Many developmental processes involve the emergence of intercellular fluid-filled lumina. This process of luminogenesis results in a build up of hydrostatic pressure and signalling molecules in the lumen. However, the potential roles of lumina in cellular functions, tissue morphogenesis and patterning have yet to be fully explored. In this Review, we discuss recent findings that describe how pressurized fluid expansion can provide both mechanical and biochemical cues to influence cell proliferation, migration and differentiation. We also review emerging techniques that allow for precise quantification of fluid pressure in vivo and in situ Finally, we discuss the intricate interplay between luminogenesis, tissue mechanics and signalling, which provide a new dimension for understanding the principles governing tissue self-organization in embryonic development. © 2020. Published by The Company of Biologists Ltd.Determining mechanisms of resistance to αPD-1/PD-L1 immune-checkpoint immunotherapy is key to developing new treatment strategies. Cancer-associated fibroblasts (CAF) have many tumor-promoting functions and promote immune evasion through multiple mechanisms, but as yet, no CAF-specific inhibitors are clinically available. Here we generated CAF-rich murine tumor models (TC1, MC38, and 4T1) to investigate how CAFs influence the immune microenvironment and affect response to different immunotherapy modalities [anticancer vaccination, TC1 (HPV E7 DNA vaccine), αPD-1, and MC38] and found that CAFs broadly suppressed response by specifically excluding CD8+ T cells from tumors (not CD4+ T cells or macrophages); CD8+ T-cell exclusion was similarly present in CAF-rich human tumors. RNA sequencing of CD8+ T cells from CAF-rich murine tumors and immunochemistry analysis of human tumors identified significant upregulation of CTLA-4 in the absence of other exhaustion markers; inhibiting CTLA-4 with a nondepleting antibodyPHICAL ABSTRACT http//cancerres.aacrjournals.org/content/canres/00/0/000/F1.large.jpg. ©2020 American Association for Cancer Research.OBJECTIVES To determine how soon after commencement of the seasonal influenza vaccination programme, the AusVaxSafety active vaccine safety surveillance system, currently in use across Australia, would have detected a safety signal had it been operating in 2010 when there was an unprecedented number of febrile seizures in young children associated with one specific influenza vaccine brand, Fluvax (CSL Biotherapies). DESIGN Simulation study. SETTING Western Australian vaccine influenza coverage and adverse event surveillance data. OUTCOME MEASURES Simulated solicited responses from caregivers who would have received an SMS survey about adverse events experienced following seasonal influenza vaccination of their children aged 6 months to 90% probability of a safety signal being detected by AusVaxSafety based on solicited reports for either fever or medical attendance at or before the week ending 28 March 2010, 3 weeks after the start of vaccine distribution. Suspension of the national paediatric influenza vaccination programme as a result of the passive adverse events surveillance operating at the time did not occur until 23 April 2010. CONCLUSIONS Active vaccine safety surveillance leading to rapid detection of a safety signal would likely have resulted in earlier suspension of Fluvax from the vaccination programme, prevention of many febrile convulsions and maintenance of public confidence in influenza vaccination for young children. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.Radiotherapy is a critical component of many current, curative cancer treatments, yet it is accompanied by unavoidable irradiation of normal tissues. selleck kinase inhibitor Abdominal and pelvic radiation almost always results in some dose delivered to the bowel with deleterious effects to the small and large intestines. While the likelihood of enteritis is dose dependent, there is also considerable variation between patients in both the extent of symptoms of enteritis as well as their duration. In this article, Martin and colleagues hypothesized that the radiation sensitivity of intestinal organoids could predict the sensitivity of individual patients to enteritis and have taken the first steps to develop such an assay.See related article by Martin et al., p. 1219. ©2020 American Association for Cancer Research.Chromosomal resistance islands containing the methicillin resistance gene mecD (McRI mecD ) have been reported in Macrococcus caseolyticus Here, we identified novel macrolide resistance genes in Macrococcus canis on similar elements, called McRI msr These elements were also integrated into the 3′-end of the 30S ribosomal protein S9 gene (rpsI), delimited by characteristic attachment (att) sites and carried a related site-specific integrase (int) at the 5′-end. They carried novel macrolide resistance genes belonging to the msr family of ABC-F type ribosomal protection protein [lsqb]msr(F) and msr(H)[rsqb] and the macrolide efflux mef family [lsqb]mef(D)[rsqb]. Highly related mef(D)-msr(F) fragments were found on diverse McRI msr in M. canis, M. caseolyticus and Staphylococcus aureus Another McRI msr -like element identified in a M. canis strain lacked the classical att site at the 3′-end and carried the msr(H) gene but no neighboring mef gene. Expression of the novel resistance genes in S. aureus resulted in a low to moderate increase in the MIC of erythromycin but not streptogramin B. In the mef(D)-msr(F) operon, the msr(F) gene was shown to be the crucial determinant for macrolide resistance. Detection of circular forms of McRI msr and the mef(D)-msr(F) fragment suggested mobility of both the island and the resistance gene subunit. The discovery of McRI msr in different Macrococcus species and S. aureus indicates that these islands have a potential for dissemination of antibiotic resistance within the Staphylococcaceae family. Copyright © 2020 American Society for Microbiology.Staphylococcus aureus biofilms are a significant problem in healthcare settings, in part, owing to the presence of a non-dividing, antibiotic tolerant sub-population. Here we evaluated treatment of S. aureus UAMS-1 biofilms with HT61, a quinoline derivative shown to be effective against non-dividing Staphylococcal spp HT61 was effective in reducing biofilm viability, associated with increased expression of cell wall stress and division proteins, confirming its potential as a treatment for S. aureus biofilm infections. Copyright © 2020 Frapwell et al.