Gotowa bibliografia na temat „Púrpura de la rosa”

Abstract During hematopoiesis, transcription factors can not only direct differentiation of committed progenitors but also drive lineage commitment decisions from uncommitted multipotent progenitors. To further study their instructive role, we asked whether critical steps in the hematopoietic differentiation pathway could be reversed, and more specifically, whether myeloid transcription factors, C/EBP alpha and C/EBP beta, could re-direct committed T lymphoid progenitors into a myeloid fate. Previously in our laboratory, it was shown that C/EBP alpha efficiently reprograms CD19+ B cells to Mac1+ Gr1+ functional macrophages (Xie et al. (2004) Cell 117:663). To address lineage conversion of T to myeloid cells, we purified T cell subsets by MACS enrichment or FACS sorting and infected these cells with retroviruses expressing C/EBP alpha or C/EBP beta. Cells were cultured on myeloid supporting stroma with myeloid cytokines and analyzed for expression of antigens and marker genes by flow cytometry and RT-PCR. To rule out the presence of contaminating myeloid progenitors in our cultures, we started with a marked population of T lymphoid progenitors derived from Lck-Cre Rosa-EYFP reporter mice in which T cells are irreversibly marked with EYFP upon T cell commitment. T cell origin was further verified using PCR to detect TCRbeta DJ rearrangements. Using double negative DN3 and DN4 T cells, we show that a large proportion of EYFP+ DN cells infected with C/EBP alpha or C/EBP beta are induced to express surface antigens Mac1 and Gr1, express myeloid cytokine receptors and Fc receptors, and exhibit a myeloid morphology, compared to control infected cells. The reprogrammed cells are also functional as they can bind and phagocytose sheep red blood cells. In addition, the pan-T cell marker Thy1 and other T lineage genes including Lck, Rag2, and preT alpha are downregulated in reprogrammed cells. Furthermore, using a conditional knockout approach developed in Daniel Tenen’s laboratory, we show that endogenous expression of PU.1 is required for activation of Mac1 during this process. In conclusion, C/EBP alpha acts alone to extinguish the T lymphoid program while, in concert with PU.1, it activates the myeloid program leading to reprogramming of the T cell phenotype.

AbstractThe special formulation MA212 (Rosaxan) is composed of rosehip (Rosa canina L.) puree/juice concentrate, nettle (Urtica dioica L.) leaf extract, and devilʼs claw (Harpagophytum procumbens DC. ex Meisn. or Harpagophytum zeyheri Decne.) root extract and also supplies vitamin D. It is a food for special medical purposes ([EU] No 609/2013) for the dietary management of pain in patients with gonarthritis.This 12-week randomized, placebo-controlled double-blind parallel-design study aimed to investigate the efficacy and safety of MA212 versus placebo in patients with gonarthritis.A 3D-HPLC-fingerprint (3-dimensional high pressure liquid chromatography fingerprint) of MA212 demonstrated the presence of its herbal ingredients. Ninety-two randomized patients consumed 40 mL of MA212 (n = 46) or placebo (n = 44) daily. The Western Ontario and McMaster Universities Arthritis Index (WOMAC), quality-of-life scores at 0, 6, and 12 weeks, and analgesic consumption were documented. Statistically, the initial WOMAC subscores/scores did not differ between groups. During the study, their means significantly improved in both groups. The mean pre-post change of the WOMAC pain score (primary endpoint) was 29.87 in the MA212 group and 10.23 in the placebo group. The group difference demonstrated a significant superiority in favor of MA212 (pU < 0.001; pt < 0.001). Group comparisons of all WOMAC subscores/scores at 6 and 12 weeks reached same significances. Compared to placebo, both physical and mental quality of life significantly improved with MA212. There was a trend towards reduced analgesics consumption with MA212, compared to placebo. In the final efficacy evaluation, physicians (pChi < 0.001) and patients (pChi < 0.001) rated MA212 superior to placebo. MA212 was well tolerated.This study demonstrates excellent efficacy for MA212 in gonarthritis patients.

Abstract Immunotherapy has brought hope for cancer treatment, but its clinical success remains limited. Recently, overexpression of the transcription factors PU.1, IRF8 and BATF3 (PIB) was shown to induce direct reprogramming of tumor cells into antigen-presenting type 1 conventional dendritic cells (cDC1s), a rare subset of immune cells with pivotal role in anti-cancer immunity. This strategy might open avenues to enhance cancer cell recognition and elimination by the immune system. However, currently existing in-vitro and in-vivo testing platforms do not qualify to reproduce all complex cell interactions essential for the approbation of this hypothesis. Here, we report the development of the InSphero 3D InSight™ Oncology Platform for in-vitro assessment of efficacy and immune-stimulatory effects of this novel cancer immunotherapy approach. The feasibility of 3D spheroid formation for several GFP-expressing tumor cell lines was evaluated by varying seeding conditions in AKURA 96 well plate. We have measured the growth (ATP content) and GFP signal overtime and analyzed the morphology of the spheroids by IHC. With this, we have established spheroid models of T98G (glioblastoma), PK59 (pancreatic cancer), and A375 (melanoma) cell lines that are growing and viable for at least 10 days. In parallel, using 2D cultures, we have identified the optimal multiplicity of infection of a lentiviral vector encoding for PIB and mCherry to enable high transduction (mCherry+ cells), reprogramming efficiency (mCherry+CD45+HLA-DR+ cells), and cell viability, quantified by flow cytometry and IHC. Then, we have demonstrated that cDC1 reprogramming progresses in the context of 3D cancer spheroids and tumor cells acquire expression of CD45+ and HLA-DR+ cells using IHC and confocal microscopy analysis. We developed an algorithm enabling automated analysis of confocal images and quantification of cDC1 reprogramming efficiency from individual image stacks calculated as a ratio of mCherry+, CD45+ and HLA-DR+ cells versus the number of DAPI+ nuclei. Using the new algorithm we have evaluated the reprogramming efficacy of the different virus dosages in all three types of 3D tumor spheroids. Lastly, we have cocultured tumor spheroids transduced with PIB with naïve or activated HLA-matched PBMCs and evaluated cytokine secretion as a readout of immune cell activation. We observed that reprogramming induces activation of T cells and correlated it to the number of reprogrammed cells in the tumor spheroid, evaluated by the HC imaging. In summary, we developed the InSphero 3D InSight™ Oncology Platform that allowed us to demonstrate the effects of direct reprogramming of tumor cells into immunogenic dendritic cells. Combined with high-content imaging analysis, this platform offers a powerful solution for preclinical translational research. Citation Format: Irina Agarkova, Nadezhda Rotankova, Michal Rudnik, Silvan Strebel, Olga Zimmermannova, Andre Rosa, Fabio F. Rosa, Wolfgang Moritz, Carlos-Filipe Pereira, Christiana F. Pires. Assessing efficacy and immune-stimulatory effects of tumor-derived dendritic cell reprogramming using immuno-competent 3D tumor spheroid model. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4550.

Abstract Immunotherapy is revolutionizing cancer treatment, but success is limited to a fraction of patients. Tumor immunosurveillance and immunotherapy relies on presentation of tumor-associated antigens by conventional dendritic cells type 1 (cDC1). However, tumors develop mechanisms to avoid immune recognition such as downregulation of antigen presentation and exclusion of cDC1. We have previously demonstrated that enforced expression of the transcription factors PU.1, IRF8 and BATF3 (PIB) imposes the lineage conversion of fibroblasts to cDC1 by direct cell reprogramming. Here, we hypothesize that PIB reprograms cancer cells directly into functional tumor-antigen presenting cells (tumor-APCs) with enhanced immunogenicity. First, we show that enforced expression of PIB in a wide range of murine and human cancer cells from different origins is sufficient to induce surface expression of hematopoietic and DC-lineage specific markers (CD45 and Clec9a). Moreover, reprogramming restored the expression of antigen presentation complexes (MHC-I and MHC-II) and activated the expression of the co-stimulatory molecules CD40, CD80 and CD86, required for productive T cell activation. Transcriptomic analysis using mRNA-sequencing showed that PIB imposes a global cDC1 gene signature and an antigen presentation program in tumor cells as early as day 3 of reprogramming, overriding the original cancer cell program. Furthermore, Assay for Transposase-Accessible Chromatin (ATAC) sequencing analysis revealed that PIB-mediated cDC1 reprogramming elicited rapid epigenetic remodeling followed by gradual rewiring of transcriptional program and stabilization of cDC1 identity. Functionally, tumor-APCs present endogenous antigens on MHC-I, prime naïve CD8+ T and become prone to CD8+ T cell mediated killing. Tumor-APCs secrete pro-inflammatory cytokines (IL-12) and chemoattractants (CXCL10), uptake and process exogenous antigens, phagocyte dead cells, and cross-present exogenous antigens to activate naïve T-cells. In addition, reprogrammed tumor cells harboring TP53, KRAS and PTEN mutations downregulated proliferation and showed impaired tumorigenicity in vitro and in vivo. Importantly, we show that intra-tumoral injection of reprogrammed tumor-APCs elicited tumour growth control in vivo alongside increasing infiltration of CD8+ T and NK cells in B16-OVA tumors. Finally, we showed that our approach can be employed to convert primary cancer cells derived from melanoma, lung, breast, pancreatic, urothelial, and head and neck carcinomas as well as cancer associated fibroblasts. In summary, we provide evidence for the direct reprogramming of tumor cells into immunogenic cDC1-like cells, with restored antigen presentation capacity and the ability to reinstate anti-tumor immunity. Our approach elicits the immune system against cancer and counteract major tumor evasion mechanisms including tumor heterogeneity and impaired antigen presentation, laying the foundation for developing immunotherapeutic strategies based on the cellular reprogramming of human cancer cells. Citation Format: Alexandra G. Ferreira, Olga Zimmermannova, Ervin Ascic, Ilia Kurochkin, Diego Soto-Cabrera, Ariane Eceiza, Hreinn Benonisson, Inês Caiado, Rita Silvério-Alves, Fábio F. Rosa, Cristiana F. Pires, David Gomez-Jimenez, Carina Bernardo, Monika Bauden, Roland Anderson, Mattias Höglund, Kenichi Miharada, Yukio Nakamura, Lennart Greiff, Malin Lindstedt, Carlos-Filipe Pereira. Restoring tumor immunogenicity with dendritic cell reprogramming [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy; 2022 Oct 21-24; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(12 Suppl):Abstract nr A40.

Uma prisão feminina em Portugal foi caso de estudo sobre práticas de leitura nesse quotidiano. Consideram-se teorias sobre a prisão feminina (M.I. Cunha e C.R. Fonseca) e de uma perspetiva feminista e comparativa (M. Bosworth, B.H. Zaitzow & J. Thomas). Para compreender o que, por que e com que significados as mulheres liam, cruzando dimensões sociais, desenhou-se uma abordagem qualitativa, metodologicamente diversificada (etnografia, entrevistas individuais e grupais com leitoras e com intermediadores), incluindo usos do espaço físico e social e do tempo, relações com familiares, com outras detidas e com pessoal prisional. Analisaram-se títulos favoritos (romances cor-de-rosa, literatura industrial, light ou kitsch), tendo-se em conta gêneros literários para públicos femininos e desconstruindo-se preconceitos de gênero e classe associados à sua crítica. A interpretação foi construída com um quadro teórico diverso (A. Amorós, M. Calinescu, R. Felski, J. Radway e M. Sweeney). A análise de práticas, concetualizações e representações desvelou traços interessantes e eventualmente inesperados sobre os modos de leitura. Palavras-chave: Prisões femininas. Leitura. Literatura light. Literatura kitsch. Romances cor-de-rosa.READING IN WOMEN’S PRISON: from the library to questioning tastes Paula Sequeiros A women’s prison in Portugal was the case study about reading practices in this environment. The female prison system (M.I. Cunha and C.R. Fonseca) and a feminist comparative perspective (M. Bosworth, B.H. Zaitzow & J. Thomas) were used as reference. In order to understand what, why and with what meanings these women read, crossing social dimensions, this study had a qualitative approach with different methodologies (ethnography, individual and group interviews with readers and mediators), and included uses of the physical and social spaces and of time, family relations, relations with other inmates and with the prison staff. The favorite titles were analyzed (chick lit, industrial, light and kitsch literature), taking into account literary genres for women and deconstructing gender and class prejudices that were connected to them. Interpretation was carried out with a diverse theoretical chart (A. Amorós, M. Calinescu, R. Felski, J. Radway and M. Sweeney). The analysis of practices, concepts and representations revealed interesting and eventually unexpected traces about their forms of reading. Keywords: Women’s prison. Reading. Light literature. Kitsch literature. Chick lit.LA LECTURE DANS UNE PRISON FÉMININE: de la bibliothèque à la question des goûts Paula Sequeiros Une prison de femmes au Portugal a fait l’objet d’une étude sur les pratiques de lecture dans le cadre de ce quotidien. Le système pénitentiaire féminin (M.I. Cunha e C.R. Fonseca) et une perspective féministe et comparative (M. Bosworth, B.H. Zaitzow & J. Thomas) ont servi de référence à cette étude. Afin de comprendre le quoi, le pourquoi et en vue de quoi les femmes prisonnières lisent, et après avoir fait des croisements entre les diverses dimensions sociales, une approche qualitative a pu être élaborée, diversifiée sur le plan méthodologique (ethnographie, interviews individuelles et en groupes avec les lectrices et avec des intermédiaires) en y incluant l’utilisation de l’espace physique et social ainsi que la dimension du temps, les relations avec des membres de la famille, d’autres prisonnières et le personnel pénitentiaire. Les livres préférés ont été analysés (romans à l’eau de rose, littérature industrielle, light ou kitsch), en tenant compte des genres littéraires destinés au public féminin et en déconstruisant les préjugés de genre et de classe accompagnant leur critique. L’interprétation a été construite dans un cadre théorique diversifié (A. Amorós, M. Calinescu, R. Felski, J. Radway e M. Sweeney). L’analyse des pratiques, des conceptualisations et des représentations a dévoilé des traits intéressants voire inattendus concernant les modes de lecture. Mots-clés: Prisons de femmes. Lecture. Littérature light. Littérature kitsch. Romans à l’eau de rose. Publicação Online do Caderno CRH no Scielo: http://www.scielo.br/ccrh Publicação Online do Caderno CRH: http://www.cadernocrh.ufba.br

Introduction Daffodil Day, usually held in spring, raises funds for cancer awareness and research using this symbol of hope. On that day, people who donate money to this good cause are usually given a yellow daffodil pin to wear. When I lived in Auckland, New Zealand, on the last Friday in August most people walking around the city centre proudly wore a cheerful yellow flower. So many people generously participated in this initiative that one almost felt obliged to join the cause in order to wear the ‘uniform’ – the daffodil pin – as everyone else did on that day. To donate and to wear a daffodil is the social expectation, and operating in social environment people often endeavour to meet the expectation by doing the ‘appropriate things’ defined by societies or communities. After all, who does not like to receive a beam of acceptance and appreciation from a fellow daffodil bearer in Auckland’s Queen Street? States in international society are no different. In some ways, states wear ‘uniforms’ while executing domestic and foreign affairs just as human beings do within their social groups. States develop the understandings of desirable behaviour from the international community with which they interact and identify. They are ‘socialised’ to act in line with the expectations of international community. These expectations are expressed in the form of international norms, a prescriptive set of ideas about the ‘appropriate behaviour for actors with a given identity’ (Finnemore and Sikkink 891). Motivated by this logic of appropriateness, states that comply with certain international norms in world politics justify and undertake actions that are considered appropriate for their identities. This essay starts with examining how international norms can be spread to different countries through the process of ‘state socialisation’ (how the countries are ‘talked into’ wearing the ‘uniform’). Second, the essay investigates the idea of ‘cultural match’: how domestic actors comply with an international norm by interpreting and manipulating it according to their local political and legal practices (how the countries wear the ‘uniform’ differently). Lastly, the essay probes the current international normative community and the liberal values embedded in major international norms (whether states would continue wearing the ‘uniform’). International Norms and State Socialisation: Why Do States Wear the ‘Uniforms’? Norm diffusion is related to the efforts of ‘norm entrepreneurs’ using various platforms to convince a critical mass of states to embrace new norms (Finnemore and Sikkink 895-896). Early studies of norm diffusion tend to emphasise nongovernmental organisations (NGOs) as norm entrepreneurs and advocates, such as Oxfam and its goal of reducing poverty and hunger worldwide (Capie 638). In other empirical research, intergovernmental organisations (IGOs) were shown to serve as ‘norm teachers,’ such as UNESCO educating developing countries the value of science policy organisations (Finnemore 581-586). Additionally, states and other international actors can also play important roles in norm diffusion. Powerful states with more communication resources sometimes enjoy advantages in creating and promoting new norms (Florini 375). For example, the United States and Western European countries have often been considered as the major proponents of free trade. Norm emergence and state socialisation in a normative community often occurs during critical historical periods, such as wars and major economic downturns, when international changes and domestic crises often coincide with each other (Ikenberry and Kupchan 292). For instance, the norm entrepreneurs of ‘responsible power/state’ can be traced back to the great powers (mainly the United States, Great Britain, and the Soviet Union) and their management of international order at the end of WWII (see Bull). With their negotiations and series of international agreements at the Cairo, Tehran, Yalta, and Potsdam Conference in the 1940s, these great powers established a post-World War international society based on the key liberal values of international peace and security, free trade, human rights, and democracy. Human beings are not born to know what appropriate behaviour is; we learn social norms from parents, schools, peers, and other community members. International norms are collective expectations and understanding of how state governments should approach their domestic and foreign affairs. States ‘learn’ international norms while socialising with a normative community. From a sociological perspective, socialisation summarises ‘how and to what extent diverse individuals are meshed with the requirement of collective life’ at the societal level (Long and Hadden 39). It mainly consists of the process of training and shaping newcomers by the group members and the social adjustment of novices to the normative framework and the logic of appropriateness (Long and Hadden 39). Similarly, social psychology defines socialisation as the process in which ‘social organisations influence the action and experience of individuals’ (Gold and Douvan 145). Inspired by sociology and psychology, political scientists consider socialisation to be the mechanism through which norm entrepreneurs persuade other actors (usually a norm novice) to adhere to a particular prescriptive standard (Johnston, “Social State” 16). Norm entrepreneurs can change novices’ behaviour by the methods of persuasion and social influence (Johnston, “Treating International Institutions” 496-506). Socialisation sometimes demands that individual actors should comply with organisational norms by changing their interests or preferences (persuasion). Norm entrepreneurs often attempt to construct an appealing cognitive frame in order to persuade the novices (either individuals or states) to change their normative preferences or adopt new norms. They tend to use language that can ‘name, interpret and dramatise’ the issues related to the emerging norm (Finnemore and Sikkink 987). As a main persuasive device, ‘framing’ can provide a singular interpretation and appropriate behavioural response for a particular situation (Payne 39). Cognitive consistency theory found in psychology has suggested the mechanism of ‘analogy’, which indicates that actors are more likely to accept new ideas that share some similarities to the extant belief or ideas that they have already accepted (see Hybel, ch. 2). Based on this understanding, norm entrepreneurs usually frame issues in a way that can associate and resonate with the shared value of the targeted novices (Payne 43). For example, Finnemore’s research shows that when it promoted the creation of state science bureaucracies in the 1960s, UNESCO associated professional science policy-making with the appropriate role of a modern state, which was well received by the post-war developing countries in Latin America, the Middle East, and Southeast Asia (Finnemore 565-597). Socialisation can also emanate actors’ pro-norm behaviour through a cost-benefit calculation made with social rewards and punishments (social influence). A normative community can use the mechanism of back-patting and opprobrium to distribute social reward and punishment. Back-patting – ‘recognition, praise and normative support’ – is offered for a novice’s or member’s cooperative and pro-norm behaviour (Johnston, “Treating International Institutions” 503). In contrast, opprobrium associated with status denial and identity rejection can create social and psychological costs (Johnston 504). Both the reward and punishment grow in intensity with the number of co-operators (Johnston 504). A larger community can often create more criticism towards rule-breakers, and thus greatly increase the cost of disobedience. For instance, the lack of full commitment from major powers, such as China, the United States, and some other OECD countries, has arguably made global collective action towards mitigating climate change more difficult, as the cost of non-compliance is relatively low. While being in a normative environment, novice or emerging states that have not yet been socialised into the international community can respond to persuasion and social influence through the processes of identification and mimicking. Social psychology indicates that when one actor accepts persuasion or social influence based on its desire to build or maintain a ‘satisfying self-defining relationship’ to another actor, the mechanism of identification starts to work (Kelman 53). Identification among a social group can generate ‘obligatory’ behaviour, where individual states make decisions by attempting to match their perceptions of ‘who they are’ (national identity) with the expectation of the normative community (Glodgeier and Tetlock 82). After identifying with the normative community, a novice state would then mimic peer states’ pro-norm behaviour in order to be considered as a qualified member of the social group. For example, when the Chinese government was deliberating over its ratification of the Cartagena Protocol on Biosafety in 2003, a Ministry of Environmental Protection brief noted that China should ratify the Protocol as soon as possible because China had always been a country ‘keeping its word’ in international society, and non-ratification would largely ‘undermine China’s international image and reputation’ (Ministry of Environmental Protection of PRC). Despite the domestic industry’s disagreement with entering into the Protocol, the Chinese government’s self-identification as a ‘responsible state’ that performs its international promises and duties played an important role in China’s adoption of the international norm of biosafety. Domestic Salience of International Norms: How Do States Wear the ‘Uniforms’ Differently? Individual states do not accept international norms passively; instead, state governments often negotiate and interact with domestic actors, such as major industries and interest groups, whose actions and understandings in turn impact on how the norm is understood and implemented. This in turn feeds back to the larger normative community and creates variations of those norms. There are three main factors that can contribute to the domestic salience of an international norm. First, as the norm-takers, domestic actors can decide whether and to what extent an international norm can enter the domestic agenda and how it will be implemented in policy-making. These actors tend to favour an international norm that can justify their political and social programs and promote their interests in domestic policy debates (Cortell and Davis, “How Do International Institutions Matter?” 453). By advocating the existence and adoption of an international norm, domestic actors attempt to enhance the legitimacy and authority of their current policy or institution (Acharya, “How Ideas Spread” 248). Political elites can strengthen state legitimacy by complying with an international norm in their policy-making, and consequently obtain international approval with reputation, trust, and credibility as social benefits in the international community (Finnemore and Sikkink 903). For example, when the UN General Assembly adopted the Declaration on the Rights of Indigenous Peoples (UNDRIP), only four states – Australia, Canada, New Zealand, and the United States – voted against the Declaration. They argued that their constitutional and national policies were sufficiently responsive to the type of Indigenous self-determination envisioned by UNDRIP. Nevertheless, given the opprobrium directed against these states by the international community, and their well-organised Indigenous populations, the four state leaders recognised the value of supporting UNDRIP. Subsequently all four states adopted the Declaration, but in each instance state leaders observed UNDRIP’s ‘aspirational’ rather than legal status; UNDRIP was a statement of values that these states’ policies should seek to incorporate into their domestic Indigenous law. Second, the various cultural, political, and institutional strategies of domestic actors can influence the effectiveness of norm empowerment. Political rhetoric and political institutions are usually created and used to promote a norm domestically. Both state and societal leaders can make the performative speech act of an international norm work and raise its importance in a national context by repeated declarations on the legitimacy and obligations brought by the norm (Cortell and Davis, “Understanding the Domestic Impact” 76). Moreover, domestic actors can also develop or modify political institutions to incorporate an international norm into the domestic bureaucratic or legal system (Cortell and Davis, “Understanding the Domestic Impact” 76). These institutions provide rules for domestic actors and articulate their rights and obligations, which transforms the international norm’s legitimacy and authority into local practices. For example, the New Zealand Government adopted a non-nuclear policy in the 1980s. This policy arose from the non-nuclear movement that was leading the development of the Raratonga Treaty (South Pacific Nuclear Free Zone) and peace and Green party movements across Europe who sought to de-nuclearise the European continent. The Lange Labour Government’s 1984 adoption of an NZ anti-nuclear policy gained impetus because of these larger norm movements, and these movements in turn recognised the normative importance of a smaller power in international relations. Third, the characteristics of the international norm can also impact on the likelihood that the norm will be accepted by domestic actors. A ‘cultural match’ between international norm and local values can facilitate norm diffusion to domestic level. Sociologists suggest that norm diffusion is more likely to be successful if the norm is congruent with the prior values and practices of the norm-taker (Acharya, “Asian Regional Institutions” 14). Norm diffusion tends to be more efficient when there is a high degree of cultural match such that the global norm resonates with the target country’s domestic values, beliefs or understandings, which in turn can be reflected in national discourse, as well as the legal and bureaucratic system (Checkel 87; Cortell and Davis, “Understanding the Domestic Impact” 73). With such cultural consistency, domestic actors are more likely to accept an international norm and treat it as a given or as ‘matter-of-fact’ (Cortell and Davis, “Understanding the Domestic Impact” 74). Cultural match in norm localisation explains why identical or similar international socialisation processes can lead to quite different local developments and variations of international norms. The debate between universal human rights and the ‘Asian values’ of human rights is an example where some Asian states, such as Singapore and China, prioritise citizen’s economic rights over social and political rights and embrace collective rights instead of individual rights. Cultural match can also explain why one country may easily accept a certain international norm, or some aspect of one particular norm, while rejecting others. For example, when Taiwanese and Japanese governments adapted the United Nations Declaration on the Rights of Indigenous Peoples into their local political and legal practice, various cultural aspects of Indigenous rights have been more thoroughly implemented compared to indigenous economic and political rights (Gao et al. 60-65). In some extreme cases, the norm entrepreneurs even attempt to change the local culture of norm recipients to create a better cultural match for norm localisation. For example, when it tried to socialise India into its colonial system in the early nineteenth century, Britain successfully shaped the evolution of Indian political culture by adding British values and practices into India’s social, political, and judicial system (Ikenberry and Kupchan 307-309). The International Normative Community: Would States Continue Wearing ‘Uniforms’? International norms evolve. Not every international norm can survive and sustain. For example, while imperialism and colonial expansion, where various European states explored, conquered, settled, and exploited other parts of the world, was a widely accepted idea and practice in the nineteenth century, state sovereignty, equality, and individual rights have replaced imperialism and become the prevailing norms in international society today. The meanings of the same international norm can evolve as well. The Great Powers first established the post-war international norms of ‘state responsibility’ based on the idea of sovereign equality and non-intervention of domestic affairs. However, the 1980s saw the emergence of many international organisations, which built new standards and offered new meanings for a responsible state in international society: a responsible state must actively participate in international organisations and comply with international regimes. In the post-Cold War era, international society has paid more attention to states’ responsibility to offer global common goods and to promote the values of human rights and democracy. This shift of focus has changed the international expectation of state responsibility again to embrace collective goods and global values (Foot, “Chinese Power” 3-11). In addition to the nature and evolution of international norms, the unity and strength of the normative community can also affect states’ compliance with the norms. The growing size of the community group or the number of other cooperatives can amplify the effect of socialisation (Johnston, “Treating International Institutions” 503-506). In other words, individual states are often more concerned about their national image, reputation and identity regarding norm compliance when a critical mass of states have already subscribed into the international norm. How much could this critical mass be? Finnemore and Sikkink suggest that international norms reach the threshold global acceptance when the norm entrepreneurs have persuaded at least one third of all states to adopt the new norm (901). The veto record of the United Nation Security Council (UNSC) shows this impact. China, for example, has cast a UNSC veto vote 17 times as of 2022, but it has rarely excised its veto power alone (Security Council Report). For instance, though being sceptical of the notion of ‘Responsibility to Protect’, which prioritises human right over state sovereignty, China did not veto Resolution 1973 (2011) regarding the Libyan civil war. The Resolution allowed the international society to take ‘all necessary measure to protect civilians’ from a failed state government, and it received wide support among UNSC members (no negative votes from the other 14 members). Moreover, states are not entirely equal in terms of their ‘normative weight’. When Great Powers act as norm entrepreneurs, they can usually utilise their wealth and influence to better socialise other norm novice states. In the history of promoting biological diversity norms which are embedded in the Convention on Biological Diversity (CBD), the OECD countries, especially France, UK, Germany, and Japan, have been regarded as normative leaders. French and Japanese political leaders employed normative language (such as ‘need’ and ‘must’) in various international forums to promote the norms and to highlight their normative commitment (see e.g. Chirac; Kan). Additionally, both governments provided financial assistance for developing countries to adopt the biodiversity norms. In the 2011 annual review of CBD, Japan reaffirmed its US$12 million contribution to assisting developing countries (Secretariat of the Convention on Biological Diversity 9). France joined Japan’s commitment by announcing a financial contribution of €1 million along, with some additional funding from Norway and Switzerland (Secretariat of the Convention on Biological Diversity 9). Today, biological diversity has been one of the most widely accepted international environmental norms, which 196 states/nations have ratified (United Nations). While Great Powers can make more substantial contributions to norm diffusion compared to many smaller powers with limited state capacity, Great Powers’ non-compliance with the normative ‘uniform’ can also significantly undermine the international norms’ validity and the normative community’s unity and reputation. The current normative community of climate change is hardly a unified one, as it is characterised by a low degree of consensus. Major industrial countries, such as the United States, Canada, and Australia, have not yet reached an agreement concerning their individual responsibilities for reducing greenhouse emissions. This lack of agreement, which includes the amount of cuts, the feasibility and usefulness of such cuts, and the relative sharing of cuts across various states, is complicated by the fact that large developing countries, such as China, Brazil, and India, also hold different opinions towards climate change regimes (see Vidal et al.). Experts heavily criticised the major global powers, such as the European Union and the United States, for their lack of ambition in phasing out fossil fuels during the 2022 climate summit in Egypt (COP27; Ehsan et al.). In international trade, both China and the United States are among the leading powers because of their large trade volume, capacity, and transnational network; however, both countries have recently undermined the world trade system and norms. China took punitive measures against Australian export products after Australia’s Covid-19 inquiry request at the World Health Organisation. The United States, particularly under the Trump Administration, invoked the WTO national security exception in Article XXI of the General Agreement on Tariffs and Trade (GATT) to justify its tariffs on steel and aluminium. Lastly, norm diffusion and socialisation can be a ‘two-way path,’ especially when the norm novice state is a powerful and influential state in the international system. In this case, the novices are not merely assimilated into the group, but can also successfully exert some influence on other group members and affect intra-group relations (Moreland 1174). As such, the novices can be both targets of socialisation and active agents who can shape the content and outcome of socialisation processes (Pu 344). The influence from the novices can create normative contestation and thus influence the norm evolution (Thies 547). In other words, novice states can influence international society and shape the international norm during the socialisation process. For example, the ‘ASEAN Way’ is a set of norms that regulate member states’ relationships within the Association of Southeast Asian Nations (ASEAN). It establishes a diplomatic and security culture characterised by informality, consultation, and dialogue, and consensus-building in decision-making processes (Caballero-Anthony). From its interaction with ASEAN, China has been socialised into the ‘ASEAN Way’ (Ba 157-159). Nevertheless, China’s relations with the ASEAN Regional Forum (ARF) also suggest that there exists a ‘feedback’ process between China and ARF which resulted in institutional changes in ARF to accommodate China’s response (Johnston, “The Myth of the ASEAN Way?” 291). For another example, while the Western powers generally promote the norm of ‘shared responsibility’ in global environment regimes, the emerging economies, such as the BRICS countries (Brazil, Russia, India, China, and South Africa), have responded to the normative engagement and proposed a ‘Common but Differentiated Responsibilities’ regime where the developing countries shoulder less international obligations. Similarly, the Western-led norm of ‘Responsibility to Protect’, which justifies international humanitarian intervention, has received much resistance from the countries that only adhere to the conventional international rules regarding state sovereignty rights and non-intervention to domestic affairs. Conclusion International norms are shared expectations about what constitutes appropriate state behaviour. They are the ‘uniforms’ for individual states to wear when operating at the international level. States comply with international norms in order to affirm their preferred national identities as well as to gain social acceptance and reputation in the normative community. When the normative community is united and sizable, states tend to receive more social pressure to consistently wear these normative uniforms – be they the Geneva Conventions or nuclear non-proliferation. Nevertheless, in the post-pandemic world where liberal values, such as individual rights and rule of law, face significant challenges and democracies are in decline, the future success of the global normative community may be at risk. Great Powers are especially responsible for the survival and sustainability of international norms. The United States under President Trump adopted a nationalist ‘America First’ security agenda: alienating traditional allies, befriending authoritarian regimes previously shunned, and rejecting multilateralism as the foundation of the post-war global order. While the West has been criticised of failing to live up to its declared values, and has suffered its own loss of confidence in the liberal model, the rising powers have offered their alternative version of the world system. Instead of merely adapting to the Western-led global norms, China has created new institutions, such as the Belt and Road Initiatives, to promote its own preferred values, and has reshaped the global order where it deems the norms undesirable (Foot, “Chinese Power in a Changing World Order” 7). Great Power participation has reshaped the landscape of global normative community, and sadly not always in positive ways. Umberto Eco lamented the disappearance of the beauty of the past in his novel The Name of the Rose: ‘stat rosa pristina nomine, nomina nuda tenemus’ ('yesterday’s rose endures in its name, we hold empty names'; Eco 538). If the international community does not want to witness an era where global norms and universal values are reduced to nominalist symbols, it must renew and reinvigorate its commitment to global values, such as human rights and democracy. It must consider wearing these uniforms again, properly. 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