The oxidative demethylase ALKBH3 marks hyperactive gene promoters in human cancer cells

BACKGROUND: The oxidative DNA demethylase ALKBH3 targets single-stranded DNA (ssDNA) in order to perform DNA alkylation damage repair. ALKBH3 becomes upregulated during tumorigenesis and is necessary for proliferation. However, the underlying molecular mechanism remains to be understood. METHODS: To further elucidate the function of ALKBH3 in cancer, we performed ChIP-seq to investigate the genomic binding pattern of endogenous ALKBH3 in PC3 prostate cancer cells coupled with microarray experiments to examine the expression effects of ALKBH3 depletion. RESULTS: We demonstrate that ALKBH3 binds to transcription associated locations, such as places of promoter-proximal paused RNA polymerase II and enhancers. Strikingly, ALKBH3 strongly binds to the transcription initiation sites of a small number of highly active gene promoters. These promoters are characterized by high levels of transcriptional regulators, including transcription factors, the Mediator complex, cohesin, histone modifiers, and active histone marks. Gene expression analysis showed that ALKBH3 does not directly influence the transcription of its target genes, but its depletion induces an upregulation of ALKBH3 non-bound inflammatory genes. CONCLUSIONS: The genomic binding pattern of ALKBH3 revealed a putative novel hyperactive promoter type. Further, we propose that ALKBH3 is an intrinsic DNA repair protein that suppresses transcription associated DNA damage at highly expressed genes and thereby plays a role to maintain genomic integrity in ALKBH3-overexpressing cancer cells. These results raise the possibility that ALKBH3 may be a potential target for inhibiting cancer progression. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13073-015-0180-0) contains supplementary material, which is available to authorized users

Everyday norms have become more permissive over time and vary across cultures

Every social situation that people encounter in their daily lives comes with a set of unwritten rules about what behavior is considered appropriate or inappropriate. These everyday norms can vary across societies: some societies may have more permissive norms in general or for certain behaviors, or for certain behaviors in specific situations. In a preregistered survey of 25,422 participants across 90 societies, we map societal differences in 150 everyday norms and show that they can be explained by how societies prioritize individualizing moral foundations such as care and liberty versus binding moral foundations such as purity. Specifically, societies with more individualistic morality tend to have more permissive norms in general (greater liberty) and especially for behaviors deemed vulgar (less purity), but they exhibit less permissive norms for behaviors perceived to have negative consequences in specific situations (greater care). By comparing our data with available data collected twenty years ago, we find a global pattern of change toward more permissive norms overall but less permissive norms for the most vulgar and inconsiderate behaviors. This study explains how social norms vary across behaviors, situations, societies, and time

ביטחון עצמי ואטרקטיביות כגורמים המשפיעים על מידת השכנוע

In this study we sought to examine whether the two following variables "degree of attractiveness of the presenter" and "the level of self-confidence of the participant" have an effect on "the degree of persuasion of the participant". We hypothesized that the degree of persuasion would be higher in the group among those with low self-confidence, and that those exposed to an advertisement featuring an attractive presenter would be more convinced, compared to exposure to the other (unattractive) presenter. In addition, we hypothesized that participants with low self-confidence would show a more significant difference in the degree of persuasion as a factor of the attractiveness of the character shown, compared to the other group. In this project, the data component includes a file of all raw data from the study, the material includes all relevant studies we made use of and/or based our working hypothesis on. Finally, the summary component includes the power point presentations used to explain the study and show our results in class

?כיצד רמת האטרקטיביות של מעביר מסר ומידת ההערכה העצמית של מקבל המסר משפיעים על שכנוע

In this study we sought to examine whether the two following variables "degree of attractiveness of the presenter" and "the level of self-confidence of the participant" have an effect on "the degree of persuasion of the participant". We hypothesized that the degree of persuasion would be higher in the group among those with low self-confidence, and that those exposed to an advertisement featuring an attractive presenter would be more convinced, compared to exposure to the other (unattractive) presenter. In addition, we hypothesized that participants with low self-confidence would show a more significant difference in the degree of persuasion as a factor of the attractiveness of the character shown, compared to the other group. In this project, the data component includes a file of all raw data from the study, the material includes all relevant studies we made use of and/or based our working hypothesis on. Finally, the summary component includes the power point presentations used to explain the study and show our results in class

Long-term Breast Shape Analysis After Short-scar Reduction Mammaplasty: A Critical View

Background:. Over the past 2 decades, vertical scar reduction mammaplasty techniques have been gaining more acceptance. However, many surgeons are still hesitant to use it routinely because of the uncertainty of the effectiveness of vertical scar techniques in managing lower pole skin excess. We aimed to test its efficacy by using objective anthropometric measurements to evaluate long-term breast shape and lower pole stability. Methods:. The study population included 40 of 129 consecutive women with short-scar reduction mammaplasty followed up for at least 1 year. Breasts were measured preoperatively, perioperatively, and at least 1 year postoperatively. All women also completed the BREAST-Q questionnaire at their most recent visit. Results:. The mean sternal notch-to-nipple and upper breast-to-nipple distances decreased postoperatively by 22% and 43%, respectively, and remained stable over a mean time of 110.1 ± 65.58 weeks. The nipple-to-inframammary fold distance, which was intraoperatively shortened by an average of 63%, elongated back to 88% of its preoperative measurements. No correlation was detected between the long-term changes across all 3 measurements, the amount of tissue removed or the satisfaction reported by patients. Mean BREAST-Q satisfaction rates in all parameters evaluated were 75.79–98.12. Conclusions:. The 12% improvement in the nipple-to-inframammary fold measurement implies that the short-scar technique might properly address the horizontal dimension of the hypertrophic-ptotic breast but falls short in addressing its vertical dimension. The search for a modification that mirrors the advantages of the vertical scar technique in terms of shape and projection, while guaranteeing a steady lower pole, remains ongoing

Characterizing unknown systematics in large scale structure surveys

Photometric large scale structure (LSS) surveys probe the largest volumes in the Universe, but are inevitably limited by systematic uncertainties. Imperfect photometric calibration leads to biases in our measurements of the density fields of LSS tracers such as galaxies and quasars, and as a result in cosmological parameter estimation. Earlier studies have proposed using cross-correlations between different redshift slices or cross-correlations between different surveys to reduce the effects of such systematics. In this paper we develop a method to characterize unknown systematics. We demonstrate that while we do not have sufficient information to correct for unknown systematics in the data, we can obtain an estimate of their magnitude. We define a parameter to estimate contamination from unknown systematics using cross-correlations between different redshift slices and propose discarding bins in the angular power spectrum that lie outside a certain contamination tolerance level. We show that this method improves estimates of the bias using simulated data and further apply it to photometric luminous red galaxies in the Sloan Digital Sky Survey as a case study. © 2014 IOP Publishing Ltd and Sissa Medialab srl