Effects of chronic estradiol treatment on acquisition and reacquisition of working memory and cell proliferation in the dentate gyrus

Beyond its role in reproduction, estrogen exerts profound effects on cognition and behaviour as well as influencing the structural and electrophysiological properties of the brain. The present studies investigate the effect of chronic estradiol treatment on acquisition and reacquisition of the prefrontal cortex-dependent delayed non-matched to position T-maze task and on cell proliferation in the dentate gyrus of adult female rats. Experiment 1 investigates the effect of estradiol on non-spatial working memory during the T-maze task. Ovariectomized (OVX) female rats were injected for 21d with estradiol benzoate (0.3, 5 or 10 μg/0.1 ml sesame oil) or vehicle (sesame oil, 0.1 ml). Approximately 2hr after each injection, animals were trained daily on the T-maze with an initial delay of 10s. Following a month with no estradiol treatment animals were injected for 21d with the same initial doses of estradiol and re-trained (reacquisition) at a 40s delay. Days to reach criterion (one error per day for three consecutive days), mean total errors (entries into previously baited arms), errors across blocks (3d per block), change in performance across training (acquisition subtracted from reacquisition), and latency to reach goal arm, were scored. Compared to OVX rats without estrogen administration, a dose of 0.3 of estradiol (low-to-medium physiological) significantly decreased the number of working memory errors during a 10s delay (acquisition), while doses of both 5 μg (high physiological) and 10 μg (supraphysiological) of estradiol significantly increased the number of working memory errors during a 40s delay (reacquisition). Experiment 2 investigated the effect of chronic estradiol treatment on the proliferation of cells in the dentate gyrus of adult female rats. Ovariectomized (OVX) female rats were injected for 21d with estradiol benzoate (0.3, 5 or 10 μg /0.1 ml) or vehicle (sesame oil; 0.1 ml). Four hours after the last hormone injection on day 21 animals were injected i.p. with bromodeoxyuridine (BrdU; 200mg/kg), a thymidine analogue and were perfused 24h later. Stereo logical counts of BrdU-labelled cells and dentate gyrus volume were correlated with serum estradiol levels. Results revealed that regardless of dose, estradiol treatment produced no significant change in the number of BrdU-labelled cells observed relative to vehicle-controls. Similarly, estradiol treatment produced no significant change in the number of pyknotic cells observed across treatment conditions relative to vehicle controls. However, chronic treatment with supraphysiological levels of estradiol (10 μg) significantly increased dentate gyrus volume. There was no significant correlation between serum estradiol levels and number of BrdU-labelled cells, however DG volume correlated positively with serum estradiol dose. These data demonstrate that chronic estradiol has a significant differential effect on acquisition and reacquisition of prefrontal cortex dependent working memory. While chronic estradiol did not significantly affect the number of BrdU-labelled cells, serum estradiol was positively correlated with DG volume.Medicine, Faculty ofGraduat

Linked-Data based Constraint-Checking (LDCC) to support look-ahead planning in construction

This is a substantially extended and enhanced version of the paper presented at the CIB W78 Annual Conference held at Northumbria University in Newcastle UK in September 2019. We would like to acknowledge the editorial contributions of Professor Bimal Kumar of Northumbria University and Dr. Farzad Rahimian of Teesside University in the publication of this paper. The first author's PhD research is co-funded by Bentley systems the UK and through a Skempton Scholarship, the Department of Civil and Environmental Engineering, Imperial College London. During this work, the first author was also supported by the PhD enrichment scholarship from The Alan Turing Institute. The authors acknowledge the supervisory inputs offered by Dr. David Birch and Dean Bowman and also acknowledges the guidance offered by Prof. Jakob Beetz. The second author is supported by the European Commission (H2020 MSCA-IF ga. No. 754446). The third author acknowledges the support of Laing O'Rourke and the Royal Academy of Engineering for cosponsoring her Professorship.In the construction sector, complex constraints are not usually modeled in conventional scheduling and 4D building information modeling software, as they are highly dynamic and span multiple domains. The lack of embedded constraint relationships in such software means that, as Automated Data Collection (ADC) technologies become used, it cannot automatically deduce the effect of deviations to schedule. This paper presents a novel method, using semantic web technologies, to model and validate complex scheduling constraints. It presents a Linked-Data based Constraint-Checking (LDCC) approach, using the Shapes Constraint Language (SHACL). A prototype web application is developed using this approach and evaluated using an OpenBIM dataset. Results demonstrate the potential of LDCC to check for constraint violation in distributed construction data. This novel method (LDCC) and its first prototype is a contribution that can be extended in future research in linked-data, BIM based rule-checking, lean construction and ADC.Bentley systems the UKSkempton Scholarship, the Department of Civil and Environmental Engineering, Imperial College LondonAlan Turing InstituteEuropean Commission 754446Laing O'RourkeRoyal Academy of Engineering - U

Early Pregnancy Levels of Pregnancy-Associated Plasma Protein A and the Risk of Intrauterine Growth Restriction, Premature Birth, Preeclampsia, and Stillbirth

The risk of adverse perinatal outcome among 8839 women recruited to a multicenter, prospective cohort study was related to maternal circulating concentrations of trophoblast-derived proteins at 8-14 wk gestation. Women with a pregnancy-associated plasma protein A (PAPP-A) in the lowest fifth percentile at 8-14 wk gestation had an increased risk of intrauterine growth restriction [adjusted odds ratio, 2.9; 95% confidence interval (CI), 2.0-4.1], extremely premature delivery (adjusted odds ratio, 2.9; 95% CI, 1.6-5.5), moderately premature delivery (adjusted odds ratio, 2.4; 95% CI, 1.7-3.5), pre-eclampsia (adjusted odds ratio, 2.3; 95% CI, 1.6-3.3), and stillbirth (adjusted odds ratio, 3.6; 95% CI, 1.2-11.0). The strengths of the associations were similar when the test was performed before 13 wk gestation or between 13 and 14 wk gestation. In contrast, levels of free beta-human CG, another circulating protein synthesized by the syncytiotrophoblast, were not predictive of later outcome in multivariate analysis. PAPP-A has been identified as a protease specific for IGF binding proteins. We conclude that control of the IGF system in the first and early second trimester trophoblast may have a key role in determining subsequent pregnancy outcome