Expression of AT1R, AT2R and AT4R and their roles in extravillous trophoblast invasion in the human

The placental renin-angiotensin system (RAS) is active from early pregnancy and may have a role in placentation. Angiotensin II (AngII) acts via binding to receptor types AT1R and AT2R. Recently smaller peptide members of the angiotensin family have been recognised as having biological relevance. Angiotensin (3-8) (AngIV) has a specific receptor (AT4R) and evokes hypertrophy, vasodilatation and vascular inflammatory response. The aim of this study was to characterise placental expression of AT1R, AT2R and AT4R, and to determine whether AngII and AngIV regulate extravillous trophoblast (EVT) invasion, apoptosis and proliferation. Placental samples were obtained from women undergoing elective surgical termination of pregnancy (TOP) at 8-10 weeks gestation (early TOP), 12-14 weeks gestation (mid TOP) or at delivery following normal pregnancy or with pre-eclampsia (PE). Immunohistochemistry and qRT-PCR were performed to determine placental mRNA and protein expression of AT1R, AT2R and AT4R was done at all gestational ages. EVT invasion following culture with AngII or AngIV was assessed in early placental tissue using Matrigel invasion assays. Invasion was assessed on day 6 of culture and placental explants were harvested for immunohistochemical analysis of apoptosis and proliferation. The results from qRT-PCR and immunohistochemistry showed placental AT1R expression which did not vary with gestation. The highest levels of expression of AT2R were found in early and mid TOP placentae compared to term pregnancy. Expression of AT4R was increased in term placentae, with a significant reduction in PE placentae. Moreover, culture with AngIV or AngII increased EVT invasion from placental explants, which showed increased trophoblast proliferation and reduced apoptosis. This study has characterised expression of AT4R and AT1R and AT2R in human placenta throughout normal pregnancy and in PE. Both AngIV and AngII may play an important role in normal pregnancy

Placental expression of adenosine A2A receptor and hypoxia inducible factor-1 alpha in early pregnancy, term and pre-eclamptic pregnancies: interactions with placental renin-angiotensin system

Normal placentation occurs under low oxygen tensions yet hypoxia is also implicated in placental pathologies such as pre-eclampsia (PE). Hypoxia-inducible factors (HIFs), adenosine and tissue renin-angiotensin-system (RAS) are known to promote angiogenesis and vascularisation. We hypothesised that placental adenosine A2AR receptor and HIF-1α would change through pregnancy in association with the RAS. Placentae were obtained from women undergoing elective surgical termination of pregnancy (TOP) at ≤10 weeks’ (early TOP) and >10 weeks’ (mid TOP) gestations; at delivery from normotensive (NT) and PE pregnancy. Results were compared to our previously reported data on the angiotensin receptors: AT1R, AT2R and AT4R. Protein expression of both A2AR and HIF-1α was highest in early TOP and positively correlated through pregnancy (P<0.0001): expression was higher in PE than NT at delivery (P<0.0001 for both). The A2AR positively correlated with the AT4R in placentae in early pregnancy (r=0.53; P=0.035), but not in 3rd trimester samples. Our findings suggest a role for adenosine and RAS in promoting placentation and as a potential adaptation to poor placental perfusion in pre-eclampsia

On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)

A randomized trial comparing the effectiveness and preference of a touch-screen computer system with a leaflet for providing women with information on urinary symptoms suggestive of detrusor instability

Objectives To evaluate how well women learned and retained information given to them by either a leaflet or a computer-generated information system, and which system they preferred to use for obtaining information about urinary symptoms. Subjects and methods Forty women answered 11 questions on the aetiology, investigation and treatment of lower urinary tract symptoms. They were then randomized to use one of the information systems for 20 min, after which they answered the same urological questions. The women then crossed over to use the other information system for 20 min and afterwards completed a preference questionnaire. Results The mean baseline scores from a possible total of 11 were 3.9 and 4.3 for the computer and leaflet groups, respectively. The mean improvements in scores were 3.6 (P < 0.001) and 2.8 (P < 0.001) for the computer and leaflet groups, respectively. Both information systems were well liked by all of the women and 26 (65%) said they would prefer to use a computer-generated system in the future if given a choice. Conclusions Women significantly increased their knowledge of urinary problems after using a computer-generated information system or a leaflet. Although there were few subjects, there appeared to be a trend for the computer system to be both better liked and slightly more effective

Reconstituting European social democracy: Germany's pivotal role

After a long period of dominance by the centre‐right, social democracy is once more in the ascendancy in Europe. At the same time social democracy is cross‐cut by competing ideological paradigms, ranging from an unreformed or ‘traditional’ model through to the neo‐liberal tinged ‘Third Way’ agenda. With social democratic‐led governments in power in France, Germany and Great Britain, this ideological competition has to a certain extent been mapped onto these member states’ statecraft agendas. The article makes three points. First, that there is a high degree of institutional ‘fit’ between of the Federal Republic and the European Union and that this potentially favours the successful transfer of German policy initiatives to the EU level. Second, that the ‘Red‐Green model’ of political co‐operation between the SPD and Greens is grounded within the parameters of sub‐national politics and is not easily adapted to the demands of the national and supranational levels. Third, that as a result of this, any distinctively ‘German’ social democratic agenda for Europe is more likely to have the ideas of the ‘Neue Mitte’ at its core

Genetic covariance structure of incisor crown size in twins

Previous studies of tooth size in twins and their families have suggested a high degree of genetic control, although there have been difficulties separating the various genetic and environmental effects. A genetic analysis of variation in crown size of the permanent incisors of South Australian twins was carried out, with structural equation modeling used to determine the relative contributions of genetic and environmental factors. Maximum mesiodistal crown dimensions of maxillary and mandibular permanent incisors were recorded from dental models of 298 pairs of twins, including 149 monozygous (MZ) and 149 dizygous (DZ) pairs. The analysis revealed that: (i) an adequate fit required additive genetic and unique environmental components; (ii) augmenting the model with non-additive genetic variation did not lead to a significant improvement in fit; (iii) there was evidence of shared environmental influences in the upper central incisors of males; (iv) the additive genetic component constituted a general factor loading on all eight teeth, with group factors loading on antimeric pairs of teeth; (v) unique environmental effects were mostly variable-specific; (vi) most factor loadings on antimeric tooth pairs could be constrained to be equal, indicating a symmetry of genetic and environmental influences between left and right sides; and (vii) estimated heritability of the incisor mesiodistal dimensions varied from 0.81 to 0.91