No claim to original U.S. Government Works.Aroma contributes to the unique flavors of fruits and is important for fruit quality evaluation. Among the many volatiles in peach (Prunus persicus) fruits, γ-decalactone has the greatest contribution to the characteristic peach aroma. Some peach cultivars have γ-decalactone contents that are too low to detect. Comparison of the transcriptomes and metabolomes of a high-aroma cultivar, 'Fenghuayulu', and a low-aroma cultivar, 'Achutao', suggested that amino acid substitutions in ALCOHOL ACYLTRANSFERASE (PpAAT1) are responsible for the undetectable levels of γ-decalactone in 'Achutao' fruit. Modeling and molecular docking analysis of PpAAT1 indicated that the substituted residues might determine substrate recognition or act as control channels to the active site. In vitro enzyme assays on PpAAT1 heterologously expressed and purified from Escherichia coli, and in vivo assays using transient PpAAT1 expression in Nicotiana benthamiana or the oleaginous yeast Yarrowia lipolytica indicated that PpAAT1 from high-aroma cultivars was more efficient than PpAAT1 from low-aroma cultivars in catalyzing the conversion of 4-hydroxydecanoyl-CoA into γ-decalactone. Examination of loss-of-function mutations of PpAAT1 generated by CRISPR/Cas9 in 'Fenghuayulu' showed that fruits with PpAAT1 mutations had significantly lower γ-decalactone contents. Expression of the version of PpAAT1 from 'Fenghuayulu' in 'Achutao' restored γ-decalactone levels to those measured in 'Fenghuayulu', confirming the specific contribution of PpAAT1 to the formation of this key aroma compound. These results show how the biosynthesis of the peach aroma compound γ-decalactone is compromised in some low-aroma cultivars and illustrate the physiological role of PpAAT1 in plant lactone biosynthesis. copyright, serif 2020 American Society of Plant Biologists. All rights reserved.BACKGROUND Despite reported injury rates of up to 3 per 1000 hours exposure, there are no evidence-based prevention programmes in tennis. PURPOSE To evaluate the effectiveness of an e-health prevention programme for reducing tennis injury prevalence. STUDY DESIGN Two-arm, researcher-blinded randomised controlled trial. METHODS Adult tennis players of all playing levels were randomised in an unsupervised programme lasting 12 weeks (TennisReady group or control group). The primary outcome was the overall injury prevalence over a 16-week period, measured at 2 weekly intervals with the Oslo Sports and Trauma Research Centre questionnaire. Estimates for the primary outcome and associated 95% CIs were obtained using generalised estimating equation models. Secondary outcome scores included prevalence of substantial injuries, overall incidence, adherence and time-loss injuries. RESULTS A total of 579 (83%) (TennisReady n=286, control n=293) participants were included in the primary analysis. The mean injury prevalence was 37% (95% CI 33% to 42%) in the TennisReady vs 38% (95% CI 34% to 42%) in the control group (adjusted p-value 0.93). Adenosine 5′-diphosphate The prevalence of substantial injuries was 11% (95% CI 9% to 14%) in the TennisReady vs 12% (95% CI 9% to 15%) in the control group (p value of 0.79). Analysis of the secondary outcome scores showed no difference between groups. The mean prevalence rates between high (8%) and low (92%) adherent groups were 32% (95% CI 23% to 44%) and 37% (95% CI 33% to 42%), respectively (p value 0.36). CONCLUSION Providing an unsupervised e-health tennis-specific exercise programme did not reduce the injury rates and should not be implemented. TRIAL REGISTRATION NUMBER NTR6443. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.Primary resistance to CD19-directed chimeric antigen receptor T cell therapy (CART19) occurs in 10-20% of patients with acute lymphoblastic leukemia (ALL), however the mechanisms of this resistance remain elusive. Using a genome-wide loss-of-function screen, we identified that impaired death receptor signaling in ALL led to rapidly progressive disease despite CART19 treatment. This was mediated by an inherent resistance to T cell cytotoxicity which permitted antigen persistence and was subsequently magnified by the induction of CAR T cell functional impairment. These findings were validated using samples from two CAR T cell clinical trials in ALL, where we found that reduced expression of death receptor genes was associated with worse overall survival and reduced T cell fitness. Our findings suggest that inherent dysregulation of death receptor signaling in ALL directly leads to CAR T cell failure by impairing T cell cytotoxicity and promoting progressive CAR T cell dysfunction. Copyright ©2020, American Association for Cancer Research.OBJECTIVES Alzheimer disease (AD) shows a broad array of clinical presentations, but the mechanisms underlying these phenotypic variants remain elusive. Aging-related astrogliopathy (ARTAG) is a relatively recent term encompassing a broad array of tau deposition in astroglia outside the range of traditional tauopathies. White matter thorn-shaped astrocyte (WM-TSA) clusters, a specific ARTAG subtype, has been associated with atypical language presentation of AD in a small study lacking replication. To interrogate the impact of WM-TSA in modifying clinical phenotype in AD, we investigated a clinicopathologic sample of 83 persons with pure cortical AD pathology and heterogeneous clinical presentations. METHODS We mapped WM-TSA presence and density throughout cortical areas and interrogated whether WM-TSA correlated with atypical AD presentation or worse performance in neuropsychological testing. RESULTS WM-TSA was present in nearly half of the cases and equally distributed in typical and atypical AD presentations. Worsening language and visuospatial functions were correlated with higher WM-TSA density in language-related and visuospatial-related regions, respectively. These findings were unrelated to regional neurofibrillary tangle burden. Next, unsupervised clustering divided the participants into 2 groups a high-WM-TSA (n = 9) and low-WM-TSA (n = 74) pathology signature. The high-WM-TSA group scored significantly worse in language but not in other cognitive domains. CONCLUSIONS The negative impact of WM-TSA pathology to language and possibly visuospatial networks suggests that WM-TSA is not as benign as other ARTAG types and may be explored as a framework to understand the mechanisms and impact of astrocytic tau deposition in AD in humans. © 2020 American Academy of Neurology.