Basis of catalytic assembly of the mitotic checkpoint complex.

In mitosis, for each daughter cell to inherit an accurate copy of the genome from the mother cell, sister chromatids in the mother cell must attach to microtubules emanating from opposite poles of the mitotic spindle, a process known as bi-orientation. A surveillance mechanism, termed the spindle assembly checkpoint (SAC), monitors the microtubule attachment process and can temporarily halt the separation of sister chromatids and the completion of mitosis until bi-orientation is complete(1). SAC failure results in abnormal chromosome numbers, termed aneuploidy, in the daughter cells, a hallmark of many tumours. The HORMA-domain-containing protein mitotic arrest deficient 2 (MAD2) is a subunit of the SAC effector mitotic checkpoint complex (MCC). Structural conversion from the open to the closed conformation of MAD2 is required for MAD2 to be incorporated into the MCC1. In vitro, MAD2 conversion and MCC assembly take several hours(2-4), but in cells the SAC response is established in a few minutes(5-7). Here, to address this discrepancy, we reconstituted a near-complete SAC signalling system with purified components and monitored assembly of the MCC in real time. A marked acceleration in MAD2 conversion and MCC assembly was observed when monopolar spindle 1 (MPS1) kinase phosphorylated the MAD1-MAD2 complex, triggering it to act as the template for MAD2 conversion and therefore contributing to the establishment of a physical platform for MCC assembly. Thus, catalytic activation of the SAC depends on regulated protein-protein interactions that accelerate the spontaneous but rate-limiting conversion of MAD2 required for MCC assembly

The association between diabetes mellitus and urinary incontinence in adult women.

Item does not contain fulltextINTRODUCTION AND HYPOTHESIS: The purpose of the study was to investigate the relationship of diabetes mellitus and urinary incontinence in adult women. METHODS: We conducted a cross-sectional, comparative study with a case-control design. One thousand three hundred eighty-one women (aged 20-87 years) attending six Primary Healthcare Centers in Turkey were enrolled in this study, after giving their informed consent. Subjects were dichotomized into cases and controls according to presence of diabetes mellitus (DM) and were matched for the confounding factors age, body mass index (BMI), and reproductive history. RESULTS: Nine hundred ten women were included: 273 diabetics and 637 non-diabetics. Diabetes was shown to be associated with a 2.5-fold risk increase for urinary incontinence (UI), and age and BMI were weakly associated with UI. UI was significantly more prevalent in diabetic women: 41% diabetic and 22.1% non-diabetic women reported UI (p < 0.001). Age, BMI, and DM were revealed as independent determinants of UI in adult women. Urge incontinence was more prevalent in non-diabetic women, whereas stress and mixed incontinence were more prevalent among diabetic women. CONCLUSIONS: DM is the most important independent determinant of UI