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Ionotropic glutamate receptors in GtoPdb v.2025.4
Get PDFThe ionotropic glutamate receptors comprise members of the NMDA (N-methyl-D-aspartate), AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid) and kainate receptor classes, named originally according to their preferred, synthetic, agonist [60, 99, 163]. Receptor heterogeneity within each class arises from the homo-oligomeric, or hetero-oligomeric, assembly of distinct subunits into cation-selective tetramers. Each subunit of the tetrameric complex comprises an extracellular amino terminal domain (ATD), an extracellular ligand binding domain (LBD), 3 TM domains (M1, M3 and M4), a channel lining re-entrant \u27p-loop\u27 (M2) located between M1 and M3 and an intracellular carboxy- terminal domain (CTD) [106, 74, 115, 163, 88]. The X-ray structure of a homomeric ionotropic glutamate receptor (GluA2- see below) has recently been solved at 3.6Å resolution [151] and although providing the most complete structural information current available may not be representative of the subunit arrangement of, for example, the heteromeric NMDA receptors [77]. It is beyond the scope of this supplement to discuss the pharmacology of individual ionotropic glutamate receptor isoforms in detail; such information can be gleaned from [60, 72, 34, 83, 44, 122, 27, 71, 163, 120, 121, 171]. Agents that discriminate between subunit isoforms are, where appropriate, noted in the tables and additional compounds that distinguish between receptor isoforms are indicated in the text below.The classification of glutamate receptor subunits has been re-addressed by NC-IUPHAR [31]. The scheme developed recommends a nomenclature for ionotropic glutamate receptor subunits that is adopted here.NMDA receptorsNMDA receptors assemble as obligate heteromers that may be drawn from GluN1, GluN2A, GluN2B, GluN2C, GluN2D, GluN3A and GluN3B subunits. Alternative splicing can generate eight isoforms of GluN1 with differing pharmacological properties. Various splice variants of GluN2B, 2C, 2D and GluN3A have also been reported. Activation of NMDA receptors containing GluN1 and GluN2 subunits requires the binding of two agonists, glutamate to the S1 and S2 regions of the GluN2 subunit and glycine to S1 and S2 regions of the GluN1 subunit [43, 28]. The minimal requirement for efficient functional expression of NMDA receptors in vitro is a di-heteromeric assembly of GluN1 and at least one GluN2 subunit variant, as a dimer of heterodimers arrangement in the extracellular domain [50, 106, 77]. However, more complex tri-heteromeric assemblies, incorporating multiple subtypes of GluN2 subunit, or GluN3 subunits, can be generated in vitro and occur in vivo. The NMDA receptor channel commonly has a high relative permeability to Ca2+ and is blocked, in a voltage-dependent manner, by Mg2+ such that at resting potentials the response is substantially inhibited.AMPA and Kainate receptorsAMPA receptors assemble as homomers, or heteromers, that may be drawn from GluA1, GluA2, GluA3 and GluA4 subunits. Transmembrane AMPA receptor regulatory proteins (TARPs) of class I (i.e. γ2, γ3, γ4 and γ8) act, with variable stoichiometry, as auxiliary subunits to AMPA receptors and influence their trafficking, single channel conductance gating and pharmacology (reviewed in [45, 110, 161, 70]). Functional kainate receptors can be expressed as homomers of GluK1, GluK2 or GluK3 subunits. GluK1-3 subunits are also capable of assembling into heterotetramers (e.g. GluK1/K2; [94, 127, 126]). Two additional kainate receptor subunits, GluK4 and GluK5, when expressed individually, form high affinity binding sites for kainate, but lack function, but can form heteromers when expressed with GluK1-3 subunits (e.g. GluK2/K5; reviewed in [127, 71, 126]). Kainate receptors may also exhibit \u27metabotropic\u27 functions [94, 139]. As found for AMPA receptors, kainate receptors are modulated by auxiliary subunits (Neto proteins, [126, 95]). An important function difference between AMPA and kainate receptors is that the latter require extracellular Na+ and Cl- for their activation [13, 128]. RNA encoding the GluA2 subunit undergoes extensive RNA editing in which the codon encoding a p-loop glutamine residue (Q) is converted to one encoding arginine (R). This Q/R site strongly influences the biophysical properties of the receptor. Recombinant AMPA receptors lacking RNA edited GluA2 subunits are: (1) permeable to Ca2+; (2) blocked by intracellular polyamines at depolarized potentials causing inward rectification (the latter being reduced by TARPs); (3) blocked by extracellular argiotoxin and joro spider toxins and (4) demonstrate higher channel conductances than receptors containing the edited form of GluA2 [147, 69]. GluK1 and GluK2, but not other kainate receptor subunits, are similarly edited and broadly similar functional characteristics apply to kainate receptors lacking either an RNA edited GluK1, or GluK2, subunit [94, 126]. Native AMPA and kainate receptors displaying differential channel conductances, Ca2+ permeabilities and sensitivity to block by intracellular polyamines have been identified [33, 69, 98]. GluA1-4 can exist as two variants generated by alternative splicing (termed ‘flip’ and ‘flop’) that differ in their desensitization kinetics and their desensitization in the presence of cyclothiazide which stabilises the nondesensitized state. TARPs also stabilise the non-desensitized conformation of AMPA receptors and facilitate the action of cyclothiazide [110]. Splice variants of GluK1-3 also exist which affects their trafficking [94, 126]
Defining and legitimizing violence in the modern world by Valeria Couttolenc Gonzalez
Get PDFThis article aims to explore understandings of violence beyond the use of force and aggression through an analysis of the persistent and evolving nature of violence within the context of late-stage capitalism, (neo)colonialism, and imperialism, arguing that violence is not just a physical or immediate phenomenon but also a systemic, symbolic, and slow process embedded within the structures of modern global societies, The text draws on the work of decolonial and Global South scholars to propose how despite decolonization movements, colonial legacies persist in the structures of neoliberalism, albeit in a less visible manner, and in the continued exploitation of the Global South by Global North countries through new forms of colonialism and capitalism. This piece proposes defining and understanding violence through different lenses and frameworks - acknowledging socio-political, economic, and structural factors and how they interplay into systems of oppression and harm to perpetuate violence; offering criticisms on violent legacies of the past as well as violent practices of the present through imperialism and different modern-day expressions of colonialism. Moreover, discussions on the weaponization of language to inflict and legitimize violence are explored, in tandem with presenting other conceptualizations of violence such as slow violence (with an environmentalist emphasis), economic exploitation through trade, and the forcing into debt of Global South countries in the name of development/modernity. To conclude, the text invites a critical reflection of the current economic and political systems and their impacts on our everyday lives to address the constant metamorphoses of violence as it continues to permeate the world we exist in and in different manifestations of violence beyond the use of force and aggression
The Digital Mirage: India\u27s Evolving Legal Battle Against Deepfake Technology
Get PDFThe proliferation of deepfake technology in India presents unprecedented challenges to existing legal frameworks, threatening individual dignity, democratic processes, and social harmony. This research conducts a comprehensive analysis of India\u27s legal response to Artificial Intelligence-generated (AI-generated) synthetic media through doctrinal examination, empirical case studies, and comparative jurisprudence.
The study reveals critical gaps in India\u27s current legal architecture. While provisions under the Information Technology Act 2000, Indian Penal Code 1860, The Bharatiya Nyaya Sanhita, 2023 (BNS), and emerging data protection laws offer partial protection, they lack specificity for deepfake-related harms. The research examines landmark cases including Arijit Singh v. Codible Ventures LLP and high-profile celebrity deepfake incidents, demonstrating judicial evolution toward protective personality rights jurisprudence despite legislative ambiguity.
Through systematic analysis of enforcement mechanisms, the study identifies significant implementation challenges including technical detection limitations, jurisdictional complexities, and inadequate institutional capacity. Empirical assessment of complaint data from the National Crime Records Bureau and state cybercrime cells reveals poor conviction rates and prolonged resolution timelines, highlighting the enforcement-legislation disconnect.
The research proposes a comprehensive regulatory framework centred on a dedicated Synthetic Media Regulation Act, incorporating graduated harm-based penalties, platform accountability standards, and victim compensation mechanisms. The proposed multi-stakeholder governance model balances innovation promotion with fundamental rights protection through safe harbour provisions for legitimate uses while criminalizing non-consensual creation and distribution.
Key contributions include the first systematic legal analysis of India\u27s deepfake regulatory landscape, evidence-based policy recommendations, and an implementation roadmap addressing short-term enforcement needs and long-term institutional reforms. The study positions India to lead global synthetic media governance while protecting citizens from AI-generated deception in an increasingly digital society
Mr Haldane’s Hermitage: Re-discovering a Late 18th Century Immersive Poetry Tableau at Airthrey Estate, Bridge of Allan, Stirling, a Case of Disguising East India Company Profits
Get PDFThis article explores a previously unrecorded, late 18th century grotto in the grounds of the former Airthrey Estate, Stirling (now Stirling University) that appears to have been constructed to provide the physical setting for an immersive rendering of Oliver Goldsmith’s poem The Hermit (also known as ‘Edwin and Angelina’ from Chapter 8 of Goldsmith’s novel the Vicar of Wakefield where it is described as ‘ballad’). The article describes the structure and its history and places it in context of then fashionable Scottish garden design trends
Scraper reduction at the Early Neolithic site of Hurst Fen, Suffolk, England
Get PDFPrior analyses of Neolithic flaked stone assemblages in Britain have tended to focus on the relative abundance of different implement types as a basis for inferring the structure of settlement and subsistence patterns during this period, with dorsally retouched ‘scrapers’ dominating the retouched components of most assemblages. Here we investigate the relationship between scraper morphology and reduction intensity at the classic Early Neolithic site of Hurst Fen in Suffolk, England. We hypothesize that the morphological variability underpinning the distinction between formal scraper types at Hurst Fen is largely a product of increasing reduction intensity. To test this hypothesis, we apply a range of quantitative measures of reduction intensity to a sample of 175 complete scrapers from the site, including: Kuhn’s (1990) Geometric Index of Unifacial Reduction (GIUR), Hiscock and Attenbrow\u27s (2002; 2005) retouch curvature and retouched zone indices, perimeter of retouch, and retouched edge angle. Correlation statistics and descriptive plots of the relationship between Kuhn’s GIUR and the remaining retouch characteristics reveal universally positive and statistically significant relationships, albeit with the correlation between the GIUR and retouched edge angle markedly weaker than for the other retouch characteristics. Collectively, the results of our analyses support the hypothesis that the extent to which scrapers were reduced throughout their respective use-lives was a critical factor in the creation of morphological and, by extension, typological variability in the Hurst Fen scraper assemblage. At the same time, our data suggest that Early Neolithic knappers at Hurst Fen habitually knapped and resharpened scrapers in such a manner that a relatively low edge angle of around 60˚ was continually reproduced, raising the possibility of preconceived ‘designs’ that were primarily expressed in the morphological features of retouched edges. We propose a model of scraper reduction that accounts for most of the differences in scraper morphology at Hurst Fen and evaluate the analytical utility of Clark’s hugely influential typological scheme in view of this. We also consider the implications of our findings for interpretations of morphological patterning in British Neolithic scraper assemblages more broadly
Tidal Thinking for artist-researcher collaboration:: beachcombing located memories and place values
No full textOceans are fundamental to life on Earth, yet they face escalating pressures that demand solutions across society. Addressing these challenges requires approaches that span disciplines and ways of knowing. Bridging art and research offers great possibilities but comes with its own distinct challenges. Inspired by Oceanic movement and our coastal experiences, particularly SCUBA diving, we consider connections between arts and research through rhythm and sense of place. Marine places further benefit from approaches suited to their fluidity, such as ‘Oceanic thinking’ and embodied maritime practices. Based on conversations between the authors (artist and researcher) which became the supporting text for an exhibition, we propose ‘tidal thinking’ as an approach which resonates with our art and research practices. Tidal thinking emphasises dynamic cycles, creating liminal terrains, exposing learnings, and carrying us through tension and release. This cycle has supported our collaborative work, including a participatory mapping and sketching activity outlined below: ‘beachcombing located memories’. To evoke beachcombing, this activity echoes tidal cycles with sketching, scattering, combing, and sharing located images to elicit personal associations with coastal spaces towards shared reflection. Inspired by marine processes and artefacts, we offer tidal thinking as both a conceptual and practical tool to support educators, artists, and researchers in developing transdisciplinary collaborations that contribute to viable and just Ocean futures
The Needs of Teachers of Adult Community Education: Six Narratives
No full textThe current study described the experiences, challenges, and needs of first time adult community education teachers in the USA. Although the adult education literature often emphasizes the context of learners and their instructional settings, less is known and has been studied about how first-time teachers prepare to teach. Engaging six adult community education first-time teachers who ranged in age from 39 to 74, reflective journaling was used to identify their experiences before, during, and after their teaching experience. Using open-coding, five consistent themes were identified: initial self-doubt, recognition of adult learners\u27 experiences, the importance of flexibility, reliance on interactive and hands-on strategies, and the mutual growth between teachers and their students. The teachers also noted that their credibility came less from their expertise and more from their adaptability, humility, and classroom management that fostered respect and engagement. Implications from these findings include the possibility of improving the experience for teachers by strengthening the onboarding process and providing professional development opportunities for adult community education teachers