Bentsenmcclure3744

Etoposide is an extensively prescribed anticancer drug that, unfortunately, causes therapy-related leukemia. The mechanisms by which etoposide induces secondary hematopoietic malignancies are poorly documented. However, etoposide-related leukemogenesis is known to depend on oxidative metabolites of etoposide, notably etoposide quinone, that can react with protein cysteine residues such as in topoisomerases II. CREBBP is a major histone acetyltransferase that functions mainly as a transcriptional co-activator. This epigenetic enzyme is considered as a tumor suppressor that plays a major role in hematopoiesis. Genetic alterations affecting CREBBP activity are highly common in hematopoietic malignancies. We report here that CREBBP is impaired by etoposide quinone. Molecular and kinetic analyses show that this inhibition occurs through the rapid and covalent (kinhib = 16.102 M-1. s-1) adduction of etoposide quinone with redox sensitive cysteine residues within the RING and PHD Zn2+-fingers of CREBBP catalytic core leading to subsequent release of Zn2+. In agreement with these findings, experiments conducted in cells and in mice treated with etoposide showed irreversible inhibition of endogenous CREBBP activity and decreased H3K18 and H3K27 acetylation. As shown for topoisomerases II, our work thus suggests that the leukemogenic metabolite etoposide quinone can impair the epigenetic CREBBP acetyltransferase through reaction with redox sensitive cysteine residues.The perception of verticality can be altered with age or due to neurological diseases. Different procedures have been described to measure the subjective postural vertical (SPV). A deviation from the earth vertical was either described as a single position or as a sector defined by two positions representing the edges of the perceived verticality. In this study, for the first time, we investigated if these two methods produce equal values, and consequently can be merged to set normative values. SPV in standing was tested in 24 healthy young adults (28.4 (5.2) years of age, 12 women). Each participant performed both methods in the sagittal and the frontal plane. Absolute and constant error values were found to be similar for both methods in both planes with a mean difference of less than 0.3° (p > 0.148). The mean width of the SPV sector was 3.9° (0.9°) in the sagittal and 3.7° (1.4°) in the frontal plane, ranging in the mean from -5.5° to 8.1° in the sagittal and -5.3° to 4.3° in the frontal plane. SPV values significantly differed in range between both methods in both planes with a mean difference of more than 3.1° (p less then 0.002). Results show that both methods, SPVposition and SPVsector, produce equal error values when applied with otherwise similar methodological settings and can therefore be used alternatively or within the same meta-analysis. The SPVsector, however, led to wider range values and was less frequently rated as the preferred method to represent the participants' subjective verticality.In order to investigate the processes of emotional faces in major depressive disorder (MDD) patients, we recorded and analyzed the N170 and early posterior negativity (EPN) components elicited by schematic faces with happy and angry expressions. It was found that the N170 was significantly reduced in depressive patients than that in the control group, regardless of happy or angry faces. Neither MDD patients nor controls showed the affective effects of N170. The EPN was significantly delayed and lower in MDD patients than that in the control group. In controls, the EPN was significantly enhanced for happy than angry faces, but this emotional effect was not evident in MDD patients. These data provide further electrophysiological evidence for the dysfunction of processing emotional faces in MDD patients.Recent studies have reported that microRNAs are abnormally expressed in brain tissues of Alzheimers disease (AD) patients. However, the accurate function of miR-20b-5p in AD has not been elucidated. We intended to investigate the role and underlying mechanism of miR-20b-5p in AD. The expression of miR-20b-5p was increased, and the expression of RhoC was decreased in the hippocampus of Appswe/PS△E 9 mice. In order to construct a cell model in vitro to study the underlying action mechanism, PC12 cells were treated with Aβ25-35. The cell apoptosis detected by flow cytometry and the expression of cleaved-caspase-3 detected by western blot were both remarkably increased in PC12 cells treated with Aβ25-35, but they were reduced by miR-20b-5p inhibitor. this website In addition, MTT test showed that the cell survival rate in Aβ25-35 + miR-20b-5p inhibitor group was higher than that in Aβ25-35 + NC inhibitor group. Double luciferase reporter gene analysis confirmed that the binding site of miR-20b-5p was in 3'- UTR of RhoC mRNA. Knockdown of RhoC increased neuronal apoptosis induced by Aβ25-35 and the expression of cleaved-caspase-3, while miR-20b-5p inhibitor reversed these effects. Knockdown of RhoC aggravated the inhibition effect on cell viability induced by Aβ25-35, while miR-20b-5p inhibitor diminished these effects. In conclusion, inhibition of miR-20b-5p attenuates apoptosis induced by Aβ25-35 in PC12 cells through targeting RhoC. Therefore, miR-20b-5p may be a perspective curative target for AD.Prolong exposure to high intensity white noise (HIWN), defined as a heterogeneous mixture of sound waves extending over a wide frequency range, has detrimental peripheral and central consequences including cardiovascular and emotional effects. Anxiety is a common manifestation of HIWN. Although gender-dependent differences in manifestation of anxiety and/or response to treatment of this condition has been amply documented, potential differences in response to HIWN, a common exposure in combat, construction and rave disco, has not been adequately investigated. In this study, both male and female Wistar rats were subjected to HIWN for 10 consecutive days, 1 h/day. On day 11, a day after the last exposure, the performance of the rats in open field (OF) and elevated plus maze (EPM) was evaluated. Male rats showed a higher anxiety-like response to HIWN as evidenced by lower number of entries into the open arm of the EPM, lower number of entries into central zone of OF, excess grooming in OF and more boluses in closed arm of EPM.