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Timely and precise control of Aurora B kinase, the chromosomal passenger complex (CPC) catalytic subunit, is essential for accurate chromosome segregation and cytokinesis. Post-translational modifications of CPC subunits are directly involved in controlling Aurora B activity. Here, we identified a highly conserved acidic STD-rich motif of INCENP that is phosphorylated during mitosis in vivo and by Plk1 in vitro and is involved in controlling Aurora B activity. By using an INCENP conditional-knockout cell line, we show that impairing the phosphorylation status of this region disrupts chromosome congression and induces cytokinesis failure. In contrast, mimicking constitutive phosphorylation not only rescues cytokinesis but also induces ectopic furrows and contractile ring formation in a Plk1- and ROCK1-dependent manner independent of cell cycle and microtubule status. Our experiments identify the phospho-regulation of the INCENP STD motif as a novel mechanism that is key for chromosome alignment and cytokinesis. This article has an associated First Person interview with the first author of the paper., Highlighted Article: Phospho-regulation of the INCENP STD motif acts as a novel switch that is key to Aurora B activity modulation, chromosome alignment and cytokinesis.

The requirement for condensin in chromosome formation in somatic cells remains unclear, as imperfectly condensed chromosomes do form in cells depleted of condensin by conventional methodologies. In order to dissect the roles of condensin at different stages of vertebrate mitosis, we have established a versatile cellular system that combines auxin-mediated rapid degradation with chemical genetics to obtain near-synchronous mitotic entry of chicken DT40 cells in the presence and absence of condensin. We analyzed the outcome by live- and fixed-cell microscopy methods, including serial block face scanning electron microscopy with digital reconstruction. Following rapid depletion of condensin, chromosomal defects were much more obvious than those seen after a slow depletion of condensin. The total mitotic chromatin volume was similar to that in control cells, but a single mass of mitotic chromosomes was clustered at one side of a bent mitotic spindle. Cultures arrest at prometaphase, eventually exiting mitosis without segregating chromosomes. Experiments where the auxin concentration was titrated showed that different condensin levels are required for anaphase chromosome segregation and formation of a normal chromosome architecture.

Packaging of DNA into condensed chromosomes during mitosis is essential for the faithful segregation of the genome into daughter nuclei. Although the structure and composition of mitotic chromosomes have been studied for over 30 years, these aspects are yet to be fully elucidated. Here, we used stable isotope labeling with amino acids in cell culture (SILAC) to compare the proteomes of mitotic chromosomes isolated from cell lines harboring conditional knockouts of members of the condensin (SMC2, CAP-H, CAP-D3), cohesin (Scc1/Rad21), and SMC5/6 (SMC5) complexes. Our analysis revealed that these complexes associate with chromosomes independently of each other, with the SMC5/6 complex showing no significant dependence on any other chromosomal proteins during mitosis. To identify subtle relationships between chromosomal proteins, we employed a nano Random Forest (nanoRF) approach to detect protein complexes and the relationships between them. Our nanoRF results suggested that as few as 113 of 5,058 detected chromosomal proteins are functionally linked to chromosomestructure and segregation. Furthermore, nanoRF data revealed 23 proteins that were not previously suspected to have functional interactions with complexes playing important roles in mitosis. Subsequent small-interfering-RNA-based validation and localization tracking by green fluorescent protein-tagging highlighted novel candidates that might play significant roles in mitotic progression.

Khiem A Tran,1,* Michelle Y Cheng,1,* Anupam Mitra,1 Hiromi Ogawa,1 Vivian Y Shi,1 Laura P Olney,1 April M Kloxin,2Emanual Maverakis1 1Department of Dermatology, University of California, Davis, Sacramento, CA, USA;2Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE, USA *These authors contributed equally tothis work Abstract: The treatment of melanoma has improved markedly over the last several years with the advent of more targeted therapies. Unfortunately, complex compensation mechanisms, such as those of the mitogen-activated protein kinase (MAPK) pathway, have limited the clinical benefit of these treatments. Recently, a better understanding of melanoma resistance mechanisms has given way to intelligently designed multidrug regimes. Herein, we review the extensive pathways of BRAF inhibitor (vemurafenib and dabrafenib) resistance. We also review the advantages of dual therapy, including the addition of an MEK inhibitor (cobimetinib or trametinib), which has proven to increase progression-free survival when compared to BRAF inhibitor monotherapy. Finally, this review touches on future treatment strategies that are being developed for advanced melanoma, including the possibility of triple therapy with immune checkpoint inhibitors and the work on optimizing sequential therapy. Keywords: cobimetinib, trametinib, vemurafenib, dabrafenib, BRAF inhibitor, MAPK pathway

In late years, the mass outbreak of the "measles" patient was conveyed in the universities of Kanto area mainly, and it caused the closure of school successively.Through the spread of this measles, the preventive correspondence to infectious disease, such as antibody inspection and vaccination, came to be demanded in not only children but also university students.New influenza A (H1N1) which occurred in Mexico in this March speeded all over the world, and WHO declared the caution as six phase of pandemic on June 12, 2009.The virus was brought into island Japan equally in the beginning of May, and the infection opens now for eight months.We had the report of the infecte in our college in the beginning of September and a few outbreaks were watched, but afterwards it doesn't lead to the closure of school.In the spot of group education, the safe management and the crisis control predicting various infections is demanded today.So, we looked back on the precaution of infectious disease in this college and considered about the making of system which corresponds to more demand for new infectious diseases.In late years, as for the outbreak of infectious disease in the school, such as revival of tuberculosis, group lunch infection by O157 and SARS of new infectious disease etc., the correspondence to the crisis control became the important matter of the school., 8, KJ00006220899, 論文

In late years, the children who are required the particular support became a big issue.We think that in its background, there is the increase of children needing medical care in a general school, and the most of them are needing the action of medical care, such as absorption of the phlegm, self withdrawing of urine and the tubal feeding, and these cause embarrassment of teacher whether or not it is possible for the action of the medical care.We think today, so it is going to be placed these medical actions as a new role of the Yogo teacher, teacher will be required the recognition for the medical action.However, now, these educations and trainings of medical care are not established for the students aiming for teacher and teachers yet.Therefore, In this study , through "the guide learning" as one of the way of educational method about the training of the medical care, we tried to grasp the evidence of the promotion of the student's learning will and needs for school nurse.We analyzed the obtained result, through the accomplishment degree of nursing training I, and clarified the effectiveness and problem of "the guide learning" in the medical care., 6, KJ00006220839, 論文

Caspase-activated DNase (CAD) is a major apoptotic nuclease, responsible for DNA fragmentation and chromatin condensation during apoptosis. CAD is normally activated in apoptosis as a result of caspase cleavage of its inhibitory chaperone ICAD. Other aspects of CAD regulation are poorly understood. In particular, it has been unclear whether direct CAD activation in non-apoptotic living cells can trigger cell death. Taking advantage of the auxin-inducible degron (AID) system, we have developed a suicide system with which ICAD is rapidly degraded in living cells in response to the plant hormone auxin. Our studies demonstrate that rapid ICAD depletion is sufficient to activate CAD and induce cell death in DT40 and yeast cells. In the vertebrate cells, ectopic CAD activation triggered caspase activation and subsequent hallmarks of caspase-dependent apoptotic changes, including phosphatidylserine exposure and nuclear fragmentation. These observations not only suggest that CAD activation drives apoptosis through a positive feedback loop, but also identify a unique suicide system that can be used for controlling gene-modified organisms.

The CPC [chromosomal passenger complex INCENP (inner centromere protein) Aurora B kinase survivin and borealin] is implicated in many mitotic processes In the present paper we describe how we generated DT40 conditional knockout cell lines for incenp1 and survivin1 to better understand the role of these CPC subunits in the control of Aurora B kinase activity These lines enabled us to reassess current knowledge of survivin function and to show that INCENP acts as a rheostat for Aurora B activity