STUDY QUESTION
Can the pronuclei (PN) morphology and the time of PN breakdown (PNB) predict the potential of embryos to result in live birth?
SUMMARY ANSWER
In comparison to embryos resulting in no ...live birth, PNB occurred significantly later in embryos resulting in live birth and never earlier than 20 h 45min. None of the tested scoring systems were shown to predict the live birth outcome in a time-lapse set-up.
WHAT IS KNOWN ALREADY
The PN morphology is supported as a prominent embryo selection parameter in single light microscopy observations, although controversial results have been reported.
STUDY DESIGN, SIZE, DURATION
This was a prospective study of 159 embryos, all of which were later transferred. The PN morphology of 46 embryos which resulted in live birth was compared with that of 113 embryos which resulted in no live birth.
PARTICIPANTS, SETTING
From 1 March 2010 to 30 August 2011, 130 couples underwent fertility treatment by ICSI. Embryo culture was performed in a time-lapse set-up from fertilization to intrauterine transfer. PN morphological assessment was performed on every embryo replaced, using six different scoring systems at different times.
MAIN RESULTS AND THE ROLE OF CHANCE
No embryo with PNB earlier than 20 h 45 min resulted in live birth. All six PN assessment models showed no significant distribution of scores (P = NS) between the live birth and no live birth groups at 16 h post-fertilization (PF), 18 h PF and 40 min before PNB. The outcomes of assessments changed significantly (P < 0.001) over time and the time of PNB was found to be the optimal stage to evaluate the PN morphology.
LIMITATIONS, REASONS FOR CAUTION
The study includes only embryos reaching the 4-cell stage after ICSI, and transferred at 44 h PF.
WIDER IMPLICATIONS OF THE FINDINGS
The PN morphology changes over time, indicating that the single light microscopy observation approach is deficient in comparison to time-lapse. Although the assessment of the PN morphology does not improve embryo selection, the timing of PNB should be included in embryo selection parameters.
STUDY FUNDING/COMPETING INTEREST(S)
None.
TRIAL REGISTRATION NUMBER
Approval number from the National Ethical Committee of Medical Science of Denmark: SJ-250.
Similar to the human skin, a monolayer of packed particles capillary bound to a liquid interface wrinkles when subjected to compressive stress. The induced wrinkles absorb the applied stress and do ...not disappear unless the stress is removed. Experimental and theoretical investigations of wrinkle formation typically concern flat particle monolayers subjected to uniaxial stress. In this work, we extend the results on wrinkling of particle-covered interfaces to the investigation of mechanical properties of particle films on a curved interface, that is, we study particle shells formed on droplets and subjected to hoop stress. Opposed to flat particle layers where liquid buoyancy alone acts as the effective stiffness, the mechanical properties of particle layers on small droplets are also affected by the surface curvature. We show here that this leads to formation of wrinkles with different characteristic wavelengths compared to those found at flat interfaces. Our experimental results also reveal that the wrinkle wavelength of particle shells is proportional to the square root of particle size and the size of the droplets on which the shells are formed. Wrinkling of particle layers composed of microparticles with diameters ranging from around 1–100 μm was induced using a novel approach combining electrodeformation and electrohydrodynamic flows. We demonstrate that our contactless approach for studying the mechanical properties of particle shells enables estimation of elasticity, particle film thickness, and bending stiffness of particle shells. The proposed approach is insensitive to both particle coverage and electric field strength. In addition, it enables manipulation of particle packing that is intimately linked with formation of wrinkling patterns. With a wide range of applications depending on accurate mechanical properties (e.g., drug-delivery capsules to self-healing materials), this work provides a valuable method to characterize the mechanical properties of shells and tailor their surface properties (i.e., permeability and roughness).
•We have determined the native oxide film thickness on several Al samples.•The results obtained from XRR and XPS show excellent agreement.•The results obtained from EIS show consistently thinner ...oxide films.•The oxides on the alloys are thicker than the oxides on the single crystals.
We present results from measurements of the native oxide film thickness on four different industrial aluminum alloys and three different aluminum single crystals. The thicknesses were determined using X-ray reflectivity, X-ray photoelectron spectroscopy, and electrochemical impedance spectroscopy. In addition, atomic force microscopy was used for micro-structural studies of the oxide surfaces. The reflectivity measurements were performed in ultra-high vacuum, vacuum, ambient, nitrogen and liquid water conditions. The results obtained using X-ray reflectivity and X-ray photoelectron spectroscopy demonstrate good agreement. However, the oxide thicknesses determined from the electrochemical impedance spectroscopy show a larger discrepancy from the above two methods. In the present contribution the reasons for this discrepancy are discussed. We also address the effect of the substrate type and the presence of water on the resultant oxide thickness.
STUDY QUESTION
Which genes and molecular mechanisms are involved in the human ovulatory cascade and final oocyte maturation?
SUMMARY ANSWER
Up-regulated genes in granulosa cells (GC) represented ...inflammation, angiogenesis, extracellular matrix, growth factors and genes previously associated with ovarian cancer, while down-regulated genes mainly represented cell cycle and proliferation.
WHAT IS KNOWN ALREADY
Radical changes occur in the follicle during final follicle maturation after the ovulatory trigger: these range from ensuring an optimal milieu for the oocyte in meiotic arrest to the release of a mature oocyte and remodeling into a corpus luteum. A wide range of mediators of final follicle maturation has been identified in rodents, non-human primates and cows.
STUDY DESIGN, SIZE, DURATION
Prospective cohort study including 24 women undergoing ovarian stimulation with the long gonadotrophin-releasing hormone agonist protocol during 2010–2012 at Holbæk Fertility Clinic. Nine paired samples of GC and 24 paired samples of follicular fluid (FF) were obtained before and after recombinant human chorionic gonadotrophin (rhCG) administration.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Nine paired (nine arrays before rhCG and nine arrays after rhCG) samples of GC mRNA were amplified and hybridized to Affymetrix Human Gene 1.0 ST GeneChip arrays, compared and bioinformatically analyzed. Eleven selected genes were validated by quantitative reverse transcriptase PCR. FF hormones were analyzed by enzyme-linked immunosorbent assay.
MAIN RESULTS AND THE ROLE OF CHANCE
Eleven hundred and eighty-six genes were differentially expressed (>2-fold, P<0.0001, false discovery rate <0.0012) when comparing GC isolated before and 36 h after hCG, among those were genes known to be expressed at ovulation, i.e. ADAMTS1 and HAS2. Many new ovulation-related genes were revealed, such as CD24, ANKRD22, CLDN11 and FBXO32. FF estrogen, androstenedione and anti-Müllerian hormone decreased significantly while progesterone increased, accompanied by radical changes in the expression of steroidogenic genes (CYP17A, CYP19A, HSD11B1 and HSD11B2, StAR). Genes related to inflammation, angiogenesis, extracellular matrix formation, growth factors and cancer were up-regulated while cell cycle genes were massively down-regulated. Seventy-two genes previously described in connection with ovarian cancer were among the highly regulated genes. In silico analysis for top upstream regulators of the ovulatory trigger suggested—besides LH—TNF, IGF1, PGR, AR, EGR1 (early growth response 1), ERK1/2 (extracellular signal regulated kinase 1/2) and CDKN1A (cyclin-dependent kinase inhibitor 1A) as potential mediators of the LH/hCG response.
LIMITATIONS, REASONS FOR CAUTION
The present dataset was generated from women under hormonal stimulation. However, comparison with a macaque natural cycle whole follicle ovulation dataset revealed major overlap, supporting the idea that the ovulation-related genes found in this study are relevant in the human natural cycle.
WIDER IMPLICATIONS OF THE FINDINGS
These data will serve as a research resource for genes involved in human ovulation and final oocyte maturation. Ovulation-related genes might be good candidate biomarkers of follicle and oocyte health. Further, some of the ovulation-related genes may serve as future ovarian cancer biomarkers.
STUDY FUNDING/COMPETING INTEREST(S)
Grants from the Research Fund of Region Sjælland are gratefully acknowledged. None of the authors declared any conflict of interest.
TRIAL REGISTRATION NUMBER
Not applicable.
Meltwater drainage across the surface of the Greenland ice sheet (GrIS) is well constrained by measurements and modeling, yet despite its critical role, knowledge of its transit through the ...subglacial environment remains limited. Here we present a subglacial hydrological analysis of a land‐terminating sector of the GrIS at unprecedented resolution that predicts the routing of surface‐derived meltwater once it has entered the basal drainage system. Our analysis indicates the probable existence of small subglacial lakes that remain undetectable by methods using surface elevation change or radar techniques. Furthermore, the analysis suggests transient behavior with rapid switching of subglacial drainage between competing catchments driven by seasonal changes in the basal water pressure. Our findings provide a cautionary note that should be considered in studies that attempt to relate and infer future response from surface temperature, melt, and runoff from point measurements and/or modeling with measurements of proglacial discharge and ice dynamics.
Key Points
We present a high‐resolution subglacial hydrological analysis of the Greenland ice sheet
Small subglacial lakes remain undetectable by methods using surface elevation or radar techniques
We identify the first evidence for subglacial water piracy beneath the Greenland ice sheet
P4-ATPases comprise a family of P-type ATPases that actively transport or flip phospholipids across cell membranes. This generates and maintains membrane lipid asymmetry, a property essential for a ...wide variety of cellular processes such as vesicle budding and trafficking, cell signaling, blood coagulation, apoptosis, bile and cholesterol homeostasis, and neuronal cell survival. Some P4-ATPases transport phosphatidylserine and phosphatidylethanolamine across the plasma membrane or intracellular membranes whereas other P4-ATPases are specific for phosphatidylcholine. The importance of P4-ATPases is highlighted by the finding that genetic defects in two P4-ATPases ATP8A2 and ATP8B1 are associated with severe human disorders. Recent studies have provided insight into how P4-ATPases translocate phospholipids across membranes. P4-ATPases form a phosphorylated intermediate at the aspartate of the P-type ATPase signature sequence, and dephosphorylation is activated by the lipid substrate being flipped from the exoplasmic to the cytoplasmic leaflet similar to the activation of dephosphorylation of Na(+)/K(+)-ATPase by exoplasmic K(+). How the phospholipid is translocated can be understood in terms of a peripheral hydrophobic gate pathway between transmembrane helices M1, M3, M4, and M6. This pathway, which partially overlaps with the suggested pathway for migration of Ca(2+) in the opposite direction in the Ca(2+)-ATPase, is wider than the latter, thereby accommodating the phospholipid head group. The head group is propelled along against its concentration gradient with the hydrocarbon chains projecting out into the lipid phase by movement of an isoleucine located at the position corresponding to an ion binding glutamate in the Ca(2+)- and Na(+)/K(+)-ATPases. Hence, the P4-ATPase mechanism is quite similar to the mechanism of these ion pumps, where the glutamate translocates the ions by moving like a pump rod. The accessory subunit CDC50 may be located in close association with the exoplasmic entrance of the suggested pathway, and possibly promotes the binding of the lipid substrate. This review focuses on properties of mammalian and yeast P4-ATPases for which most mechanistic insight is available. However, the structure, function and enigmas associated with mammalian and yeast P4-ATPases most likely extend to P4-ATPases of plants and other organisms.
Supraglacial lakes represent an ephemeral storage buffer for meltwater runoff and lead to significant, yet short-lived, episodes of ice-flow acceleration by decanting large meltwater and energy ...fluxes into the ice sheet's hydrological system. Here, a methodology for calculating lake volume is used to quantify storage and drainage across Russell Glacier, West Greenland, between 2002 and 2012. Using 502 MODIS scenes, water volume at ~200 seasonally occurring lakes was derived using a depth-reflectance relationship, which was independently calibrated and field validated against lake bathymetry. The inland expansion of lakes is strongly correlated with air temperature: during the record melt years of 2010 and 2012, lakes formed and drained earlier, attaining their maximum volume 38 and 20 days earlier than the 11 yr mean, as well as occupying a greater area and forming at higher elevations (> 1800 m) than previously. Despite occupying under 2% of the study area, lakes delay the transmission of up to 7-13% of the bulk meltwater discharged. Although the results are subject to an observational bias caused by periods of cloud cover, we estimate that across Russell Glacier, 28% of supraglacial lakes drain rapidly (< 4 days). Clustering of such events in space and time suggests a synoptic trigger mechanism. Further, we find no evidence to support a unifying critical size or depth-dependent drainage threshold.
The discovery of topological insulators, materials with bulk band gaps and protected cross-gap surface states in compounds such as Bi2Se3, has generated much interest in identifying topological ...surface states (TSSs) in other classes of materials. In particular, recent theoretical calculations suggest that TSSs may be found in half-Heusler ternary compounds. If experimentally realizable, this would provide a materials platform for entirely new heterostructure spintronic devices that make use of the structurally identical but electronically varied nature of Heusler compounds. Here we show the presence of a TSS in epitaxially grown thin films of the half-Heusler compound PtLuSb. Spin- and angle-resolved photoemission spectroscopy, complemented by theoretical calculations, reveals a surface state with linear dispersion and a helical tangential spin texture consistent with previous predictions. This experimental verification of topological behaviour is a significant step forward in establishing half-Heusler compounds as a viable material system for future spintronic devices.
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