Prolonged mitosis often results in apoptosis1. Shortened mitosis causes tumorigenic aneuploidy, but it is unclear whether it also activates the apoptotic machinery2. Separase, a cysteine protease and trigger of all eukaryotic anaphases, has a caspase-like catalytic domain but has not previously been associated with cell death3,4. Here we show that human cells that enter mitosis with already active separase rapidly undergo death in mitosis owing to direct cleavage of anti-apoptotic MCL1 and BCL-XL by separase. Cleavage not only prevents MCL1 and BCL-XL from sequestering pro-apoptotic BAK, but also converts them into active promoters of death in mitosis. Our data strongly suggest that the deadliest cleavage fragment, the C-terminal half of MCL1, forms BAK/BAX-like pores in the mitochondrial outer membrane. MCL1 and BCL-XL are turned into separase substrates only upon phosphorylation by NEK2A. Early mitotic degradation of this kinase is therefore crucial for preventing apoptosis upon scheduled activation of separase in metaphase. Speeding up mitosis by abrogation of the spindle assembly checkpoint results in a temporal overlap of the enzymatic activities of NEK2A and separase and consequently in cell death. We propose that NEK2A and separase jointly check on spindle assembly checkpoint integrity and eliminate cells that are prone to chromosome missegregation owing to accelerated progression through early mitosis.An amendment to this paper has been published and can be accessed via a link at the top of the paper.An amendment to this paper has been published and can be accessed via a link at the top of the paper.The initiation of an intestinal tumour is a probabilistic process that depends on the competition between mutant and normal epithelial stem cells in crypts1. Intestinal stem cells are closely associated with a diverse but poorly characterized network of mesenchymal cell types2,3. However, whether the physiological mesenchymal microenvironment of mutant stem cells affects tumour initiation remains unknown. Here we provide in vivo evidence that the mesenchymal niche controls tumour initiation in trans. By characterizing the heterogeneity of the intestinal mesenchyme using single-cell RNA-sequencing analysis, we identified a population of rare pericryptal Ptgs2-expressing fibroblasts that constitutively process arachidonic acid into highly labile prostaglandin E2 (PGE2). Specific ablation of Ptgs2 in fibroblasts was sufficient to prevent tumour initiation in two different models of sporadic, autochthonous tumorigenesis. Mechanistically, single-cell RNA-sequencing analyses of a mesenchymal niche model showed thate mesenchymal niche and reveals a mechanism by which rare pericryptal Ptgs2-expressing fibroblasts exert paracrine control over tumour-initiating stem cells via the druggable PGE2-Ptger4-Yap signalling axis.Ultrafast measurements in the extreme ultraviolet (XUV) spectral region targeting femtosecond timescales rely until today on two complementary XUV laser sources free electron lasers (FELs) and high-harmonic generation (HHG) based sources. The combination of these two source types was until recently not realized. The complementary properties of both sources including broad bandwidth, high pulse energy, narrowband tunability and femtosecond timing, open new opportunities for two-color pump-probe studies. Here we show first results from the commissioning of a high-harmonic beamline that is fully synchronized with the free-electron laser FLASH, installed at beamline FL26 with permanent end-station including a reaction microscope (REMI). An optical parametric amplifier synchronized with the FEL burst mode drives the HHG process. First commissioning tests including electron momentum measurements using REMI, demonstrate long-term stability of the HHG source over more than 14 hours. Lorundrostat datasheet This realization of the combination of these light sources will open new opportunities for time-resolved studies targeting different science cases including core-level ionization dynamics or the electron dynamics during the transformation of a molecule within a chemical reaction probed on femtosecond timescales in the ultraviolet to soft X-ray spectral region.BACKGROUND Processed foods have been implicated in the pathogenesis of inflammatory bowel diseases (IBD). Our goal was to develop a validated processed foods frequency questionnaire (PFQ) and assess its reliability and validity. METHODS We recruited adult IBD patients to fill-in a PFQ in this prospective single-center study. Food intake was categorized into three groups of processed food levels unprocessed, processed, and ultra-processed. Reliability was assessed by comparing the PFQ results of each patient at 2 time points. Validity was assessed by comparing the PFQ results to a 3-7 day food diary (FD), and by comparing urine sodium as a biomarker for the high intake of sodium that is mostly present in processed food. RESULTS Eighty-six IBD patients were enrolled. Good test-retest reliability was indicated by intraclass correlation of 0.75-0.88 for the different food processing levels. Validity was fair-to-strong as assessed by correlations for different levels of processed food intake between FDs and PFQ, ranging between 0.43 and 0.64 (Pearsonr, P  less then  0.001), and further supported by higher mean urine sodium levels in patients with high processed foods consumption compared with low consumption (104.57 ± 53.26 vs. 78.62 ± 39.08 mmol/L, respectively, P = 0.022). Agreement between PFQ and the FD in categorizing patients to high and low processed food consumption groups was fair (Kappa 0.23-0.35). CONCLUSIONS The PFQ is a reliable and valid tool for the assessment of processed foods consumption in IBD patients and can be utilized for studying the association between processed food consumption and IBD etiopathogenesis.BACKGROUND Although several studies have reported the effects that dietary fiber intake from different types of grains and fiber components have on bowel movements, insufficient attention has been paid to comparing and evaluating the effects of rice-based and wheat-based diets. This study compared and evaluated the effects of ingesting rice-based (brown rice-based diet BRD; white rice-based diet WRD) and wheat-based diet (WD) on the bowel movements of young women with functional constipation. METHOD Based on an open, randomized, controlled, and parallel design, 39 subjects were assigned to BRD, WRD, and WD groups (13 in each group). Each participant had received three types of experimental diets over the course of 4 weeks and we recommended that the subjects eat only the test diet provided during the study. Primary outcomes (total colon transit time TCTT) and secondary outcomes (bowel movements, short-chain fatty acid content, and fecal enzyme activity) were compared before and after the 4-week intervention period.