Maintaining disorder: the micropolitics of drugs policy in Iran

This is the final version. Available from the publisher via the DOI in this record.This article analyses the ways in which the state ‘treats’ addiction among precarious drug (ab)users in Iran. While most Muslim-majority as well as some Western states have been reluctant to adopt harm reduction measures, the Islamic Republic of Iran has done so on a nationwide scale and through a sophisticated system of welfare intervention. Additionally, it has introduced devices of management of ‘addiction’ (the ‘camps’) that defy statist modes of punishment and private violence. What legal and ethical framework has this new situation engendered? And what does this new situation tell us about the governmentality of the state? Through a combination of historical analysis and ethnographic fieldwork, the article analyses the paradigm of government of the Iranian state with regard to disorder as embodied by the lives of poor drug (ab)users.Wellcome Trus

Under the bridge in Tehran: Addiction, Poverty and Capital

This is the final version. Available from Sage publications via the DOI in this record. The article provides an ethnographic study of the lives of the ‘dangerous class’ of drug users based on fieldwork carried out among different drug using ‘communities’ in Tehran between 2012 and 2016. The primary objective is to articulate the presence of this category within modern Iran, its uses and its abuses in relation to the political. What drives the narration is not only the account of this lumpen, plebeian group vis à vis the state, but also the way power has affected their agency, their capacity to be present in the city, and how capital/power and the dangerous/lumpen life come to terms, to conflict, and to the production of new situations which affect urban life.Wellcome TrustÉcole des hautes études en sciences sociales (EHESS

Passive, Silent and Revolutionary: The 'Arab Spring' Revisited.

This is the author accepted manuscript. The final version is freely available from Taylor & Francis (Routledge) via the DOI in this record.To counter the trend toward mechanization of research and aridity of critical analysis, this article makes a case for an interdisciplinary quest. To borrow Felix Guattari and Gilles Deleuze's phrase, we are convinced that 'everything is political, but every politics is simultaneously a macropolitics and a micropolitics.' With an eye to open-ended research questions, this article attempts to build a body of theoretical, political and anthropological considerations, which, it is hoped, could function as a case of enquiry into the mechanics of power, revolt and revolution. The objective is to draw comparative and phenomenological lines between the events of the 2011 'Arab Spring,' in its local ecologies of protest, with its global reverberations as materialized in the slogans, acts and ideals of Greek and Spanish Indignados and the UK and US occupy movements. In order to do so, it proposes to clarify terminological ambiguities and to bring into the analytical scenario new subjects, new means and new connections. The article resolves to lay the ground for a scholarship of silence, by which the set of unheard voices, hidden actions and defiant tactics of the ordinary, through extraordinary people, find place in the interpretation of phenomena such as revolts and revolutions

Islam and cannabis: Legalisation and religious debate in Iran

This is the final version. Available from Elsevier via the DOI in this record. Iran is currently discussing cannabis and opium regulations, which could bring a legalisation of drug consumption through a state supervised system. The article engages with the question of cannabis by looking at the legal interpretation of religious authorities in the Islamic Republic of Iran. The choice of Iran is justified for several reasons: firstly, Iran has a long history of drug use and cannabis has been part of the country’s intoxicant traditions since times immemorial; secondly, the Iranian state is unique in that it combines religious exegesis with political machination through official channels; finally, among all Middle East and Islamic countries, Iran is at the avant-garde in experimenting in the field of drugs policy which makes an excellent case for the study of cannabis regulation. The article is the result of a direct engagement with Iran’s leading Shi’a authorities, the maraje’-e taqlid, ‘source of emulation’. The authors redacted a list of eight questions (estefta’at) about the status of cannabis in Iranian society. It questioned cannabis’ legality in Islam, its potential medical use, the feasibility of domestic production and other relevant aspects of its social-religious life. Based on the responses, the authors analysed the difference in opinions among the religious scholars and speculate on the possibility of policy reform. Given the dearth of scholarly work about illicit drugs in the Islamic world, about which many readers might not be familiar, the article opens with an overview of the place of cannabis in the history of Islamic societies. It discusses terminological ambiguities, references in religious texts and traditions, and the general interpretations within Muslim religious schools of thought. Then, it discusses the status of cannabis in contemporary Iran before tackling the responses provided by the religious scholars. Eventually, the paper puts forward reflections about the potential implications for future policy developments on cannabis.Wellcome Trus

Critique of everyday narco-capitalism

This is the final version. Available from Taylor & Francis via the DOI in this record. Capitalism is not only an economic mode of production; it is also a form of life. This also applies to a historical type of capitalism, which is the capitalism founded on (illicit) drugs – in other words: narco-capitalism. The article discusses how capitalism alters life at the nexus of drug production, trade and consumption through a study of drug heartlands in Colombia, Afghanistan and Myanmar. What forms of life emerge under narco-capitalism? And how do people seek change and express agency in the exploitative conditions governed by narco-capital? To do so, the article proceeds through the following sections: first, it elucidates its definition of the ‘everyday’ as a conceptual and methodological scheme to understand capitalist forms of life. Then it uses material collected from people’s everyday encounter with narco-capitalism in Afghanistan, Myanmar and Colombia to discuss mystification, predation and alienation. The article explores how capitalism produces forms of life that make use of drugs and narco-capital to dispossess and alienate collectivities. Finally, the article argues that to move beyond this alienating condition, drug wars and/or development are not a solution, because drugs are not the problem. Instead, it is people’s organisation and world-building in dialectical mode to capitalist forms of life that can transform everyday life beyond predation and alienation.Wellcome TrustEconomic and Social Research Counci

The mythological machine in the Great Civil War (2001–2021): oikos and polis in nation-making

This is the final version. Available from Routledge via the DOI in this record. The article revisits ‘sectarianism’ as an epistemic venue within the context of a Great Civil War in the Middle East (2001-2021), a label that includes the overarching narratives of political life in the aftermath of 9/11 up to the aftermath of the so-called ‘Arab Spring.’ By introducing the notion of the ‘mythological machine,’ it argues that ‘sectarianism’ is a myth, something that does not exist in real terms, but which has real world effects. The mythological machine is a device that produces epiphanies and myths; it is a gnoseological process, which has cultural, social and political effects through the generation of mythological facts and, as a machine, it does so through both guiding and automatized mechanisms. Through this interpretive shift, the article proceeds through several theoretical steps using a variety of cases from across West Asia and North Africa, contextualizing them within global political events. Firstly, the article argues that it is ‘civil war,’ shaped by the work of the mythological machine that governs state-society relations and transnational politics in the Middle East. Then, the article discusses how the mythological machine incorporates a semantic othering via mythological thinking, speak and practice that shapes the perception and experience of civil wars. To conclude, the article discusses how the mythological machine displaces people’s status in the context of civil wars leading to the emergence of new forms of belonging and nationmaking. Ultimately, the mythological machine creates what Giorgio Agamben defines as a state without people, a condition exhausting the value of citizenship and the political.Wellcome TrustWellcome TrustESRC-GCRFESRC-GCR

Probing the SAM Binding Site of SARS-CoV-2 nsp14 in vitro Using SAM Competitive Inhibitors Guides Developing Selective bi-substrate Inhibitors

The COVID-19 pandemic has clearly brought the healthcare systems world-wide to a breaking point along with devastating socioeconomic consequences. The SARS-CoV-2 virus which causes the disease uses RNA capping to evade the human immune system. Non-structural protein (nsp) 14 is one of the 16 nsps in SARS-CoV-2 and catalyzes the methylation of the viral RNA at N7-guanosine in the cap formation process. To discover small molecule inhibitors of nsp14 methyltransferase (MT) activity, we developed and employed a radiometric MT assay to screen a library of 161 in house synthesized S-adenosylmethionine (SAM) competitive methyltransferase inhibitors and SAM analogs. Among seven identified screening hits, SS148 inhibited nsp14 MT activity with an IC50 value of 70 ± 6 nM and was selective against 20 human protein lysine methyltransferases indicating significant differences in SAM binding sites. Interestingly, DS0464 with IC50 value of 1.1 ± 0.2 μM showed a bi-substrate competitive inhibitor mechanism of action. Modeling the binding of this compound to nsp14 suggests that the terminal phenyl group extends into the RNA binding site. DS0464 was also selective against 28 out of 33 RNA, DNA, and protein methyltransferases. The structure-activity relationship provided by these compounds should guide the optimization of selective bi-substrate nsp14 inhibitors and may provide a path towards a novel class of antivirals against COVID-19, and possibly other coronaviruses

Epitope-specific antibody responses differentiate COVID-19 outcomes and variants of concern

BACKGROUND. The role of humoral immunity in COVID-19 is not fully understood, owing, in large part, to the complexity of antibodies produced in response to the SARS-CoV-2 infection. There is a pressing need for serology tests to assess patient-specific antibody response and predict clinical outcome. METHODS. Using SARS-CoV-2 proteome and peptide microarrays, we screened 146 COVID-19 patients’ plasma samples to identify antigens and epitopes. This enabled us to develop a master epitope array and an epitope-specific agglutination assay to gauge antibody responses systematically and with high resolution. RESULTS. We identified linear epitopes from the spike (S) and nucleocapsid (N) proteins and showed that the epitopes enabled higher resolution antibody profiling than the S or N protein antigen. Specifically, we found that antibody responses to the S-811–825, S-881–895, and N-156–170 epitopes negatively or positively correlated with clinical severity or patient survival. Moreover, we found that the P681H and S235F mutations associated with the coronavirus variant of concern B.1.1.7 altered the specificity of the corresponding epitopes. CONCLUSION. Epitope-resolved antibody testing not only affords a high-resolution alternative to conventional immunoassays to delineate the complex humoral immunity to SARS-CoV-2 and differentiate between neutralizing and non-neutralizing antibodies, but it also may potentially be used to predict clinical outcome. The epitope peptides can be readily modified to detect antibodies against variants of concern in both the peptide array and latex agglutination formats. FUNDING. Ontario Research Fund (ORF) COVID-19 Rapid Research Fund, Toronto COVID-19 Action Fund, Western University, Lawson Health Research Institute, London Health Sciences Foundation, and Academic Medical Organization of Southwestern Ontario (AMOSO) Innovation Fund

Tissue eosinophilia: a morphologic marker for assessing stromal invasion in laryngeal squamous neoplasms

BACKGROUND: The assessment of tumor invasion of underlying benign stroma in neoplastic squamous proliferation of the larynx may pose a diagnostic challenge, particularly in small biopsy specimens that are frequently tangentially sectioned. We studied whether thresholds of an eosinophilic response to laryngeal squamous neoplasms provides an adjunctive histologic criterion for determining the presence of invasion. METHODS: Eighty-seven(n = 87) cases of invasive squamous cell carcinoma and preinvasive squamous neoplasia were evaluated. In each case, the number of eosinophils per high power field(eosinophils/hpf), and per 10 hpf in the tissue adjacent to the neoplastic epithelium, were counted and tabulated. For statistical purposes, the elevated eosinophils were defined and categorized as: focally and moderately elevated (5–9 eos/hpf), focally and markedly increased(>10/hpf), diffusely and moderately elevated(5–19 eos/10hpf), and diffusely and markedly increased (>20/10hpf). RESULTS: In the invasive carcinoma, eosinophil counts were elevated focally and /or diffusely, more frequently seen than in non-invasive neoplastic lesions. The increased eosinophil counts, specifically >10hpf, and >20/10hpf, were all statistically significantly associated with stromal invasion. Greater than 10 eosinophils/hpf and/or >20 eosinophils/10hpf had highest predictive power, with a sensitivity, specificity and positive predictive value of 82%, 93%, 96% and 80%, 100% and 100%, respectively. Virtually, greater than 20 eosinophils/10 hpf was diagnostic for tumor invasion in our series. CONCLUSION: Our study suggests for the first time that the elevated eosinophil count in squamous neoplasia of the larynx is a morphologic feature associated with tumor invasion. When the number of infiltrating eosinophils exceeds 10/hpf and or >20/10 hpf in a laryngeal biopsy with squamous neoplasia, it represents an indicator for the possibility of tumor invasion. Similarly, the presence of eosinophils meeting these thresholds in an excisional specimen should prompt a thorough evaluation for invasiveness, when evidence of invasion is absent, or when invasion is suspected by conventional criteria in the initial sections

Large-scale interaction profiling of PDZ domains through proteomic peptide-phage display using human and viral phage peptidomes

The human proteome contains a plethora of short linear motifs (SLiMs) that serve as binding interfaces for modular protein domains. Such interactions are crucial for signaling and other cellular processes, but are difficult to detect because of their low to moderate affinities. Here we developed a dedicated approach, proteomic peptide-phage display (ProP-PD), to identify domain-SLiM interactions. Specifically, we generated phage libraries containing all human and viral C-terminal peptides using custom oligonucleotide microarrays. With these libraries we screened the nine PSD-95/ Dlg/ZO-1 (PDZ) domains of human Densin-180, Erbin, Scribble, and Disks large homolog 1 for peptide ligands. We identified several known and putative interactions potentially relevant to cellular signaling pathways and confirmed interactions between fulllength Scribble and the target proteins β-PIX, plakophilin-4, and guanylate cyclase soluble subunit a-2 using colocalization and coimmunoprecipitation experiments. The affinities of recombinant Scribble PDZ domains and the synthetic peptides representing the C termini of these proteins were in the 1- to 40-μM range. Furthermore, we identified several well-established host-virus protein- protein interactions, and confirmed that PDZ domains of Scribble interact with the C terminus of Tax-1 of human T-cell leukemia virus with micromolar affinity. Previously unknown putative viral protein ligands for the PDZ domains of Scribble and Erbin were also identified. Thus, we demonstrate that our ProP-PD libraries are useful tools for probing PDZ domain interactions. The method can be extended to interrogate all potential eukaryotic, bacterial, and viral SLiMs and we suggest it will be a highly valuable approach for studying cellular and pathogen-host protein-protein interactions