Proper chromosome segregation is essential for faithful cell division and if not maintained results in defective cell function caused by the abnormal distribution of genetic information. Polo-like kinase 1-interacting checkpoint helicase (PICH) is a DNA translocase essential for chromosome bridge resolution during mitosis. Its function in resolving chromosome bridges requires both DNA translocase activity and ability to bind chromosomal proteins modified by the small ubiquitin-like modifier (SUMO). However, it is unclear how these activities cooperate to resolve chromosome bridges. Here, we show that PICH specifically disperses SUMO2/3 foci on mitotic chromosomes. This PICH function is apparent toward SUMOylated topoisomerase IIα (TopoIIα) after inhibition of TopoIIα by ICRF-193. Conditional depletion of PICH using the auxin-inducible degron (AID) system resulted in the retention of SUMO2/3-modified chromosomal proteins, including TopoIIα, indicating that PICH functions to reduce the association of these proteins with chromosomes. Replacement of PICH with its translocase-deficient mutants led to increased SUMO2/3 foci on chromosomes, suggesting that the reduction of SUMO2/3 foci requires the remodeling activity of PICH. In vitro assays showed that PICH specifically attenuates SUMOylated TopoIIα activity using its SUMO-binding ability. Taking the results together, we propose a novel function of PICH in remodeling SUMOylated proteins to ensure faithful chromosome segregation.The oxidation activity of multicopper-oxidases overlaps with different substrates of laccases and bilirubin oxidases, thus in the present study an integrated approach of bioinformatics using homology modeling, docking, and experimental validation was used to confirm the type of multicopper-oxidase in Myrothecium verrucaria ITCC-8447. The result of peptide sequence of M. verrucaria ITCC-8447 enabled to predict the 3 D-structure of multicopper-oxidase.  https://www.selleckchem.com/products/MLN-2238.html  It was overlapped with the structure of laccase and root mean square deviation (RMSD) was 1.53 Å for 533 and, 171 residues. The low binding energy with azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) (-5.64) as compared to bilirubin (-4.39) suggested that M. verrucaria ITCC-8447 have laccase-like activity. The experimental analysis confirmed high activity with laccase specific substrates, phenol (18.3 U/L), ampyrone (172.4 U/L) and, ampyrone phenol coupling (50 U/L) as compared to bilirubin oxidase substrate bilirubin (16.6 U/L). In addition, lowest binding energy with ABTS (-5.64), syringaldazine SYZ (-4.83), guaiacol GCL (-4.42), and 2,6-dimethoxyphenol DMP (-4.41) confirmed the presence of laccase. Further, complete remediation of two hazardous model pollutants i.e., phenol and resorcinol (1.5 mM) after 12 h of incubation and low binding energy of -4.32 and, -4.85 respectively confirmed its removal by laccase. The results confirmed the presence of laccase in M. verrucaria ITCC-8447 and its effective bioremediation potential.Purpose We investigated associations between maternal comfort with lesbian, gay, and bisexual (LGB) people during the participant's adolescence and their health indicators in adulthood. Methods Data came from a prospective cohort, Growing Up Today Study (N = 7476), limited to men and women who provided information during their adulthood about recent binge drinking, cigarette smoking, or disordered weight control behaviors (DWCB) and whose mothers provided information during the participant's adolescence about her comfort with LGB people. Results Increased maternal comfort with LGB people was associated with increased engagement in health indicators for heterosexual but not sexual minority adults (binge drinking, cigarette smoking, and DWCB for women; binge drinking for men). No association existed between maternal comfort with LGB people and binge drinking or cigarette smoking for sexual minority women, and binge drinking for sexual minority men. This resulted in statistically smaller differences across sexual orientation in cigarette smoking for women when their mothers were highly comfortable with LGB people compared with those whose mothers were uncomfortable with LGB people. There were no differences in binge drinking (women and men) and DWCB (women only) across sexual orientation when mothers were highly comfortable with LGB people. Conclusion Maternal comfort with LGB people is associated with certain sexual orientation-related disparities in health indicators through adulthood, due to increased engagement in health indicators by heterosexual adults. Exposure to sexual orientation stigma in adolescence, measured as maternal comfort with LGB people, possibly drives well-known differences in drinking, smoking, and DWCB during adulthood between heterosexual and sexual minority adults.
  Prehospital care for traumatic brain injury (TBI) is important to prevent secondary brain injury. We aim to compare prehospital care systems within Europe and investigate the association of system characteristics with the stability of patients at hospital arrival.
 
  We studied TBI patients who were transported to CENTER-TBI centers, a pan-European, prospective TBI cohort study, by emergency medical services between 2014 and 2017. The association of demographic factors, injury severity, situational factors, and interventions associated with on-scene time was assessed using linear regression. We used mixed effects models to investigate the case mix adjusted variation between countries in prehospital times and interventions. The case mix adjusted impact of on-scene time and interventions on hypoxia (oxygen saturation <90%) and hypotension (systolic blood pressure <100mmHg) at hospital arrival was analyzed with logistic regression.
 
  Among 3878 patients, the greatest driver of longer on-scene time was intubstantial variation in prehospital care exists for patients after TBI in Europe, which is only partially explained by patient factors.
 Hypoxia and hypotension continue to occur in patients who suffer a TBI, and remain relatively common in severe TBI. Substantial variation in prehospital care exists for patients after TBI in Europe, which is only partially explained by patient factors.