APCFZR1 prevents nondisjunction in mouse oocytes by controlling meiotic spindle assembly timing

FZR1 is an anaphase-promoting complex (APC) activator best known for its role in the mitotic cell cycle at M-phase exit, in G1, and in maintaining genome integrity. Previous studies also established that it prevents meiotic resumption, equivalent to the G2/M transition. Here we report that mouse oocytes lacking FZR1 undergo passage through meiosis I that is accelerated by ?1 h, and this is due to an earlier onset of spindle assembly checkpoint (SAC) satisfaction and APC(CDC20) activity. However, loss of FZR1 did not compromise SAC functionality; instead, earlier SAC satisfaction was achieved because the bipolar meiotic spindle was assembled more quickly in the absence of FZR1. This novel regulation of spindle assembly by FZR1 led to premature bivalent attachment to microtubules and loss of kinetochore-bound MAD2. Bivalents, however, were observed to congress poorly, leading to nondisjunction rates of 25%. We conclude that in mouse oocytes FZR1 controls the timing of assembly of the bipolar spindle and in so doing the timing of SAC satisfaction and APC(CDC20) activity. This study implicates FZR1 as a major regulator of prometaphase whose activity helps to prevent chromosome nondisjunction.<br/

Reduced chromosome cohesion measured by interkinetochore distance is associated with aneuploidy even in oocytes from young mice

It is becoming clear that reduced chromosome cohesion is an important factor in the rise of maternal age-related aneuploidy. This reduction in cohesion has been observed both in human and mouse oocytes, and it can be measured directly by an increase with respect to maternal age in interkinetochore (iKT) distance between a sister chromatid pair. We have observed variations in iKT distance even in oocytes from young mice and wondered if such differences may predispose those oocytes displaying the greatest iKT distances to be becoming aneuploid. Therefore, we used two methods, one pharmacological (Aurora kinase inhibitor) and one genetic (Fzr1 knockout), to raise aneuploidy rates in oocytes from young mice (age, 1-3 mo) and to examine if those oocytes that were aneuploid had greater iKT distances. We observed that for both Aurora kinase inhibition and Fzr1 knockout, iKT distances were significantly greater in those oocytes that became aneuploid compared to those that remained euploid. Based on these results, we propose that individual oocytes undergo loss in chromosomal cohesion at different rates and that the greater this loss, the greater the risk for becoming aneuploid

Introduction: Dispersed Minorities and Non-Territorial Autonomy

The concept of non-territorial autonomy gives rise to at least two important questions: the range of functional areas over which autonomy extends, and the extent to which this autonomy is indeed non-territorial. A widely used early description significantly labelled this ‘national cultural autonomy’, implying that its focus is mainly on cultural matters, such as language, religion, education and family law. In many of the cases that are commonly cited, ‘autonomy’ may not even extend this far: its most visible expression is the existence of separate electoral registers or quotas for the various groups. Part of the dilemma lies in the difficulty of devolving substantial power on a non-territorial basis: to the extent that devolved institutions are state-like, they ideally require a defined territory. Ethnic groups, however, vary in the extent to which they are territorially concentrated, and therefore in the degree to which any autonomous arrangements for them are territorial or non-territorial. This article explores the dilemma generated by this tension between ethnic geography (pattern of ethnic settlement) and political autonomy (degree of selfrule), and introduces a set of case studies where the relationship between these two features is discussed further: the Ottoman empire and its successor states, the Habsburg monarchy, the Jewish minorities of Europe, interwar Estonia, contemporary Belgium, and two indigenous peoples, the Sa´mi in Norway and the Maori in New Zealand

Protecting Marine Biodiversity: A Comparison of Individual Habitat Quota (IHQs) and Marine Protected Areas

Fisheries managers in the United States are required to identify and mitigate the adverse impacts of fishing activity on essential fish habitat (EFH). There are additional concerns that the viability of noncommercial species, animals that are habitat dependent and/or are themselves constituents of fishery habitat may still be threatened. We consider a cap-and-trade system for habitat conservation, individual habitat quotas for fisheries, to achieve habitat conservation and species protection goals cost effectively. Individual quotas of habitat impact units (HIUs) would be distributed to fishers with an aggregate quota set to maintain a target habitat stock of EFH conservation. Using a dynamic, spatially explicit fishery simulation model we explore the efficiency and cost effectiveness of an IHQ policy versus alternative marine protected area (MPA) configurations, at reducing the risk of extinguishing a habitat dependent species of unknown spatial distribution. Our findings indicate that an IHQ policy with a conservatively established habitat target is better suited to the protection of non-target species than a rotating or fixed MPA policy