Reductional chromosome segregation in germ cells, where sister chromatids are pulled to the same pole, accompanies the protection of cohesin at centromeres from separase cleavage. Here, we show that mammalian shugoshin Sgo2 is expressed in germ cells and is solely responsible for the centromeric localization of PP2A and the protection of cohesin Rec8 in oocytes, proving conservation of the mechanism from yeast to mammals. However, this role of Sgo2 contrasts with its mitotic role in protecting centromeric cohesin only from prophase dissociation, but never from anaphase cleavage. We demonstrate that, in somatic cells, shugoshin colocalizes with cohesin in prophase or prometaphase, but their localizations become separate when centromeres are pulled oppositely at metaphase. Remarkably, if tension is artificially removed from the centromeres at the metaphase-anaphase transition, cohesin at the centromeres can be protected from separase cleavage even in somatic cells, as in germ cells. These results argue for a unified view of centromeric protection by shugoshin in mitosis and meiosis.

Imaging of neurofibrillary pathology in the brain helps in diagnosing dementia, tracking disease progression, and evaluating the therapeutic efficacy of antidementia drugs. The radiotracers used in this imaging must be highly sensitive and specific for tau protein fibrils in the human brain. We developed a novel tau PET tracer, 18 F-THK5351, through compound optimization of arylquinoline derivatives. Methods: The in vitro binding properties, pharmacokinetics, and safety of 18 F-THK5351 were investigated, and a clinical study on Alzheimer disease (AD) patients was performed. Results: 18 F-THK5351 demonstrated higher binding affinity for hippocampal homogenates from AD brains and faster dissociation from whitematter tissue than did 18 F-THK5117. The THK5351 binding amount correlated with the amount of tau deposits in human brain samples. Autoradiography of brain sections revealed that THK5351 bound to neurofibrillary tangles selectively and with a higher signal-tobackground ratio than did THK5117. THK5351 exhibited favorable pharmacokinetics and no defluorination in mice. In first-in-human PET studies in AD patients, 18 F-THK5351 demonstrated faster kinetics, higher contrast, and lower retention in subcortical white matter than 18 F-THK5117. Conclusion: 18 F-THK5351 is a useful PET tracer for the early detection of neurofibrillary pathology in AD patients.

Background Malignancy is a secondary cause of sarcopenia, which is associated with impaired cancer treatment outcomes. The aim of this study was to investigate the prevalence of preoperative sarcopenia among elderly gastric cancer patients undergoing gastrectomy and the differences in preoperative dietary intake and postoperative complications between sarcopenic and non-sarcopenic patients. Methods Ninety-nine patients over 65 years of age who underwent gastrectomy for gastric cancer were analyzed. All patients underwent gait and handgrip strength testing, and whole-body skeletal muscle mass was measured using a bioimpedance analysis technique based on the European Working Group on Sarcopenia in Older People (EWGSOP) algorithm for the evaluation of sarcopenia before surgery. Preoperative dietary intake was assessed using a food frequency questionnaire. Results Of these patients, 21 (21.2 %) were diagnosed with sarcopenia. Sarcopenic patients consumed fewer calories and less protein preoperatively (23.9 vs. 27.8 kcal/ kg ideal weight/day and 0.86 vs. 1.04 g/kg ideal weight/-day; P = 0.001 and 0.0005, respectively). Although the overall incidence of postoperative complications was similar in the two groups (57.1 % vs. 35.9 %; P = 0.08), the incidence of severe (Clavien-Dindo grade C IIIa) complications was significantly higher in the sarcopenic group than in the non-sarcopenic group (28.6 % vs. 9.0 %; P = 0.029). In the multivariate analysis, sarcopenia alone was identified as a risk factor for severe postoperative complications (odds ratio, 4.76; 95 % confidence interval, 1.03-24.30; P = 0.046). Conclusions Preoperative sarcopenia as defined by the EWGSOP algorithm is a risk factor for severe postoperative complications in elderly gastric cancer patients undergoing gastrectomy.

Malnutrition, a risk factor for SSI, was prevalent in gastric cancer patients preoperatively. Well-managed preoperative nutritional support decreased the incidence of postoperative SSIs in malnourished patients.