Maternally encoded stem-loop-binding protein is degraded in 2-cell mouse embryos by the co-ordinated activity of two separately regulated pathways

AbstractOocytes accumulate mRNAs and proteins that direct early embryonic development. Although subsequent development requires the timely degradation of these maternal products, little is known of the underlying mechanisms. The stem-loop-binding protein (SLBP), which regulates the stability and translation of mRNAs encoding histones and is synthesized during S-phase and degraded during G2 in somatic cells, accumulates during oogenesis. Maternal SLBP is required for mouse embryos to develop beyond the 2-cell stage, but must be degraded to allow the cell-cycle-regulated expression of somatic cells to be established. We report that the quantity of maternal SLBP changes little following fertilization until 44–52 h post-hCG, corresponding to mid-/late G2 of the 2-cell stage, when it decreases by 75%. Efficient degradation requires two pathways. The first requires activity of cyclin-dependent kinases (cdk) and embryonic transcription, preferentially targets nuclear SLBP, and likely corresponds to the pathway that degrades SLBP at G2 in somatic cells. The second does not require cdk activity or transcription and becomes active at 44–52 h post-hCG independently of cell-cycle progression to mid-/late G2, but is not solely regulated by the time elapsed since hCG injection. Thus, the co-ordinated activity of two separately regulated pathways eliminates maternally encoded SLBP from early mouse embryos

Stem–loop binding protein expressed in growing oocytes is required for accumulation of mRNAs encoding histones H3 and H4 and for early embryonic development in the mouse

AbstractGrowing oocytes accumulate mRNAs and proteins that support early embryogenesis. Among the most abundant of these maternal factors are the histones. Histone mRNA accumulation and translation are mainly restricted to S-phase in somatic cells, and the mechanism by which oocytes produce histones is unknown. In somatic cells, replication-dependent histone synthesis requires the stem–loop binding protein (SLBP). SLBP is expressed during S-phase, binds to the 3′-untranslated region of non-polyadenylated transcripts encoding the histones, and is required for their stabilization and translation. SLBP is expressed in oocytes of several species, suggesting a role in histone synthesis. To test this, we generated transgenic mice whose oocytes lack SLBP. mRNAs encoding histones H3 and H4 failed to accumulate in these oocytes. Unexpectedly, mRNAs encoding H2A and H2B were little affected. Embryos derived from SLBP-depleted oocytes reached the 2-cell stage, but most then became arrested. Histones H3 and H4, but not H2A or H2B, were substantially reduced in these embryos. The embryos also expressed high levels of γH2A.X. Injection of histones into SLBP-depleted embryos rescued them from developmental arrest. Thus, SLBP is an essential component of the mechanism by which growing oocytes of the mouse accumulate the histones that support early embryonic development

The stem-loop binding protein regulates translation of histone mRNA during mammalian oogenesis

Although messenger RNAs encoding the histone proteins are among the most abundant in mammalian oocytes, the mechanism regulating their translation has not been identified. The stem-loop binding protein (SLBP) binds to a highly conserved sequence in the 3′-untranslated region (utr) of the non-polyadenylated histone mRNAs in somatic cells and mediates their stabilization and translation. We previously showed that SLBP, which is expressed only during S-phase of proliferating cells, is expressed in growing oocytes at G2 of the cell cycle and accumulates substantially during meiotic maturation. We report here that elevating the amount of SLBP in immature (G2) oocytes is sufficient to increase translation of a reporter mRNA bearing the histone 3′-utr and endogenous histone synthesis and that this effect is not mediated through increased stability of the encoding mRNAs. We further report that translation of the reporter mRNA increases dramatically during meiotic maturation coincident with the accumulation of SLBP. Conversely, when SLBP accumulation during maturation is prevented using RNA interference, both translation of the reporter mRNA and synthesis of endogenous histones are significantly reduced. This effect is not mediated by a loss of the encoding mRNAs. Moreover, following fertilization, SLBP-depleted oocytes also show a significant decrease in pronuclear size and in the amount of acetylated histone detectable on the chromatin. These results demonstrate that histone synthesis in immature and maturing oocytes is governed by a translational control mechanism that is directly regulated by changes in the amount of SLBP

Resonant Mie Scattering (RMieS) correction of infrared spectra from highly scattering biological samples

Infrared spectra of single biological cells often exhibit the “dispersion artefact” observed as a sharp decrease in intensity on the high wavenumber side of absorption bands, in particular the Amide I band at ~1655 cm-1, causing a downward shift of the true peak position. The presence of this effect makes any biochemical interpretation of the spectra unreliable. Recent theory has shed light on the origins of the ‘dispersion artefact’ which has been attributed to resonant Mie scattering (RMieS). In this paper a preliminary algorithm for correcting RMieS is presented and evaluated using simulated data. Results show that the ‘dispersion artefact’ appears to be removed, however, the correction is not perfect. An iterative approach was subsequently implemented whereby the reference spectrum is improved after each iteration, resulting in a more accurate correction. Consequently the corrected spectra become increasingly more representative of the pure absorbance spectra. Using this correction method reliable peak positions can be obtained

Quantum Gates and Memory using Microwave Dressed States

Trapped atomic ions have been successfully used for demonstrating basic elements of universal quantum information processing (QIP). Nevertheless, scaling up of these methods and techniques to achieve large scale universal QIP, or more specialized quantum simulations remains challenging. The use of easily controllable and stable microwave sources instead of complex laser systems on the other hand promises to remove obstacles to scalability. Important remaining drawbacks in this approach are the use of magnetic field sensitive states, which shorten coherence times considerably, and the requirement to create large stable magnetic field gradients. Here, we present theoretically a novel approach based on dressing magnetic field sensitive states with microwave fields which addresses both issues and permits fast quantum logic. We experimentally demonstrate basic building blocks of this scheme to show that these dressed states are long-lived and coherence times are increased by more than two orders of magnitude compared to bare magnetic field sensitive states. This changes decisively the prospect of microwave-driven ion trap QIP and offers a new route to extend coherence times for all systems that suffer from magnetic noise such as neutral atoms, NV-centres, quantum dots, or circuit-QED systems.Comment: 9 pages, 4 figure

Silica cycling and isotopic composition in northern Marguerite Bay on the rapidly-warming western Antarctic Peninsula

The Southern Ocean is a key region for silica (Si) cycling, and the isotopic signatures established here influence the rest of the world's oceans. The climate and ecosystem of the Southern Ocean are changing rapidly, with the potential to impact Si cycling and isotope dynamics. This study examines high-resolution time-series dataset of dissolved Si concentrations and isotopic signatures, particulate Si concentrations and diatom speciation at a coastal site on the western Antarctic Peninsula (WAP), in order to characterise changes in Si cycling with respect to changes occurring in productivity and diatom assemblages. Dissolved and particulate Si phases reflect the dominant control of biological uptake, and combined with isotopic fractionation were consistent with a season of low/intermediate productivity. Biogenic Si is tightly coupled to both chlorophyll and particulate organic carbon at the sampling site, consistent with diatom-dominated phytoplankton assemblages along the WAP. Variability in diatom speciation has a negligible impact on the isotopic signature of dissolved Si in surface waters, although this is unlikely to hold for sediments due to differential dissolution of diatom species. A continued decline in diatom productivity along the WAP would likely result in an increasing unused Si inventory, which can potentially feed back into Si-limited areas, promoting diatom growth and carbon drawdown further afield

Impact of rapid near-patient STI testing on service delivery outcomes in an integrated sexual health service in the United Kingdom:a controlled interrupted time series study

OBJECTIVES: To evaluate the impact of a new clinic-based rapid sexually transmitted infection testing, diagnosis and treatment service on healthcare delivery and resource needs in an integrated sexual health service. DESIGN: Controlled interrupted time series study. SETTING: Two integrated sexual health services (SHS) in UK: Unity Sexual Health in Bristol, UK (intervention site) and Croydon Sexual Health in London (control site). PARTICIPANTS: Electronic patient records for all 58 418 attendances during the period 1 year before and 1 year after the intervention. INTERVENTION: Introduction of an in-clinic rapid testing system for gonorrhoea and chlamydia in combination with revised treatment pathways. OUTCOME MEASURES: Time-to-test notification, staff capacity, cost per episode of care and overall service costs. We also assessed rates of gonorrhoea culture swabs, follow-up attendances and examinations. RESULTS: Time-to-notification and the rate of gonorrhoea swabs significantly decreased following implementation of the new system. There was no evidence of change in follow-up visits or examination rates for patients seen in clinic related to the new system. Staff capacity in clinics appeared to be maintained across the study period. Overall, the number of episodes per week was unchanged in the intervention site, and the mean cost per episode decreased by 7.5% (95% CI 5.7% to 9.3%). CONCLUSIONS: The clear improvement in time-to-notification, while maintaining activity at a lower overall cost, suggests that the implementation of clinic-based testing had the intended impact, which bolsters the case for more widespread rollout in sexual health services

Spectroscopic signatures of youth in low-mass kinematic candidates of young moving groups

This article has been accepted for publication in Monthly Notices of the Royal Astronomical Society ©: 2014 by the Authors. Published by Oxford University Press on behalf of the Royal Astronomical Society. All rights reserved.We present a study of age-related spectral signatures observed in 25 young low-mass objects that we have previously determined as possible kinematic members of five young moving groups: the Local Association (Pleiades moving group, age = 20–150 Myr), the Ursa Major group (Sirius supercluster, age = 300 Myr), the Hyades supercluster (age = 600 Myr), IC 2391 supercluster (age = 35–55 Myr) and the Castor moving group (age = 200 Myr). In this paper we characterize the spectral properties of observed high- or low-resolution spectra of our kinematic members by fitting theoretical spectral distributions. We study signatures of youth, such as lithium I 6708Å, Hα emission and other age-sensitive spectroscopic signatures in order to confirm the kinematic memberships through age constraints. We find that 21 (84 per cent) targets show spectroscopic signatures of youth in agreement with the age ranges of the moving group to which membership is implied. For two further objects, age-related constraints remain difficult to determine from our analysis. In addition, we confirm two moving group kinematic candidates as brown dwarfs.Peer reviewe

Epidemiology of Subpatent Plasmodium Falciparum Infection: Implications for Detection of Hotspots with Imperfect Diagnostics.

At the local level, malaria transmission clusters in hotspots, which may be a group of households that experience higher than average exposure to infectious mosquitoes. Active case detection often relying on rapid diagnostic tests for mass screen and treat campaigns has been proposed as a method to detect and treat individuals in hotspots. Data from a cross-sectional survey conducted in north-western Tanzania were used to examine the spatial distribution of Plasmodium falciparum and the relationship between household exposure and parasite density. Dried blood spots were collected from consenting individuals from four villages during a survey conducted in 2010. These were analysed by PCR for the presence of P. falciparum, with the parasite density of positive samples being estimated by quantitative PCR. Household exposure was estimated using the distance-weighted PCR prevalence of infection. Parasite density simulations were used to estimate the proportion of infections that would be treated using a screen and treat approach with rapid diagnostic tests (RDT) compared to targeted mass drug administration (tMDA) and Mass Drug Administration (MDA). Polymerase chain reaction PCR analysis revealed that of the 3,057 blood samples analysed, 1,078 were positive. Mean distance-weighted PCR prevalence per household was 34.5%. Parasite density was negatively associated with transmission intensity with the odds of an infection being subpatent increasing with household exposure (OR 1.09 per 1% increase in exposure). Parasite density was also related to age, being highest in children five to ten years old and lowest in those > 40 years. Simulations of different tMDA strategies showed that treating all individuals in households where RDT prevalence was above 20% increased the number of infections that would have been treated from 43 to 55%. However, even with this strategy, 45% of infections remained untreated. The negative relationship between household exposure and parasite density suggests that DNA-based detection of parasites is needed to provide adequate sensitivity in hotspots. Targeting MDA only to households with RDT-positive individuals may allow a larger fraction of infections to be treated. These results suggest that community-wide MDA, instead of screen and treat strategies, may be needed to successfully treat the asymptomatic, subpatent parasite reservoir and reduce transmission in similar settings

The freshwater system west of the Antarctic Peninsula : spatial and temporal changes

Author Posting. © American Meteorological Society, 2013. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Climate 26 (2013): 1669–1684, doi:10.1175/JCLI-D-12-00246.1.Climate change west of the Antarctic Peninsula is the most rapid of anywhere in the Southern Hemisphere, with associated changes in the rates and distributions of freshwater inputs to the ocean. Here, results from the first comprehensive survey of oxygen isotopes in seawater in this region are used to quantify spatial patterns of meteoric water (glacial discharge and precipitation) separately from sea ice melt. High levels of meteoric water are found close to the coast, due to orographic effects on precipitation and strong glacial discharge. Concentrations decrease offshore, driving significant southward geostrophic flows (up to ~30 cm s−1). These produce high meteoric water concentrations at the southern end of the sampling grid, where collapse of the Wilkins Ice Shelf may also have contributed. Sea ice melt concentrations are lower than meteoric water and patchier because of the mobile nature of the sea ice itself. Nonetheless, net sea ice production in the northern part of the sampling grid is inferred; combined with net sea ice melt in the south, this indicates an overall southward ice motion. The survey is contextualized temporally using a decade-long series of isotope data from a coastal Antarctic Peninsula site. This shows a temporal decline in meteoric water in the upper ocean, contrary to expectations based on increasing precipitation and accelerating deglaciation. This is driven by the increasing occurrence of deeper winter mixed layers and has potential implications for concentrations of trace metals supplied to the euphotic zone by glacial discharge. As the regional freshwater system evolves, the continuing isotope monitoring described here will elucidate the ongoing impacts on climate and the ecosystem.The Palmer LTER participants acknowledge Award 0823101 from the Organisms and Ecosystems program in NSF OPP2013-09-0