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Failure of remyelination underlies the progressive nature of demyelinating diseases such as multiple sclerosis. Macrophages and microglia are crucially involved in the formation and repair of demyelinated lesions. Here we show that myelin uptake temporarily skewed these phagocytes toward a disease-resolving phenotype, while sustained intracellular accumulation of myelin induced a lesion-promoting phenotype. This phenotypic shift was controlled by stearoyl-CoA desaturase-1 (SCD1), an enzyme responsible for the desaturation of saturated fatty acids. Monounsaturated fatty acids generated by SCD1 reduced the surface abundance of the cholesterol efflux transporter ABCA1, which in turn promoted lipid accumulation and induced an inflammatory phagocyte phenotype. Pharmacological inhibition or phagocyte-specific deficiency of Scd1 accelerated remyelination ex vivo and in vivo. These findings identify SCD1 as a novel therapeutic target to promote remyelination. © 2020 Bogie et al.Ion channels represent a large class of drug targets, but their role in brain cancer is underexplored. Here, we identify that chloride intracellular channel 1 (CLIC1) is overexpressed in human central nervous system malignancies, including medulloblastoma, a common pediatric brain cancer. While global knockout does not overtly affect mouse development, genetic deletion of CLIC1 suppresses medulloblastoma growth in xenograft and genetically engineered mouse models. Mechanistically, CLIC1 enriches to the plasma membrane during mitosis and cooperates with potassium channel EAG2 at lipid rafts to regulate cell volume homeostasis. CLIC1 deficiency is associated with elevation of cell/nuclear volume ratio, uncoupling between RNA biosynthesis and cell size increase, and activation of the p38 MAPK pathway that suppresses proliferation. Concurrent knockdown of CLIC1/EAG2 and their evolutionarily conserved channels synergistically suppressed the growth of human medulloblastoma cells and Drosophila melanogaster brain tumors, respectively. These findings establish CLIC1 as a molecular dependency in rapidly dividing medulloblastoma cells, provide insights into the mechanism by which CLIC1 regulates tumorigenesis, and reveal that targeting CLIC1 and its functionally cooperative potassium channel is a disease-intervention strategy. © 2020 Francisco et al.Despite increasing recognition of the importance of GM-CSF in autoimmune disease, it remains unclear how GM-CSF is regulated at sites of tissue inflammation. Using GM-CSF fate reporter mice, we show that synovial NK cells produce GM-CSF in autoantibody-mediated inflammatory arthritis. Synovial NK cells promote a neutrophilic inflammatory cell infiltrate, and persistent arthritis, via GM-CSF production, as deletion of NK cells, or specific ablation of GM-CSF production in NK cells, abrogated disease. Synovial NK cell production of GM-CSF is IL-18-dependent. Furthermore, we show that cytokine-inducible SH2-containing protein (CIS) is crucial in limiting GM-CSF signaling not only during inflammatory arthritis but also in experimental allergic encephalomyelitis (EAE), a murine model of multiple sclerosis. Thus, a cellular cascade of synovial macrophages, NK cells, and neutrophils mediates persistent joint inflammation via production of IL-18 and GM-CSF. Endogenous CIS provides a key brake on signaling through the GM-CSF receptor. These findings shed new light on GM-CSF biology in sterile tissue inflammation and identify several potential therapeutic targets. learn more © 2020 Louis et al.The incidence of acute myeloid leukemia (AML) increases with age. Intensive induction chemotherapy containing cytarabine and an anthracycline has been part of the upfront and salvage treatment of AML for decades. Anthracyclines are associated with a significant risk of cardiotoxicity (especially anthracycline-related left ventricular dysfunction [ARLVD]). In the older adult population, the higher prevalence of cardiac comorbidities and risk factors may further increase the risk of ARLVD. In this article of the Young International Society of Geriatric Oncology group, we review the prevalence of ARLVD in patients with AML and factors predisposing to ARLVD, focusing on older adults when possible. In addition, we review the assessment of cardiac function and management of ARLVD during and after treatment. It is worth noting that only a minority of clinical trials focus on alternative treatment strategies in patients with mildly declined left ventricular ejection fraction or at a high risk for ARLVD. The limited evidence for preventive strategies to ameliorate ARLVD and alternative strategies to anthracycline use in the setting of cardiac comorbidities are discussed. Based on extrapolation of findings from younger adults and nonrandomized trials, we recommend a comprehensive baseline evaluation of cardiac function by imaging, cardiac risk factors, and symptoms to risk stratify for ARLVD. Anthracyclines remain an appropriate choice for induction although careful risk-stratification based on cardiac disease, risk factors, and predicted chemotherapy-response are warranted. In case of declined left ventricular ejection fraction, alternative strategies should be considered. © 2020 by The American Society of Hematology.Identifying the cause(s) of postoperative thrombocytopenia is challenging. The postoperative period includes numerous interventions, including fluid administration and transfusion of blood products, medication use (including heparin), and increased risk of organ dysfunction and infection. Understanding normal thrombopoietin physiology and the associated expected postoperative platelet count changes is the crucial first step in evaluation. Timing of thrombocytopenia is the most important feature when differentiating causes of postoperative thrombocytopenia. Thrombocytopenia within 4 days of surgery is commonly caused by hemodilution and increased perioperative platelet consumption prior to thrombopoietin-induced platelet count recovery and transient platelet count overshoot. A much broader list of possible conditions that can cause late-onset thrombocytopenia (postoperative day 5 [POD5] or later) is generally divided into consumptive and destructive causes. The former includes common (eg, infection-associated disseminated intravascular coagulation) and rare (eg, postoperative thrombotic thrombocytopenic purpura) conditions, whereas the latter includes such entities as drug-induced immune thrombocytopenia or posttransfusion purpura.