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Treatment of naphtho-9-crown-3 ether with Fe[Cl.sub.3] and aqueous [H.sub.2]S[O.sub.4] generates bis-naphtho-9-crown-3 ether in ca. 30% yield. This compound crystallizes in the monoclinic [P2.sub.1]/n space group; a = 9.2004(9), b = 18.0868(17), and c = 13.2078(13) [Angstrom], [beta] = 97.799(2)[degrees] and Z = 4. [sup.1]H and [sup.13]C NMR data have been obtained in solution, and the solid-state [sup.13]C NMR spectrum is included for comparison. A chemical shift range of ca. 12 ppm has been found for the oxygenated aliphatic carbons in the solid state, in contrast to the 3 ppm range in the solution [sup.13]C NMR spectrum. These results are discussed in terms of the torsional environments of the carbon sites in the crystal structure. Key words: crown ether, stereochemistry, oxidative dimerization.

Systematic efforts to sequence the cancer genome have identified large numbers of relevant mutations and copy number alterations in human cancers; however, elucidating their functional consequences, and their interactions to drive or maintain oncogenic states, is still a significant challenge. Here we introduce REVEALER, a computational method that identifies combinations of mutually exclusive genomic alterations correlated with functional phenotypes, such as the activation or gene-dependency of oncogenic pathways or the sensitivity to a drug treatment. We use REVEALER to uncover complementary genomic alterations associated with the transcriptional activation of β-catenin and NRF2, MEK-inhibitor sensitivity, and KRAS dependency. REVEALER successfully identified both known and new associations demonstrating the power of combining functional profiles with extensive characterization of genomic alterations in cancer genomes.

The aim of this study is to evaluate the importance of toxicological analysis in acute intoxications by pesticides through the experience of the laboratory of the Poison Control and Pharmacovigilance Center of Morocco (CAPM). This is a retrospective study from January 2014 to September 2020, concerning suspected pesticides poisoning cases. The cholinesterase activity was measured in whole blood and the chromatographic analyzes (GC-MS and LC-MS-MS) were conducted in blood, urine and gastric lavage fluid. In this study, 398 tests were involved. The median age of the patients was 14 with an interquartile range of [4-26 years]. The sex ratio (F / M) was 1.5. The requests were from the region of Rabat-Salé-Kénitra in 82.8% of cases (north-western Morocco). The cholinesterase activity measurement was performed for 295 patients with low values in 3.7% of cases. The toxicological screening by GC-MS and LC-MS-MS detected the pesticide responsible of poisoning in 62 cases as insecticides in 38% of cases, redenticides (33% of cases) and herbicides (5% of cases). Toxicological analysis plays an essential role in the diagnosis and the management of acute pesticides poisoning. Interpretation of results is carried over by analyst with close cooperation with clinical toxicologist.

Introduction: Methanol intoxication is a public health problem that mainly affects poor populations in developed and developing countries. Despite all the advanced treatment methods, high mortality rates are still observed due to late admission to hospital and late diagnosis and treatment. Many mass poisoning have been described, following the misuse of methanol in the manufacture of adulterated alcohol in some Eastern European, Asian and African countries, resulting in several hundred each year. Objective: The objective of our study was to describe four cases of methanol intoxication that were received by the au toxicology and pharmacology laboratory of the Moroccan poison control centre CAPM-LAB. Materiel and methods: The epidemiological characteristics of patients intoxicated and dying by methanol in a collective setting were described as well as the results. Ethanol and methanol were determined in whole blood by gas chromatography with a flame ionisation detector coupled to the Head speace (CPG-FID-HS). Results: Following the consumption of adulterated alcohol (locally prepared alcohol); the CAPM-LAB received three samples from the city of El-Hajeb. The patients were aged of 46, 58 and 26 years and presented visual and consciousness disorders and vomiting, they presented average methanolemia of 1,34g/l. The CAPM-LAB also received samples from another patient from the city of Marrakech, aged 44 years, following a collective intoxication (three people) with adulterated alcohol, with methanol level of 2,52g/l. The patients died as a result of heart failure. Conclusion: Methanol can cause fatal intoxication, due to its easy availability in our country and the illegal production of alcoholic beverages.

Abstract: The immobilized Vitamin B12 (Vit-B12) within the nanoreactors of MCM-41 as molecular sieves was characterized by X-ray powder diffraction (XRD), FT-IR, chemical analysis and nitrogen adsorption–desorption. XRD and N2 adsorption–desorption isotherms showed that the well ordered hexagonal structure of MCM-41 is presented and surface area, pore volumes and pore diameters decrease after immobilization of Vit-B12 within nanoreactors of MCM-41. It was found that Vit-B12/MCM-41 successfully catalyzes the oxygen transfer of tert-butylhydroperoxide (TBHP) to norbornene and trans-2-hexene-1-ol and formation of the corresponding epoxides with 90% reactivity and 100% selectivity. Moreover, cyclohexane, cyclohexene and cyclohexanol are converted to the corresponding alcohols and ketones. On the other hand, styrene undergoes oxidative degradation with the formation of benzaldehyde and benzoic acid. [Copyright &y& Elsevier]

Microsatellite instability-high (MSI-H) tumors are malignant tumors that, despite harboring a high mutational burden, often have intact TP53. One of the most frequent mutations in MSI-H tumors is a frameshift mutation in RPL22, a ribosomal protein. Here, we identified RPL22 as a modulator of MDM4 splicing through an alternative splicing switch in exon 6. RPL22 loss increases MDM4 exon 6 inclusion and cell proliferation and augments resistance to the MDM inhibitor Nutlin-3a. RPL22 represses the expression of its paralog, RPL22L1, by mediating the splicing of a cryptic exon corresponding to a truncated transcript. Therefore, damaging mutations in RPL22 drive oncogenic MDM4 induction and reveal a common splicing circuit in MSI-H tumors that may inform therapeutic targeting of the MDM4-p53 axis and oncogenic RPL22L1 induction., Competing Interests: Declaration of interests F.V. receives research support from the Dependency Map Consortium, Riva Therapeutics, Bristol Myers Squibb, Merck, Illumina, and Deerfield Management. F.V. is on the scientific advisory board of GSK, is a consultant and holds equity in Riva Therapeutics, and is a co-founder and holds equity in Jumble Therapeutics., (Published by Elsevier Inc.)

Here, we present FusionInspector for in silico characterization and interpretation of candidate fusion transcripts from RNA sequencing (RNA-seq) and exploration of their sequence and expression characteristics. We applied FusionInspector to thousands of tumor and normal transcriptomes and identified statistical and experimental features enriched among biologically impactful fusions. Through clustering and machine learning, we identified large collections of fusions potentially relevant to tumor and normal biological processes. We show that biologically relevant fusions are enriched for relatively high expression of the fusion transcript, imbalanced fusion allelic ratios, and canonical splicing patterns, and are deficient in sequence microhomologies between partner genes. We demonstrate that FusionInspector accurately validates fusion transcripts in silico and helps characterize numerous understudied fusions in tumor and normal tissue samples. FusionInspector is freely available as open source for screening, characterization, and visualization of candidate fusions via RNA-seq, and facilitates transparent explanation and interpretation of machine-learning predictions and their experimental sources., Competing Interests: A.R. is a co-founder and equity holder of Celsius Therapeutics, an equity holder in Immunitas, and was a scientific advisory board member of Thermo Fisher Scientific, Syros Pharmaceuticals, Neogene Therapeutics, and Asimov until July 31, 2020. From August 1, 2020, A.R. has been an employee of Genentech. M.G. is a current employee and stockholder at Monte Rosa Therapeutics., (© 2023 The Authors.)

This study aims to investigate the impact of a novel environmental intervention-Emotive Intelligent Spaces (EIS) on young children's self-regulation and working memory using a single-subject reversal design (ABAB). EIS is a semi-private space with coloured lights that could adapt to each child's preferred colour based on the child's self-reported emotional state. A total of 29 three-to-seven-year-old participants completed the experiment from fall 2020 to summer 2021. Self-regulation was measured by the Head-Toes-Knees-Shoulders task; working memory was measured by the Woodcock-Johnson Numbers Reversed subset. Children's age was controlled as a covariate. Descriptive statistics indicated that the group means of self-regulation scores were higher in the intervention conditions. However, the group means of working memory scores were lower in the intervention conditions. We conducted repeated measure ANCOVA for the main analysis, and results showed no statistically significant differences in children's self-regulation and working memory scores between baseline and intervention conditions. It is recommended that future studies should take the illuminance level into consideration of the intervention effect. Further, our study implies that avoiding visual overstimulation in the classroom (e.g. heavily decorated walls) may create an optimal level of visual arousal and promote focused attention., Competing Interests: Disclosure statement No potential conflict of interest was reported by the authors.

With the advances in sequencing technologies, a huge amount of biological data is extracted nowadays. Analyzing this amount of data is beyond the ability of human beings, creating a splendid opportunity for machine learning methods to grow. The methods, however, are practical only when the sequences are converted into feature vectors. Many tools target this task including iLearnPlus, a Python-based tool which supports a rich set of features. In this paper, we propose a holistic tool that extracts features from biological sequences (i.e. DNA, RNA and Protein). These features are the inputs to machine learning models that predict properties, structures or functions of the input sequences. Our tool not only supports all features in iLearnPlus but also 30 additional features which exist in the literature. Moreover, our tool is based on R language which makes an alternative for bioinformaticians to transform sequences into feature vectors. We have compared the conversion time of our tool with that of iLearnPlus: we transform the sequences much faster. We convert small nucleotides by a median of 2.8X faster, while we outperform iLearnPlus by a median of 6.3X for large sequences. Finally, in amino acids, our tool achieves a median speedup of 23.9X., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

A facile and efficient synthetic approach to various valuable 3-aryl- and 3-aroylcoumarins by the direct arylation and aroylation of coumarins with glyoxals in a metal-free manner is presented. The aryl glyoxal is for the first time recognized to serve as an aryl surrogate in addition to its role as an aroyl transfer reagent via a simple switch in reaction conditions. The approach accommodates a broad substrate scope and high yields of the two types of cross-coupling reactions starting from identical starting materials.

In cancer, telomere maintenance is critical for the development of replicative immortality. Using genome sequences from the Cancer Cell Line Encyclopedia and Genomics of Drug Sensitivity in Cancer Project, we calculated telomere content across 1299 cancer cell lines. We find that telomerase reverse transcriptase ( TERT ) expression correlates with telomere content in lung, central nervous system, and leukemia cell lines. Using CRISPR/Cas9 screening data, we show that lower telomeric content is associated with dependency of CST telomere maintenance genes. Increased dependencies of shelterin members are associated with wild-type TP53 status. Investigating the epigenetic regulation of TERT , we find widespread allele-specific expression in promoter-wildtype contexts. TERT promoter-mutant cell lines exhibit hypomethylation at PRC2-repressed regions, suggesting a cooperative global epigenetic state in the reactivation of telomerase. By incorporating telomere content with genomic features across comprehensively characterized cell lines, we provide further insights into the role of telomere regulation in cancer immortality., Competing Interests: KH, FH No competing interests declared, MG MG is an employee and holds equity in Monte Rosa Therapeutics and is a founding member at Cambridge Data Science LLC., (© 2021, Hu et al.)

Cancer genomes often harbor hundreds of somatic DNA rearrangement junctions, many of which cannot be easily classified into simple (e.g., deletion) or complex (e.g., chromothripsis) structural variant classes. Applying a novel genome graph computational paradigm to analyze the topology of junction copy number (JCN) across 2,778 tumor whole-genome sequences, we uncovered three novel complex rearrangement phenomena: pyrgo, rigma, and tyfonas. Pyrgo are "towers" of low-JCN duplications associated with early-replicating regions, superenhancers, and breast or ovarian cancers. Rigma comprise "chasms" of low-JCN deletions enriched in late-replicating fragile sites and gastrointestinal carcinomas. Tyfonas are "typhoons" of high-JCN junctions and fold-back inversions associated with expressed protein-coding fusions, breakend hypermutation, and acral, but not cutaneous, melanomas. Clustering of tumors according to genome graph-derived features identified subgroups associated with DNA repair defects and poor prognosis., Competing Interests: Declaration of Interests J.S.R.-F. reports receiving personal/consultancy fees from VolitionRx, Paige.AI, Goldman Sachs, REPARE Therapeutics, GRAIL, Ventana Medical Systems, Roche, Genentech, and InviCRO outside of the scope of the submitted work., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Assays to study cancer cell responses to pharmacologic or genetic perturbations are typically restricted to using simple phenotypic readouts such as proliferation rate. Information-rich assays, such as gene-expression profiling, have generally not permitted efficient profiling of a given perturbation across multiple cellular contexts. Here, we develop MIX-Seq, a method for multiplexed transcriptional profiling of post-perturbation responses across a mixture of samples with single-cell resolution, using SNP-based computational demultiplexing of single-cell RNA-sequencing data. We show that MIX-Seq can be used to profile responses to chemical or genetic perturbations across pools of 100 or more cancer cell lines. We combine it with Cell Hashing to further multiplex additional experimental conditions, such as post-treatment time points or drug doses. Analyzing the high-content readout of scRNA-seq reveals both shared and context-specific transcriptional response components that can identify drug mechanism of action and enable prediction of long-term cell viability from short-term transcriptional responses to treatment.