P11.43 Deletions on Y chromosome are associated with shorter survival in glioblastoma

BACKGROUND Apart from few exceptions, men are more likely to be diagnosed with cancer during their lifetime, including glioblastoma (GBM), but the gender-related differences in GBM are poorly understood. Loss of chromosome Y (LOY) in peripheral blood cells is associated with physiological ageing, but also with disorders like cardiovascular disease, Alzheimer’s disease and different cancer types. In this study, we determined deletions on Y chromosome in tumor tissue of male patients with GBM, and studied the impact of LOY on survival. MATERIAL AND METHODS Ten genes, serving as markers, were selected on both arms of chromosome Y for copy number analysis with droplet digital PCR (ddPCR), enabling detection of loss of a marker in a fraction of the tumor cells used for DNA extraction. A total of 114 tumor samples from male patients were used, derived from a cohort of IDH wild type GBM patients treated with standard radio-chemo therapy. For 61 of these 114 patients, corresponding blood samples were available and analyzed. Different cut-off values were tested for each marker and Kaplan-Meier log-rank analysis was used to estimate overall survival. The mRNA expression for nine of the ten tested genes was available in TCGA, and 225 IDH wild type male GBM were included in a separate survival analysis, where median value of expression was used as group separator. RESULTS Fractional loss, as well as gain of markers was detected. Decreased copy number of the following markers was associated with significantly shorter survival; amelogenin Y-linked (AMELY) (13.5 vs. 19.3 months, p=0.017), neuroligin 4 Y-linked (NLGN4Y) (11.8 vs. 18.9 months, p=0.03) and sex determining region Y (SRY) (10.3 vs. 18.7 months, p=0.002). Additional analysis of SRY in the blood samples verified that copy number alterations were predominantly present in tumors. Survival analysis using mRNA expression data from TCGA showed that reduced expression of SRY was associated with significantly shorter OS (13.8 vs. 19.8 months, p=0.008), but no significant correlation with OS for any of the other markers. CONCLUSION Our data suggests a clonal or at least sporadic occurrence of fractional loss of Y chromosome markers in GBM, as detected with ddPCR. Interestingly, such dosage changes may contribute to shorter survival in men and explain some of the sex disparity seen in GBM. More research is needed to elucidate the molecular mechanisms of LOY and the role of specific Y-linked genes in GBM but also other diseases.

Single Grain (U-Th)/He Ages from EET14074, an Acapulcoite Meteorite

EET14074 is a member of the acapulcoite-lodranite family of meteorites and was discovered in Antarctica in 2014 by the Korean Polar Research Institute (KOPRI). Herein, we obtained (U-Th)/He ages from 20 phosphate aggregates in EET14074 to constrain the sample’s thermal history. The ages range between 116.8 Ma ± 145.7 Ma (1σ) and 4211.5 Ma ± 1089.1 Ma, with an average of 2530 ± 260 Ma (n=20). Excluding outlier ages with large uncertainties, the 13 most concentrated ages yielded a theoretical minimum age of 3000 ± 150 Ma. This age corresponds to a fraction helium loss (f) of ~31% assuming crystallization age of ~4.55 Ga. The uranium abundances in single aliquots are in the range of 1.52 - 289.93 fmol, with an average of 58.00 fmol (n = 20), whereas the thorium abundance ranges between 2.51 and 2337.06 fmol with an average of 1149.29 fmol (n = 20). To explain the observed He loss, thermal diffusion modeling was performed with an assumption that the He loss occurred during a recent passage of the meteorite in Earth’s atmosphere. For the most likely t-T condition of compressional heating in Earth’s atmosphere of this meteorite (T = ~430 ˚C, t = ~10 sec), a fractional loss of 29.3% was calculated when the diffusion domain radius (r) of 92.8 µm was assumed. This estimation is nearly indistinguishable from the observed fractional loss of 31.3%. Additionally, diffusion modeling for another set of data with a different size (r = 40.4 µm) yielded a very similar fractional loss. Therefore, the observed (U-Th)/He age distribution is likely derived from compressional heating during the passage of EET14074 in Earth’s atmosphere.

MANIPULATING CATEGORIES IN PUBLIC SPEECHES AND THEIR TRANSLATIONS: COGNITIVE RHETORICAL APPLICATION OF VANTAGE THEORY

The article applies Vantage Theory, which studies the ways of categorization with respect to human orientation in space-time, to revealing three types of manipulating categories structuring the addressee’s worldview: overcategorization, decategorization and new category construction. It is found that overcategorization, aimed at intensifying the parameters constituting the categorical focus, is reflected in the use of words denoting the utmost intensification of the focal categorical parameters, while partial categorization is expressed by the lexical units intensifying focal parameters to a certain degree. Decategorization is shown to reflect five ways of diminishing focal parameters. Similarly to overcategorization, the absolute and partial decategorizations reflect the utmost and fractional loss of focal features respectively; the situational decategorization concerns the reduction of the focal parameters denoted by the inclusive deictic unit we; the generalizing variant is rendered by the units extending the limits of a particular category; the universal type refers to the superordinate categorization level. New category construction consists in representing novel entities by word formation in the Russian original and by construction formation in the English translation with the sender being more daring in these passages than the translator who in the majority of other cases follows the vantage construction suggested by the speaker.

How relevant is the deposition of mercury onto snowpacks? – Part 1: A statistical study on the impact of environmental factors

A portion of the highly toxic methylmercury that bioaccumulates in aquatic life is created from mercury entering bodies of water with snowpack meltwater. To determine the importance of meltwater as a source of aquatic mercury, it is necessary to understand the environmental processes that govern the behavior of snowpack-related mercury. In this study we investigate relationships among 5 types of snowpack-related mercury observations and 20 model environmental variables. The observation types are the 24-h fractional loss of mercury from surface snow, and the concentrations of mercury in surface snow, seasonal snowpacks, the snowpack meltwater's ionic pulse, and long-term snowpack-related records. The model environmental variables include those related to atmospheric mercury, insolation, wind, atmospheric stability, snowpack physical characteristics, atmospheric pressure, and solid precipitation. Correlation coefficients and multiple linear regressions were calculated twice: once with all observations, and once with observations from locations presumably affected by oxidizing and stabilizing snowpack-related halogens excluded. We find that the presence of snowpack-related halogens has a significant impact on the behavior of snowpack-related mercury. Physically, snowpack-related mercury observations are most strongly controlled by the dry and wet depositions of oxidized mercury. The burial of mercury by fresh snowfalls and the wind driven ventilation of snowpacks are important processes. Indeed, in the absence of snowpack-related halogens, the 24-h fractional loss of mercury from surface snow is fully controlled by mercury deposition and surface-level atmospheric wind speed, stability, and surface pressure. The concentration of mercury in long-term records is affected by latitude, ventilation and surface pressure.