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As German forces took control of their country, a group of young Belgians conceived an audacious plan to smuggle downed Allied airmen and other evaders from Belgium, through France and over the Spanish border. So began the Comet line. Many incredible escapes followed, from safe houses in Brussels, along hazardous train journeys via Lille to Paris, to goat paths through the Pyrenees mountains, evading both German and Spanish border patrols. In this study, Alexander Stilwell reveals the personalities and motives of the Comet line founders, the British intelligence organisation (MI9) that supported it, the campaign by the Gestapo to destroy it, and the work of the Nazi collaborators who infiltrated the Comet line with disastrous results. Above all, this is the story of the incredibly brave civilians who risked their lives to help Allied airmen and other evaders to escape from occupied Europe.

Purpose Control of hydration status is an important constituent of adequate and efficient hemodialysis (HD) treatment. Nevertheless, there are no precise clinical indices for early recognition of small changes in fluid status of patients undergoing chronic hemodialysis therapy. This study aimed to evaluate and compare the widely used and reliable method of indexed inferior vena cava diameter (IVCDi) with established and more recently available techniques (bioelectrical impedance analysis [BIA], continuous blood volume monitoring [Crit-line], and the B-line score [BLS] with lung ultrasonography) for estimating the hydration status of patients on HD. Methods Fifty-three patients undergoing chronic HD thrice weekly were included in the study. Evaluation of hydration status methods (IVCDi, BLS, BIA, and Crit-line) was performed thrice weekly before and after HD. Receiver operating characteristic curve analysis was performed to evaluate the discriminative power of (methods) the BLS, BIA, and Crit-line for predicting over- and underhydration of patients, as determined by the reference method, IVCDi. Results BLS showed the most promising results in predicting overhydration, as determined by IVCDi, compared with BIA and Crit-line and presented a sensitivity of 77% and specificity of 74%. The accuracy of the BLS was higher than that of BIA (0.81 vs. 0.71, p  = 0.032) and Crit-line (0.61, p  = 0.001). BLS also showed more promising results in predicting underhydration, as determined by IVCDi, than BIA and Crit-line and presented a sensitivity of 78% and a specificity of 73%. The accuracy of the BLS was higher than that of BIA (0.83 vs. 0.76, p  = 0.035) and Crit-line (0.50, p  < 0.001). Conclusions The BLS is a useful and easily performed technique that has recently become available for accurate evaluation of dry weight and fluid status in patients with end-stage renal disease undergoing chronic HD. This method might help recognize asymptomatic lung congestion in these patients.

Background There are no data on usefulness of optic nerve sheath diameter (ONSD) as a marker of patient's fluid status in preeclampsia. The objective was to examine potential correlation between ONSD and lung ultrasound estimates of extravascular lung water in severe preeclampsia. Patients and methods Thirty patients with severe preeclampsia were included. Optic and lung ultrasound were performed within 24 hours from delivery. ONSD was measured 3 mm behind the globe. Lung ultrasound Echo Comet Score (ECS) was obtained summing B-lines (\"comet tails\") in parasternal intercostal spaces bilaterally. Pearson's correlation analysis was used to assess the relationship between ONSD and ECS (p < 0.05 significant). Results Median ONSD was 5.7 mm (range 3.8-7.5 mm). Median ECS value was 19 (range 0-24). Statistically significant correlation was found between ONSD and ECS (r2 = 0.464; p < 0.001). Conclusions Significant correlation between ONSD and ECS suggests optic ultrasound could be used for assessing fluid status and guiding peripartum fluid therapy in patients with severe preeclampsia.

The detection of iron and nickel vapours in a broad range of Solar System comets, and of nickel vapour in a comet from outside the Solar System, provides a glimpse into the organic chemistry of young planetary systems. Emission spectra of pure metal atoms detected in cometary comae.

With a direct link to cancer, aging, and heritable diseases as well as a critical role in cancer treatment, the importance of DNA damage is well-established. The intense interest in DNA damage in applications ranging from epidemiology to drug development drives an urgent need for robust, high throughput, and inexpensive tools for objective, quantitative DNA damage analysis. We have developed a simple method for high throughput DNA damage measurements that provides information on multiple lesions and pathways. Our method utilizes single cells captured by gravity into a microwell array with DNA damage revealed morphologically by gel electrophoresis. Spatial encoding enables simultaneous assays of multiple experimental conditions performed in parallel with fully automated analysis. This method also enables novel functionalities, including multiplexed labeling for parallel single cell assays, as well as DNA damage measurement in cell aggregates. We have also developed 24- and 96-well versions, which are applicable to high throughput screening. Using this platform, we have quantified DNA repair capacities of individuals with different genetic backgrounds, and compared the efficacy of potential cancer chemotherapeutics as inhibitors of a critical DNA repair enzyme, human AP endonuclease. This platform enables high throughput assessment of multiple DNA repair pathways and subpathways in parallel, thus enabling new strategies for drug discovery, genotoxicity testing, and environmental health.

Cr(III) and Co(II) can be potentially toxic to cells and induce a number of morphological and biochemical changes. These metals are widely used in many industries and can cause environmental pollution. They are the components of dietary supplements, vitamin and mineral products, and energy drinks. Moreover, these metals are used in dentistry and orthopedics as components of implants. Data about the mechanism of genotoxic effects of Cr(III) and Co(II) are still incomplete. The aim of this study was to analyze the genotoxic effects of chromium(III) and cobalt(II) and their mixtures on two cell lines: mouse embryo fibroblast cell line BALB/3T3 and human hepatocellular carcinoma cell line G2 (HepG2). The BALB/3T3 and HepG2 cell lines were exposed to chromium chloride and cobalt chloride at concentrations ranging from 100 to 1400 µM. The genotoxicity assays used were the comet and micronucleus assays. On the basis of the results obtained from the first stage of the research, the concentrations of elements were selected in order to determine the interactions between them. The tested cell lines were treated with mixtures of the following compounds: chromium chloride at the concentration of 200 μM and cobalt chloride at the concentration of 1000 μM or chromium chloride at the concentration of 1000 μM and cobalt chloride at the concentration of 200 μM in the genotoxicity assays. This study shows that both cobalt(II) and chromium(III) cause genotoxic effects in the BALB/3T3 and HepG2 cell lines. A statistically significant increase in the percentage of comets was observed with increasing concentrations of Co(II) and Cr(III) compared to the control. A statistically significant induction of chromosomal aberrations was also observed in the micronucleus test. Moreover, chromium(III) at a concentration of 200 µM had a protective effect against the toxic concentration of cobalt(II) at a concentration of 1000 µM. The toxic effect of cobalt chloride and chromium chloride was confirmed in this study. Further research is needed on the genotoxic effects of cobalt(II) and chromium(III), especially due to the growing popularity of dietary supplements containing compounds of these metals and doubts as to the safety of their use.

Many efforts have been made in the last 30 years to develop more relevant in vitro models to study genotoxic responses of drugs and environmental contaminants. While 2D HepaRG cells are one of the most promising models for liver toxicology, a switch to 3D cultures that integrate both in vivo architecture and cell-cell interactions has occurred to achieve even more predictive models. Preliminary studies have indicated that 3D HepaRG cells are suitable for liver toxicity screening. Our study aimed to evaluate the response of HepaRG spheroids exposed to various genotoxic compounds using the single cell gel electrophoresis assay. HepaRG spheroids were used at 10 days after seeding and exposed for 24 and 48 hours to certain selected chemical compounds (methylmethansulfonate (MMS), etoposide, benzo[a]pyrene (B[a]P), cyclophosphamide (CPA), 7,12-dimethylbenz[a]anthracene (DMBA), 2-acetylaminofluorene (2-AAF), 4-nitroquinoline (4-NQO), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3-methylimidazo[4,5-f]quinolone (IQ), acrylamide, and 2-4-diaminotoluene (2,4-DAT)). After treatment, the comet assay was performed on single cell suspensions and cytotoxicity was determined by the ATP assay. Comet formation was observed for all compounds except IQ, etoposide and 2,4-DAT. Treatment of spheroids with rifampicin increased CYP3A4 activity, demonstrating the metabolic capacity of HepaRG spheroids. These data on genotoxicity in 3D HepaRG spheroids are promising, but further experiments are required to prove that this model can improve the predictivity of in vitro models to detect human carcinogens.

Human liver-derived metabolically competent HepaRG cells have been successfully employed in both two-dimensional (2D) and 3D spheroid formats for performing the comet assay and micronucleus (MN) assay. In the present study, we have investigated expanding the genotoxicity endpoints evaluated in HepaRG cells by detecting mutagenesis using two error-corrected next generation sequencing (ecNGS) technologies, Duplex Sequencing (DS) and High-Fidelity (HiFi) Sequencing. Both HepaRG 2D cells and 3D spheroids were exposed for 72 h to N-nitrosodimethylamine (NDMA), followed by an additional incubation for the fixation of induced mutations. NDMA-induced DNA damage, chromosomal damage, and mutagenesis were determined using the comet assay, MN assay, and ecNGS, respectively. The 72-h treatment with NDMA resulted in concentration-dependent increases in cytotoxicity, DNA damage, MN formation, and mutation frequency in both 2D and 3D cultures, with greater responses observed in the 3D spheroids compared to 2D cells. The mutational spectrum analysis showed that NDMA induced predominantly A:T → G:C transitions, along with a lower frequency of G:C → A:T transitions, and exhibited a different trinucleotide signature relative to the negative control. These results demonstrate that the HepaRG 2D cells and 3D spheroid models can be used for mutagenesis assessment using both DS and HiFi Sequencing, with the caveat that severe cytotoxic concentrations should be avoided when conducting DS. With further validation, the HepaRG 2D/3D system may become a powerful human-based metabolically competent platform for genotoxicity testing.

Symmetric cell division requires the even partitioning of genetic information and cytoplasmic contents between daughter cells. Whereas the mechanisms coordinating the segregation of the genome are well known, the processes that ensure organelle segregation between daughter cells remain less well understood 1 . Here we identify multiple actin assemblies with distinct but complementary roles in mitochondrial organization and inheritance in mitosis. First, we find a dense meshwork of subcortical actin cables assembled throughout the mitotic cytoplasm. This network scaffolds the endoplasmic reticulum and organizes three-dimensional mitochondrial positioning to ensure the equal segregation of mitochondrial mass at cytokinesis. Second, we identify a dynamic wave of actin filaments reversibly assembling on the surface of mitochondria during mitosis. Mitochondria sampled by this wave are enveloped within actin clouds that can spontaneously break symmetry to form elongated comet tails. Mitochondrial comet tails promote randomly directed bursts of movement that shuffle mitochondrial position within the mother cell to randomize inheritance of healthy and damaged mitochondria between daughter cells. Thus, parallel mechanisms mediated by the actin cytoskeleton ensure both equal and random inheritance of mitochondria in symmetrically dividing cells. During mitosis, complementary actin-based mechanisms ensure equal and random distributions of mitochondria among daughter cells following symmetrical cell division.

This study aims to prepare folic acid coated tin oxide nanoparticles (FA-SnO2 NPs) for specifically targeting human ovarian cancer cells with minimum side effects against normal cells. The prepared FA-SnO2 NPs were characterized by FT-IR, UV-vis spectroscopy, XRD, SEM and TEM. The inhibition effects of FA-SnO2 NPs against SKOV3 cancer cell were tested by MTT and LDH assay. Apoptosis induction in FA-SnO2 NPs treated SKOV3 cells were investigated using Annexin V/PI, AO/EB and Comet assays and the possible mechanisms of the cytotoxic action were studied by Flow cytometry, qRT-PCR, Immunohistochemistry, and Western blotting analyses. The effects of FA-SnO2 NPs on reactive oxygen species generation in SKOV3 cells were also examined. Additionally, the safety of utilization FA-SnO2 NPs were studied in vivo using Wister rats. The obtained FA-SnO2 NPs displayed amorphous spherical morphology with an average diameter of 157 nm and a zeta potential value of -24 mV. Comparing to uncoated SnO2 NPs, FA-SnO2 NPs had a superior inhibition effect towards SKOV3 cell growth that was suggested to be mediated through higher reactive oxygen species generation. It was showed that FA-SnO2 NPs increased significantly the % of apoptotic cells in the sub- G1 and G2/M phases with a higher intensity comet nucleus in SKOV3 treated cells. Furthermore, FA-SnO2 NPs was significantly increased the expression levels of P53, Bax, and cleaved Caspase-3 and accompanied with a significant decrease of Bcl-2 in the treated SKOV3 cells. Overall, the results suggested that an increase in cellular FA-SnO2 NPs internalization resulted in a significant induced cytotoxicity in SKOV3 cancer cells in dose-dependent mode through ROS-mediated cell apoptosis that may have occurred through mitochondrial pathway. Additionally, the results confirmed the safety of utilization FA-SnO2 NPs against living systems. So, FA-SnO2 NPs with a specific targeting moiety may be a promising therapeutic candidate for human ovarian cancer.