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The joint ESA/NASA Mass-change And Geosciences International Constellation (MAGIC) has the objective to extend time-series from previous gravity missions, including an improvement of accuracy and spatio-temporal resolution. The long-term monitoring of Earth's gravity field carries information on mass change induced by water cycle, climate change and mass transport processes between atmosphere, cryosphere, oceans and solid Earth. MAGIC will be composed of two satellite pairs flying in different orbit planes. The NASA/DLR-led first pair (P1) is expected to be in a near-polar orbit around 500 km of altitude; while the second ESA-led pair (P2) is expected to be in an inclined orbit of 65°–70° at approximately 400 km altitude. The ESA-led pair P2 Next Generation Gravity Mission shall be launched after P1 in a staggered manner to form the MAGIC constellation. The addition of an inclined pair shall lead to reduction of temporal aliasing effects and consequently of reliance on de-aliasing models and post-processing. The main novelty of the MAGIC constellation is the delivery of mass-change products at higher spatial resolution, temporal (i.e. subweekly) resolution, shorter latency and higher accuracy than the Gravity Recovery and Climate Experiment (GRACE) and Gravity Recovery and Climate Experiment Follow-On (GRACE-FO). This will pave the way to new science applications and operational services. In this paper, an overview of various fields of science and service applications for hydrology, cryosphere, oceanography, solid Earth, climate change and geodesy is provided. These thematic fields and newly enabled applications and services were analysed in the frame of the initial ESA Science Support activities for MAGIC. The analyses of MAGIC scenarios for different application areas in the field of geosciences confirmed that the double-pair configuration will significantly enlarge the number of observable mass-change phenomena by resolving smaller spatial scales with an uncertainty that satisfies evolved user requirements expressed by international bodies such as IUGG. The required uncertainty levels of dedicated thematic fields met by MAGIC unfiltered Level-2 products will benefit hydrological applications by recovering more than 90 per cent of the major river basins worldwide at 260 km spatial resolution, cryosphere applications by enabling mass change signal separation in the interior of Greenland from those in the coastal zones and by resolving small-scale mass variability in challenging regions such as the Antarctic Peninsula, oceanography applications by monitoring meridional overturning circulation changes on timescales of years and decades, climate applications by detecting amplitude and phase changes of Terrestrial Water Storage after 30 yr in 64 and 56 per cent of the global land areas and solid Earth applications by lowering the Earthquake detection threshold from magnitude 8.8 to magnitude 7.4 with spatial resolution increased to 333 km. [ABSTRACT FROM AUTHOR]

Background: High-grade serous ovarian carcinoma (HGSOC) is the most common and aggressive subtype of epithelial ovarian carcinoma. It is primarily diagnosed at stage III or IV when the 5-year survival rate ranges between 20% and 40%. Here, we aimed to validate the hypothesis, based on HGSOC cell lines, that proposed the existence of two distinct groups of HGSOC cells with high and low oxidative phosphorylation (OXPHOS) metabolism, respectively, which are associated with their responses to glucose and glutamine withdrawal., Methods: We isolated and cultivated primary cancer cell cultures from HGSOC and nontransformed ovarian fibroblasts from the surrounding ovarium of 45 HGSOC patients. We tested the metabolic flexibility of the primary cells, particularly in response to glucose and glutamine depletion, analyzed and modulated endoplasmic reticulum stress, and searched for indices of the existence of previously reported groups of HGSOC cells with high and low OXPHOS metabolism., Results: The primary HGSOC cells did not form two groups with high and low OXPHOS that responded differently to glucose and glutamine availabilities in the cell culture medium. Instead, they exhibited a continuum of OXPHOS phenotypes. In most tumor cell isolates, the responses to glucose or glutamine withdrawal were mild and surprisingly correlated with those of nontransformed ovarian fibroblasts from the same patients. The growth of tumor-derived cells in the absence of glucose was positively correlated with the lipid trafficking regulator FABP4 and was negatively correlated with the expression levels of HK2 and HK1. The correlations between the expression of electron transport chain (ETC) proteins and the oxygen consumption rates or extracellular acidification rates were weak. ER stress markers were strongly expressed in all the analyzed tumors. ER stress was further potentiated by tunicamycin but not by the recently proposed ER stress inducers based on copper(II)-phenanthroline complexes. ER stress modulation increased autophagy in tumor cell isolates but not in nontransformed ovarian fibroblasts., Conclusions: Analysis of the metabolism of primary HGSOC cells rejects the previously proposed hypothesis that there are distinct groups of HGSOC cells with high and low OXPHOS metabolism that respond differently to glutamine or glucose withdrawal and are characterized by ETC protein levels., (© 2024. The Author(s).)

Intact (whole) cell MALDI TOF mass spectrometry is a commonly used tool in clinical microbiology for several decades. Recently it was introduced to analysis of eukaryotic cells, including cancer and stem cells. Besides targeted metabolomic and proteomic applications, the intact cell MALDI TOF mass spectrometry provides a sufficient sensitivity and specificity to discriminate cell types, isogenous cell lines or even the metabolic states. This makes the intact cell MALDI TOF mass spectrometry a promising tool for quality control in advanced cell cultures with a potential to reveal batch-to-batch variation, aberrant clones, or unwanted shifts in cell phenotype. However, cellular alterations induced by change in expression of a single gene has not been addressed by intact cell mass spectrometry yet. In this work we used a well-characterized human ovarian cancer cell line SKOV3 with silenced expression of a tumor suppressor candidate 3 gene (TUSC3). TUSC3 is involved in co-translational N-glycosylation of proteins with well-known global impact on cell phenotype. Altogether, this experimental design represents a highly suitable model for optimization of intact cell mass spectrometry and analysis of spectral data. Here we investigated five machine learning algorithms (k-nearest neighbors, decision tree, random forest, partial least squares discrimination, and artificial neural network) and optimized their performance either in pure populations or in two-component mixtures composed of cells with normal or silenced expression of TUSC3. All five algorithms reached accuracy over 90 % and were able to reveal even subtle changes in mass spectra corresponding to alterations of TUSC3 expression. In summary, we demonstrate that spectral fingerprints generated by intact cell MALDI-TOF mass spectrometry coupled to a machine learning classifier can reveal minute changes induced by alteration of a single gene, and therefore contribute to the portfolio of quality control applications in routine cell and tissue cultures., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)