Why do countries comply with international agreements? While scholars have done rigorous work to address compliance and enforcement in an international game, less analytical attention has been paid to domestic mechanisms of compliance+ However, because international agreements have domestic distributional consequences, there exist domestic sources of enforcement+ In this article, I develop an analytical framework of domestic accountability, where I identify specific channels of influence through which domestic constituencies can influence national compliance+ Using a game theoretic model, I show that a government's compliance decision reflects the electoral leverage and the informational status of domestic constituencies+ This framework further provides a theoretical rationale for why and how international institutions may influence states' compliance through domestic mechanisms+ The European acid rain regime offers an empirical illustration of the domestic constituency argument+ I have benefited from the generous help of many colleagues and friends in the course of this research+ I would particularly like to thank the editor-in-chief of IO, anonymous reviewers of this article, as well as

The proliferation of international institutions and their impact has become a central issue in international relations. Why do countries comply with international agreements and how do international institutions influence national policies? Most theories focus on the extent to which international institutions can wield 'carrots and sticks' directly in their relations with states. Xinyuan Dai presents an alternative framework in which they influence national policies indirectly by utilizing non-state actors (NGOs, social movements) and empowering domestic constituencies. In this way, even weak international institutions that lack 'carrots and sticks' may have powerful effects on states. Supported by empirical studies of environmental politics, human rights and economic and security issues, this book sheds fresh light on how and why international institutions matter. It will be of interest to students, scholars and policymakers in both international relations and international law.

Among the over 150 RNA modifications, N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic RNAs, not only in messenger RNAs, but also in microRNAs and long non-coding RNAs. It is a dynamic and reversible process in mammalian cells, which is installed by “writers,” consisting of METTL3, METTL14, WTAP, RBM15/15B, and KIAA1429 and removed by “erasers,” including FTO and ALKBH5. Moreover, m6A modification is recognized by “readers,” which play the key role in executing m6A functions. IYT521-B homology (YTH) family proteins are the first identified m6A reader proteins. They were reported to participate in cancer tumorigenesis and development through regulating the metabolism of targeted RNAs, including RNA splicing, RNA export, translation, and degradation. There are many reviews about function of m6A and its role in various diseases. However, reviews only focusing on m6A readers, especially YTH family proteins are few. In this review, we systematically summarize the recent advances in structure and biological function of YTH family proteins, and their roles in human cancer and potential application in cancer therapy.

Evidence suggests that metformin might be a potential candidate for breast cancer treatment. Yet, its relevant molecular mechanisms remain to be fully investigated. We found that metformin could suppress the N6-methyladenosine (m6A) level in breast cancer cells significantly. The latter has an essential role in breast cancer progression and is newly considered as a therapeutic target. In this study, we measured the m6A level by m6A colorimetric analysis and dot blot assay. We then performed qRT-PCR, western blot, MeRIP, dual-luciferase reporter assay, and others to explore the m6A-dependent pathway associated with metformin. In vivo effect of metformin was investigated using a mouse tumorigenicity model. In addition, breast cancer and normal tissues were used to determine the role of METTL3 in breast cancer. Metformin could reduce the m6A level via decreasing METTL3 expression mediated by miR-483-3p in breast cancer. METTL3 is known to be able to promote breast cancer cell proliferation by regulating the p21 expression by an m6A-dependent manner. Metformin can take p21 as the main target to inhibit such effect. To specify, this study exhibited that metformin can inhibit breast cancer cell proliferation through the pathway miR-483-3p/METTL3/m6A/p21. Our findings suggest that METTL3 may be considered as a potential therapeutic target of metformin for breast cancer.

One of the most influential arguments in international relations is that international institutions influence states' behavior by monitoring their compliance with treaties, which in turn facilitates reciprocity. Empirically, however, many treaty organizations are not mandated to monitor compliance. The article develops a parsimonious theoretical framework to address the empirical diversity of monitoring arrangements. By mapping strategic environments onto monitoring arrangements, it accounts for who detects noncompliance and who brings it to light. In particular, two factors—the interest alignment between noncompliance victims and their states and the availability of noncompliance victims as low-cost monitors—largely shape the organizational forms of information systems. This simple theory sheds light on a wide range of substantiveh/important treaty regimes.

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Growing evidence indicates N6-methyladenosine (m6A) has biological function in oncogenesis. METTL3, the catalytic component, is the most important part of methyltransferase complex and plays a crucial role in cancers. However, the biological function of circRNAs derived from METTL3 in breast cancer and the underlying molecular mechanism remains unclear. Herein, we report circMETTL3, which has not been explored in breast cancer, and it is markedly upregulated in breast cancer. Moreover, we uncovered that circMETTL3 could facilitate cell proliferation, migration and invasion in breast cancer. Mechanism investigation showed that circMETTL3 might act as a competing endogenous RNA (ceRNA) of miR-31-5p and upregulate its target cyclin-dependent kinases (CDK1). Moreover, m6A modification of circMETTL3 might affect its expression. Taken together, our results elucidate that circMETTL3 promotes breast cancer progression through circMETTL3/miR-31-5p/CDK1 axis. Moreover, METTL3, the host gene of circMETTL3, may regulate circMETTL3 expression in an m6A-dependent manner, while circMETTL3 has no effect on METTL3 expression, providing a new relationship between the circRNA and the corresponding host gene. Thus, it may serve as a new therapeutic target for breast cancer.

This article sheds light on the design of the global climate change regime by drawing lessons from the literature produced by international cooperation, international institutions and other international regimes in diverse issue areas. It is argued that sound policy implications for the design of a global climate change regime require a solid understanding of how (in what ways and under what conditions) international instruments influence national governments and domestic policies. While scholars and policy-makers alike often look towards strong and powerful international institutions such as the International Monetary Fund, the World Bank, and the World Trade Organization for design inspiration, the majority of international institutions are those that in fact lack enforcement power. Despite these shortcomings, many of these international institutions often influence national policies in a variety of indirect but effective ways. At the heart of these indirect mechanisms is the mobilization of domestic action. Utilizing and further empowering stakeholders (decentralized and spreading over various levels) is thus the key. The indirect channels of institutional influence are particularly relevant to climate change and provide policy implications for the design of the global climate change regime. Ce papier aide à comprendre la conception du régime mondial sur le changement climatique en tirant des leçons de la coopération internationale, les institutions internationales et autres régimes internationaux relevant de divers thèmes. Il faut entendre que la portée des bonnes politiques sur la structure du régime mondial sur le changement climatique demande une bonne compréhension de comment (c'est-à-dire de quelle manière et sous quelles conditions) les instruments internationaux influencent les gouvernements nationaux et les politiques domestiques. Alors que les chercheurs ainsi que les décideurs s'inspirent souvent des institutions internationales fortes et puissantes telles que leFonds monétaire international, la Banque mondiale, et l'Organisation mondiale du commerce en matière de structure, la majorité des institutions internationales manquent justement de pouvoir d'exécution. Malgré ces limitations, nombre de ces institutions internationales influencent souvent les politiques nationales de diverses manières indirectes mais conséquentes. La mobilisation de l'action domestique est au coeur de ces mécanismes indirects. La clé réside de ce fait dans l'écoute et la capacitation accrue des parties prenantes (de manière décentralisée et répartie sur plusieurs niveaux). Les réseaux indirects d'influence institutionnelle sont particulièrement adaptés au changement climatique et fournissent des impératifs politiques alimentant la structure du régime du changement climatique mondial.