The sphingoid long chain bases (LCBs) and their phosphorylated derivatives (LCB-Ps) are important signaling molecules in eukaryotic organisms. The cellular levels of LCB-Ps are tightly controlled by the coordinated action of the LCB kinase activity responsible for their synthesis and the LCB-P phosphatase and lyase activities responsible for their catabolism. Although recent studies have implicated LCB-Ps as regulatory molecules in plants, in comparison with yeast and mammals, much less is known about their metabolism and function in plants. To investigate the functions of LCB-Ps in plants, we have undertaken the identification and characterization of Arabidopsis genes that encode the enzymes of LCB-P metabolism. In this study the Arabidopsis At1g27980 gene was shown to encode the only detectable LCB-P lyase activity in Arabidopsis. The LCB-P lyase activity was characterized, and mutant plant lines lacking the lyase were generated and analyzed. Whereas in other organisms loss of LCB-P lyase activity is associated with accumulation of high levels of LCB/LCB-Ps and developmental abnormalities, the sphingolipid profiles of the mutant plants were remarkably similar to those of wild-type plants, and no developmental abnormalities were observed. Thus, these studies indicate that the lyase plays a minor role in maintenance of sphingolipid metabolism during normal plant development and growth. However, a clear role for the lyase was revealed upon perturbation of sphingolipid synthesis by treatment with the inhibitor of ceramide synthase, fumonisin B 1 .Sphingolipids are ubiquitous membrane components that are critical for normal membrane function. Sphingolipid metabolites, including sphingoid long chain bases (LCBs), 3 phosphorylated LCBs (LCB-Ps), and ceramides, also function as signaling molecules in eukaryotic cells (1-4). For example, sphingosine 1-phosphate, a key sphingolipid second messenger, regulates proliferation, invasiveness, and programmed cell death. These effects of LCB-Ps have been observed in organisms as diverse as yeast and humans (5). Although far less is known about sphingolipid functions in plants (6, 7), recent studies indicate that sphingolipid-derived metabolites also act as signaling molecules in plants. For example, sphingosine 1-phosphate and more recently phytosphingosine 1-phosphate have been implicated in abscisic aciddependent guard cell closure through a G-protein-mediated pathway (8 -10). In addition, disruption of a ceramide kinase gene has been found to cause enhanced apoptosis in the Arabidopsis ACD5 mutant, suggesting that ceramides regulate programmed cell death in plants (11). Similarly, inhibition of the ceramide synthase step of sphingolipid biosynthesis by the fungal toxins fumonisin and Alternaria alternata f.sp. lycopersici toxin has also been shown to promote programmed cell death (12-15).Despite their possible importance as signaling molecules, the synthesis and metabolism of LCB-Ps in plants and the role of LCB-Ps in plant physiology remain largely unknown. It is clear tha...

Acute myeloid leukemia (AML) presenting with a high leukocyte count has been associated with an increase in induction mortality and poor results in a number of other survival measures. However, the level at which an elevated leukocyte count has prognostic significance in AML remains unclear. In this report on a series of 375 adult (non-M3) AML patients undergoing induction chemotherapy at a single institution, leukocyte count analyzed as a continuous variable is shown to be a better predictor of induction death (ID) and overall survival (OS) than a leukocyte count of > or = 100 x 10(9)/L, a value characteristically associated with "hyperleukocytosis" (HL). In this patient cohort, a presenting leukocyte count of > or = 30 x 10(9)/L had high sensitivity and specificity for predicting ID, and both performance status (PS) and leukocyte count more accurately predicted for ID than age. Considering these parameters in newly-diagnosed AML patients may facilitate the development of strategies for reducing induction mortality.

BackgroundChronic exposure to sleep deprivation may increase the risk of depression in young people who are particularly vulnerable to changes in sleep and mental health. Sleep deprivation and incident depression may also differ by gender. We investigated the prospective association between cumulative sleep deprivation and subsequent levels of depressive symptomatology among adolescents from a gender perspective.MethodsA longitudinal study of 3071 young people in the British Columbia Adolescent Substance Use Survey (BASUS) cohort with three sleep time and two depression measures over 12 months (2011–12). Multivariable linear regression models with interaction terms estimated gender-specific associations between self-reported chronic sleep deprivation and changes in depressive symptomatology; post-estimation analysis calculated adjusted mean depression scores for each level of cumulative sleep deprivation.ResultsCumulative sleep deprivation was associated with a monotonic increase in depression scores at follow-up in young women, but no consistent pattern was seen in young men. During follow-up, 15% of young women were chronically sleep deprived and 29% were depressed (CESD ≥24). Young women reporting chronic exposure to sleep deprivation had higher CESD scores at follow-up (21.50 points, [CI95 19.55–23.45]), than those reporting no history (16.59 [15.72–17.45]); that remained after multivariable adjustment (19.48 [17.59–21.38]).ConclusionResults suggested that chronic sleep deprivation increases the risk of major depression among young women. Mental health promotion for young people should include relevant strategies to ensure young women can achieve recommended amounts of sleep.Electronic supplementary materialThe online version of this article (10.1186/s12889-018-5656-6) contains supplementary material, which is available to authorized users.