Equality, Diversity and Inclusion in Global Mental Health: a Human Library Reading Event

Stigma, discrimination, and social exclusion across cultural settings are among the greatest barriers to achieving equitable healthcare globally. Students on the Mental Health and Disability: International Law and Policy course explore ways of minimising stigma and discrimination. They also learn about mental health legislation and policies based on core equality and inclusivity principles. Given that the pillars of the MVLS Education Strategy are underpinned by the core values of equality, diversity, inclusion, integrity, and respect, (https://www.gla.ac.uk/media/Media_842672_smxx.pdf ) the Global Mental Health (GMH) Team aimed to introduce a novel and innovative means of embedding these concepts into the curriculum. With funding from the MVLS College Equality Diversity and Inclusion (EDI) Committee we hosted a learning facilitated by the Human Library. The Human Library Organisation (https://humanlibrary.org) provides an international learning platform that enables safe and confidential dialogue between volunteers representing a stigmatised group (i.e. ‘Books’) and learners (i.e. ‘Readers’). Drawing on personal experience Books answer questions put to them by small groups of Readers, helping to challenge stereotypes and stigmatising beliefs. The session aims to encourage those attending to ‘unjudge someone’. The event was held on the 1st of March 2023 and around 20 students attended. Six Books and Three Librarians engaged in the session with diversity areas including: mental illness, religion, physical disability, gang membership, survivor of abuse, transgender and eating disorder. Feedback from students who completed the evaluation questionnaire was very positive. With 94% (15/16) either strongly agreeing or agreeing that the event was informative and made them reflect on their personal views. One student reported: ‘I thoroughly enjoyed this event. I had never heard of this organization before and I think that it is an incredible concept. This was easily one of my favorite class days. I can't think of anything in particular that could've been done better.

Mister aeroplane man, take me up to heaven, help me out if you [first line of chorus]

Performers: Charlie MelsonPiano, Voice and Chord

Cryptic protein-protein interaction motifs in the cytoplasmic domain of MHCI proteins

Background: Major histocompatibility complex class I (MHCI) proteins present antigenic peptides for immune surveillance and play critical roles in nervous system development and plasticity. Most MHCI are transmembrane proteins. The extracellular domain of MHCI interacts with immunoreceptors, peptides, and co-receptors to mediate immune signaling. While the cytoplasmic domain also plays important roles in endocytic trafficking, cross-presentation of extracellularly derived antigens, and CTL priming, the molecular mediators of cytoplasmic signaling by MHCI remain largely unknown. Results: Here we show that the cytoplasmic domain of MHCI contains putative protein-protein interaction domains known as PDZ (PSD95/disc large/zonula occludens-1) ligands. PDZ ligands are motifs that bind to PDZ domains to organize and mediate signaling at cell-cell contacts. PDZ ligands are short, degenerate motifs, and are therefore difficult to identify via sequence homology alone, but several lines of evidence suggest that putative PDZ ligand motifs in MHCI are under positive selective pressure. Putative PDZ ligands are found in all of the 99 MHCI proteins examined from diverse species, and are enriched in the cytoplasmic domain, where PDZ interactions occur. Both the position of the PDZ ligand and the class of ligand motif are conserved across species, as well as among genes within a species. Non-synonymous substitutions, when they occur, frequently preserve the motif. Of the many specific possible PDZ ligand motifs, a handful are strikingly and selectively overrepresented in MHCI’s cytoplasmic domain, but not elsewhere in the same proteins. Putative PDZ ligands in MHCI encompass conserved serine and tyrosine residues that are targets of phosphorylation, a post-translational modification that can regulate PDZ interactions. Finally, proof-of-principle in vitro interaction assays demonstrate that the cytoplasmic domains of particular MHCI proteins can bind directly and specifically to PDZ1 and PDZ4&5 of MAGI-1, and identify a conserved PDZ ligand motif in the classical MHCI H2-K that is required for this interaction. Conclusions: These results identify cryptic protein interaction motifs in the cytoplasmic domain of MHCI. In so doing, they suggest that the cytoplasmic domain of MHCI could participate in previously unsuspected PDZ mediated protein-protein interactions at neuronal as well as immunological synapses

[Ni(cyclam)] 2+ and [Ni(R,S-Me6cyclam)] 2+ as Linkers or Counterions In Uranyl–Organic Species with cis-and trans-1,2-Cyclohexanedicarboxylate Ligands

International audienceThe macrocyclic species [Ni(cyclam)] 2+ and [Ni(R,S-Me6cyclam)] 2+ were used as additional cations in the solvo-hydrothermal synthesis of five uranyl ion complexes with cis-or trans-1,2-cyclohexanedicarboxylic acids (c-1,2-chdcH2 and t-1,2-chdcH2). In the complex [UO2(c-chdc)2Ni(cyclam)(H2O)] (1), dimeric uranyl dicarboxylate subunits are assembled into a two-dimensional (2D) network through axial coordination of Ni II to carboxylate groups. Although they involve different isomers, the complexes [(UO2)2(c-chdc)2(c-chdcH)2Ni(cyclam)] (2) and [(UO2)2(t-chdc)2(t-chdcH)2Ni(cyclam)] (3) are very similar, both containing uranyl-based one dimensional (1D) subunits which are assembled into 2D networks by bridging [Ni(cyclam)] 2+ groups. The orientation of the uncoordinated carboxylic group is different in 2 and 3, the layers in 2 being hydrogen bonded to each other through carboxylic acid dimer formation. Using the pure (1R,2R) enantiomer of t-1,2-chdcH2 gives the complex [Ni(cyclam)][(UO2)5(R-t-chdc)3(R-t-chdcH)(O)2(CH3COO)] (4), in which pentanuclear uranyl subunits are assembled into 1D chains by dicarboxylic/ate ligands in the usual bis(equatorial) chair conformation, another ligand in the divergent bis(axial) conformation uniting these chains into a 2D assembly; the [Ni(cyclam)] 2+ ions are simple counterions and are stacked in parallel fashion between the layers. [Ni(R,S-Me6cyclam)][Ni(R,S-Me6cyclam)(H2O)2][(UO2)2(t-chdc)2(O)]2 (5), in which the (1R,2R) enantiomer used has undergone racemization, contains discrete bis(µ3-oxo)-centered tetranuclear uranyl complexes, organized into columns and layers by extensive hydrogen bonding to the counterions. The discoidal shape, available axial coordination sites and hydrogen bond donor potential of these macrocyclic Ni II complexes make them efficient assembling agents in uranyl–organic coordination polymers. As often observed in the presence of d-block metal cations, uranyl luminescence is either completely or partially quenched in complexes 1 and 3, respectively

Additional file 2: Figure S2. of Cryptic protein-protein interaction motifs in the cytoplasmic domain of MHCI proteins

PDZ ligand motifs identified in the cytoplasmic domains of 16 mouse MHCI and MHCI-like proteins. Putative PDZ ligand motifs are highlighted in red, and previously noted conserved serines and tyrosine (see text) are underlined in bold. Consensus motifs: class 1 PDZ, [S/T X Φ]; class 2 PDZ, [ΦXΦ]; class 3 PDZ, [D/E X Φ]; Φ = Y, F, W, C, M, V, I, L, or A [44]. H2-T23 is also known as Qa-1. No ligand motifs were found in the cytoplasmic domain of H2-M2 or -M9, and therefore they are omitted. Soluble MHCI proteins including H2-Q10 lack a cytoplasmic domain and were not considered in this analysis. (PPTX 37 kb

Additional file 3: Figure S3. of Cryptic protein-protein interaction motifs in the cytoplasmic domain of MHCI proteins

Frequency of occurrence of specific class 2 and 3 PDZ ligand motifs in the cytoplasmic domains of 99 MHCI proteins from 21 species. A. Class 2 PDZ ligand motifs ([ΦXΦ], where Φ = V, I, L, M, F, W, or C), or B. class 3 PDZ ligand motifs ([D/E X Φ) [46]) in the cytoplasmic domains of 99 MHCI proteins from 21 species (data used to create pie charts in Fig. 2e and f, respectively). Shown are the number of occurrences of each motif as well as the fraction they represent of the total motifs observed in each domain. Class 2 PDZ ligand forms that were never observed in either domain are not shown. (PPTX 73 kb

Additional file 1: Figure S1. of Cryptic protein-protein interaction motifs in the cytoplasmic domain of MHCI proteins

Categorization of PDZ ligands. The current study made use of forms of Lenfant et al.’s [44] and Nourry et al.’s [46] criteria to identify potential PDZ ligand motifs in MHCI proteins. Related rules were proposed in [45]. (PPTX 35 kb