Function of caspase-14 in trophoblast differentiation

<p>Abstract</p> <p>Background</p> <p>Within the human placenta, the cytotrophoblast consists of a proliferative pool of progenitor cells which differentiate to replenish the overlying continuous, multi-nucleated syncytiotrophoblast, which forms the barrier between the maternal and fetal tissues. Disruption to trophoblast differentiation and function may result in impaired fetal development and preeclampsia. Caspase-14 expression is limited to barrier forming tissues. It promotes keratinocyte differentiation by cleaving profilaggrin to stabilise keratin intermediate filaments, and indirectly providing hydration and UV protection. However its role in the trophoblast remains unexplored.</p> <p>Methods</p> <p>Using RNA Interference the reaction of control and differentiating trophoblastic BeWo cells to suppressed caspase-14 was examined for genes pertaining to hormonal, cell cycle and cytoskeletal pathways.</p> <p>Results</p> <p>Transcription of hCG, KLF4 and cytokeratin-18 were increased following caspase-14 suppression suggesting a role for caspase-14 in inhibiting their pathways. Furthermore, hCG, KLF4 and cytokeratin-18 protein levels were disrupted.</p> <p>Conclusion</p> <p>Since expression of these molecules is normally increased with trophoblast differentiation, our results imply that caspase-14 inhibits trophoblast differentiation. This is the first functional study of this unusual member of the caspase family in the trophoblast, where it has a different function than in the epidermis. This knowledge of the molecular underpinnings of trophoblast differentiation may instruct future therapies of trophoblast disease.</p

Metal hydrides as electrode/catalyst materials for oxygen evolution/reduction in electrochemical devices

An at least ternary metal alloy of the formula, AB.sub.(5-Y)X(.sub.y), is claimed. In this formula, A is selected from the rare earth elements, B is selected from the elements of groups 8, 9, and 10 of the periodic table of the elements, and X includes at least one of the following: antimony, arsenic, and bismuth. Ternary or higher-order substitutions, to the base AB.sub.5 alloys, that form strong kinetic interactions with the predominant metals in the base metal hydride are used to form metal alloys with high structural integrity after multiple cycles of hydrogen sorption

Terrestrial Ozone Depletion Due to a Milky Way Gamma-Ray Burst

Based on cosmological rates, it is probable that at least once in the last Gy the Earth has been irradiated by a gamma-ray burst in our Galaxy from within 2 kpc. Using a two-dimensional atmospheric model we have performed the first computation of the effects upon the Earth's atmosphere of one such impulsive event. A ten second burst delivering 100 kJ/m^2 to the Earth penetrates to the stratosphere and results in globally averaged ozone depletion of 35%, with depletion reaching 55% at some latitudes. Significant global depletion persists for over 5 years after the burst. This depletion would have dramatic implications for life since a 50% decrease in ozone column density results in approximately three times the normal UVB flux. Widespread extinctions are likely, based on extrapolation from UVB sensitivity of modern organisms. Additional effects include a shot of nitrate fertilizer and NO2 opacity in the visible providing a cooling perturbation to the climate over a similar timescale. These results lend support to the hypothesis that a GRB may have initiated the late Ordovician mass extinction (Melott et al. 2004).Comment: 4 color figures; Revised version to be published in Astrophysical Journal Letters. Moderate revisions, including more detail on atmospheric processes, on probable climactic and biogeochemical effects, an improved color scheme for graphics, and an animation of computed DNA damage leve

Arduous implementation: Does the Normalisation Process Model explain why it's so difficult to embed decision support technologies for patients in routine clinical practice

Background: decision support technologies (DSTs, also known as decision aids) help patients and professionals take part in collaborative decision-making processes. Trials have shown favorable impacts on patient knowledge, satisfaction, decisional conflict and confidence. However, they have not become routinely embedded in health care settings. Few studies have approached this issue using a theoretical framework. We explained problems of implementing DSTs using the Normalization Process Model, a conceptual model that focuses attention on how complex interventions become routinely embedded in practice.Methods: the Normalization Process Model was used as the basis of conceptual analysis of the outcomes of previous primary research and reviews. Using a virtual working environment we applied the model and its main concepts to examine: the 'workability' of DSTs in professional-patient interactions; how DSTs affect knowledge relations between their users; how DSTs impact on users' skills and performance; and the impact of DSTs on the allocation of organizational resources.Results: conceptual analysis using the Normalization Process Model provided insight on implementation problems for DSTs in routine settings. Current research focuses mainly on the interactional workability of these technologies, but factors related to divisions of labor and health care, and the organizational contexts in which DSTs are used, are poorly described and understood.Conclusion: the model successfully provided a framework for helping to identify factors that promote and inhibit the implementation of DSTs in healthcare and gave us insights into factors influencing the introduction of new technologies into contexts where negotiations are characterized by asymmetries of power and knowledge. Future research and development on the deployment of DSTs needs to take a more holistic approach and give emphasis to the structural conditions and social norms in which these technologies are enacte

The Possible Role of Placental Morphometry in the Detection of Fetal Growth Restriction

Fetal growth restriction (FGR) is often the result of placental insufficiency and is characterized by insufficient transplacental transport of nutrients and oxygen. The main underlying entities of placental insufficiency, the pathophysiologic mechanism, can broadly be divided into impairments in blood flow and exchange capacity over the syncytiovascular membranes of the fetal placenta villi. Fetal growth restriction is not synonymous with small for gestational age and techniques to distinguish between both are needed. Placental insufficiency has significant associations with adverse pregnancy outcomes (perinatal mortality and morbidity). Even in apparently healthy survivors, altered fetal programming may lead to long-term neurodevelopmental and metabolic effects. Although the concept of fetal growth restriction is well appreciated in contemporary obstetrics, the appropriate detection of FGR remains an issue in clinical practice. Several approaches have aimed to improve detection, e.g., uniform definition of FGR, use of Doppler ultrasound profiles and use of growth trajectories by ultrasound fetal biometry. However, the role of placental morphometry (placental dimensions/shape and weight) deserves further exploration. This review article covers the clinical relevance of placental morphometry during pregnancy and at birth to help recognize fetuses who are growth restricted. The assessment has wide intra- and interindividual variability with various consequences. Previous studies have shown that a small placental surface area and low placental weight are associated with a slower growth of the fetus. Parameters such as placental surface area, placental volume and placental weight in relation to birth weight can help to identify FGR. In the future, a model including sophisticated antenatal placental morphometry may prove to be a clinically useful method for screening or diagnosing growth restricted fetuses, in order to provide optimal monitoring

Reference intervals for selected serum biochemistry analytes in cheetahs (Acinonyx jubatus)

Published haematologic and serum biochemistry reference intervals are very scarce for captive cheetahs and even more for free-ranging cheetahs. The current study was performed to establish reference intervals for selected serum biochemistry analytes in cheetahs. Baseline serum biochemistry analytes were analysed from 66 healthy Namibian cheetahs. Samples were collected from 30 captive cheetahs at the AfriCat Foundation and 36 free-ranging cheetahs from central Namibia. The effects of captivity-status, age, sex and haemolysis score on the tested serum analytes were investigated. The biochemistry analytes that were measured were sodium, potassium, magnesium, chloride, urea and creatinine. The 90% confidence interval of the reference limits was obtained using the non-parametric bootstrap method. Reference intervals were preferentially determined by the non-parametric method and were as follows: sodium (128 mmol/L – 166 mmol/L), potassium (3.9 mmol/L – 5.2 mmol/L), magnesium (0.8 mmol/L – 1.2 mmol/L), chloride (97 mmol/L – 130 mmol/L), urea (8.2 mmol/L – 25.1 mmol/L) and creatinine (88 μmol/L – 288 μmol/L). Reference intervals from the current study were compared with International Species Information System values for cheetahs and found to be narrower. Moreover, age, sex and haemolysis score had no significant effect on the serum analytes in this study. Separate reference intervals for captive and free-ranging cheetahs were also determined. Captive cheetahs had higher urea values, most likely due to dietary factors. This study is the first to establish reference intervals for serum biochemistry analytes in cheetahs according to international guidelines. These results can be used for future health and disease assessments in both captive and free- ranging cheetahs.The South African Veterinary Foundation (SAVF), the Wildlife Group of the South African Veterinary Association (SAVA), the Messerli Foundation in Switzerland and the Research Committee of the University of Pretoria.http://www.jsava.co.zaam2016Companion Animal Clinical Studie

The Heavy Photon Search test detector

The Heavy Photon Search (HPS), an experiment to search for a hidden sector photon in fixed target electroproduction, is preparing for installation at the Thomas Jefferson National Accelerator Facility (JLab) in the Fall of 2014. As the first stage of this project, the HPS Test Run apparatus was constructed and operated in 2012 to demonstrate the experiment׳s technical feasibility and to confirm that the trigger rates and occupancies are as expected. This paper describes the HPS Test Run apparatus and readout electronics and its performance. In this setting, a heavy photon can be identified as a narrow peak in the e+e− invariant mass spectrum above the trident background or as a narrow invariant mass peak with a decay vertex displaced from the production target, so charged particle tracking and vertexing are needed for its detection. In the HPS Test Run, charged particles are measured with a compact forward silicon microstrip tracker inside a dipole magnet. Electromagnetic showers are detected in a PbW04 crystal calorimeter situated behind the magnet, and are used to trigger the experiment and identify electrons and positrons. Both detectors are placed close to the beam line and split top-bottom. This arrangement provides sensitivity to low-mass heavy photons, allows clear passage of the unscattered beam, and avoids the spray of degraded electrons coming from the target. The discrimination between prompt and displaced e+e− pairs requires the first layer of silicon sensors be placed only 10 cm downstream of the target. The expected signal is small, and the trident background huge, so the experiment requires very large statistics. Accordingly, the HPS Test Run utilizes high-rate readout and data acquisition electronics and a fast trigger to exploit the essentially 100% duty cycle of the CEBAF accelerator at JLab

Large-Scale Streamwise Vortices in Turbulent Channel Flow Induced by Active Wall Actuations

© 2017, Springer Science+Business Media B.V., part of Springer Nature. Direct numerical simulations of turbulent flow in a plane channel using spanwise alternatively distributed strips (SADS) are performed to investigate the characteristics of large-scale streamwise vortices (LSSVs) induced by small-scale active wall actuations, and their role in suppressing flow separation. SADS control is obtained by alternatively applying out-of-phase control (OPC) and in-phase control (IPC) to the wall-normal velocity component of the lower channel wall, in the spanwise direction. Besides the non-controlled channel flow simulated as a reference, four controlled cases with 1, 2, 3 and 4 pairs of OPC/IPC strips are studied at M = 0.2 and Re = 6,000, based on the bulk velocity and the channel half height. The case with 2 pairs of strips, whose width is Δz+ = 264 based on the friction velocity of the non-controlled case, is the most effective in terms of generating large-scale motions. It is also found that the OPC (resp. IPC) strips suppress (resp. enhance) the coherent structures and that leads to the creation of a vertical shear layer, which is responsible for the LSSVs presence. They are in a statistically steady state and their cores are located between two neighbouring OPC and IPC strips. These motions contribute significantly to the momentum transport in the wall-normal and spanwise directions showing potential for flow separation suppression

Communications Biophysics

Contains research objectives and summary of research.National Institutes of Health (Grant 5 PO1 GM14940-07)National Institutes of Health (Grant 1 RO1 NS11000-01)Clarence J. LeBel FundNational Institutes of Health (Grant 1 RO1 NS10737-01)National Aeronautics and Space Administration (Grant NGL 22-009-304)Boston City Hospital Purchase Order 1176-21335B-D Electrodyne Division, Becton Dickinson and Company (Grant)Chicago Musical Instrument Company (Grant