Natural micropolymorphism in human leukocyte antigens provides a basis for genetic control of antigen recognition

Human leukocyte antigen (HLA) gene polymorphism plays a critical role in protective immunity, disease susceptibility, autoimmunity, and drug hypersensitivity, yet the basis of how HLA polymorphism influences T cell receptor (TCR) recognition is unclear. We examined how a natural micropolymorphism in HLA-B44, an important and large HLA allelic family, affected antigen recognition. T cell–mediated immunity to an Epstein-Barr virus determinant (EENLLDFVRF) is enhanced when HLA-B*4405 was the presenting allotype compared with HLA-B*4402 or HLA-B*4403, each of which differ by just one amino acid. The micropolymorphism in these HLA-B44 allotypes altered the mode of binding and dynamics of the bound viral epitope. The structure of the TCR–HLA-B*4405EENLLDFVRF complex revealed that peptide flexibility was a critical parameter in enabling preferential engagement with HLA-B*4405 in comparison to HLA-B*4402/03. Accordingly, major histocompatibility complex (MHC) polymorphism can alter the dynamics of the peptide-MHC landscape, resulting in fine-tuning of T cell responses between closely related allotypes

RNA Recognition and Stress Granule Formation by TIA Proteins

Stress granule (SG) formation is a primary mechanism through which gene expression is rapidly modulated when the eukaryotic cell undergoes cellular stresses (including heat, oxidative, viral infection, starvation). In particular, the sequestration of specifically targeted translationally stalled mRNAs into SGs limits the expression of a subset of genes, but allows the expression of heatshock proteins that have a protective effect in the cell. The importance of SGs is seen in several disease states in which SG function is disrupted. Fundamental to SG formation are the T cell restricted intracellular antigen (TIA) proteins (TIA-1 and TIA-1 related protein (TIAR)), that both directly bind to target RNA and self-associate to seed the formation of SGs. Here a summary is provided of the current understanding of the way in which TIA proteins target specific mRNA, and how TIA self-association is triggered under conditions of cellular stress

Authenticities: A Semiotic Exploration

Charles Taylor has called ours an “Age of Authenticity”, and authenticity is a popular object of scholarly examination, not least in anthropology. A considerable number of scholars have even proposed models for multiple “authenticities”. None, however, has brought a modified Peircean theoretical tool-kit together with ethnographic evidence that “the natives know” that there are many authenticities. This article seeks to fill that gap. Working with Peirce’s model of the sign and with postmodern theories of originals and replicas, we draw on Wilce’s Finnish fieldwork to analyze what we consider clear evidence of four authenticities arising in recent debates surrounding traditional Karelian lament and particularly highly organized attempts in Finland to “revive” the practice. We call performances arising out of the revival “neolaments”. We treat authenticities as strictly relational, metasemiotic, and ideological phenomena. Authenticities that appear salient to actors on the revivalist scene may involve the following relationships : that between any neolament performance and any particular Karelian lament performances, with the question being whether the former is adequately “traditional” (i.e. relationship between replica and original); between a particular lament performance and the generic essence of that which makes lament a lament (i.e. token and type); between a lament performance and emotion – a relationship ideologically construed as “expressive” (i.e. sign and object); and finally, a relationship between some sort of dynamic interpretant of particular old Karelian laments (lament1) and new dynamic interpretants generated in and through new lament performances (lament2 or habitual participation in such performance) that in some way replicates the old dynamical interpretant (interpretant1 and interpretant2).Charles Taylor a baptisé notre époque “l’Âge de l’Authenticité”. Certes, l’authenticité est un sujet populaire dans la recherche académique, surtout en anthropologie. Un nombre important de chercheurs sont allés jusqu’à proposer des modèles “d’authenticités multiples”. Aucun, cependant, n’a offert jusqu’à présent une “boîte à outils théorique peircéenne modifiée” qui mettrait en évidence le fait que les “autochtones savent” qu’il existe de nombreuses authenticités. Le présent article vise à combler cette lacune.En combinant le modèle sémiotique de Peirce avec les théories postmodernes sur les originaux et les copies, nous nous sommes appuyés sur le travail mené sur le terrain en Finlande par Wilce pour analyser ce qui nous semble être une évidence, à savoir que quatre formes d’authenticités sont présentes dans les récents débats sur la lamentation carélienne et, en particulier, dans les tentatives entreprises en Finlande pour “faire revivre” cette pratique. Nous appelons “néolamentations” les expressions issues de ce renouveau et traitons les questions d’authenticité qu’elles suscitent comme des phénomènes strictement relationnels, metasémiotiques et idéologiques. Les authenticités qui paraissent saillantes aux acteurs de la scène revivaliste font émerger les rapports suivants : 1) le rapport entre l’usage de la néolamentation et celui de toute autre forme de lamentation carélienne, dans le but de déterminer si la première est adéquatement “traditionnelle” (soit : la relation entre la copie et l’original); 2) le rapport entre la performance d’une lamentation et l’essence même qui lui octroie son identité de lamentation (soit : la relation du token et du type); 3) le rapport entre performance et émotion – une relation idéologiquement interprétée comme ‘expressive’ (soit : la relation du signe à son objet); 4) enfin, le rapport entre une sorte d’interprétant dynamique d’anciennes lamentations caréliennes (lamentation1) et des interprétants dynamiques nouveaux produits par des performances nouvelles de la lamentation (lamentation2 ou participation habituelle dans pareilles performances) et qui, d’une certaine manière, visent la reproduction de l’interprétant dynamique ancien (soit : la relation entre un interprétant1 et interprétant2)

Language and emotion

Bahasa adalah sarana yang kita gunakan untuk mengkomunikasikan perasaan; kami juga merefleksikan secara emosional bahasa yang kami dan orang lain gunakan.viii, 200 p.: ill.; 23 c

The crystal structure of DehI reveals a new α-haloacid dehalogenase fold and active-site mechanism

Haloacid dehalogenases catalyse the removal of halides from organic haloacids and are of interest for bioremediation and for their potential use in the synthesis of industrial chemicals. We present the crystal structure of the homodimer DehI from Pseudomonas putida strain PP3, the first structure of a group I α-haloacid dehalogenase that can process both l- and d-substrates. The structure shows that the DehI monomer consists of two domains of ∼ 130 amino acids that have ∼ 16% sequence identity yet adopt virtually identical and unique folds that form a pseudo-dimer. Analysis of the active site reveals the likely binding mode of both l- and d-substrates with respect to key catalytic residues. Asp189 is predicted to activate a water molecule for nucleophilic attack of the substrate chiral centre resulting in an inversion of configuration of either l- or d-substrates in contrast to d-only enzymes. These details will assist with future bioengineering of dehalogenases

Language and emotion

Bahasa adalah sarana yang kita gunakan untuk mengkomunikasikan perasaan; kami juga merefleksikan secara emosional bahasa yang kami dan orang lain gunakan.viii, 200 p.: ill.; 23 c