Furthermore, the overexpression of oncogenic ΔNp63 was associated with human OSCC. In conclusion, these results in mice indicate the biological significance of p16INK4a-specific loss with retention of p19Arf in oral squamous cell carcinogenesis, and ΔNp63 may be a potential target for OSCC. Eosinophils are a major cause of tissue injury in allergic conjunctivitis. The biological nature of eosinophils in the conjunctiva and the mechanisms that control eosinophils’ responses in allergic conjunctivitis are currently not completely understood. Here, we report that conjunctival eosinophils comprise two populations-Siglec─Fint and Siglec─Fhi-in different life stages. Siglec─Fint eosinophils partly expressed CD34 and were in the immature (or steady) state. Siglec─Fhi eosinophils did not express CD34, sharply increased in number after short ragweed (SRW) pollen challenge, and were in the mature (or activated) state. Moreover, chemical sympathectomy by 6─hydroxydopamine reduced the recruitment and activation of eosinophils, while the activation of sympathetic nerve system (SNS) with restraint stress accelerated the recruitment and activation of eosinophils in SRW─induced conjunctivitis. We also found that two eosinophil populations expressed alpha─1a─adrenergic receptors (α1a─ARs); in SRW─induced conjunctivitis, treatment with an α1a─AR antagonist decreased eosinophil responses, whereas treatment with an α1a─AR agonist aggravated eosinophil responses. Thus, eosinophil responses in conjunctivitis are regulated by the SNS via α1a─AR signaling. SNS inputs or α1a─AR function may be potential targets for the treatment of allergic conjunctivitis. The complement membrane attack complex (MAC) is classically known as a cytolytic effector of innate and adaptive immunity that forms pores in the plasma membrane of pathogens or targeted cells leading to osmolysis. Nucleated cells resist MAC-mediated cytolysis by expression of inhibitors that block MAC assembly or by rapid removal of MAC through endocytosis or shedding. In the absence of lysis, MAC may induce intracellular signaling and cell activation, responses implicated in a variety of autoimmune, inflammatory, and transplant disease settings. selleck chemicals llc New discoveries into the structure and biophysical properties of MAC revealed heterogenous MAC precursors and conformations that provide insights into MAC function. Additionally, new mechanisms of MAC-mediated signaling and its contribution to disease pathogenesis have recently come to light. MAC-activated cells have been found to express pro-inflammatory proteins, often through nuclear factor kappa B (NF-κB)-dependent transcription, assemble inflammasomes enabling processing, and secretion of Interleukin-1β and interleukin-18, as well as other signaling pathways. These recent insights into the mechanisms of action of MAC provide an updated framework to therapeutic approaches that can target MAC assembly, signaling, and proinflammatory effects in various complement-mediated diseases. The distribution of tumor infiltrating lymphocytes (TIL) within the tumor microenvironment provides strong prognostic value, which is increasingly important with the arrival of new immunotherapy modalities. Both visual and image analysis based assays are developed to assess the immune contexture of the tumors. We propose an automated method based on grid-subsampling of microscopy image analysis data to extract the tumor-stroma interface zone (IZ) of controlled width. The IZ is a ranking of tissue areas by their distance to the tumor edge which is determined by a set of explicit rules. TIL density profiles across the IZ are used to compute a set of novel Immunogradient indicators which reflect TIL “gradient towards the tumor”. We applied the method on CD8 immunohistochemistry images of surgically excised hormone receptor-positive breast and colorectal cancers to predict overall patient survival. In both cohorts the Immunogradient indicators enabled strong and independent prognostic stratification, outperforming clinical and pathology variables. Breast cancer patients with low Immunogradient revealed a prominent drop of survival probability 5 years after surgery. Our study provides proof-of-concept that data-driven, automated, operator-independent IZ sampling enables spatial immune response measurement in the tumor/host interaction frontline for prediction of disease outcomes. Previously, adult zebrafish with a mutation in the gene encoding the glucocorticoid receptor (Gr) were demonstrated to display anxiety- and depression-like behavior that could be reversed by treatment with antidepressant drugs, suggesting that this model system could be applied to study novel therapeutic strategies against depression. Subsequent studies with zebrafish larvae from this grs357 line and a different gr mutant have not confirmed these effects. To investigate this discrepancy, we have analyzed the anxiety-like behavior in 5 dpf grs357 larvae using a dark/tapping stimulus test and a light/dark preference test. In addition, grs357 adult fish were subjected to an open field test. The results showed that in larvae the mutation mainly affected general locomotor activity (decreased velocity in the dark/tapping stimulus test, increased velocity in the light/dark preference test). However, parameters considered specific readouts for anxiety-like behavior (response to dark/tapping stimulus, time spent in dark zone) were not altered by the mutation. In adults, the mutants displayed a profound increase in anxiety-like behavior (time spent in outer zone in open field test), besides changes in locomotor activity (decreased velocity, increased angular velocity and freezing time). We conclude that the neuronal circuitry involved in anxiety- and depression-like behavior is largely affected by deficient Gr signaling in adult fish but not in larvae, indicating that this circuitry only fully develops after the larval stages in zebrafish. This makes the zebrafish an interesting model to study the ontology of anxiety- and depression-related pathology which results from deficient glucocorticoid signaling.