Primate TNF Promoters Reveal Markers of Phylogeny and Evolution of Innate Immunity

Background. Tumor necrosis factor (TNF) is a critical cytokine in the immune response whose transcriptional activation is controlled by a proximal promoter region that is highly conserved in mammals and, in particular, primates. Specific single nucleotide polymorphisms (SNPs) upstream of the proximal human TNF promoter have been identified, which are markers of human ancestry. Methodology/Principal findings. Using a comparative genomics approach we show that certain fixed genetic differences in the TNF promoter serve as markers of primate speciation. We also demonstrate that distinct alleles of most human TNF promoter SNPs are identical to fixed nucleotides in primate TNF promoters. Furthermore, we identify fixed genetic differences within the proximal TNF promoters of Asian apes that do not occur in African ape or human TNF promoters. Strikingly, protein-DNA binding assays and gene reporter assays comparing these Asian ape TNF promoters to African ape and human TNF promoters demonstrate that, unlike the fixed differences that we define that are associated with primate phylogeny, these Asian ape-specific fixed differences impair transcription factor binding at an Sp1 site and decrease TNF transcription induced by bacterial stimulation of macrophages. Conclusions/significance. Here, we have presented the broadest interspecies comparison of a regulatory region of an innate immune response gene to date. We have characterized nucleotide positions in Asian ape TNF promoters that underlie functional changes in cell type- and stimulus-specific activation of the TNF gene. We have also identified ancestral TNF promoter nucleotide states in the primate lineage that correspond to human SNP alleles. These findings may reflect evolution of Asian and African apes under a distinct set of infectious disease pressures involving the innate immune response and TNF

Privacy Considerations for Public Storytelling

The popularity of the web and social media have afforded researchers unparalleled access to content about the daily lives of people. Human research ethics guidelines, while actively expanding to meet the new challenges posed by web research, still rely on offline principles of interaction that are a poor fit to modern technology. In this context, we present a study of the identifiability of authors of socially sensitive content. With the goal of identity obfuscation, we compare this to the identifiability of the same content translated to and then back from a foreign language, focusing on how easily a person could locate the original source of the content. We discuss the risk to these authors presented by dissemination of their content, and consider the implications for research ethics guidelines

Content-Based Similarity Measures of Weblog Authors

With recent research interest in the confounding roles of homophily and contagion in studies of social influence, there is a strong need for reliable content-based measures of the similarity between people. In this paper, we investigate the use of text similarity measures as a way of predicting the similarity of prolific weblog authors. We describe a novel method of collecting human judgments of overall similarity between two authors, as well as demographic, political, cultural, religious, values, hobbies/interests, personality, and writing style similarity. We then apply a range of automated textual similarity measures based on word frequency counts, and calculate their statistical correlation with human judgments. Our findings indicate that commonly used text similarity measures do not correlate well with human judgments of author similarity. However, various measures that pay special attention to personal pronouns and their context correlate significantly with different facets of similarity

Different Strokes of Different Folks Searching for Health Narratives in Weblogs

Abstract—The utility of storytelling in the interaction between healthcare providers and patients is now firmly established, but the potential use of large-scale story collections for health-related inquiry has not yet been explored. In particular, the enormous scale of storytelling in personal weblogs offers investigators in health-related fields new opportunities to study the behavior and beliefs of diverse patient populations outside of clinical settings. In this paper we address the technical challenges in identifying personal stories about specific health issues from corpora of millions of weblog posts. We describe a novel infrastructure for collecting and indexing the stories posted each day to Englishlanguage weblogs, coupled with user interfaces designed to support targeted searches of these collections. We evaluate the effectiveness of this search technology in an effort to identify hundreds of first person and third person accounts of strokes, for the purpose of studying gender differences in the way that these health emergencies are described. Results indicate that the use of relevance feedback significantly improves the effectiveness of the search. We conclude with a discussion of sample biases that are inherent in weblog storytelling and heightened by our approach, and propose ways to mitigate these biases. Keywords- weblogs, storytelling, health, information retrieval I