Investigation of the Liverpool Bay mixing front using POLCOMS

Liverpool Bay, northwest UK, is a region of freshwater influence and hypertidal conditions. The river inflow from the 3 large estuary systems (Dee, Mersey and Ribble) forms a coastal front that moves < 10 km in response to semi-diurnal tidal straining and < 35 km due to the spring-neap cycle. The time variability of the density gradients in this coastal region are mainly controlled by salinity. Coastal observations are used in this study to improve the numerical simulation of the exchange process occurring at this front through improved spatial structure and temporal variability. A decade of Conductivity Temperature Depth (CTD) sensor observations were collected during cruises across a nearshore grid of monitoring stations. These data are used in addition to fixed mooring data that are near-continuous in time to validate numerical simulations using the 1-way nested Proudman Oceanographic Laboratory Coastal Ocean Modelling System (POLCOMS) at ~1.8km and 180m horizontal resolution. A downscaled simulation is used to investigate the influence of model resolution, inclusion of wetting and drying, diffusivity, turbulence advection and the influence of model boundary and initial conditions for select cruise periods in 2008. This year is chosen as a typical year with periods of calm and stormy conditions with variable river influence to investigate the seasonal frontal structure. A method to validate the spatial structure of the front is presented demonstrating the importance of a fine-resolution grid and improved physics to capture the details

Fine particle retention and deposition in regions of cyclonic tidal current rotation

Benthic sediments in continental shelf seas control a variety of biogeochemical processes, yet their composition, especially that of fine sediment, remains difficult to predict. Mechanisms for mud or fine sediment deposition and retention are not fully understood. Using sediment data and a hydrodynamic model of the Northwest European shelf seas, a relationship is shown to exist between fine benthic sediment composition and regions of cyclonic tidal current rotation. The reduced thickness of cyclonic tidal benthic boundary layers compared with the anticyclonic case promotes deposition of fine sediment and trapping of resuspended material. Adding the effects of the benthic boundary layer thickness, as influenced by ellipticity or not, sheds some light on the limitations of approaches only focusing on bed shear stress and sediment pathways to predict the location of mud deposits. A tidal boundary layer predictor that includes ellipticity alongside tidal current magnitude and depth was shown to spatially agree with maps of mud deposits

The Two-Spectra Inverse Problem for Semi-Infinite Jacobi Matrices in The Limit-Circle Case

We present a technique for reconstructing a semi-infinite Jacobi operator in the limit circle case from the spectra of two different self-adjoint extensions. Moreover, we give necessary and sufficient conditions for two real sequences to be the spectra of two different self-adjoint extensions of a Jacobi operator in the limit circle case.Comment: 26 pages. Changes in the presentation of some result

Global embeddings of scalar-tensor theories in (2+1)-dimensions

We obtain (3+3)- or (3+2)-dimensional global flat embeddings of four uncharged and charged scalar-tensor theories with the parameters B or L in the (2+1)-dimensions, which are the non-trivially modified versions of the Banados-Teitelboim-Zanelli (BTZ) black holes. The limiting cases B=0 or L=0 exactly are reduced to the Global Embedding Minkowski Space (GEMS) solution of the BTZ black holes.Comment: 19 pages, 2 figure

Placental expression of eNOS, iNOS and the major protein components of caveolae in women with pre-eclampsia

Caveolae regulate many cardiovascular functions and thus could be of interest in relation to pre-eclampsia, a pregnancy specific disorder characterised by hypertension and proteinuria. We examined placental mRNA and protein expression/localisation of the caveolae components Caveolin 1-3, Cavin 1-4 as well as eNOS/ iNOS in normotensive control (n=24) and pre-eclamptic pregnancies (n=19). Placental mRNA expression of caveolin-1, cavin 1-3, was lower and eNOS expression was increased in pre-eclampsia (P<0.05 for all). Additionally Caveolin-1 protein expression was also reduced in pre-eclampsia (P=0.007); this could be an adaptive response in pre-eclampsia, possibly to attenuate the oxidative stress/inflammation

Thyroid hormones and their placental deiodination in normal and pre-eclamptic pregnancy

Pre-eclampsia is associated with lower serum selenium concentrations and glutathione peroxidase expression/activity; total thyroid hormones are also lower. Objectives, study design and main outcome measures: We hypothesised that the placental selenoprotein deiodinase (D3) will be protected in pre-eclampsia due to the hierarchy of selenoprotein biosynthesis in selenium deficiency. Venous blood and tissue from three standardised placental sites were obtained at delivery from 27 normotensive and 23 pre-eclamptic women. mRNA expression and enzyme activity were assessed for both deiodinases (D2 and D3); protein expression/localisation was also measured for D3. FT4, FT3 and TSH concentrations were measured in maternal and umbilical cord blood. Results: No significant differences in D3 mRNA or protein expression between normotensive and pre-eclamptic pregnancies. There was a significant effect of sampling site on placental D3 activity only in pre-eclamptic women (P = 0.034; highest activity nearest the cord). A strong correlation between D3 mRNA expression and enzyme activity existed only in the pre-eclamptic group; further strengthened when controlling for maternal selenium (P < 0.002). No significant differences were observed between groups for any of the maternal thyroid hormones; umbilical TSH concentrations were significantly higher in the pre-eclamptic samples (P < 0.001). Conclusions: D3 mRNA and protein expression appear to be independent of selenium status. Nevertheless, the positive correlation between D3 mRNA expression and activity evident only in pre-eclampsia, suggests that in normotensive controls, where selenium is higher, translation is not affected, but in pre-eclampsia, where selenium is low, enzyme regulation may be altered. The raised umbilical TSH concentrations in pre-eclampsia may be an adaptive fetal response to maximise iodide uptake

The placental renin-angiotensin system and oxidative stress in pre-eclampsia

There is an inverse correlation between human birthweight and umbilical venous angiotensin II (AngII) concentrations. Oxidative stress and increased pro-renin receptor (PRR) both enhance the cleavage of angiotensin I from angiotensinogen (AGT). Pre-eclampsia, a hypertensive disorder of pregnancy, manifests as high blood pressure and proteinuria, and is a state of increased oxidative stress. Objectives, study design and main outcome measures Hypothesis: Pre-eclampsia will be associated with increased placental expression of components of the renin–angiotensin system, which could result in reduced infant birthweight. Biopsies were taken 1 cm from the placental edge from 27 normotensive controls and 23 pre-eclamptic White European women. Immunohistochemistry was performed for AGT, PRR, glutathione peroxidase 3 (GPx3) and the AT1R and AT2R AngII receptors. Protein expression was semi-quantitatively assessed (H-score). Results: AT1R expression was significantly increased in pre-eclamptic placentae, and negatively correlated with birthweight (r = −0.529, P = 0.009). AT1R expression was also negatively correlated with GPx3 expression overall (r = −0.647; P = 0.005). AT2R expression positively correlated with AGT (r = 0.615, P = 0.002) in the pre-eclamptic placentae only. Conclusions: The raised AT1R expression in pre-eclampsia, together with inadequate antioxidant protection, possibly through lower GPx activity, might enhance the vasoconstrictor effect of locally-generated AngII, contributing to the restricted fetal growth characteristic of pre-eclampsia. Conversely, the AT2R:AGT association within the pre-eclamptic placenta may provide a compensatory mechanism

Differential expression and distribution of placental glutathione peroxidases 1, 3 and 4 in normal and preeclamptic pregnancy

Preeclampsia is a pregnancy-specific condition affecting 2-7% of women and a leading cause of perinatal and maternal morbidity and mortality; it may also predispose the mother and fetus to increased risks of adult cardiovascular disease. The selenoprotein glutathione peroxidases (GPxs) have critical roles in regulating antioxidant status. Objectives, study design and main outcome measures: Immunohistochemical measurements of GPx 1, GPx3 and GPx4 protein expression were performed on samples taken from three standardised sampling sites between the cord insertion and the periphery of the placenta from 12 normotensive, and 12 preeclamptic women to establish if their expression differed between sampling sites. Total GPx activities were also examined from the three sampling sites of these placentae. Results: There were highly significant reductions in overall immunohistochemical staining of all 3 GPxs in the preeclampsia compared to normotensive placentae (GPx1: P = 0.016; GPx3: P = 0.003; GPx4: P < 0.001). Furthermore, graded differences in expression between the standardised placental sampling sites were also found for GPx3 (higher in the inner region, P = 0.05) and GPx4 (higher in the periphery, P = 0.02) but not GPx1. Placental GPx enzyme activity was also significantly reduced in tissue from preeclamptic women as compared to normotensive women (P = 0.007; the difference was more pronounced nearest the cord insertion). Conclusions: We have shown highly significant reductions in expression of all three major classes of GPx in placentae from women with preeclampsia, and distribution gradients in activity, which may relate to the differential oxygenation of regions of the placenta

Expression of catalytic mutants of the mtDNA helicase Twinkle and polymerase POLG causes distinct replication stalling phenotypes

The mechanism of mitochondrial DNA replication is a subject of intense debate. One model proposes a strand-asynchronous replication in which both strands of the circular genome are replicated semi-independently while the other model proposes both a bidirectional coupled leading- and lagging-strand synthesis mode and a unidirectional mode in which the lagging-strand is initially laid-down as RNA by an unknown mechanism (RITOLS mode). Both the strand-asynchronous and RITOLS model have in common a delayed synthesis of the DNA-lagging strand. Mitochondrial DNA is replicated by a limited set of proteins including DNA polymerase gamma (POLG) and the helicase Twinkle. Here, we report the effects of expression of various catalytically deficient mutants of POLG1 and Twinkle in human cell culture. Both groups of mutants reduced mitochondrial DNA copy number by severe replication stalling. However, the analysis showed that while induction of POLG1 mutants still displayed delayed lagging-strand synthesis, Twinkle-induced stalling resulted in maturated, essentially fully double-stranded DNA intermediates. In the latter case, limited inhibition of POLG with dideoxycytidine restored the delay between leading- and lagging-strand synthesis. The observed cause-effect relationship suggests that Twinkle-induced stalling increases lagging-strand initiation events and/or maturation mimicking conventional strand-coupled replication