A rank based social norms model of how people judge their levels of drunkenness whilst intoxicated

Background: A rank based social norms model predicts that drinkers’ judgements about their drinking will be based on the rank of their breath alcohol level amongst that of others in the immediate environment, rather than their actual breath alcohol level, with lower relative rank associated with greater feelings of safety. This study tested this hypothesis and examined how people judge their levels of drunkenness and the health consequences of their drinking whilst they are intoxicated in social drinking environments. Methods: Breath alcohol testing of 1,862 people (mean age = 26.96 years; 61.86 % male) in drinking environments. A subset (N = 400) also answered four questions asking about their perceptions of their drunkenness and the health consequences of their drinking (plus background measures). Results: Perceptions of drunkenness and the health consequences of drinking were regressed on: (a) breath alcohol level, (b) the rank of the breath alcohol level amongst that of others in the same environment, and (c) covariates. Only rank of breath alcohol level predicted perceptions: How drunk they felt (b 3.78, 95 % CI 1.69 5.87), how extreme they regarded their drinking that night (b 3.7, 95 % CI 1.3 6.20), how at risk their long-term health was due to their current level of drinking (b 4.1, 95 % CI 0.2 8.0) and how likely they felt they would experience liver cirrhosis (b 4.8. 95 % CI 0.7 8.8). People were more influenced by more sober others than by more drunk others. Conclusion: Whilst intoxicated and in drinking environments, people base judgements regarding their drinking on how their level of intoxication ranks relative to that of others of the same gender around them, not on their actual levels of intoxication. Thus, when in the company of others who are intoxicated, drinkers were found to be more likely to underestimate their own level of drinking, drunkenness and associated risks. The implications of these results, for example that increasing the numbers of sober people in night time environments could improve subjective assessments of drunkenness, are discussed

An update on salicylic acid biosynthesis, its induction and potential exploitation by plant viruses.

Salicylic acid (SA) is a plant hormone essential for effective resistance to viral and non-viral pathogens. SA biosynthesis increases rapidly in resistant hosts when a dominant host resistance gene product recognizes a pathogen. SA stimulates resistance to viral replication, intercellular spread and systemic movement. However, certain viruses stimulate SA biosynthesis in susceptible hosts. This paradoxical effect limits virus titer and prevents excessive host damage, suggesting that these viruses exploit SA-induced resistance to optimize their accumulation. Recent work showed that SA production in plants does not simply recapitulate bacterial SA biosynthetic mechanisms, and that the relative contributions of the shikimate and phenylpropanoid pathways to the SA pool differ markedly between plant species.Work by AMM and JPC was supported by grants from UK Biotechnological and Biological Sciences Research Council (SCPRID grant number BB/J011762/1, and GCRF grant number BB/P023223/1). Work by TZ was supported by grants from the Ministry of Agriculture and Rural Affairs of China (2018YFD020062, 2016ZX08010-001), the National Natural Science Foundation of China (31371912) and a grant from the Ministry of Education of China (the 111 Project B13006)

Search for domain wall dark matter with atomic clocks on board global positioning system satellites

Cosmological observations indicate that 85% of all matter in the Universe is dark matter (DM), yet its microscopic composition remains a mystery. One hypothesis is that DM arises from ultralight quantum fields that form macroscopic objects such as topological defects. Here we use GPS as a ~ 50,000 km aperture DM detector to search for such defects in the form of domain walls. GPS navigation relies on precision timing signals furnished by atomic clocks hosted on board GPS satellites. As the Earth moves through the galactic DM halo, interactions with topological defects could cause atomic clock glitches that propagate through the GPS satellite constellation at galactic velocities ~ 300 km/s. Mining 16 years of archival GPS data, we find no evidence for DM in the form of domain walls at our current sensitivity level. This allows us to improve the limits on certain quadratic scalar couplings of domain wall DM to standard model particles by several orders of magnitude.Comment: 7 pages (main text), and 12 pages for Supplementary Information. v3: Update titl

Review of Engaging Education: Developing Emotional Literacy, Equity and Co-education. Brian Matthews. (Book Review)

The book is only about a fraction of its title Engaging Education. His section on ‘engaging the emotions’ sums this up: whereas the book is largely about engaging the emotions positively, the definition of ‘Engaging’ is more far reaching: “that pupils should be involved in their learning; be active and absorbed and not just passive recipients of a set curriculum. Additionally, they should feel engaged in the processes of education and have some input into creating their own agendas for learning” (p.2). Exploring the full impact of this statement across the curriculum really needs a different book

RNA-dependent RNA polymerase 1 in potato (Solanum tuberosum) and its relationship to other plant RNA-dependent RNA polymerases.

Cellular RNA-dependent RNA polymerases (RDRs) catalyze synthesis of double-stranded RNAs that can serve to initiate or amplify RNA silencing. Arabidopsis thaliana has six RDR genes; RDRs 1, 2 and 6 have roles in anti-viral RNA silencing. RDR6 is constitutively expressed but RDR1 expression is elevated following plant treatment with defensive phytohormones. RDR1 also contributes to basal virus resistance. RDR1 has been studied in several species including A. thaliana, tobacco (Nicotiana tabacum), N. benthamiana, N. attenuata and tomato (Solanum lycopersicum) but not to our knowledge in potato (S. tuberosum). StRDR1 was identified and shown to be salicylic acid-responsive. StRDR1 transcript accumulation decreased in transgenic potato plants constitutively expressing a hairpin construct and these plants were challenged with three viruses: potato virus Y, potato virus X, and tobacco mosaic virus. Suppression of StRDR1 gene expression did not increase the susceptibility of potato to these viruses. Phylogenetic analysis of RDR genes present in potato and in a range of other plant species identified a new RDR gene family, not present in potato and found only in Rosids (but apparently lost in the Rosid A. thaliana) for which we propose the name RDR7.LJRH was supported by a studentship co-funded by the James Hutton Institute (formerly Scottish Crop Research Institute) and the UK Biotechnological and Biological Sciences Research Council (BBSRC). Work in the JPC lab is funded by The Leverhulme Trust (RPG-2012-667), BBSRC (BB/D014376/1, BB/J011762/1) and the Cambridge University Newton Trust. SFB was funded by Leverhulme grant F/09-741/G to Professor Beverley Glover. KG was funded by an EMBO Short Term Fellowship. Work in the PP lab is funded by grant number NRF-2013R1A2A2A01016282 from the Korean National Research Foundation.This is the author accepted manuscript. The final version is available from Nature Publishing Group via https://doi.org/10.1038/srep2308

Heme-Mediated SPI-C Induction Promotes Monocyte Differentiation into Iron-Recycling Macrophages

Splenic red pulp macrophages (RPM) degrade senescent erythrocytes and recycle heme-associated iron. The transcription factor SPI-C is selectively expressed by RPM and is required for their development, but the physiologic stimulus inducing Spic is unknown. Here, we report that Spic also regulated the development of F4/80^+VCAM1^+ bone marrow macrophages (BMM) and that Spic expression in BMM and RPM development was induced by heme, a metabolite of erythrocyte degradation. Pathologic hemolysis induced loss of RPM and BMM due to excess heme but induced Spic in monocytes to generate new RPM and BMM. Spic expression in monocytes was constitutively inhibited by the transcriptional repressor BACH1. Heme induced proteasome-dependent BACH1 degradation and rapid Spic derepression. Furthermore, cysteine-proline dipeptide motifs in BACH1 that mediate heme-dependent degradation were necessary for Spic induction by heme. These findings are the first example of metabolite-driven differentiation of a tissue-resident macrophage subset and provide new insights into iron homeostasis

Identifying and Targeting Sporadic Oncogenic Genetic Aberrations in Mouse Models of Triple-Negative Breast Cancer

Triple-negative breast cancers (TNBC) are genetically characterized by aberrations in TP53 and a low rate of activating point mutations in common oncogenes, rendering it challenging in applying targeted therapies. We performed whole-exome sequencing (WES) and RNA sequencing (RNA-seq) to identify somatic genetic alterations in mouse models of TNBCs driven by loss of Trp53 alone or in combination with Brca1. Amplifications or translocations that resulted in elevated oncoprotein expression or oncoprotein-containing fusions, respectively, as well as frameshift mutations of tumor suppressors were identified in approximately 50% of the tumors evaluated. Although the spectrum of sporadic genetic alterations was diverse, the majority had in common the ability to activate the MAPK/PI3K pathways. Importantly, we demonstrated that approved or experimental drugs efficiently induce tumor regression specifically in tumors harboring somatic aberrations of the drug target. Our study suggests that the combination of WES and RNA-seq on human TNBC will lead to the identification of actionable therapeutic targets for precision medicine–guided TNBC treatment.National Institutes of Health (U.S.) (Grant R35 CA197588)National Institutes of Health (U.S.) (Grant R01 GM041890)National Institutes of Health (U.S.) (Grant PSOC U54 CA210184)Breast Cancer Research Foundation (award BCRF-16-021)Jon and Mindy Gray FoundationEntertainment Industry Foundation. Stand Up to Cancer Colorectal Cancer Dream Team (Tranlational Research Grant No. SU2C-AACR-DT22-17)Susan Komen postdoctoral fellowshipBreast Cancer AllianceNovo Nordisk STAR Postdoctoral Fellowshi