yet challenging concepts in evolutionary ...biology. This groundbreaking book provides the first mechanistically based theory of what homology is and how it arises in evolution.
Günter Wagner, one of the preeminent researchers in the field, argues that homology, or character identity, can be explained through the historical continuity of character identity networks-that is, the gene regulatory networks that enable differential gene expression. He shows how character identity is independent of the form and function of the character itself because the same network can activate different effector genes and thus control the development of different shapes, sizes, and qualities of the character. Demonstrating how this theoretical model can provide a foundation for understanding the evolutionary origin of novel characters, Wagner applies it to the origin and evolution of specific systems, such as cell types; skin, hair, and feathers; limbs and digits; and flowers.
The first major synthesis of homology to be published in decades,Homology, Genes, and Evolutionary Innovationreveals how a mechanistically based theory can serve as a unifying concept for any branch of science concerned with the structure and development of organisms, and how it can help explain major transitions in evolution and broad patterns of biological diversity.
Heat shock protein 90 (Hsp90) is an ATP-dependent molecular chaperone which is essential in eukaryotes. It is required for the activation and stabilization of a wide variety of client proteins and ...many of them are involved in important cellular pathways. Since Hsp90 affects numerous physiological processes such as signal transduction, intracellular transport, and protein degradation, it became an interesting target for cancer therapy. Structurally, Hsp90 is a flexible dimeric protein composed of three different domains which adopt structurally distinct conformations. ATP binding triggers directionality in these conformational changes and leads to a more compact state. To achieve its function, Hsp90 works together with a large group of cofactors, termed co-chaperones. Co-chaperones form defined binary or ternary complexes with Hsp90, which facilitate the maturation of client proteins. In addition, posttranslational modifications of Hsp90, such as phosphorylation and acetylation, provide another level of regulation. They influence the conformational cycle, co-chaperone interaction, and inter-domain communications. In this review, we discuss the recent progress made in understanding the Hsp90 machinery.
Super-enhancers (SEs), which are composed of large clusters of enhancers densely loaded with the Mediator complex, transcription factors and chromatin regulators, drive high expression of genes ...implicated in cell identity and disease, such as lineage-controlling transcription factors and oncogenes. BRD4 and CDK7 are positive regulators of SE-mediated transcription. By contrast, negative regulators of SE-associated genes have not been well described. Here we show that the Mediator-associated kinases cyclin-dependent kinase 8 (CDK8) and CDK19 restrain increased activation of key SE-associated genes in acute myeloid leukaemia (AML) cells. We report that the natural product cortistatin A (CA) selectively inhibits Mediator kinases, has anti-leukaemic activity in vitro and in vivo, and disproportionately induces upregulation of SE-associated genes in CA-sensitive AML cell lines but not in CA-insensitive cell lines. In AML cells, CA upregulated SE-associated genes with tumour suppressor and lineage-controlling functions, including the transcription factors CEBPA, IRF8, IRF1 and ETV6 (refs 6-8). The BRD4 inhibitor I-BET151 downregulated these SE-associated genes, yet also has anti-leukaemic activity. Individually increasing or decreasing the expression of these transcription factors suppressed AML cell growth, providing evidence that leukaemia cells are sensitive to the dosage of SE-associated genes. Our results demonstrate that Mediator kinases can negatively regulate SE-associated gene expression in specific cell types, and can be pharmacologically targeted as a therapeutic approach to AML.
This article explains a shift in the way transatlantic authorities managed conflicts over the cross-border regulation of securities markets: from cooperation skewed heavily toward the preferences of ...U.S. officials and accepted grudgingly by European counterparts; to a Euro-American regulatory condominium characterized by close interactions among decision makers and mutual accommodation. In the final decades of the twentieth century, the asymmetric influence wielded by U.S. securities market authorities had few parallels in other regulatory areas. Why, then, did U.S. officials become more accommodating and European authorities more influential, and why did the turning point occur in 2002 and 2003, an unlikely moment for intensified transatlantic sovereignty sharing? My study shows that institutional change inside the EU recast the North Atlantic balance of regulatory leverage and thereby was the primary factor behind the reshaping of transatlantic cooperation. Internal EU regulatory centralization changed the expectations of U.S. and European firms and authorities and generated new incentives in Washington, D.C., for accommodation and closer transatlantic coordination. My explanation differs from models that, accepting U.S. financial pre-eminence as a given, attribute variance in cross-border regulatory cooperation to factors such as incentives derived from the particularities of issue areas or preferences rooted in domestic politics. While resonating with a well-established theme from the realist branch of IPE, my findings have broad theoretical significance, and open new avenues for dialogue between realists and constructivists about the social, political, and institutional foundations of power in global economic affairs. The transatlantic political process set off by financial transformation in Europe reveals contemporary sources of systemic change and raises questions about what the EU's ascendance as a global financial regulator will mean in the aftermath of the late-2000s crisis.
Markets: The Credit Rating Agencies White, Lawrence J.
The Journal of economic perspectives,
04/2010, Letnik:
24, Številka:
2
Journal Article
Recenzirano
Odprti dostop
This paper will explore how the financial regulatory structure propelled three credit rating agencies—Moody's, Standard & Poor's (S&P), and Fitch—to the center of the U.S. bond markets—and thereby ...virtually guaranteed that when these rating agencies did make mistakes, these mistakes would have serious consequences for the financial sector. We begin by looking at some relevant history of the industry, including the series of events that led financial regulators to outsource their judgments to the credit rating agencies (by requiring financial institutions to use the specific bond creditworthiness information that was provided by the major rating agencies) and when the credit rating agencies shifted their business model from “investor pays” to “issuer pays.” We then look at how the credit rating industry evolved and how its interaction with regulatory authorities served as a barrier to entry. We then show how these ingredients combined to contribute to the subprime mortgage debacle and associated financial crisis. Finally, we consider two possible routes for public policy with respect to the credit rating industry: One route would tighten the regulation of the rating agencies, while the other route would reduce the required centrality of the rating agencies and thereby open up the bond information process in way that has not been possible since the 1930s.
The paper examines the new concepts of Russian legislation introduced into the mechanism of legal regulation with the entry into force of the Federal Law “On Experimental Legal Regimes in the field ...of Digital Innovations in the Russian Federation” and analyzes the first projects approved as part of its implementation. Thus, one of the actively implemented types of regulatory technologies, as shown in the article, is the “regulatory sandboxes”. The establishment of an experimental legal regime within the framework of the functioning of “regulatory sandboxes” means the application to legal entities and individual entrepreneurs of a special, different from the generally established legal regulation (special regulation and general regulation – in the definitions of the law under study). The article analyzes the prerequisites and possible results of the implementation of a flexible system of legal regulation aimed at stimulating the development of technologies and preventing possible negative consequences associated, inter alia, with the use of artificial intelligence. When writing the work, of general scientific methods were used (such as: dialectical, systematic, analysis, synthesis, induction, deduction, modeling, observation) and special private scientific methods of cognition (in particular, formal legal). In the course of using this methodology, the authors described in detail the distinctive characteristics and predictively outlined the features of a flexible system of legal regulation aimed at stimulating the development of technologies, as well as drew conclusions about the possibilities arising from the use of the mechanism of “regulatory sandboxes” in modern Russia.
In recent decades, emotion regulation (ER) has been one of the most widely studied constructs within the psychological field. Nevertheless, laboratory experiments and retrospective assessments have ...been the 2 most common strands of ER research; thus, leaving open several crucial questions about ER antecedents and consequences in daily life. Beyond traditional methods, ecological momentary assessment (EMA) has the potential to capture ER dynamics during the flow of daily experiences, in real-life settings and through repeated measurements. Here, we discuss what we currently know about ER antecedents and consequences. We will compare findings from previous literature to findings from EMA studies, pointing out both similarities and differences, as well as questions that can be answered better with the EMA approach.
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