COMSOL 소프트웨어 프로그램을 이용하여 중공사형 분리막 모듈 내 용액의 속도 및 압력 분포를 포함한 유동현상을 규명하였으며 투과유속에 따른 농도분극을 수치해석하였다. 모듈의 길이, 충전율, 회수율 및 투과 유속 그리고 입구의 위치를 하단부 혹은 측면부로 변화시키면서 계산하였다. 이상의 운전변수 중 모듈의 길이가 압력 강하에 가장 큰 영향을 미침을 확인하였으며 중공사형 모듈 내의 농도분극은 입출구의 위치에 따라서 변화함을 알 수 있었다.

Accurate chromosome segregation is critical to ensure genomic integrity during cell division. This process is facilitated by the kinetochore, a multiprotein structure that is assembled on centromeric regions of chromosomes. The kinetochore establishes a mechanical link between the chromosomes and spindle microtubules and modulates cell cycle progression by regulating spindle assembly checkpoint (SAC). Defects in this process result in an aneuploidy, leading to miscarriages, infertility and various genetic disorder such as Down’s syndrome. Although the numerous kinetochore proteins have been identified and studied, the mechanisms that engaged in kinetochore assembly and chromosome segregation are poorly understood. Here we investigated the function of kinetochore protein Zwint-1 on homologous chromosome segregation during oocyte meiotic maturation. We found that Zwint-1 was localized at the kinetochore during meiotic maturation. Knockdown of Zwint-1 caused premature polar body extrusion, indicating acceleration of meiosis I. Interestingly, Zwint-1 knockdown impaired the recruitment of Mad2 at the kinetochores. However, BubR1 localization at the kinetochores was not affected by Zwint-1 knockdown, suggesting that Zwint-1 selectively regulates the recruitment of SAC components into the kinetochores. We also found that Zwint-1 knockdown abrogated chromosome alignment and segregation, thereby resulting in a high incidence of aneuploidy. These chromosomal defects were mostly due to the abnormal kinetochore-microtubule (kMT) attachments. Intriguingly, chromosome misalignment mediated by SAC inactivation was repaired, when anaphase onset was delayed by treating oocytes with proteasome inhibitor MG132. However, surprisingly, chromosomal defects following Zwint-1 knockdown were not restored by delaying anaphase onset. This result suggests that chromosomal defects induced by Zwint-1 knockdown are less likely associated with the failure of SAC activation. In addition, we observed that Aurora B/C kinase activity was not affected by Zwint-1 knockdown. Nevertheless, the meiotic defects induced by Zwint-1 knockdown were similar to those observed in Aurora B/C inhibition, suggesting that Zwint-1 is a downstream effector of Aurora B/C kinase during meiosis. Consistent with this, in Zwint-1 knockdown oocytes chromosomal defects following Aurora B/C inhibition were not restored when Aurora B/C inhibitor was removed, whereas the defects were well rescued in control oocytes after removing Aurora B/C inhibitor. This result suggests that the role of Aurora B/C kinases that correct erroneous kMT attachment is primarily regulated by Zwint-1. Collectively, our results demonstrated for the first time that Zwint-1 is an essential downstream effector of Aurora B/C kinase that corrects erroneous kMT attachment and regulates SAC activity, which ensures accurate homologous chromosome segregation during oocyte meiosis.