Notes

Valproic acid increases the efficiency regarding radiation therapy by safeguarding normal hippocampal nerves as well as sensitizing dangerous glioblastoma cellular material.
phyB-independent growth restriction of the jazD mutant was tightly correlated with upregulation of the tryptophan biosynthetic pathway but not changes in central carbon metabolism. Interestingly, jazD and jazD phyB plants were insensitive to a chemical inhibitor of tryptophan biosynthesis, which is a phenotype previously observed in plants expressing hyperactive MYC transcription factors that cannot bind JAZ repressors. These data provide evidence that the mechanisms underlying the JA-mediated growth-defense balance depend on the level of defense, and further establish an association between growth inhibition at high levels of defense and dysregulation of tryptophan biosynthesis. copyright, serif 2020 American Society of Plant Biologists. All rights reserved.P granules are phase-separated liquid droplets that play important roles in the maintenance of germ cell fate in Caenorhabditis elegans Both the localization and formation of P granules are highly dynamic, but mechanisms that regulate such processes remain poorly understood. Here we show evidence that the VASA-like germline RNA helicase GLH-1 couples distinct steps of its ATPase hydrolysis cycle to control the formation and disassembly of P granules. In addition, we found that the FGG repeats in GLH-1 promote its localization at the perinucleus. Proteomic analyses of the GLH-1 complex with a GLH-1 mutation that interferes P granule disassembly revealed transient interactions of GLH-1 with several Argonautes and RNA binding proteins. Finally, we found that defects in recruiting the P granule component PRG-1 to perinuclear foci in the adult germline correlate with the fertility defects observed in various GLH-1 mutants. Together, our results highlight the versatile roles of an RNA helicase in controlling the formation of liquid droplets in space and time. Copyright © 2020, Genetics.Emerging large-scale biobanks pairing genotype data with phenotype data present new opportunities to prioritize shared genetic associations across multiple phenotypes for molecular validation. Past research, by our group and others, has shown gene-level tests of association produce biologically interpretable characterization of the genetic architecture of a given phenotype. SAR439859 clinical trial Here we present a new method, Ward clustering to identify Internal Node branch length outliers using Gene Scores (WINGS), for identifying shared genetic architecture among multiple phenotypes. The objective of WINGS is to identify groups of phenotypes, or "clusters," sharing a core set of genes enriched for mutations in cases. We validate WINGS using extensive simulation studies and then combine gene-level association tests with WINGS to identify shared genetic architecture among 81 case-control and seven quantitative phenotypes in 349,468 European-ancestry individuals from the UK Biobank. We identify eight prioritized phenotype clusters and recover multiple published gene-level associations within prioritized clusters. Copyright © 2020, Genetics.BACKGROUND Risk prediction models may be useful for precision breast-cancer screening. We aimed to evaluate the performance of breast cancer risk models developed in European-ancestry studies in a Korean population. METHODS We compared discrimination and calibration of three multivariable risk models in a cohort of 77,457 women from the Korean Cancer Prevention Study (KCPS)-II. The first incorporated US breast-cancer incidence and mortality rates, US risk-factor distributions, and relative risk (RR) estimates from European-ancestry studies. The second recalibrated the first by using Korean incidence and mortality rates and Korean risk factor distributions, while retaining the European-ancestry RR estimates. Finally, we derived a Korea-specific model incorporating the RR estimates from KCPS. RESULTS The US European-ancestry breast cancer risk model was well calibrated among Korean women less then 50 years (Expected/Observed=1.124 (0.989, 1.278)) but markedly overestimated the risk for those ≥50 years (E/O=2.472 (2.005, 3.049)). Recalibrating absolute risk estimates using Korean breast cancer rates and risk distributions markedly improved the calibration in women ≥50 (E/O=1.018 (0.825, 1.255)). The model incorporating Korean-based RRs had similar but not clearly improved performance relative to the recalibrated model. CONCLUSIONS The poor performance of the US European-ancestry breast cancer risk model among older Korean women highlights the importance of tailoring absolute risk models to specific populations. Recalibrating the model using Korean incidence and mortality rates and risk factor distributions greatly improved performance. IMPACT The data will provide valuable information to plan and evaluate actions against breast cancer focused on primary prevention and early detection in Korean women. Copyright ©2020, American Association for Cancer Research.BACKGROUND Synovial sarcoma is a rare cancer with peak incidence in the young adult period. Despite poor outcomes of this aggressive cancer, there is little epidemiologic research addressing its etiology. METHODS We collected birth characteristic data on synovial sarcoma cases born 1978-2015 and diagnosed 1988-2015 in California (n=244), and 12,200 controls frequency-matched on year of birth. We also constructed a dataset of cancer cases in siblings of sarcoma subjects to assess familial risk. RESULTS In multivariable logistic regression analyses, synovial sarcoma was more frequent in Hispanics compared to non-Hispanic whites [odds ratio (OR) = 1.48; 95% confidence interval (CI) 1.06-2.08]. Higher birthweight was a risk factor in Hispanics - each 500 g increase in birthweight was associated with a 22% increase in disease risk (OR = 1.22; 95% CI1.00- 1.48). Also, a strong role for birth order was suggested, with highest risk for the first born (second child compared to first OR = 0.61, 95% CI 0.44-0.84; third or later compared to first OR = 0.53, 95% CI 0.36-0.77). Siblings of synovial sarcoma patients did not display elevated cancer incidence, suggesting the low likelihood that strong familial predisposition alleles play a significant role in this disease. CONCLUSIONS The associations with birthweight and birth order suggest that nutritional, developmental, and environmental factors may play a role in the etiology of synovial sarcoma. IMPACT Further epidemiologic research on synovial sarcoma should evaluate epigenetic and developmental mechanisms and the formation of the archetypical t(X;18) translocation that defines this disease. Copyright ©2020, American Association for Cancer Research.
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