Mutant p53 Mediates Sensitivity to Cancer Treatment Agents in Oesophageal Adenocarcinoma Associated with MicroRNA and SLC7A11 Expression

TP53 gene mutations occur in 70% of oesophageal adenocarcinomas (OACs). Given the central role of p53 in controlling cellular response to therapy we investigated the role of mutant (mut-) p53 and SLC7A11 in a CRISPR-mediated JH-EsoAd1 TP53 knockout model. Response to 2 Gy irradiation, cisplatin, 5-FU, 4-hydroxytamoxifen, and endoxifen was assessed, followed by a TaqMan OpenArray qPCR screening for differences in miRNA expression. Knockout of mut-p53 resulted in increased chemo- and radioresistance (2 Gy survival fraction: 38% vs. 56%, p < 0.0001) and in altered miRNA expression levels. Target mRNA pathways analyses indicated several potential mechanisms of treatment resistance. SLC7A11 knockdown restored radiosensitivity (2 Gy SF: 46% vs. 73%; p = 0.0239), possibly via enhanced sensitivity to oxidative stress. Pathway analysis of the mRNA targets of differentially expressed miRNAs indicated potential involvement in several pathways associated with apoptosis, ribosomes, and p53 signaling pathways. The data suggest that mut-p53 in JH-EsoAd1, despite being classified as non-functional, has some function related to radio- and chemoresistance. The results also highlight the important role of SLC7A11 in cancer metabolism and redox balance and the influence of p53 on these processes. Inhibition of the SLC7A11-glutathione axis may represent a promising approach to overcome resistance associated with mut-p53.     

Sludge Pre-Treatment through Ozone Application: Alternative Sludge Reuse Possibilities for Recirculating Aquaculture System Optimization

Recirculating Aquaculture Systems (RAS) reduce water consumption by efficient filtration to maintain appropriate levels of accumulating compounds and sludge. Sludge is mechanically separated by drum filters and disposed of to the detriment of overall system water budgets. Dissolved nitrogen compounds are reduced via nitrification–denitrification filters, requiring commercial external carbon sources. The reuse of sludge after ozone pre-treatment may represent the next step in RAS optimization. The present study analyzes the content of sludge from RAS and tests ozonation as a pre-treatment for recycling as carbon source. The dissociative effect of ozone and the physicochemical changes due to ozonation lead to a significant increase in soluble carbon availability. Predominantly long-chain fatty acid (FA) (saturated and unsaturated) with 16 and 18 carbon atoms independently of the treatment were found in the profiles. Saturated FA concentrations in solution increased after 20, 40, and 60 min ozonation. The solid content of the sludge was practically unaffected by ozonation in terms of FA profile: only saturated FA slightly increases after 40 min treatment. The implications of these findings for denitrifying bacteria are discussed.

Abbreviations: Recirculating Aquaculture Systems (RAS); Advanced Oxidation Processes (AOPs)     

Konstruktion und Test eines Gradientensystems für NMR‐Diffusionsuntersuchungen in Grenzflächensystemen

A z‐gradient system for NMR diffusion measurements with intensive pulsed field gradients was redesigned. The gradient field of an actively screened gradient coil was optimized using finite element analysis. The gradient system was constructed with glass ceramic as coil support material. It does not show any background ¹H NMR signal and has a high current‐to‐gradient conversion factor of 0.37 T m^–1A^–1. The functionality of the system for studying slow diffusion processes in interface systems is demonstrated by observing isotropic and anisotropic diffusion in aqueous solutions of a PEO‐PPO‐PEO triblock copolymer and of methane in two different microporous crystalline absorbencies.     

The Multifaceted Inhibitory Effects of an Alkylquinolone on the Diatom Phaeodactylum tricornutum

The mechanisms underlying interactions between diatoms and bacteria are crucial to understand diatom behaviour and proliferation, and can result in far-reaching ecological consequences. Recently, 2-alkyl-4-quinolones have been isolated from marine bacteria, both of which (the bacterium and isolated chemical) inhibited growth of microalgae, suggesting these compounds could mediate diatom–bacteria interactions. The effects of several quinolones on three diatom species have been investigated. The growth of all three was inhibited, with half-maximal inhibitory concentrations reaching the sub-micromolar range. By using multiple techniques, dual inhibition mechanisms were uncovered for 2-heptyl-4-quinolone (HHQ) in Phaeodactylum tricornutum. Firstly, photosynthetic electron transport was obstructed, primarily through inhibition of the cytochrome b₆f complex. Secondly, respiration was inhibited, leading to repression of ATP supply to plastids from mitochondria through organelle energy coupling. These data clearly show how HHQ could modulate diatom proliferation in marine environments.     

MicroRNA Profiling in Oesophageal Adenocarcinoma Cell Lines and Patient Serum Samples Reveals a Role for miR-451a in Radiation Resistance

Many patients with Oesophageal Adenocarcinoma (OAC) do not benefit from chemoradiotherapy treatment due to therapy resistance. To better understand the mechanisms involved in resistance and to find potential biomarkers, we investigated the association of microRNAs, which regulate gene expression, with the response to individual treatments, focusing on radiation. Intrinsic radiation resistance and chemotherapy drug resistance were assessed in eight OAC cell lines, and miRNA expression profiling was performed via TaqMan OpenArray qPCR. miRNAs discovered were either uniquely associated with resistance to radiation, cisplatin, or 5-FU, or were common to two or all three of the treatments. Target mRNA pathway analyses indicated several potential mechanisms of treatment resistance. miRNAs associated with the in vitro treatment responses were then investigated for association with pathologic response to neoadjuvant chemoradiotherapy (nCRT) in pre-treatment serums of patients with OAC. miR-451a was associated uniquely with resistance to radiation treatment in the cell lines, and with the response to nCRT in patient serums. Inhibition of miR-451a in the radiation resistant OAC cell line OE19 increased radiosensitivity (Survival Fraction 73% vs. 87%, p = 0.0003), and altered RNA expression. Pathway analysis of effected small non-coding RNAs and corresponding mRNA targets suggest potential mechanisms of radiation resistance in OAC.     

Study of the efficiency of technical grade nonionic surfactants

Parameters concerning the microemulsion phase behavior of nonionic surfactants of the alkyl polyglycol ether type have extensively been investigated in the last years. By studying these, essential parameters for future applications can be determined. Especially in the field of enhanced oil recovery, lubricants, and cosmetic applications these parameters are of special interest. In this work, the influence of technical grade nonionic surfactants on the phase behavior and the resulting surfactant efficiency has been studied. For this, the alkyl chain length, the degree, type, and order of alkoxylation of the surfactant have been varied. The investigation of these parameters has been conducted by measuring the phase behavior via the Kahlweit fish diagram. It has been found that varying the C-chain length has a great impact on the efficiency, whereas the influence of the ethoxylation degree is minor. By the introduction of propylene oxide, the efficiency has been improved significantly. Additionally, it is important to have the right order of alkoxylation. If the fatty alcohol is first ethoxylated and afterwards propoxylated the efficiency is significantly decreased.     

Consumer’s perception of high gloss furniture: instrumental gloss measurement versus visual gloss evaluation

The overall impression of a glossy surface is an important parameter for consumer’s choice of wooden products. A new gloss parameter, called gloss impression, which calculates a reflexion structure image, was developed in order to complement the measurements made by industrial glossmeters, which are highly limited in describing the visual human perception, for example the commonly used gloss value. The objective of this study is to investigate to what extent the new measurement method of surface gloss is applicable to describe human gloss perception, in other words, to validate the new method. In order to analyse the concordance of the new methodology with human perception, 113 naïve observers had to rank the glossiness of eight series of black and white samples. The results were compared to both gloss impression and gloss value. The statistical evaluation by means of Pearson’s chi-squared tests revealed that the new method has an overall better correspondence to human perception than the gloss value. For black samples, it describes human perception significantly better than the gloss value and gives better results than those which would be achieved by guessing.     

Effects of Quantum and Dielectric Confinement on the Emission of Cs-Pb-Br Composites

The halide perovskite CsPbBr₃ belongs to the Cs-Pb-Br material system, which features two additional thermodynamically stable ternary phases, Cs₄PbBr₆ and CsPb₂Br₅. The coexistence of these phases and their reportedly similar photoluminescence (PL) have resulted in a debate on the nature of the emission in these systems. Herein, optical and microscopic characterizations are combined with an effective mass, correlated electron–hole model of excitons in confined systems, to investigate the emission properties of the ternary phases in the Cs-Pb-Br system. It is found that all Cs-Pb-Br phases exhibit green emission and the non-perovskite phases exhibit PL quantum yields orders of magnitude larger than CsPbBr₃. In particular, blue- and red-shifted emission for the Cs- and Pb-rich phases, respectively, are measured, stemming from embedded CsPbBr₃ nanocrystals (NCs). This model reveals that the difference in emission shift is caused by the combined effects of NC size and different band mismatch. Furthermore, the importance of including the dielectric mismatch in the calculation of the emission energy for Cs-Pb-Br composites is demonstrated. The results explain the reportedly limited blue shift in CsPbBr₃@Cs₄PbBr₆ composites and rationalize some of its differences with CsPb₂Br₅.