Lipid profiling revealed ala4/5 rosettes had perturbations in glycerolipid and sphingolipid content. Assays in yeast revealed that ALA5 can flip a variety of glycerolipids and the sphingolipid sphingomyelin across membranes. These results support a model whereby the flippase activity of ALA4/5 impacts the homeostasis of both glycerolipids and sphingolipids and is important for cellular expansion during vegetative growth. copyright, serif 2020 American Society of Plant Biologists. All rights reserved.Prior small reports have postulated a link between gastrointestinal polyposis and childhood and young adulthood cancer (CYAC) treatment (therapy-associated polyposis; TAP), but this remains a poorly understood phenomenon. The aim of this study was to describe the phenotypic spectrum of TAP in a multi-institutional cohort. TAP cases were identified from eight high-risk cancer centers. Cases were defined as patients with ≥10 gastrointestinal polyps without known causative germline alteration or hereditary colorectal cancer predisposition syndrome who had a history of prior treatment with chemotherapy and/or radiotherapy for CYAC. A total of 34 TAP cases were included (original CYAC 27 Hodgkin lymphoma, three neuroblastoma, one acute myeloid leukemia, one medulloblastoma, one nephroblastoma, and one non-Hodgkin lymphoma). Gastrointestinal polyposis was first detected at a median of 27 years (interquartile range, 20-33) after CYAC treatment. A total of 12 of 34 (35%) TAP cases had ≥50 colorectal polyps. A total of 32 of 34 (94%) had >1 histologic polyp type. A total of 25 of 34 (74%) had clinical features suggestive of ≥1 colorectal cancer predisposition syndrome [e.g., attenuated familial adenomatous polyposis (FAP), serrated polyposis syndrome, extracolonic manifestations of FAP, mismatch repair-deficient colorectal cancer, or hamartomatous polyposis] including 8 of 34 (24%) with features of multiple such syndromes. TAP is an apparently acquired phenomenon that should be considered in patients who develop significant polyposis without known causative germline alteration but who have had prior treatment for a CYAC. Patients with TAP have features that may mimic various hereditary colorectal cancer syndromes, suggesting multiple concurrent biologic mechanisms, and recognition of this diagnosis may have implications for cancer risk and screening. ©2020 American Association for Cancer Research.INTRODUCTION Non-adherence to antipsychotic medications for individuals with serious mental illness increases risk of relapse and hospitalisation. Real time monitoring of adherence would allow for early intervention. AI2 is a both a personal nudging system and a clinical decision support tool that applies machine learning on Medicare prescription and benefits data to raise alerts when patients have discontinued antipsychotic medications without supervision, or when essential routine health checks have not been performed. METHODS AND ANALYSIS We outline two intervention models using AI2. In the first use-case, the personal nudging system, patients receive text messages when an alert of a missed medication or routine health check is detected by AI2. In the second use-case, as a clinical decision support tool, AI2 generated alerts are presented as flags through a dashboard to the community mental health professionals. Implementation protocols for different scenarios of AI2, along with a mixed-methods evaluation, are planned to identify pragmatic issues necessary to inform a larger randomised control trial, as well as improve the application. ETHICS AND DISSEMINATION This study protocol has been approved by The Southern Adelaide Clinical Human Research Ethics Committee. The dissemination of this trial will serve to inform further implementation of the AI2 into daily personal and clinical practice. © 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.SUMMARYHerpes simplex virus 1 (HSV-1) can be responsible for life-threatening HSV encephalitis (HSE). The mortality rate of patients with HSE who do not receive antiviral treatment is 70%, with most survivors suffering from permanent neurological sequelae. The use of intravenous acyclovir together with improved diagnostic technologies such as PCR and magnetic resonance imaging has resulted in a reduction in the mortality rate to close to 20%. However, 70% of surviving patients still do not recover complete neurological functions. Thus, there is an urgent need to develop more effective treatments for a better clinical outcome. It is well recognized that cerebral damage resulting from HSE is caused by viral replication together with an overzealous inflammatory response. Both of these processes constitute potential targets for the development of innovative therapies against HSE. In this review, we discuss recent progress in therapy that may be used to ameliorate the outcome of patients with HSE, with a particular emphasis on immunomodulatory agents. Ideally, the administration of adjunctive immunomodulatory drugs should be initiated during the rise of the inflammatory response, and its duration should be limited in time to reduce undesired effects. This critical time frame should be optimized by the identification of reliable biomarkers of inflammation. Copyright © 2020 American Society for Microbiology.Olufunmilayo Olopade, MD, discusses her research on genomic sequencing and breast cancer, which has led to insights into how the disease progresses-and how it can be prevented. What's key, she says, is that one-size-fits-all screening shouldn't be recommended. ©2020 American Association for Cancer Research.Rapid cold hardening (RCH) is a type of phenotypic plasticity that allows ectotherms to quickly enhance cold tolerance in response to brief chilling (lasting minutes to hours). In this Review, we summarize the current state of knowledge of this important phenotype and provide new directions for research. As one of the fastest adaptive responses to temperature known, RCH allows ectotherms to cope with sudden cold snaps and to optimize their performance during diurnal cooling cycles. RCH and similar phenotypes have been observed across a diversity of ectotherms, including crustaceans, terrestrial arthropods, amphibians, reptiles, and fish. In addition to its well-defined role in enhancing survival to extreme cold, RCH also protects against nonlethal cold injury by preserving essential functions following cold stress, such as locomotion, reproduction, and energy balance. learn more The capacity for RCH varies across species and across genotypes of the same species, indicating that RCH can be shaped by selection and is likely favored in thermally variable environments.