DNA double strand breaks but not interstrand crosslinks prevent progress through meiosis in fully grown mouse oocytes

There is some interest in how mammalian oocytes respond to different types of DNA damage because of the increasing expectation of fertility preservation in women undergoing chemotherapy. Double strand breaks (DSBs) induced by ionizing radiation and agents such as neocarzinostatin (NCS), and interstrand crosslinks (ICLs) induced by alkylating agents such as mitomycin C (MMC), are toxic DNA lesions that need to be repaired for cell survival. Here we examined the effects of NCS and MMC treatment on oocytes collected from antral follicles in mice, because potentially such oocytes are readily collected from ovaries and do not need to be in vitro grown to achieve meiotic competency. We found that oocytes were sensitive to NCS, such that this ionizing radiation mimetic blocked meiosis I and caused fragmented DNA. In contrast, MMC had no impact on the completion of either meiosis I or II, even at extremely high doses. However, oocytes treated with MMC did show ?-H2AX foci and following their in vitro maturation and parthenogenetic activation the development of the subsequent embryos was severely compromised. Addition of MMC to 1-cell embryos caused a similarly poor level of development, demonstrating oocytes have eventual sensitivity to this ICL-inducing agent but this does not occur during their meiotic division. In oocytes, the association of Fanconi Anemia protein, FANCD2, with sites of ICL lesions was not apparent until entry into the embryonic cell cycle. In conclusion, meiotic maturation of oocytes is sensitive to DSBs but not ICLs. The ability of oocytes to tolerate severe ICL damage and yet complete meiosis, means that this type of DNA lesion goes unrepaired in oocytes but impacts on subsequent embryo quality

Measuring rainfall from above and below the sea surface

Satellites play a major role in the determination of the rainfall at sea. Researchers at Southampton Oceanography Centre (SOC) have been involved in two projects addressing this task. First they have been instrumental in developing techniques to retrieve rain rate information from the 10+ years of dual-frequency altimeter data. The TOPEX radar measures rainfall via the attenuation it causes, producing a climatology that is independent of those derived from passive microwave (PM) and infrared (IR) sensors. Because TOPEX is an active microwave sensor, it can have a much smaller footprint than PM sensors. Therefore it can be used to estimate the size of rain cells, showing that the ITCZ and mid-latitude storm tracks are characterized by larger rain systems than elsewhere. TOPEX’s simultaneous recording of wind and wave data reveal that, for mid-latitude systems, rain is most likely in association with developing seas.All satellite-based datasets require validation, and SOC's work on the development and testing of acoustic rain gauges is the second aspect of this paper. By listening at a range of frequencies, an underwater hydrophone may distinguish the spectra of wind, rain, shipping etc., and estimate the wind speed or rain rate according to the magnitude of the signals. All our campaigns have shown a good acoustic response to changes in wind speed. However the quantitative inversion for recent trials has given values that are too high, possibly because of significant acoustic reflection from the sea bottom. The changes in spectral slope often agree with other observations of rain, although validation experiments in coastal regions are hampered by the extraneous sources present. Acoustic rain gauges would eventually see service not only for routine satellite validation, but also for real-time monitoring of locations of interest

FACS-sorted putative oogonial stem cells from the ovary are neither DDX4-positive nor germ cells

Whether the adult mammalian ovary contains oogonial stem cells (OSCs) is controversial. They have been isolated by a live-cell sorting method using the germ cell marker DDX4, which has previously been assumed to be cytoplasmic, not surfacebound. Furthermore their stem cell and germ cell characteristics remain disputed. Here we show that although OSC-like cells can be isolated from the ovary using an antibody to DDX4, there is no good in silico modelling to support the existence of a surfacebound DDX4. Furthermore these cells when isolated were not expressing DDX4, and did not initially possess germline identity. Despite these unremarkable beginnings, they acquired some pre-meiotic markers in culture, including DDX4, but critically never expressed oocyte-specific markers, and furthermore were not immortal but died after a few months. Our results suggest that freshly isolated OSCs are not germ stem cells, and are not being isolated by their DDX4 expression. However it may be that culture induces some pre-meiotic markers. In summary the present study offers weight to the dogma that the adult ovary is populated by a fixed number of oocytes and that adult de novo production is a rare or insignificant event

Diversity, urban space and the right to the provincial city

Using three vignettes of the same physical space this article contributes to understanding of how the right to the city is contested in provincial England in the early twenty-first century. Oral history and ethnographic material gathered in Peterborough between 2010 and 2012 are drawn on to shed new light on the politics of diversity and urban space. This highlights the multiple place attachments and trans-spatial practices of all residents, including the white ethnic majority, as well as contrasting forms of active intervention in space with their different temporalities and affective intensities. The article carries its own diversity politics, seeking to reduce the harm done by racism through challenging the normalisation of the idea of a local, indigenous population, left out by multiculturalism. It simultaneously raises critical questions about capitalist regeneration strategies in terms of their impact both on class inequality and on the environment

Why Are Students Not Majoring in Information Systems?

The purpose of this study was to examine some of the factors that influence and impact business students when they select their major and, more particularly, to examine why students are not majoring in information systems. Students in an entry level business class responded that they were more knowledgeable about careers in management, marketing, accounting, and finance than they were about careers in information systems. These business students indicated that they are looking for majors that will be interesting, provide them with job security initially and over their careers, and pay them well. The most important information sources used by these students in their major selection decision were information on college/department websites, brochures about the major, and information on the Internet. When asked why they were not majoring in information systems, the top two reasons given were not what I wanted to do and subject not of interest

Lipid coated liquid crystal droplets for the on-chip detection of antimicrobial peptides

We describe a novel biosensor based on phospholipid-coated nematic liquid crystal (LC) droplets and demonstrate the detection of Smp43, a model antimicrobial peptide (AMP) from the venom of North African scorpion Scorpio maurus palmatus. Mono-disperse lipid-coated LC droplets of diameter 16.7 ± 0.2 μm were generated using PDMS microfluidic devices with a flow-focusing configuration and were the target for AMPs. The droplets were trapped in a bespoke microfluidic trap structure and were simultaneously treated with Smp43 at gradient concentrations in six different chambers. The disruption of the lipid monolayer by the Smp43 was detected (<6 μM) at concentrations well within its biologically active range, indicated by a dramatic change in the appearance of the droplets associated with the transition from a typical radial configuration to a bipolar configuration, which is readily observed by polarizing microscopy. This suggests the system has feasibility as a drug-discovery screening tool. Further, compared to previously reported LC droplet biosensors, this LC droplet biosensor with a lipid coating is more biologically relevant and its ease of use in detecting membrane-related biological processes and interactions has the potential for development as a reliable, low-cost and disposable point of care diagnostic tool

Decoupling of Sleep-Dependent Cortical and Hippocampal Interactions in a Neurodevelopmental Model of Schizophrenia

SummaryRhythmic neural network activity patterns are defining features of sleep, but interdependencies between limbic and cortical oscillations at different frequencies and their functional roles have not been fully resolved. This is particularly important given evidence linking abnormal sleep architecture and memory consolidation in psychiatric diseases. Using EEG, local field potential (LFP), and unit recordings in rats, we show that anteroposterior propagation of neocortical slow-waves coordinates timing of hippocampal ripples and prefrontal cortical spindles during NREM sleep. This coordination is selectively disrupted in a rat neurodevelopmental model of schizophrenia: fragmented NREM sleep and impaired slow-wave propagation in the model culminate in deficient ripple-spindle coordination and disrupted spike timing, potentially as a consequence of interneuronal abnormalities reflected by reduced parvalbumin expression. These data further define the interrelationships among slow-wave, spindle, and ripple events, indicating that sleep disturbances may be associated with state-dependent decoupling of hippocampal and cortical circuits in psychiatric diseases