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- Abbafati, Cristiana, et al.
(författare)
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- 2020
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Tidskriftsartikel (refereegranskat)
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| 5. |
- Gamble, LD, et al.
(författare)
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A G316A Polymorphism in the Ornithine Decarboxylase Gene Promoter Modulates MYCN-Driven Childhood Neuroblastoma
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:8
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Tidskriftsartikel (refereegranskat)abstract
- Ornithine decarboxylase (ODC1), a critical regulatory enzyme in polyamine biosynthesis, is a direct transcriptional target of MYCN, amplification of which is a powerful marker of aggressive neuroblastoma. A single nucleotide polymorphism (SNP), G316A, within the first intron of ODC1, results in genotypes wildtype GG, and variants AG/AA. CRISPR-cas9 technology was used to investigate the effects of AG clones from wildtype MYCN-amplified SK-N-BE(2)-C cells and the effect of the SNP on MYCN binding, and promoter activity was investigated using EMSA and luciferase assays. AG clones exhibited decreased ODC1 expression, growth rates, and histone acetylation and increased sensitivity to ODC1 inhibition. MYCN was a stronger transcriptional regulator of the ODC1 promoter containing the G allele, and preferentially bound the G allele over the A. Two neuroblastoma cohorts were used to investigate the clinical impact of the SNP. In the study cohort, the minor AA genotype was associated with improved survival, while poor prognosis was associated with the GG genotype and AG/GG genotypes in MYCN-amplified and non-amplified patients, respectively. These effects were lost in the GWAS cohort. We have demonstrated that the ODC1 G316A polymorphism has functional significance in neuroblastoma and is subject to allele-specific regulation by the MYCN oncoprotein.
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- Bastianini, S, et al.
(författare)
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Accurate discrimination of the wake-sleep states of mice using non-invasive whole-body plethysmography
- 2017
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7, s. 41698-
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Tidskriftsartikel (refereegranskat)abstract
- A major limitation in the study of sleep breathing disorders in mouse models of pathology is the need to combine whole-body plethysmography (WBP) to measure respiration with electroencephalography/electromyography (EEG/EMG) to discriminate wake-sleep states. However, murine wake-sleep states may be discriminated from breathing and body movements registered by the WBP signal alone. Our goal was to compare the EEG/EMG-based and the WBP-based scoring of wake-sleep states of mice, and provide formal guidelines for the latter. EEG, EMG, blood pressure and WBP signals were simultaneously recorded from 20 mice. Wake-sleep states were scored based either on EEG/EMG or on WBP signals and sleep-dependent respiratory and cardiovascular estimates were calculated. We found that the overall agreement between the 2 methods was 90%, with a high Cohen’s Kappa index (0.82). The inter-rater agreement between 2 experts and between 1 expert and 1 naïve sleep investigators gave similar results. Sleep-dependent respiratory and cardiovascular estimates did not depend on the scoring method. We show that non-invasive discrimination of the wake-sleep states of mice based on visual inspection of the WBP signal is accurate, reliable and reproducible. This work may set the stage for non-invasive high-throughput experiments evaluating sleep and breathing patterns on mouse models of pathophysiology.
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- Bajorath, J., et al.
(författare)
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Chemoinformatics and artificial intelligence colloquium: progress and challenges in developing bioactive compounds
- 2022
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Ingår i: Journal of Cheminformatics. - : Springer Science and Business Media LLC. - 1758-2946. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- We report the main conclusions of the first Chemoinformatics and Artificial Intelligence Colloquium, Mexico City, June 15–17, 2022. Fifteen lectures were presented during a virtual public event with speakers from industry, academia, and non-for-profit organizations. Twelve hundred and ninety students and academics from more than 60 countries. During the meeting, applications, challenges, and opportunities in drug discovery, de novo drug design, ADME-Tox (absorption, distribution, metabolism, excretion and toxicity) property predictions, organic chemistry, peptides, and antibiotic resistance were discussed. The program along with the recordings of all sessions are freely available at https://www.difacquim.com/english/events/2022-colloquium/.
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- Baumgardner, D., et al.
(författare)
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Soot reference materials for instrument calibration and intercomparisons: a workshop summary with recommendations
- 2012
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Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 5:8, s. 1869-1887
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Tidskriftsartikel (refereegranskat)abstract
- Soot, which is produced from biomass burning and the incomplete combustion of fossil and biomass fuels, has been linked to regional and global climate change and to negative health problems. Scientists measure the properties of soot using a variety of methods in order to quantify source emissions and understand its atmospheric chemistry, reactivity under emission conditions, interaction with solar radiation, influence on clouds, and health impacts. A major obstacle currently limiting progress is the absence of established standards or reference materials for calibrating the many instruments used to measure the various properties of soot. The current state of availability and practicability of soot standard reference materials (SRMs) was reviewed by a group of 50 international experts during a workshop in June of 2011. The workshop was convened to summarize the current knowledge on soot measurement techniques, identify the measurement uncertainties and limitations related to the lack of soot SRMs, and identify attributes of SRMs that, if developed, would reduce measurement uncertainties. The workshop established that suitable SRMs are available for calibrating some, but not all, measurement methods. The community of users of the single-particle soot-photometer (SP2), an instrument using laser-induced incandescence, identified a suitable SRM, fullerene soot, but users of instruments that measure light absorption by soot collected on filters did not. Similarly, those who use thermal optical analysis (TOA) to analyze the organic and elemental carbon components of soot were not satisfied with current SRMs. The workshop, and subsequent, interactive discussions, produced a number of recommendations for the development of new SRMs, and their implementation, that would be suitable for the different soot measurement methods.
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