DNA-Mediated Interferon Signature Induction by SLE Serum Occurs in Monocytes Through Two Pathways: A Mechanism to Inhibit Both Pathways

A primary mechanism for activation of innate immunity is recognition of damage or pathogen associated molecular patterns by pattern recognition receptors (PRRs). Nucleic acid is a damage associated molecular pattern molecule that when internalized into a monocyte and recognized by intracellular nucleic acid sensing toll like receptors will cause production of type 1 interferon. The process by which DNA or RNA is delivered into the cytosol of monocytes in systemic lupus erythematosus remains incompletely understood, and therapeutic approaches to prevent DNA-mediated monocyte activation are needed. We identified two mechanisms for internalization of DNA by monocytes. IgG-bound DNA was internalized by interacting with Fc gamma receptor IIa, while high-mobility group box-1 protein-bound DNA was internalized by interacting with the receptor for advanced glycation end products. Both pathways contribute to an inflammatory phenotype in monocytes exposed to serum from patients with SLE. Moreover, both of these pathways can be inhibited by a pentapeptide, DWEYS, which is a DNA mimetope. In one instance DWEYS directly competes with DNA for antibody binding and in the other DWEYS binds high-mobility group box-1 and blocks its interaction with RAGE. Our data highlight distinct pathways involved in nucleic acid enters monocytes in SLE, and identify a potential therapeutic to prevent nucleic acid internalization in SLE

Towards a map of the Upper Pleistocene loess of the Po Plain Loess Basin (Northern Italy)

Upper Pleistocene (MIS 4-2) loess sequences occur in most of continental Europe and in Northern Italy along the Po Plain Loess Basin. Loess is distributed along the flanks of the Po Plain and was deposited on glacial deposits, fluvial terraces, uplifted isolated hills, karst plateaus, slopes and basins of secondary valleys. Loess bodies are generally tiny and affected by pedogenesis, being locally slightly reworked by slope processes and bioturbation. Notwithstanding, loess in the Po Plain is an important archive of paleoenviron-mental record and its mapping provides new insights in paleoenvironmental and palaeoseismic reconstructions of Northern Ital

Towards a map of the Upper Pleistocene loess of the Po Plain Loess Basin (Northern Italy)

Upper Pleistocene (MIS 4-2) loess sequences occur in most of continental Europe and in Northern Italy along the Po Plain Loess Basin. Loess is distributed along the flanks of the Po Plain and was deposited on glacial deposits, fluvial terraces, uplifted isolated hills, karst plateaus, slopes and basins of secondary valleys. Loess bodies are generally tiny and affected by pedogenesis, being locally slightly reworked by slope processes and bioturbation. Notwithstanding, loess in the Po Plain is an important archive of paleoenviron-mental record and its mapping provides new insights in paleoenvironmental and palaeoseismic reconstructions of Northern Italy

Study 3: Emotionality Judgments of Happiness Sequences

The goal of Study 3 was to replicate the effect of target gender on judgments of emotionality from Study 2 using expressions of happiness

Study 1: Stereotype Survey

The goal of Study 1 was to ascertain if the stereotype that women are more emotional than men persists and if gender-emotion stereotypes vary for different discrete emotions

Supplementary Study: Emotionality Judgments of Sadness Sequences

We conducted two additional studies with the same design as Studies 2 and 3 but with sadness expressions and found no effect of face gender on emotionality judgments. These studies are not included in the main paper but are reported in the Supplementary Materials