A Systems Immunology Approach to the Host-Tumor Interaction: Large-Scale Patterns of Natural Autoantibodies Distinguish Healthy and Tumor-Bearing Mice

Traditionally, immunology has considered a meaningful antibody response to be marked by large amounts of high-affinity antibodies reactive with the specific inciting antigen; the detection of small amounts of low-affinity antibodies binding to seemingly unrelated antigens has been considered to be beneath the threshold of immunological meaning. A systems-biology approach to immunology, however, suggests that large-scale patterns in the antibody repertoire might also reflect the functional state of the immune system. To investigate such global patterns of antibodies, we have used an antigen-microarray device combined with informatic analysis. Here we asked whether antibody-repertoire patterns might reflect the state of an implanted tumor. We studied the serum antibodies of inbred C57BL/6 mice before and after implantation of syngeneic 3LL tumor cells of either metastatic or non-metastatic clones. We analyzed patterns of IgG and IgM autoantibodies binding to over 300 self-antigens arrayed on slides using support vector machines and genetic algorithm techniques. We now report that antibody patterns, but not single antibodies, were informative: 1) mice, even before tumor implantation, manifest both individual and common patterns of low-titer natural autoantibodies; 2) the patterns of these autoantibodies respond to the growth of the tumor cells, and can distinguish between metastatic and non-metastatic tumor clones; and 3) curative tumor resection induces dynamic changes in these low-titer autoantibody patterns. The informative patterns included autoantibodies binding to self-molecules not known to be tumor-associated antigens (including insulin, DNA, myosin, fibrinogen) as well as to known tumor-associated antigens (including p53, cytokeratin, carbonic anhydrases, tyrosinase). Thus, low-titer autoantibodies that are not the direct products of tumor-specific immunization can still generate an immune biomarker of the body-tumor interaction. System-wide profiling of autoantibody repertoires can be informative

Regulatory and Contractual Framework as an Integral Part of CLARIN Infrastructure : the Estonian and Finnish Perspectives

The article focuses on the regulatory and contractual framework in CLARIN. The discussion is based on the process analysis approach, which allows an evaluation of the functionality and shortcomings of the entire legal framework concerning language resources and technologies. The article reflects the personal knowledge and insights of the authors gained through their work with legal aspects of language resources and technologies in Estonia and Finland. The analysis may be helpful to CLARIN partners facing similar problems

Immune epitope database analysis resource

The immune epitope database analysis resource (IEDB-AR: http://tools.iedb.org) is a collection of tools for prediction and analysis of molecular targets of T- and B-cell immune responses (i.e. epitopes). Since its last publication in the NAR webserver issue in 2008, a new generation of peptide:MHC binding and T-cell epitope predictive tools have been added. As validated by different labs and in the first international competition for predicting peptide:MHC-I binding, their predictive performances have improved considerably. In addition, a new B-cell epitope prediction tool was added, and the homology mapping tool was updated to enable mapping of discontinuous epitopes onto 3D structures. Furthermore, to serve a wider range of users, the number of ways in which IEDB-AR can be accessed has been expanded. Specifically, the predictive tools can be programmatically accessed using a web interface and can also be downloaded as software packages

The prognostic significance of specific HOX gene expression patterns in ovarian cancer

YesHOX genes are vital for all aspects of mammalian growth and differentiation, and their dysregulated expression is related to ovarian carcinogenesis. The aim of the current study was to establish the prognostic value of HOX dysregulation as well as its role in platinum resistance. The potential to target HOX proteins through the HOX/PBX interaction was also explored in the con-text of platinum resistance. HOX gene expression was determined in ovarian cancer cell lines and primary EOCs by QPCR, and compared to expression in normal ovarian epithelium and fallopian tube tissue samples. Statistical analysis included one-way ANOVA and t-tests, using statistical software R and GraphPad. The analysis identified 36 of the 39 HOX genes as being overex-pressed in high grade serous EOC compared to normal tissue. We detected a molecular HOX gene-signature that predicted poor outcome. Overexpression of HOXB4 and HOXB9 was identified in high grade serous cell lines after platinum resistance developed. Targeting the HOX/PBX dimer with the HXR9 peptide enhanced the cytotoxicity of cisplatin in platinum-resistant ovarian cancer. In conclusion, this study has shown the HOX genes are highly dysregulated in ovarian cancer with high expression of HOXA13, B6, C13, D1 and D13 being predictive of poor clinical outcome. Targeting the HOX/PBX dimer in platinum–resistant cancer represents a potentially new therapeutic option that should be further developed and tested in clinical trials.This research was supported by GRACE, a gynaecological charity based in Surrey, UK

“Seen Again”: Ethnography, Immersive Technologies, and Temporality in the Siberian Collections at the Pitt Rivers Museum

This paper proposes Virtual Reality (VR) and 360 film as promising fieldwork tools for addressing problematic temporalities in ethnographic museums and for collaborating with communities of origin. Focusing on the Maria Czaplicka Siberian collections at the Pitt Rivers Museum, Oxford, we examine how previous methods of display marginalized the Evenki by denying their coevalness. Drawing on research in Evenkia in 2019 (part of the project Wandering in Other Worlds, Talking with the Spirits), we then analyze the potential of immersive technologies as fieldwork tools. While cautioning against the dangers of blindly trusting the promises of “empathy‐production” and “immersion,” we emphasize ways in which immersive technologies can facilitate the decentering of “western” observational focus. We discuss how carrying the museum into the field via VR helped to challenge the observer‐observed relationship prevalent in the museum. Studying how community members chose to share, create, and “re‐see” their own footage, we further argue that the cocreation of VR/360 film with communities from Baǐkit, Surinda, Chirinda, Tura, and Sulomay destabilized temporalities prevalent in the Pitt Rivers Museum, facilitating a shift toward an Evenki, helical timeline