Circumventricular organ apelin receptor knockdown decreases blood pressure and sympathetic drive responses in the spontaneously hypertensive rat

The central site(s) mediating the cardiovascular actions of the apelin-apelin receptor (APJ) system remains a major question. We hypothesized that the sensory circumventricular organs (CVOs), interfacing between the circulation and deeper brain structures, are sites where circulating apelin acts as a signal in the central nervous system to decrease blood pressure (BP). We show that APJ gene (aplnr) expression was elevated in the CVOs of spontaneously hypertensive rats (SHRs) compared to normotensive Wistar Kyoto (WKY) controls, and that there was a greater mean arterial BP (MABP) decrease following microinjection of [Pyr(1)]apelin-13 to the CVOs of SHRs compared to WKY rats. Lentiviral APJ-specific-shRNA (LV-APJ-shRNA) was used to knockdown aplnr expression, both collectively in three CVOs and discretely in individual CVOs, of rats implanted with radiotelemeters to measure arterial pressure. LV-APJ-shRNA-injection decreased aplnr expression in the CVOs and abolished MABP responses to microinjection of [Pyr(1)]apelin-13. Chronic knockdown of aplnr in any of the CVOs, collectively or individually, did not affect basal MABP in SHR or WKY rats. Moreover, knockdown of aplnr in any of the CVOs individually did not affect the depressor response to systemic [Pyr(1)]apelin-13. By contrast, multiple knockdown of aplnr in the three CVOs reduced acute cardiovascular responses to peripheral [Pyr(1)]apelin-13 administration in SHR but not WKY rats. These results suggest that endogenous APJ activity in the CVOs has no effect on basal BP but that functional APJ in the CVOs is required for an intact cardiovascular response to peripherally administered apelin in the SHR

β-Phase Morphology in Ordered Poly(9,9-dioctylfluorene) Nanopillars by Template Wetting Method

An efficient method based in template wetting is applied for fabrication of ordered Poly(9,9-dioctylfluorene) (PFO) nanopillars with β-phase morphology. In this process, nanoporous alumina obtained by anodization process is used as template. PFO nanostructures are prepared under ambient conditions via infiltration of the polymeric solution into the pores of the alumina with an average pore diameter of 225 nm and a pore depth of 500 nm. The geometric features of the resulting structures are characterized with environmental scanning electron microscopy (ESEM), luminescence fluorimeter (PL) and micro μ-X-ray diffractometer (μ-XRD). The characterization demonstrates the β-phase of the PFO in the nanopillars fabricated. Furthermore, the PFO nanopillars are characterized by Raman spectroscopy to study the polymer conformation. These ordered nanostructures can be used in optoelectronic applications such as polymer light-emitting diodes, sensors and organic solar cells

Abortion referendums in Ireland

Ireland was a conservative outpost on the European periphery for much of the twentieth century. From independence in 1922, the state pursued social policies heavily influenced by religious values, and indeed the 1937 constitution embedded many of these positions in the framework of the state. The constitution included a prohibition on divorce and a statement which strongly favored women remaining in the domestic sphere. These policies were supported by the majority Catholic population, but social values began to evolve by the 1960s. This can be seen in the shifting narratives in the debates on many social and political issues. This chapter will focus on a single issue – abortion. It will undertake an evaluation of the debates on the six abortion referendum question wordings, campaign narratives, and voting patterns. The analysis will provide compelling evidence of remarkable value change in just four decades

Reconceptualizing CSR in the media industry as relational accountability

In this paper, we reconceptualize CSR in the media industries by combining empirical data with theoretical perspectives emerging from the communication studies and business ethics literature. We develop a new conception of what corporate responsibility in media organizations may mean in real terms by bringing Bardoel and d’Haenens’ (European Journal of Communication 19 165–194 2004) discussion of the different dimensions of media accountability into conversation with the empirical results from three international focus group studies, conducted in France, the USA and South Africa. To enable a critical perspective on our findings, we perform a philosophical analysis of its implications for professional, public, market, and political accountability in the media, drawing on the insights of Paul Virilio. We come to the conclusion that though some serious challenges to media accountability exist, the battle for responsible media industries is not lost. In fact, the speed characterizing the contemporary media environment may hold some promise for fostering the kind of relational accountability that could underpin a new understanding of CSR in the media

Somatostatin and dopamine receptors as targets for medical treatment of Cushing's Syndrome

Somatostatin (SS) and dopamine (DA) receptors are widely expressed in neuroendocrine tumours that cause Cushing's Syndrome (CS). Increasing knowledge of specific subtype expression within these tumours and the ability to target these receptor subtypes with high-affinity compounds, has driven the search for new SS- or DA-based medical therapies for the various forms of CS. In Cushing's disease, corticotroph adenomas mainly express dopamine receptor subtype 2 (D2) and somatostatin receptor subtype 5 (sst5), whereas sst2is expressed at lower levels. Activation of these receptors can inhibit ACTH-release in primary cultured corticotroph adenomas and compounds that target either sst5(pasireotide, or SOM230) or D2(cabergoline) have shown significant efficacy in subsets of patients in recent clinical studies. Combination therapy, either by administration of both types of compounds separately or by treatment with novel somatostatin-dopamine chimeric molecules (e.g. BIM-23A760), appears to be a promising approach in this respect. In selected cases of Ectopic ACTH-producing Syndrome (EAS), the sst2-preferring compound octreotide is able to reduce cortisol levels effectively. A recent study showed that D2receptors are also significantly expressed in the majority of EAS and that cabergoline may decrease cortisol levels in subsets of these patients. In both normal adrenal tissue as well as in adrenal adenomas and carcinomas that cause CS, sst and DA receptor expression has been demonstrated. Although selected cases of adrenal CS may benefit from sst or DA-targeted treatment, its total contribution to the treatment of these patients is likely to be low as surgery is effective in most cases

Barriers to the uptake and use of feedback in the context of summative assessment

Despite calls for feedback to be incorporated in all assessments, a dichotomy exists between formative and summative assessments. When feedback is provided in a summative context, it is not always used effectively by learners. In this study we explored the reasons for this. We conducted individual interviews with 17 students who had recently received web based feedback following a summative assessment. Constant comparative analysis was conducted for recurring themes. The summative assessment culture, with a focus on avoiding failure, was a dominant and negative influence on the use of feedback. Strong emotions were prevalent throughout the period of assessment and feedback, which reinforced the focus on the need to pass, rather than excel. These affective factors were heightened by interactions with others. The influence of prior learning experiences affected expectations about achievement and the need to use feedback. The summative assessment and subsequent feedback appeared disconnected from future clinical workplace learning. Socio-cultural influences and barriers to feedback need to be understood before attempting to provide feedback after all assessments. A move away from the summative assessment culture may be needed in order to maximise the learning potential of assessments

Synaptic tagging and capture in the living rat

In isolated hippocampal slices, decaying long-term potentiation can be stabilized and converted to late long-term potentiation lasting many hours, by prior or subsequent strong high-frequency tetanization of an independent input to a common population of neurons—a phenomenon known as ‘synaptic tagging and capture’. Here we show that the same phenomenon occurs in the intact rat. Late long-term potentiation can be induced in CA1 during the inhibition of protein synthesis if an independent input is strongly tetanized beforehand. Conversely, declining early long-term potentiation induced by weak tetanization can be converted into lasting late long-term potentiation by subsequent strong tetanization of a separate input. These findings indicate that synaptic tagging and capture is not limited to in vitro preparations; the past and future activity of neurons has a critical role in determining the persistence of synaptic changes in the living animal, thus providing a bridge between cellular studies of protein synthesis-dependent synaptic potentiation and behavioural studies of memory persistence