Access all areas: multisensory science exhibitions tailored toward blind, low‐vision and diverse‐needs communities

Monash Sensory Science is a scientific outreach initiative specifically tailored to members of the community who are blind, have low vision and have diverse needs. The purpose of this initiative is to showcase Australian science and encourage greater participation in science from these often‐overlooked communities. This article presents our experience in establishing Monash Sensory Science at Monash University and inspiring other institutions to launch similar outreach events

Structural basis of T cell receptor specificity and cross-reactivity of two HLA-DQ2.5-restricted gluten epitopes in celiac disease

Celiac disease is a T cell-mediated chronic inflammatory condition often characterized by human leukocyte antigen (HLA)-DQ2.5 molecules presenting gluten epitopes derived from wheat, barley, and rye. Although some T cells exhibit cross-reactivity toward distinct gluten epitopes, the structural basis underpinning such cross-reactivity is unclear. Here, we investigated the T-cell receptor specificity and cross-reactivity of two immunodominant wheat gluten epitopes, DQ2.5-glia-α1a (PFPQPELPY) and DQ2.5-glia-ω1 (PFPQPEQPF). We show by surface plasmon resonance that a T-cell receptor alpha variable (TRAV) 4+-T-cell receptor beta variable (TRBV) 29-1+ TCR bound to HLA-DQ2.5-glia-α1a and HLA-DQ2.5-glia-ω1 with similar affinity, whereas a TRAV4- (TRAV9-2+) TCR recognized HLA-DQ2.5-glia-ω1 only. We further determined the crystal structures of the TRAV4+-TRBV29-1+ TCR bound to HLA-DQ2.5-glia-α1a and HLA-DQ2.5-glia-ω1, as well as the structure of an epitope-specific TRAV9-2+-TRBV7-3+ TCR-HLA-DQ2.5-glia-ω1 complex. We found that position 7 (p7) of the DQ2.5-glia-α1a and DQ2.5-glia-ω1 epitopes made very limited contacts with the TRAV4+ TCR, thereby explaining the TCR cross-reactivity across these two epitopes. In contrast, within the TRAV9-2+ TCR-HLA-DQ2.5-glia-ω1 ternary complex, the p7-Gln was situated in an electrostatic pocket formed by the hypervariable CDR3β loop of the TCR and Arg70β from HLA-DQ2.5, a polar network which would not be supported by the p7-Leu residue of DQ2.5-glia-α1a. In conclusion, we provide additional insights into the molecular determinants of TCR specificity and cross-reactivity to two closely-related epitopes in celiac disease

Discriminative T-cell receptor recognition of highly homologous HLA-DQ2–bound gluten epitopes

Celiac disease (CeD) provides an opportunity to study the specificity underlying human T-cell responses to an array of similar epitopes presented by the same human leukocyte antigen II (HLA-II) molecule. Here, we investigated T-cell responses to the two immunodominant and highly homologous HLA-DQ2.5–restricted gluten epitopes, DQ2.5-glia-α1a (PFPQPELPY) and DQ2.5-glia-ω1 (PFPQPEQPF). Using HLA-DQ2.5–DQ2.5-glia-α1a and HLA-DQ2.5–DQ2.5-glia-ω1 tetramers and single-cell αβ T-cell receptor (TCR) sequencing, we observed that despite similarity in biased variable-gene usage in the TCR repertoire responding to these nearly identical peptide–HLA-II complexes, most of the T cells are specific for either of the two epitopes. To understand the molecular basis of this exquisite fine specificity, we undertook Ala substitution assays revealing that the p7 residue (Leu/Gln) is critical for specific epitope recognition by both DQ2.5-glia-α1a– and DQ2.5-glia-ω1–reactive T-cell clones. We determined high-resolution binary crystal structures of HLA-DQ2.5 bound to DQ2.5-glia-α1a (2.0 Å) and DQ2.5-glia-ω1 (2.6 Å). These structures disclosed that differences around the p7 residue subtly alter the neighboring substructure and electrostatic properties of the HLA-DQ2.5–peptide complex, providing the fine specificity underlying the responses against these two highly homologous gluten epitopes. This study underscores the ability of TCRs to recognize subtle differences in the peptide–HLA-II landscape in a human disease setting

T cell receptor cross-reactivity between gliadin and bacterial peptides in celiac disease

The human leukocyte antigen (HLA) locus is strongly associated with T cell-mediated autoimmune disorders. HLA-DQ2.5-mediated celiac disease (CeD) is triggered by the ingestion of gluten, although the relative roles of genetic and environmental risk factors in CeD is unclear. Here we identify microbially derived mimics of gliadin epitopes and a parental bacterial protein that is naturally processed by antigen-presenting cells and activated gliadin reactive HLA-DQ2.5-restricted T cells derived from CeD patients. Crystal structures of T cell receptors in complex with HLA-DQ2.5 bound to two distinct bacterial peptides demonstrate that molecular mimicry underpins cross-reactivity toward the gliadin epitopes. Accordingly, gliadin reactive T cells involved in CeD pathogenesis cross-react with ubiquitous bacterial peptides, thereby suggesting microbial exposure as a potential environmental factor in CeD

Anchoring of Iron Oxyhydroxide Clusters at H and L Ferritin Subunits

Ferritin (Fn) proteins or their isolated subunits can be used as biomolecular templates for the selectively heterogeneous nucleation and growth of nanoparticles, in particular of iron oxyhydroxides. To shed light on the atomistic mechanisms of ferritin-promoted mineralization, in this study we perform molecular dynamics simulations to investigate the anchoring sites for Fe­(III) clusters on Fn subunit assemblies using models of goethite and ferrihydrite nanoparticles. For this aim, we develop and parametrize a classical force field for Fe­(III) oxyhydroxides based on reference density functional theory calculations. We then reveal that stable Fn–nanoparticle contacts are formed not only via negatively charged amino acid residues (glutamic and aspartic acid) but also, in a similar amount, via positively charged (lysine and arginine) and neutral (histidine) residues. A large majority of the anchoring sites are situated at the inner side of protein cages, consistent with the natural iron storage function of ferritin in many organisms. A slightly different distribution of anchoring sites is observed on heavy (H) and light (L) Fn subunits, with the former offering a larger amount of negative and neutral sites than the latter. This finding is exploited to develop a Fn mineralization protocol in which immobilized Fn subunits are first loaded with Fe²⁺ ions in a long “activation” step before starting their oxidation to Fe³⁺. This leads to the formation of very dense and uniform iron oxide films, especially when H subunits are employed

América Latina interdisciplinar e plural: Territórios liminares: violências, direitos e sensibilidades

Coleção 'América Latina Interdisciplinar e Plural' contempla trabalhos de discentes, docentes, egressos(as) e convidados(as) externos(as) do Programa de Pós-Graduação Interdisciplinar em Estudos Latino-Americanos (PPGIELA) da Universidade Federal da Integração Latino-Americana (UNILA).Livro financiado com recursos do PROAP-UNILA

Immoral contracts in Europe

Tekstas VDU autorių 31 p. : p. 88-92, 155-157, 197-198, 246-248, 308-309, 369-370, 431-434, 482-484, 533-534, 574-575, 622-624, 686-688This book adds an in-depth study of the law and practice on immorality of contracts in Europe to the Common Core series. It comprises country reports on 28 European legal systems, in line with the editors ’ aspiration to give a comprehensive overview of shared and diverging views on immorality of contracts in the European Union. The reports have been draft ed on the basis of 12 case scenarios, inspired by real-life cases that were adjudicated in European countries. Furthermore, given the importance of societal debate for the assessment of morality in contract law, signifi cant attention is paid to the context in which the law on specifi c cases has developed. Th e combined insights from the national reports provide an overview of the current state of a “ Common Core ” on immoral contracts in Europe. Comparative legal studies performed by a large network of academics from many different countries usually require many years of work and, indeed, a great deal of patience from all persons involved. This book, like most volumes in the Common Core series, is no exception to this rule. We presented a first draft questionnaire on immoral contracts – or, more precisely, on the limits to the validity of contracts on ground of morality or public policy – at the General Meeting of the Common Core project in 2012. After settling on the fi nal version of the questionnaire, the first draft country reports were written between 2013–2015. The comparative remarks, the introductory chapters and the second and third draft s of the country reports were completed between 2016–2018. This past year was devoted to the final editing, updating and proofreading of the book. [...]Privatinės teisės katedraTeisės fakultetasVytauto Didžiojo universiteta