Truncated human endothelin receptor A produced by alternative splicing and its expression in melanoma

In this study, reverse transcriptase polymerase chain reaction was used to amplify human endothelin receptor A (ETA) and ETB receptor mRNA. A truncated ETA receptor transcript with exons 3 and 4 skipped was found. The skipping of these two exons results in 109 amino acids being deleted from the receptor. The truncated receptor was expressed in all tissues and cells examined, but the level of expression varied. In melanoma cell lines and melanoma tissues, the truncated receptor gene was the major species, whereas the wild-type ETA was predominant in other tissues. A 1.9-kb ETA transcript was identified in melanoma cell lines by Northern blot, which was much smaller than the transcript in heart and in other tissues reported previously (4.3 kb). The cDNA coding regions of the truncated and wild-type ETA receptors were stably transfected into Chinese hamster ovary (CHO) cells. The truncated ETA receptor-transfected CHO cells did not show binding affinity to endothelin 1 (ET-1) or endothelin 3 (ET-3). The function and biological significance of this truncated ETA receptor is not clear, but it may have regulatory roles for cell responses to ETs

Splicing-dependent NMD does not require the EJC in Schizosaccharomyces pombe

Nonsense-mediated mRNA decay (NMD) is a translation-linked process that destroys mRNAs with premature translation termination codons (PTCs). In mammalian cells, NMD is also linked to pre-mRNA splicing, usually PTCs trigger strong NMD only when positioned upstream of at least one intron. The exon junction complex (EJC) is believed to mediate the link between splicing and NMD in these systems. Here, we report that in Schizosaccharomyces pombe splicing also enhances NMD, but against the EJC model prediction, an intron stimulated NMD regardless of whether it is positioned upstream or downstream of the PTC and EJC components are not required. Still the effect of splicing seems to be direct—we have found that the important NMD determinant is the proximity of an intron to the PTC, not just the occurrence of splicing. On the basis of these results, we propose a new model to explain how splicing could affect NMD

Calorimetric observation of single He2* excimers in a 100 mK He bath

We report the first calorimetric detection of individual He2* excimers within a bath of superfluid 4He. The detector used in this work is a single superconducting titanium transition edge sensor (TES) with an energy resolution of 1 eV, immersed directly in the helium bath. He2* excimers are produced in the surrounding bath using an external gamma-ray source. These excimers exist either as short-lived singlet or long-lived triplet states. We demonstrate detection (and discrimination) of both states: in the singlet case the calorimeter records the absorption of a prompt 15 eV photon, and in the triplet case the calorimeter records a direct interaction of the molecule with the TES surface, which deposits a distinct fraction of the 15 eV, released upon decay, into the surface. We also briefly discuss the detector fabrication and characterization

Workplace violence in Queensland, Australia: the results of a comparative study

[Abstract]: This paper presents the results on workplace violence from a larger study undertaken in 2004. Comparison is made with the results of a similar study undertaken in 2001. The study involved the random sampling of 3000 nurses from the Queensland Nurses’ Union’s membership in the public (acute hospital and community nursing), private (acute hospital and domiciliary nursing) and aged care sectors (both public and private aged care facilities). The self-reported results suggest an increase in workplace violence in all three sectors. Whilst there are differences in the sources of workplace violence across the sectors, the major causes of workplace violence are: clients/patients, visitors/relatives, other nurses, nursing management and medical practitioners. Associations were also found between workplace violence and gender, the designation of the nurse, hours of employment, the age of the nurse, morale and perceptions of workplace safety. Whilst the majority of nurses reported that policies were in place for the management of workplace violence, these policies were not always adequate

Associations between types and sources of dietary carbohydrates and liver fat: a UK Biobank study

Background and aims: Excess energy intake can lead to metabolic dysfunction-associated steatotic liver disease (MASLD), but the relationship between dietary carbohydrate intake and liver fat content remains unclear. This study aimed to examine the associations between types and sources of dietary carbohydrates and liver fat content. Methods: UK Biobank participants with no pre-existing diabetes, liver disease or cardiovascular disease reported dietary intake of types and sources of carbohydrates (total carbohydrates, free sugars, non-free sugars, starch from whole grains, starch from refined grains, and fibre) on at least two 24-h dietary assessments. In cross-sectional analyses, (n = 22,973), odds ratios (OR) of high liver fat content (defined as a score of ≥ 36 in the hepatic steatosis index) by quintiles of carbohydrate intakes were estimated using multivariable logistic regression models. In prospective analyses, a second sample (n = 9268) had liver proton density fat fraction (PDFF) measured by magnetic resonance imaging (2014–2020). Multivariable linear regression models estimated geometric means of PDFF (%) by quintiles of carbohydrate intakes. Models were adjusted for demographic and lifestyle confounders, including total energy intake. Results: In the cross-sectional analyses, 6894 cases of high liver fat content were identified. Inverse associations between intakes of fibre (OR of highest vs. lowest quintile 0.46 [95% CI: 0.41–0.52]), non-free sugars (0.63 [0.57–0.70]) and starch from whole grains (0.52 [0.47–0.57]) with liver fat were observed. There were positive associations between starch from refined grains and liver fat (1.33 [1.21–1.46]), but no association with free sugars (p=0.61). In prospective analyses, inverse associations with PDFF (%) were observed for intakes of fibre (− 0.48 geometric mean difference between highest and lowest quintile of intake [− 0.60 to − 0.35]), non-free sugars (− 0.37 [− 0.49 to − 0.25]) and starch from whole grains (− 0.31 [− 0.42 to − 0.19]). Free sugars, but not starch from refined grains, were positively associated with PDFF (0.17 [0.05 to 0.28]). Conclusion: This study suggests that different carbohydrate types and sources have varying associations with liver fat, which may be important for MASLD prevention. Non-free sugars, fibre, and starch from whole grains could be protective, while associations with free sugars and starch from refined grains are less clear

Deformation of Codimension-2 Surface and Horizon Thermodynamics

The deformation equation of a spacelike submanifold with an arbitrary codimension is given by a general construction without using local frames. In the case of codimension-1, this equation reduces to the evolution equation of the extrinsic curvature of a spacelike hypersurface. In the more interesting case of codimension-2, after selecting a local null frame, this deformation equation reduces to the well known (cross) focusing equations. We show how the thermodynamics of trapping horizons is related to these deformation equations in two different formalisms: with and without introducing quasilocal energy. In the formalism with the quasilocal energy, the Hawking mass in four dimension is generalized to higher dimension, and it is found that the deformation of this energy inside a marginal surface can be also decomposed into the contributions from matter fields and gravitational radiation as in the four dimension. In the formalism without the quasilocal energy, we generalize the definition of slowly evolving future outer trapping horizons proposed by Booth to past trapping horizons. The dynamics of the trapping horizons in FLRW universe is given as an example. Especially, the slowly evolving past trapping horizon in the FLRW universe has close relation to the scenario of slow-roll inflation. Up to the second order of the slowly evolving parameter in this generalization, the temperature (surface gravity) associated with the slowly evolving trapping horizon in the FLRW universe is essentially the same as the one defined by using the quasilocal energy.Comment: Latex, 61 pages, no figures; v2, type errors corrected; v3, references and comments are added, English is improved, to appear in JHE

Vandetanib-eluting radiopaque beads for chemoembolization: physicochemical evaluation and biological activity of vandetanib in hypoxia.

Vandetanib-eluting radiopaque beads (VERB) have been developed for use in transarterial chemoembolization of liver tumours, with the goal of combining embolization with local delivery of antiangiogenic therapy. The objective of this study was to investigate how embolization-induced hypoxia may affect antitumoural activity of vandetanib, an inhibitor of vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR), in the context of hepatocellular carcinoma (HCC) treatment. We studied the effect of vandetanib on proliferation, cell cycle and apoptosis of HCC cells, in hypoxic conditions, as well as the direct effects of the beads on 3D HCC spheroids. Vandetanib suppressed proliferation and induced apoptosis of HCC cells in vitro and was equipotent in hypoxic and normoxic conditions. High degrees of apoptosis were observed among cell lines in which vandetanib suppressed ERK1/2 phosphorylation and upregulated the proapoptotic protein Bim, but this did not appear essential for vandetanib-induced cell death in all cell lines. Vandetanib also suppressed the hypoxia-induced secretion of VEGF from HCC cells and inhibited proliferation of endothelial cells. Incubation of tumour spheroids with VERB led to sustained growth inhibition equivalent to the effect of free drug. We conclude that vandetanib has both antiangiogenic and direct anticancer activity against HCC cells even in hypoxic conditions, warranting the further evaluation of VERB as novel anticancer agents

Exact Black Holes and Universality in the Backreaction of non-linear Sigma Models with a potential in (A)dS4

The aim of this paper is to construct accelerated, stationary and axisymmetric exact solutions of the Einstein theory with self interacting scalar fields in (A)dS4. To warm up, the backreaction of the (non)-minimally coupled scalar field is solved, the scalar field equations are integrated and all the potentials compatible with the metric ansatz and Einstein gravity are found. With these results at hand the non-linear sigma model is tackled. The scalar field Lagrangian is generic; neither the coupling to the curvature, neither the metric in the scalar manifold nor the potential, are fixed ab initio. The unique assumption in the analysis is the metric ansatz: it has the form of the most general Petrov type D vacuum solution of general relativity; it is a a cohomogeneity two Weyl rescaling of the Carter metric and therefore it has the typical Plebanski-Demianski form with two arbitrary functions of one variable and one arbitrary functions of two variables. It is shown, by an straightforward manipulation of the field equations, that the metric is completely integrable without necessity of specifiying anything in the scalar Lagrangian. This results in that the backreaction of the scalar fields, within this class of metrics, is universal. The metric functions generically show an explicit dependence on a dynamical exponent that allows to smoothly connect this new family of solutions with the actual Plebanski-Demianski spacetime. The remaining field equations imply that the scalar fields follow geodesics in the scalar manifold with an affine parameter given by a non-linear function of the spacetime coordinates and define the on-shell form of the potential plus a functional equation that it has to satisfy. Finally, a general family of (A)dS4 static hairy black holes is explicitly constructed and its properties are outlined.Comment: Several typos correcte

Gurga Chiya and Tepe Marani: new excavations in the Shahrizor plain, Iraqi Kurdistan

Gurga Chiya and Tepe Marani are small, adjacent mounds located close to the town of Halabja in the southern part of the Shahrizor Plain, one of the most fertile regions of Iraqi Kurdistan. Survey and excavation at these previously unexplored sites is beginning to produce evidence for human settlement spanning the sixth to the fourth millennia, c. 5600–3300 cal. b.c. In Mesopotamian chronology this corresponds to the Late Neolithic through to Chalcolithic periods; the Halaf, Ubaid, and Uruk phases of conventional culture history. In Iraqi Kurdistan, documentation of these periods—which witnessed many important transformations in prehistoric village life—is currently very thin. Here we offer a preliminary report on the emerging results from the Shahrizor Plain, with a particular focus on the description of material culture (ceramic and lithic assemblages), in order to establish a benchmark for further research. We also provide a detailed report on botanical remains and accompanying radiocarbon dates, which allow us to place this new evidence in a wider comparative framework. A further, brief account is given of Late Bronze Age material culture from the upper layers at Gurga Chiya. We conclude with observations on the significance of the Shahrizor Plain for wider research into the later prehistory of the Middle East, and the importance of preserving and investigating its archaeological record

A scalar field instability of rotating and charged black holes in (4+1)-dimensional Anti-de Sitter space-time

We study the stability of static as well as of rotating and charged black holes in (4+1)-dimensional Anti-de Sitter space-time which possess spherical horizon topology. We observe a non-linear instability related to the condensation of a charged, tachyonic scalar field and construct "hairy" black hole solutions of the full system of coupled Einstein, Maxwell and scalar field equations. We observe that the limiting solution for small horizon radius is either a hairy soliton solution or a singular solution that is not a regular extremal solution. Within the context of the gauge/gravity duality the condensation of the scalar field describes a holographic conductor/superconductor phase transition on the surface of a sphere.Comment: 16 pages including 8 figures, v2: discussion on soliton solutions extended; v3: matches version accepted for publication in JHE