Overt Attention and Context Factors: The Impact of Repeated Presentations, Image Type, and Individual Motivation

The present study investigated the dynamic of the attention focus during observation of different categories of complex scenes and simultaneous consideration of individuals' memory and motivational state. We repeatedly presented four types of complex visual scenes in a pseudo-randomized order and recorded eye movements. Subjects were divided into groups according to their motivational disposition in terms of action orientation and individual rating of scene interest

Cell surface marker-based capture of neoantigen-reactive CD8+ T-cell receptors from metastatic tumor digests

Background Cellular immunotherapies using autologous tumor-infiltrating lymphocytes (TIL) can induce durable regression of epithelial cancers in selected patients with treatment-refractory metastatic disease. As the genetic engineering of T cells with tumor-reactive T-cell receptors (TCRs) comes to the forefront of clinical investigation, the rapid, scalable, and cost-effective detection of patient-specific neoantigen-reactive TIL remains a top priority.Methods We analyzed the single-cell transcriptomic states of 31 neoantigen-specific T-cell clonotypes to identify cell surface dysfunction markers that best identified the metastatic transcriptional states enriched with antitumor TIL. We developed an efficient method to capture neoantigen-reactive TCRs directly from resected human tumors based on cell surface co-expression of CD39, programmed cell death protein-1, and TIGIT dysfunction markers (CD8+ TILTP).Results TILTP TCR isolation achieved a high degree of correlation with single-cell transcriptomic signatures that identify neoantigen-reactive TCRs, making it a cost-effective strategy using widely available resources. Reconstruction of additional TILTP TCRs from tumors identified known and novel antitumor TCRs, showing that at least 39.5% of TILTP TCRs are neoantigen-reactive or tumor-reactive. Despite their substantial enrichment for neoantigen-reactive TCR clonotypes, clonal dynamics of 24 unique antitumor TILTP clonotypes from four patients indicated that most in vitro expanded TILTP populations failed to demonstrate neoantigen reactivity, either by loss of neoantigen-reactive clones during TIL expansion, or through functional impairment during cognate neoantigen recognition.Conclusions While direct usage of in vitro-expanded CD8+ TILTP as a source for cellular therapy might be precluded by profound TIL dysfunction, isolating TILTP represents a streamlined effective approach to rapidly identify neoantigen-reactive TCRs to design engineered cellular immunotherapies against cancer

Utilization of primary tumor samples for cancer neoantigen discovery

Background The use of tumor-infiltrating T lymphocytes (TIL) that recognize cancer neoantigens has led to lasting remissions in metastatic melanoma and certain cases of metastatic epithelial cancer. For the treatment of the latter, selecting cells for therapy typically involves laborious screening of TIL for recognition of autologous tumor-specific mutations, detected through next-generation sequencing of freshly resected metastatic tumors. Our study explored the feasibility of using archived formalin-fixed, paraffin-embedded (FFPE) primary tumor samples for cancer neoantigen discovery, to potentially expedite this process and reduce the need for resections normally required for tumor sequencing.Method Whole-exome sequencing was conducted on matched primary and metastatic colorectal cancer samples from 22 patients. The distribution of metastatic tumor mutations that were confirmed as neoantigens through cognate TIL screening was evaluated in the corresponding primary tumors. Mutations unique to primary tumors were screened for recognition by metastasis-derived TIL and circulating T lymphocytes.Results We found that 25 (65.8%) of the 38 validated neoantigens identified in metastatic tumors from 18 patients with colorectal cancer were also present in matched primary tumor samples. This included all 12 neoantigens encoded by putative cancer driver genes, which are generally regarded as superior targets for adoptive cell therapy. The detection rate for other neoantigens, representing mutations without an established role in cancer biology, was 50% (13/26). Gene products encoding neoantigens detected in the primary tumors were not more likely to be clonal or broadly distributed among the analyzed metastatic lesions compared with those undetected in the primary tumors. Additionally, we found that mutations detected only in primary tumor samples did not elicit recognition by metastatic tumor-derived TIL but could elicit specific recognition by the autologous circulating memory T cells.Conclusions Our findings indicate that primary FFPE tumor-derived screening libraries could be used to discover most neoantigens present in metastatic tumors requiring treatment. Furthermore, this approach can reveal additional neoantigens not present in resected metastatic tumors, prompting further research to understand their clinical relevance as potential therapeutic targets

Aspectos da anatomia foliar de algumas espécies de Paepalanthus Kunth, Eriocaulaceae da Serra do Cipó - Minas Gerais Aspects of leaf anatomy of some species of Paepalanthus Kunth, Eriocaulaceae from Serra do Cipó - Minas Gerais

O estudo da anatomia foliar das espécies de Paepalanthus Kunth.: P. bromelioides Silv.; P. macropodus Ruhl.; P. miçrophyllus (Giull.) Kunth; P. paulinus Ruhl.; P. robustus Silv.; P. scleranthus Ruhl. e P. speciosus (Bong.) Koer. mostrou uma semelhança no número e distribuição dos feixes vasculares, Em P. robustus e, menos marcadamente, em P. speciosus, estes feixes de tamanhos diferentes, encontram-se distribuídos em séries, com os feixes menores mais próximos da epiderme adaxial. As folhas revelam características xerofíticas em diferentes graus. Chama-se a atenção para a formação de feixes vasculares anfivasais no ápice das folhas.<br>The anatomical studies in species of Paepalanthus Kunth: P.bromelioides Silv.; P. macropodus Ruhl.; P. miçrophyllus (Giull.) Kunth; P. paulinus Ruhl.; P. robustus Silv.; P. scleranthus Ruhl. and P. speciosus (Bong.) Koem., show similarity in the number and distribution of the vascular bundles. In P. robustus and, to a lesser extent, in P. speciosus, theses bundles of differing sizes occur in series, the smaller ones being closer to the adaxial epidermis. The leaves exhibit varying degrees of xeromorphy. Attention is drawn to the development of anphyvasal vascular bundles in the leaf apices