Homologous chromosome segregation errors during meiosis I are common and generate aneuploid embryos. Here, we provide a reason for this susceptibility to mis-segregation by live cell imaging of mouse oocytes. Our results show that stable kinetochore-microtubule attachments form in mid-prometaphase, 3-4 hours before anaphase. This coincided with the loss Mad2 from kinetochores start anaphase-promoting complex/cyclosome (APC/C)-mediated cyclin B1 destruction. Therefore, spindle assembly...

Extensive damage to maternal DNA during meiosis causes infertility, birth defects and abortions. However, it is unknown if fully grown oocytes have a mechanism prevent the creation of DNA-damaged embryos. Here we show that activates pathway involving spindle assembly checkpoint (SAC) in response chemically induced double strand breaks, UVB ionizing radiation. can occur either before or after nuclear envelope breakdown, provides an effective block anaphase-promoting complex activity,...

As women get older their oocytes become susceptible to chromosome mis-segregation. This generates aneuploid embryos, leading increased infertility and birth defects. Here we examined the provenance of aneuploidy by tracking chromosomes kinetochores in from young aged mice. Changes consistent with cohesion deterioration were found age, including interkinetochore distance loss centromeric protector SGO2 metaphase II arrested (metII) eggs, as well a rise number weakly attached bivalents meiosis...

Currently, maternal aging in women, based on mouse models, is thought to raise oocyte aneuploidy rates, because chromosome cohesion deteriorates during prophase arrest, and Sgo2, a protector of centromeric cohesion, lost. Here we show that the most common strain, C57Bl6/J, resistant aging, showing little increase or Sgo2 loss. Instead it demonstrates significant kinetochore-associated loss spindle assembly checkpoint protein Mad2 phosphorylated Aurora C, which involved...

Abstract Whether the adult mammalian ovary contains oogonial stem cells (OSCs) is controversial. They have been isolated by a live-cell sorting method using germ cell marker DDX4, which has previously assumed to be cytoplasmic, not surface-bound. Furthermore their and characteristics remain disputed. Here we show that although OSC-like can from an antibody there no good in silico modelling support existence of surface-bound DDX4. these when were expressing DDX4 did initially possess germline...

In the first meiotic division (MI) of oocytes, cortically positioned spindle causes bivalent segregation in which only centre-facing homologue pairs are retained. 'Selfish' chromosomes known to exist, bias their orientation and hence retention egg, a process as 'meiotic drive'. Here we report on this phenomenon oocytes from F1 hybrid mice, where parental strain differences centromere size allows distinction two bivalent. Bivalents with kinetochore asymmetry show drive by rotating during...

Abstract Mouse oocytes respond to DNA damage by arresting in meiosis I through activity of the Spindle Assembly Checkpoint (SAC) and Damage Response (DDR) pathways. It is currently not known if primary trigger for arrest, or pathway sensitive levels experienced physiologically. Here, using follicular fluid from patients with disease endometriosis, which affects 10% women associated reduced fertility, we find raised Reactive Oxygen Species (ROS), generate turn on DDR-SAC pathway. Only...

Previous studies have established that when maturing mouse oocytes are continuously incubated with the Aurora inhibitor ZM447439, meiotic maturation is blocked. In this study, we observe by altering time of addition inhibitor, oocyte can actually be accelerated 1 h as measured timing polar body extrusion. ZM447439 also had ability to overcome a spindle assembly checkpoint (SAC) arrest caused nocodazole and so rescue Consistent SAC inhibit cyclin B1 degradation blocking activation...

Mouse oocytes carrying DNA damage arrest in meiosis I, thereby preventing creation of embryos with deleterious mutations. The is dependent on the spindle assembly checkpoint, which results anaphase-promoting complex (APC) inhibition. However, little understood about how this checkpoint engaged following damage. Here, we find that within minutes assembles proteins at kinetochore, not sites along chromosome arms, such APC fully inhibited 30 min. Despite robust response, there no measurable...

Directional connectivity is required to develop accurate in vitro models of the nervous system. This research investigated interaction murine neuronal outgrowths with asymmetric microstructured geometries provide insights into mechanisms governing unidirectional outgrowth bias. The structures were designed using edge-guidance and critical turning angle principles study different prohibitive permissive ratios. enable direction, while reducing direction. Outgrowth bias was probabilistic...

The spindle assembly checkpoint (SAC) prevents chromosome missegregation by coupling anaphase onset with correct attachment and tension to microtubules. It does this generating a diffusible signal from free kinetochores into the cytoplasm, inhibiting anaphase-promoting complex (APC). volume in which remains effective is unknown. This raises possibility that cell may be reason SAC weak, segregation error-prone, mammalian oocytes. Here, process of serial bisection, we analyzed influence oocyte...

FZR1 is an anaphase-promoting complex (APC) activator best known for its role in the mitotic cell cycle at M-phase exit, G1, and maintaining genome integrity. Previous studies also established that it prevents meiotic resumption, equivalent to G2/M transition. Here we report mouse oocytes lacking undergo passage through meiosis I accelerated by ~1 h, this due earlier onset of spindle assembly checkpoint (SAC) satisfaction APC(CDC20) activity. However, loss did not compromise SAC...

Levels of sound intensity were measured over periods 24 hours in 34 abattoir lairages England and Wales. The mean integrated range 12 cattle was 52 to 79 dB(A), 11 sheep lairages, 45 76 dB(A) pig 46 87 dB(A). In general, the noisiest, with spot peak recordings up 110 Typically, intensities all 10 20 higher during working day than at night. many high recorded frequently throughout night, but others very quiet, below 40 Vocalisations major sources noise there variations between them. There...

It is becoming clear that reduced chromosome cohesion an important factor in the rise of maternal age-related aneuploidy. This reduction has been observed both human and mouse oocytes, it can be measured directly by increase with respect to age interkinetochore (iKT) distance between a sister chromatid pair. We have variations iKT even oocytes from young mice wondered if such differences may predispose those displaying greatest distances aneuploid. Therefore, we used two methods, one...

We report a 5.8-W deep-ultraviolet (DUV) laser obtained from frequency-quadrupling of an all-fiberized ytterbium-doped fiber (YDF) master oscillator power amplifier (MOPA). The MOPA system delivers 585 ps pulses at 1040 nm with maximum available output 23.5 W for nonlinear frequency conversion. A lithium triborate (LBO) crystal and beta barium borate (BBO) are employed second- fourth-harmonic generation (FHG), respectively. At repetition rate 1.6 MHz, DUV 5.8 is 260 corresponding pulse...

The conjugate addition reactions of thiin-4-one and 3-methoxycarbonylthiin-4-one have been investigated. In contrast to its 3-methoxycarbonyl derivative undergoes with a range organocopper reagents, the most efficient being copper-catalysed Grignard reagents. resulting adducts converted into 2-substituted thiin-4-ones by two procedures. This methodology has used prepare thiathromboxane analogues (12a), (12b), (13) as part ten step formal synthesis dithiathromboxane A2(9).