Chiasmata Promote Monopolar Attachment of Sister Chromatids and Their Co-Segregation toward the Proper Pole during Meiosis I

The chiasma is a structure that forms between a pair of homologous chromosomes by crossover recombination and physically links the homologous chromosomes during meiosis. Chiasmata are essential for the attachment of the homologous chromosomes to opposite spindle poles (bipolar attachment) and their subsequent segregation to the opposite poles during meiosis I. However, the overall function of chiasmata during meiosis is not fully understood. Here, we show that chiasmata also play a crucial role in the attachment of sister chromatids to the same spindle pole and in their co-segregation during meiosis I in fission yeast. Analysis of cells lacking chiasmata and the cohesin protector Sgo1 showed that loss of chiasmata causes frequent bipolar attachment of sister chromatids during anaphase. Furthermore, high time-resolution analysis of centromere dynamics in various types of chiasmate and achiasmate cells, including those lacking the DNA replication checkpoint factor Mrc1 or the meiotic centromere protein Moa1, showed the following three outcomes: (i) during the pre-anaphase stage, the bipolar attachment of sister chromatids occurs irrespective of chiasma formation; (ii) the chiasma contributes to the elimination of the pre-anaphase bipolar attachment; and (iii) when the bipolar attachment remains during anaphase, the chiasmata generate a bias toward the proper pole during poleward chromosome pulling that results in appropriate chromosome segregation. Based on these results, we propose that chiasmata play a pivotal role in the selection of proper attachments and provide a backup mechanism that promotes correct chromosome segregation when improper attachments remain during anaphase I

Effect of SHe temperature on Cool-down Speed in JT-60SA CS module

The JT-60SA central solenoid (CS), which consists of four stacked modules, is cooled to an operating temperature of 4.5 K by supercritical helium (SHe). During cool-down from room temperature to 4.5 K, in order to avoid a damage on the coil, it is required to reduce thermal stress due to temperature difference in the coil. In the cool-down operation, the CS needs to control the maximum temperature difference in the longitudinal direction of the cable-in-conduit (CIC) conductor below 40 K. However, since that could damage the coil, correctly estimating the temperature distribution in the conductor is important for ensuring the cooldown operation is performed safely. In the present study, the JT- 60SA CS module was prepared and the inlet and outlet temperatures, as well as the SHe mass flow rate, were measured until the CS module was cooled to operating temperature, after which a CS module simulation was performed in order to determine the effect of the inlet temperature on the cool-down speed. From the simulation results, it was concluded that the average cool-down speed was 0.73 K/h and the CS module reached 80 K in approximately 8.3 days while maintaining the maximum temperature difference within 40 K. Furthermore, the temperature difference between the inlet and outlet was kept within 25 K in order to limit the thermal stress. Taken together, the results of our analyses provide fundamental data that can be used to evaluate the safe cool-down operation of the coil and thus protect the coil systems.Applied Superconductivity Conference 2020 (ASC2020

The MDM2–p53 Axis Represents a Therapeutic Vulnerability Unique to Glioma Stem Cells

The prevention of tumor recurrence by the successful targeting of glioma stem cells endowed with a tumor-initiating capacity is deemed the key to the long-term survival of glioblastoma patients. Glioma stem cells are characterized by their marked therapeutic resistance; however, recent evidence suggests that they have unique vulnerabilities that may be therapeutically targeted. We investigated MDM2 expression levels in glioma stem cells and their non-stem cell counterparts and the effects of the genetic and pharmacological inhibition of MDM2 on the viability of these cells as well as downstream molecular pathways. The results obtained showed that MDM2 expression was substantially higher in glioma stem cells than in their non-stem cell counterparts and also that the inhibition of MDM2, either genetically or pharmacologically, induced a more pronounced activation of the p53 pathway and apoptotic cell death in the former than in the latter. Specifically, the inhibition of MDM2 caused a p53-dependent increase in the expression of BAX and PUMA and a decrease in the expression of survivin, both of which significantly contributed to the apoptotic death of glioma stem cells. The present study identified the MDM2–p53 axis as a novel therapeutic vulnerability, or an Achilles’ heel, which is unique to glioma stem cells. Our results, which suggest that non-stem, bulk tumor cells are less sensitive to MDM2 inhibitors, may help guide the selection of glioblastoma patients suitable for MDM2 inhibitor therapy

Correction to: Recurrence with pagetoid spread arising 17 years after surgery for intramucosal rectal cancer: a case report

Abstract After publication of the original article [1] the authors noted that the following errors had occurred

Recurrence with pagetoid spread arising 17 years after surgery for intramucosal rectal cancer: a case report

Abstract Background Perianal Paget’s disease (pPD) is uncommon, with only about 180 cases documented in the literature. Anorectal carcinoma with pagetoid spread is even rarer. Case presentation An 81-year-old woman underwent rectal cancer extirpation with a transanal approach 17 years prior. She has since undergone two reoperations for local rectal cancer recurrence. Then, warts frequently appeared on the vulva on several occasions. Warts appeared on the vulva 1 year ago, which were diagnosed as pPD by biopsy. She underwent perineal tumor resection, and the final histological diagnosis was rectal cancer recurrence with pagetoid spread. The resected stump was positive for cancer cells, and tumor progression was rapid. She underwent additional abdominoperineal resection (Miles’ operation) with lymph node dissection. However, disease progression was rapid and she died 7 months after the Miles’ operation. Conclusions There are some case reports describing anorectal carcinoma with pagetoid spread, however, almost of all those cases were synchronous primary anorectal cancer. Here, we report the first case of metachronous recurrence rectal cancer with pagetoid spread arising 17 years after surgery

Self-align fabrication of nano-reservoir with NV center in diamond surface for nuclear magnetic resonance of small molecules

We propose a novel structure to confine small molecules in a nanoscale reservoir and perform nano-NMR with a single NV center created near the reservoir base. We also propose a self-align process to fabricate the nano-reservoir and the single NV center adjacently in the diamond surface using electron beam lithography, nitrogen ion implantation and oxygen plasma etching. In this paper, we discuss the feasibility of the nano-NMR using nano-reservoirs in terms of the damage induced in the diamond by dry etching, the detection volume (i.e. the implantation depth) and the electron spin coherence property of the NV center.32nd International Microprocesses and Nanotechnology Conferenc