Search

G-quadruplexes (G4s) are secondary DNA and RNA structures stabilized by positive cations in a central channel formed by stacked tetrads of Hoogsteen base-paired guanines. G4s form from G-rich sequences across the genome, whose biased distribution in regulatory regions points towards a gene-regulatory role. G4s can themselves be regulated by helicases, such as DHX36 (aliases: G4R1 and RHAU), which possess the necessary activity to resolve these stable structures. G4s have been shown to both positively and negatively regulate gene expression when stabilized by ligands, or through the loss of helicase activity. Using DHX36 knockout Jurkat cell lines, we identified widespread, although often subtle, effects on gene expression that are associated with the presence or number of observed G-quadruplexes in promoters or gene regions. Genes that significantly change their expression, particularly those that show a significant increase in RNA abundance under DHX36 knockout, are associated with a range of cellular functions and processes, including numerous transcription factors and oncogenes, and are linked to several cancers. Our work highlights the direct and indirect role of DHX36 in the transcriptome of T-lymphocyte leukemia cells and the potential for DHX36 dysregulation in cancer. [ABSTRACT FROM AUTHOR]

Background: Drug‐associated delirium is a common but potentially preventable neuropsychiatric syndrome associated with detrimental outcomes. Empirical evidence for delirium‐associated medication is uncertain due to a lack of high‐quality studies. We aimed to further investigate the body of evidence for drugs suspected to trigger delirium. Methods: A systematic update review and meta‐analyses of prospective studies presenting drug associations with incident delirium in adult study populations was conducted. Two authors independently searched MEDLINE, PsycINFO, Embase, and Google Scholar dated from October 1, 2009 to June 23, 2020, after screening a previous review published in 2011. The most reliable results on drug‐delirium associations were pooled in meta‐analyses using the random‐effects model. Quality of evidence was assessed using the GRADE‐approach. This study is preregistered with OSF (DOI https://doi.org.10.17605/OSF.IO/4PUHY). Results: The 31 eligible studies, presenting results for 24 medication classes were identified. Meta‐analyses and GRADE level of evidence ratings show no increased delirium risk for Haloperidol (OR: 0.96, 95% CI 0.72–1.28; high‐quality evidence), Olanzapine (OR: 0.25, 95% CI 0.15–0.40), Ketamine (OR: 0.72, 95% CI 0.35–1.46) or corticosteroids (OR: 0.69, 95% CI 0.32–1.50; moderate quality evidence, respectively). Low‐level evidence suggests a three‐fold increased risk for anticholinergics (OR: 3.11, 95% CI 1.04–9.26). Opioids, benzodiazepines, H1‐antihistamines, and antidepressants did not reach reliable evidence levels in our analyses. Conclusion: We investigated the retrievable body of evidence for delirium‐associated medication. The results of this systematic review were then interpreted in conjunction with other evidence‐based works and guidelines providing conclusions for clinical decision‐making. [ABSTRACT FROM AUTHOR]

Abstract: BACKGROUND: The disintegration of destarched wheat bran in water and sulfuric acid (pH 3) under subcritical conditions (275–300 °C) and at short reaction times (1–4 min) was investigated. A cascade process comprising a stepwise separation of the liquid was applied to reduce the formation of undesired degradation products. RESULTS: The highest degree of biomass disintegration (67% dry mass solubilization) was achieved by application of a cascade process at 275 °C (pH 3). Regarding the dissolution of carbohydrates (monomeric and oligomeric form), the total glucose yields remained below 60%, while the total xylose and arabinose yields were about 76% and 67%. Approximately 74% of the protein and 95% of the mineral fraction could be extracted. The application of the cascade process enabled a substantially reduced formation of degradation products. CONCLUSION: When operating hydrothermally and subcritically in order to avoid some problematic aspects of a biorefinery, an extensive disintegration and monomerization of wheat bran and its constituents remains difficult even under the tested conditions (300 °C, pH 3). However, the applied cascade process proved to be useful to increase the yields and to substantially reduce the formation of undesired degradation products. Despite this fact, increased water consumption has to be conceded. © 2018 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Hindered amine light stabilizers are an important class of stabilizers that protect synthetic polymers from degradation and thus from changing mechanical and optical properties. The current study presents an HPLC method capable of separating oligomeric hindered amine light stabilizers on a commercially available stationary phase, employing an MS-compatible novel mobile phase. Based on the exact masses observed with Q-TOF-MS, a comprehensive characterization of five different types of oligomeric hindered amine light stabilizers was achieved, leading to structural information not included in the datasheets provided by the suppliers. For the different investigated hindered amine light stabilizers, a number of recurring units up to 17 and a molecular weight of 5200 g/mol were detected. Furthermore, the analysis of stabilizer extracts of processed polypropylene samples containing different types of hindered amine light stabilizers revealed significant differences in the oligomeric pattern between standards and polymer samples. Thus, changes in the analytes' oligomeric pattern resulting from processing or aging of polymer materials can be monitored with the presented method. [ABSTRACT FROM AUTHOR]

RATIONALE High-throughput methods for identification and quantification of stabilizers in plastic materials are of significant importance in order to evaluate the suitability of materials of unknown origin for specific application areas, to clarify reasons for failure of materials, or for comparison of materials from different sources. METHODS In the present study, a highly sensitive and rapid flow injection method coupled to selected reaction monitoring mass spectrometry (MS) for comprehensive analysis of 21 polymer stabilizers in polyolefins is demonstrated. A critical factor for this approach is the choice of ionization mode, as no separation was performed prior to MS detection. Differences between several ionization techniques regarding matrix effects are reported. RESULTS Atmospheric pressure chemical ionization was found to be the most suitable ionization technique, with no significant matrix effects observed. The developed method has a linear dynamic range over two to three orders of magnitude with correlation coefficients better than 0.99 for all studied analytes. Following a multistep sample preparation protocol, the method allowed quantification down to minimum values of between 0.0001 and 0.04 wt% depending on the type of stabilizer. Results were compared to an established chromatographic approach and showed very good correlation (bias below 7.5%). CONCLUSIONS The applicability of the optimized method could be demonstrated for both the qualitative and quantitative determination of polymer stabilizers in polyolefins. Furthermore, the described approach yields a complete analysis in a much shorter time than can be achieved with commonly applied chromatographic methods. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

GGGGCC (G4C2) hexanucleotide repeat expansions in the endosomal trafficking gene C9orf72 are the most common genetic cause of ALS and frontotemporal dementia. Repeat-associated non-AUG (RAN) translation of this expansion through near-cognate initiation codon usage and internal ribosomal entry generates toxic proteins that accumulate in patients' brains and contribute to disease pathogenesis. The helicase protein DEAH-box helicase 36 (DHX36-G4R1) plays active roles in RNA and DNA G-quadruplex (G4) resolution in cells. As G4C2 repeats are known to form G4 structures in vitro, we sought to determine the impact of manipulating DHX36 expression on repeat transcription and RAN translation. Using a series of luciferase reporter assays both in cells and in vitro, we found that DHX36 depletion suppresses RAN translation in a repeat length-dependent manner, whereas overexpression of DHX36 enhances RAN translation from G4C2 reporter RNAs. Moreover, upregulation of RAN translation that is typically triggered by integrated stress response activation is prevented by loss of DHX36. These results suggest that DHX36 is active in regulating G4C2 repeat translation, providing potential implications for therapeutic development in nucleotide repeat expansion disorders. [ABSTRACT FROM AUTHOR]

Abstract: Wheat bran is multi-layered and consists of different cell types with different chemical compositions. The relatively high content of protein as well as the small amount of lignin is the key differentiator to other lignocellulose containing biomasses. Following the classical route of a biorefinery, bran may be disintegrated to a high extent and separated into fractions of high purity in order to build up new chemicals which serve as precursors for higher polymerized compounds. Secondly, bran contains substances that are per se valuables, but need to be further separated and purified. There are basically two directions of valorization, aiming at carbohydrate and non-carbohydrate based products. Both groups are of great heterogeneity, thus candidates are usually grouped according to their functionality. Due to this theoretical approach the production of glucose and fermentation to lactic acid, succinic acid or ethanol, the extraction of proteins and production of essential amino acids including γ-aminobutyric acid (GABA), the extraction of ferulic acid (FA) and its conversion to vanillin, as well as the extraction of arabinoxylans (AX) seem to be feasible and of economic relevance, which will be highlighted within this review. [Copyright &y& Elsevier]