Hormonal regulation of the Menkes and Wilson copper-transporting ATPases in human placental Jeg-3 cells

Copper deficiency during pregnancy results in early embryonic death and foetal structural abnormalities including skeletal, pulmonary and cardiovascular defects. During pregnancy, copper is transported from the maternal circulation to the foetus by mechanisms which have not been clearly elucidated. Two coppertransporting ATPases, Menkes (ATP7A; MNK) and Wilson (ATP7B; WND), are expressed in the placenta and both are involved in placental copper transport, as copper accumulates in the placenta in both Menkes and Wilson disease. The regulatory mechanisms of MNKand WNDand their exact role in the placenta are unknown. Using a differentiated polarized Jeg-3 cell culture model of placental trophoblasts, MNK and WND were shown to be expressed within these cells. Distinct roles forMNKandWND are suggested on the basis of their opposing responses to insulin. Insulin and oestrogen increased both MNK mRNA and protein levels, altered the localization of MNK towards the basolateral membrane in a copper-independent manner, and increased the transport of copper across this membrane. In contrast, levels of WND were decreased in response to insulin, and the protein was located in a tight perinuclear region, with a corresponding decrease in copper efflux across the apical membrane. These results are consistent with a model of copper transport in the placenta in which MNK delivers copper to the foetus and WND returns excess copper to the maternal circulation. Insulin and oestrogen stimulate copper transport to the foetus by increasing the expression of MNK and reducing the expression of WND. These data show for the first time that MNK and WND are differentially regulated by the hormones insulin and oestrogen in human placental cells.

Critical behavior of confined supramolecular soft materials on a microscopic scale

The formation of fiber networks and the resulting rheological properties of supramolecular soft materials are dramatically influenced when the volume of the system is reduced to a threshold. Unlike un-confined systems, the formation of fiber networks under volume confinement is independent of temperature and solute concentration.

Force amplification response of actin filaments under confined compression

Actin protein is a major component of the cell cytoskeleton, and its ability to respond to external forces and generate propulsive forces through the polymerization of filaments is central to many cellular processes. The mechanisms governing actin's abilities are still not fully understood because of the difficulty in observing these processes at a molecular level. Here, we describe a technique for studying actin–surface interactions by using a surface forces apparatus that is able to directly visualize and quantify the collective forces generated when layers of noninterconnected, end-tethered actin filaments are confined between 2 (mica) surfaces. We also identify a force-response mechanism in which filaments not only stiffen under compression, which increases the bending modulus, but more importantly generates opposing forces that are larger than the compressive force. This elastic stiffening mechanism appears to require the presence of confining surfaces, enabling actin filaments to both sense and respond to compressive forces without additional mediating proteins, providing insight into the potential role compressive forces play in many actin and other motor protein-based phenomena.

Dynamics of force generation by confined actin filaments

Forces generated by polymerizing/de-polymerizing actin filaments confined between two mica surfaces were measured using the Surface Forces Apparatus. The measurements show that confined actin filaments exhibit complex force-generation dynamics involving multiple “modes”, the predominance of which is determined by the confinement gap and the applied force (confining pressure).

Distinct kinetics of molecular gelation in a confined space and its relation to the structure and property of thin gel films

Thin films of molecular gels formed in a confined space have potential applications in transdermal delivery, artificial skin, molecular electronics, etc. The microstructures and properties of thin gel films can be significantly different from those of their bulk counterparts. However, so far a comprehensive understanding of the effects of spatial confinement on the molecular gelation kinetics, fiber network structure and related mechanical properties is still lacking. In this work, using rheological techniques, we investigated the effect of one-dimensional confinement on the formation kinetics of fiber networks in the molecular gelation process. Fractal analyses of the kinetic information in terms of an extended Dickinson model enabled us to describe quantitatively the distinct kinetic signature of molecular gelation. The structural features derived from gelation kinetics support well the fractal patterns of the fiber networks acquired by optical and electron microscopy. With the kinetics-structure correlation, we can gain an in-depth understanding of the confinement-induced differences in the structure and consequently the mechanical properties of a model molecular gelling system. Particularly, the confinement induced structural transition, from a three-dimensional, dense and compact spherulitic network composed of highly branched fibers to a quasi-two-dimensional sparse spherulitic network composed of less branched fibers and entangled fibrils at the boundary areas, renders a gel film to become less stiff but more ductile. Our study suggests here a new strategy of engineering the fiber network microstructure to achieve functional gel films with unusual but useful properties.

Experimental study of damage evolution in cuboid stirrup-confined concrete

This paper presents an experimental study on cuboid stirrup-confined concrete specimens under uniaxial monotonic loading and cyclic loading. The effects of stirrup volume ratio, stirrup yield strength, and concrete strength on damage evolution of the stirrup-confined concrete were investigated. The experimental results showed that the strength and ductility of concrete are improved by appropriate arrangement of the stirrup confinement. Firstly, with the increase of the stirrup volume ratio, the damage evolution of concrete can be relatively restrained. Secondly, higher stirrup yield strength usually leads to larger confining pressures and slower damage evolution. In contrast, higher concrete strength leads to higher brittleness, which accelerates damage evolution. Based on the experimental data, a plastic strain expression is obtained through curve fitting, and a damage evolution equation for stirrup-confined concrete is proposed by introducing a confinement factor (C). The comparisons results demonstrated that the proposed damage evolution curve can accurately describe the experimental results.

Maternal prenatal mental health and placental 11β-HSD2 gene expression: initial findings from the mercy pregnancy and emotional wellbeing study

High intrauterine cortisol exposure can inhibit fetal growth and have programming effects for the child's subsequent stress reactivity. Placental 11beta-hydroxysteroid dehydrogenase (11β-HSD2) limits the amount of maternal cortisol transferred to the fetus. However, the relationship between maternal psychopathology and 11β-HSD2 remains poorly defined. This study examined the effect of maternal depressive disorder, antidepressant use and symptoms of depression and anxiety in pregnancy on placental 11β-HSD2 gene (HSD11B2) expression. Drawing on data from the Mercy Pregnancy and Emotional Wellbeing Study, placental HSD11B2 expression was compared among 33 pregnant women, who were selected based on membership of three groups; depressed (untreated), taking antidepressants and controls. Furthermore, associations between placental HSD11B2 and scores on the State-Trait Anxiety Inventory (STAI) and Edinburgh Postnatal Depression Scale (EPDS) during 12-18 and 28-34 weeks gestation were examined. Findings revealed negative correlations between HSD11B2 and both the EPDS and STAI (r = -0.11 to -0.28), with associations being particularly prominent during late gestation. Depressed and antidepressant exposed groups also displayed markedly lower placental HSD11B2 expression levels than controls. These findings suggest that maternal depression and anxiety may impact on fetal programming by down-regulating HSD11B2, and antidepressant treatment alone is unlikely to protect against this effect.

Evaluation of the mechanical performance of short concrete column confined with CFRP and GFRP

Concrete has been successfully used to build strong and economic structures. However severe environmental exposures slowly deteriorate concrete strength until complete failure reducing its designed service life. Fiber Reinforced Polymer “FRP” has been recently introduced in the construction industry to strengthen and retrofitting several structural elements including columns. In this research two types of FRP have been used to wrap concrete column in order to increase its capacity; these are Carbon Fiber Reinforced Polymer “CFRP” and Glass Fiber Reinforced Polymer “GFRP”. Twelve short concrete columns have been wrapped with one and two FRP layers including CFRP and GFRP to evaluate their mechanical performance. Mechanical testing has shown that, in general, concrete columns wrapped with FRP produced higher modulus of elasticity compared to the control sample. Results showed that one layer of CFRP have 85.8% increases where as one layer of GFRP showed an increase of 64.5%. Furthermore, two layers of CFRP and GFRP showed 112.5% and 77.2% increase respectively.