Epigenetic control of vascular endothelial function revealed by multi-omics

Endothelial cell (EC) dysfunction is a common mechanism that can drive, and contribute substantially, to a broad range of cardiovascular diseases (CVD). ECs are a mechanical and physical barrier between the circulating blood and adjacent tissues. In response to signalling cues, ECs undergo dynamic changes, for example reshaping their structure through intricate cytoskeletal rearrangements. Such perturbations lead to endothelial dysfunction and leukocyte infiltration, which are associated with the development of CVD like atherosclerosis

Superspreading on hydrophobic substrates:effect of glycerol additive

The spreading of solutions of three trisiloxane surfactants on two hydrophobic substrates, polyethylene and polyvinylidenefluoride, was studied with the addition of 0–40 mass % of glycerol. It was found that all the surfactant solutions spread faster than silicone oil of the same viscosity, confirming the existence of a mechanism which accelerates the spreading of the surfactant solutions. For the non-superspreading surfactant, BT-233, addition of glycerol improved the spreading performance on polyvinylidenefluoride and resulted in a transition from partial to complete wetting on polyethylene. The fastest spreading was observed for BT-233 at a concentration of 2.5 g/L, independent of glycerol content. For the superspreading surfactants, BT-240 and BT-278, the concentration at which the fastest spreading occurs systematically increased with concentration of glycerol on both substrates from 1.25 g/L for solutions in water to 10 g/L for solutions in 40% glycerol/water mixture. Thus, the surfactant equilibration rate (and therefore formation of surface tension gradients) and Marangoni flow are important components of a superspreading mechanism. De-wetting of the solutions containing glycerol, once spread on the substrates, resulted in the formation of circular drop patterns. This is in contrast to the solely aqueous solutions where the spread film shrank due to evaporation, without any visible traces being left behind

Foundations of character: methodological aspects of a study of character development in three- to six-year-old children with a focus on sharing behaviours

This article focuses on methodological issues arising in a study of character development, using illustrations of ‘sharing behaviours.’ Based primarily in six early years settings in southeast England the research records naturalistic observations of peer interactions for 55 children aged three to six years. Applying grounded theory to the processes of observing, analysing and interpreting evidence required a cautious and collectively reflective approach. The methodology sought to moderate the influence of the researchers' prior knowledge of ‘grand theories’ of moral development and assumptions about relevance to the observation records. The study's originality lay in the exploration of moral development without reference to any particular grand theory as an explanatory framework; and in the reluctance to be drawn to potentially simplistic rationalisations of the children's intentions on the basis of their observed behaviours. Exploring young children's subjective experiences, this research provides insights into the intricacy of this process, steering away from ‘neat’ findings and attempting to reflect the sophistication of the children's skilful and sometimes surprising negotiations of moral dilemmas. Implications for practice relate to the complexities involved in attempts to unravel the developing moral characters of young children and the practice through which this may be nurtured

Inhibition of RSK with the novel small-molecule inhibitor LJI308 overcomes chemoresistance by eliminating cancer stem cells

ABSTRACT The triple-negative breast cancer (TNBC) subtype is enriched in cancer stem cells (CSCs) and clinically correlated with the highest rate of recurrence. Several studies implicate the RSK pathway as being pivotal for the growth and proliferation of CSCs, which are postulated to drive tumor relapse. We now address the potential for the newly developed RSK inhibitor LJI308 to target the CSC population and repress TNBC growth and dissemination. Overexpression of the Y-box binding protein-1 (YB-1) oncogene in human mammary epithelial cells (HMECs) drove TNBC tumor formation characterized by a multi-drug resistance phenotype, yet these cells were sensitive to LJI308 in addition to the classic RSK inhibitors BI-D1870 and luteolin. Notably, LJI308 specifically targeted transformed cells as it had little effect on the non-tumorigenic parental HMECs. Loss of cell growth, both in 2D and 3D culture, was attributed to LJI308-induced apoptosis. We discovered CD44+/CD49f+ TNBC cells to be less sensitive to chemotherapy compared to the isogenic CD44-/CD49f-cells. However, inhibition of RSK using LJI308, BI-D1870, or luteolin was sufficient to eradicate the CSC population. We conclude that targeting RSK using specific and potent inhibitors, such as LJI308, delivers the promise of inhibiting the growth of TNBC

Vector Casimir effect for a D-dimensional sphere

The Casimir energy or stress due to modes in a D-dimensional volume subject to TM (mixed) boundary conditions on a bounding spherical surface is calculated. Both interior and exterior modes are included. Together with earlier results found for scalar modes (TE modes), this gives the Casimir effect for fluctuating ``electromagnetic'' (vector) fields inside and outside a spherical shell. Known results for three dimensions, first found by Boyer, are reproduced. Qualitatively, the results for TM modes are similar to those for scalar modes: Poles occur in the stress at positive even dimensions, and cusps (logarithmic singularities) occur for integer dimensions $D\le1$. Particular attention is given the interesting case of D=2.Comment: 20 pages, 1 figure, REVTe

An R2R3 MYB transcription factor determines red petal colour in an Actinidia (kiwifruit) hybrid population

Background Red colour in kiwifruit results from the presence of anthocyanin pigments. Their expression, however, is complex, and varies among genotypes, species, tissues and environments. An understanding of the biosynthesis, physiology and genetics of the anthocyanins involved, and the control of their expression in different tissues, is required. A complex, the MBW complex, consisting of R2R3-MYB and bHLH transcription factors together with a WD-repeat protein, activates anthocyanin 3-O-galactosyltransferase (F3GT1) to produce anthocyanins. We examined the expression and genetic control of anthocyanins in flowers of Actinidia hybrid families segregating for red and white petal colour. Results Four inter-related backcross families between Actinidia chinensis Planch. var. chinensis and Actinidia eriantha Benth. were identified that segregated 1:1 for red or white petal colour. Flower pigments consisted of five known anthocyanins (two delphinidin-based and three cyanidin-based) and three unknowns. Intensity and hue differed in red petals from pale pink to deep magenta, and while intensity of colour increased with total concentration of anthocyanin, no association was found between any particular anthocyanin data and hue. Real time qPCR demonstrated that an R2R3 MYB, MYB110a, was expressed at significant levels in red-petalled progeny, but not in individuals with white petals. A microsatellite marker was developed that identified alleles that segregated with red petal colour, but not with ovary, stamen filament, or fruit flesh colour in these families. The marker mapped to chromosome 10 in Actinidia. The white petal phenotype was complemented by syringing Agrobacterium tumefaciens carrying Actinidia 35S::MYB110a into the petal tissue. Red pigments developed in white petals both with, and without, co-transformation with Actinidia bHLH partners. MYB110a was shown to directly activate Actinidia F3GT1 in transient assays. Conclusions The transcription factor, MYB110a, regulates anthocyanin production in petals in this hybrid population, but not in other flower tissues or mature fruit. The identification of delphinidin-based anthocyanins in these flowers provides candidates for colour enhancement in novel fruits

'Surely the most natural scenario in the world’: Representations of ‘Family’ in BBC Pre-school Television

Historically, the majority of work on British children’s television has adopted either an institutional or an audience focus, with the texts themselves often overlooked. This neglect has meant that questions of representation in British children’s television – including issues such as family, gender, class or ethnicity - have been infrequently analysed in the UK context. In this article, we adopt a primarily qualitative methodology and analyse the various textual manifestations of ‘family’, group, or community as represented in a selected number of BBC pre-school programmes. In doing so, we question the (limited amount of) international work that has examined representations of the family in children’s television, and argue that nuclear family structures do not predominate in this sphere