Systematic interrogation of tumor-infiltrating lymphocytes is key to the development of immunotherapies and the prediction of their clinical responses in cancers. Here, we perform deep single-cell RNA sequencing on 5,063 single T cells isolated from peripheral blood, tumor, and adjacent normal tissues from six hepatocellular carcinoma patients. The transcriptional profiles of these individual cells, coupled with assembled T cell receptor (TCR) sequences, enable us to identify 11 T cell subsets based on their molecular and functional properties and delineate their developmental trajectory. Specific subsets such as exhausted CD8 T cells and Tregs are preferentially enriched and potentially clonally expanded in hepatocellular carcinoma (HCC), and we identified signature genes for each subset. One of the genes, layilin, is upregulated on activated CD8 T cells and Tregs and represses the CD8 T cell functions in vitro. This compendium of transcriptome data provides valuable insights and a rich resource for understanding the immune landscape in cancers.

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It has long been a staple of psychological theory that early life experiences significantly shape the adult's understanding of and reactions to the social world. Here we consider how early concept development along with evolved motives operating early in life can come to exert a passive, unconscious influence on the human adult's higher-order goal pursuits, judgments, and actions. In particular, we focus on concepts and goal structures specialized for interacting with the physical environment (e.g., distance cues, temperature, cleanliness, and self-protection), which emerge early and automatically as a natural part of human development and evolution. It is proposed that via the process of scaffolding, these early sensorimotor experiences serve as the foundation for the later development of more abstract concepts and goals. Experiments using priming methodologies reveal the extent to which these early concepts serve as the analogical basis for more abstract psychological concepts, such that we come easily and naturally to speak of close relationships, warm personalities, moral purity, and psychological pain. Taken together, this research demonstrates the extent to which such foundational concepts are capable of influencing people's information processing, affective judgments, and goal pursuit, oftentimes outside of their intention or awareness.

Four studies support the hypothesis that expressing negative emotion is associated with positive relationship outcomes, including elicitation of support, building of new close relationships, and heightening of intimacy in the closest of those relationships. In Study 1, participants read vignettes in which another person was experiencing a negative emotion. Participants reported they would provide more help when the person chose to express the negative emotion. In Study 2, participants watched a confederate preparing for a speech. Participants provided more help to her when she expressed nervousness. In Study 3, self-reports of willingness to express negative emotions predicted having more friends, controlling for demographic variables and extraversion. In Study 4, self-reports of willingness to express negative emotion measured prior to arrival at college predicted formation of more relationships, greater intimacy in the closest of those relationships, and greater received support from roommates across participants' first semester of college.

SUMMARY The gastric pathogen Helicobacter pylori interacts intimately with the gastric mucosa to avoid the microbicidal acid in the stomach lumen. The cues H. pylori senses to locate and colonize the gastric epithelium have not been well defined. We show that metabolites emanating from human gastric organoids rapidly attract H. pylori. This response is largely controlled by the bacterial chemoreceptor TlpB, and the main attractant emanating from epithelia is urea. Our previous structural analyses show that TlpB binds urea with high affinity. Here we demonstrate that this tight binding controls highly sensitive responses, allowing detection of urea concentrations as low as 50 nanomolar. Attraction to urea requires that H. pylori urease simultaneously destroys the signal. We propose that H. pylori has evolved a sensitive urea chemodetection and destruction system that allows the bacterium to dynamically and locally modify the host environment to locate the epithelium.