Amino acid changes in the spike protein of feline coronavirus correlate with systemic spread of virus from the intestine and not with feline infectious peritonitis

Recent evidence suggests that a mutation in the spike protein gene of feline coronavirus (FCoV), which results in an amino acid change from methionine to leucine at position 1058, may be associated with feline infectious peritonitis (FIP). Tissue and faecal samples collected post mortem from cats diagnosed with or without FIP were subjected to RNA extraction and quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) to detect FCoV RNA. In cats with FIP, 95% of tissue, and 81% of faecal samples were PCR-positive, as opposed to 22% of tissue, and 60% of faecal samples in cats without FIP. Relative FCoV copy numbers were significantly higher in the cats with FIP, both in tissues (P < 0.001) and faeces (P = 0.02). PCR-positive samples underwent pyrosequencing encompassing position 1058 of the FCoV spike protein. This identified a methionine codon at position 1058, consistent with the shedding of an enteric form of FCoV, in 77% of the faecal samples from cats with FIP, and in 100% of the samples from cats without FIP. In contrast, 91% of the tissue samples from cats with FIP and 89% from cats without FIP had a leucine codon at position 1058, consistent with a systemic form of FCoV. These results suggest that the methionine to leucine substitution at position 1058 in the FCoV spike protein is indicative of systemic spread of FCoV from the intestine, rather than a virus with the potential to cause FIP

Membrane-initiated nuclear trafficking of the glucocorticoid receptor in hypothalamic neurons

Glucocorticoid binding to the intracellular glucocorticoid receptor (GR) stimulates the translocation of the GR from the cytosol to the nucleus, which leads to the transactivation or transrepression of gene transcription. However, multiple lines of evidence suggest that glucocorticoid signaling can also be initiated from the plasma membrane. Here, we provide evidence for membrane-initiated glucocorticoid signaling by a membrane-impermeant dexamethasone-bovine serum albumin (Dex-BSA) conjugate, which induced GR nuclear trafficking in hypothalamic neurons in vitro and in vivo. The GR nuclear translocation induced by a membrane-impermeant glucocorticoid suggests trafficking of an unliganded GR. The membrane-initiated GR trafficking was not blocked by inhibiting ERK MAPK, p38 MAPK, PKA, Akt, Src kinase, or calcium signaling, but was inhibited by Akt activation. Short-term exposure of hypothalamic neurons to dexamethasone (Dex) activated the glucocorticoid response element (GRE), suggesting transcriptional transactivation, whereas exposure to the Dex-BSA conjugate failed to activate the GRE, suggesting differential transcriptional activity of the liganded compared to the unliganded GR. Microarray analysis revealed divergent transcriptional regulation by Dex-BSA compared to Dex. Together, our data suggest that signaling from a putative membrane glucocorticoid receptor induces the trafficking of unliganded GR to the nucleus, which elicits a pattern of gene transcription that differs from that of the liganded receptor. The differential transcriptional signaling by liganded and unliganded receptors may contribute to the broad range of genetic regulation by glucocorticoids, and may help explain some of the different off-target actions of glucocorticoid drugs

Deciding to Parent or Remain Childfree: Comparing Sexual Minority and Heterosexual Childless Adults from Israel, Portugal and the UK

This study compared Israeli, Portuguese, and British childless lesbian, gay, bisexual (LGB) and heterosexual adults on parenthood aspirations as indicated by their desire and intent to become a parent and their concern about childlessness. For this purpose, 168 childless adults (57 self-reported as LGB) in Portugal were matched on socio-demographic variables with 168 participants from the UK and 168 participants from Israel, resulting in a sample of n=504 (Mage = 28.26, SD = 6.17). Participants were recruited through convenience sampling and completed online questionnaires assessing parenthood desire, intent, and concern about childlessness. Results indicated that participants from Israel and Portugal reported higher levels of parenthood desire, intent, and concern about childlessness than participants from the UK. Parallel patterns also appeared separately for LGB and heterosexual participants between the countries. Heterosexual participants from Israel scored higher than counterparts from Portugal on parenthood intention and concern about childlessness. Additionally, LGB participants in general reported lower levels of parenthood desire, intentions, and concern about childlessness than did heterosexual participants. The findings are interpreted in light of the different socio-cultural contexts of the countries, i.e., the individualistic values characterizing the UK versus the familistic values characterizing the Israeli and Portuguese contexts, alongside a strongly pronatalist stance evident in Israel and economic context in Portugal. The study contributes to the scant comparative literature on parenthood aspirations among LGB individuals as a function of cultural context by providing a multicontextual viewpoint on parenthood aspirations, sexual orientation, and diverse socio-cultural contexts. Implications for clinicians are discussed

From Gas Phase Observations to Solid State Reality: The Identification and Isolation of Trinuclear Salicylaldoximato Copper Complexes

Conditions have been identified in which phenolic aldoximes and ketoximes of the types used in commercial solvent extraction processes can be doubly deprotonated and generate polynuclear Cu complexes with lower extractant:Cu molar ratios than those found in commercial operations. Electrospray mass spectrometry has provided an insight into the solution speciation in extraction experiments and has identified conditions to allow isolation and characterization of polynuclear Cu-complexes. Elevation of pH is effective in enhancing the formation of trinuclear complexes containing planar {Cu3-&mu;3-O}4+ or {Cu3-&mu;3-OH}5+ units. DFT calculations suggest that such trinuclear complexes are more stable than other polynuclear species. Solid structures of complexes formed by a salicylaldoxime with a piperidino substituent ortho to the phenolic OH group (L9H2) contain two trinuclear units in a supramolecular assembly, {[Cu3OH(L9H)3(ClO4)](ClO4)} 2, formed by H-bonding between the central {Cu3-&mu;3-OH}5+ units and oxygen atoms in the ligands of an adjacent complex. Whilst the lower ligand:Cu molar ratios provide more efficient Cu-loading in solvent extraction processes, the requirement to raise the pH of the aqueous phase to achieve this will make it impractical in most commercial operations because extraction will be accompanied by the precipitation (as oxyhydroxides) of Fe(III) which is present in significant quantities in feed solutions generated by acid leaching of most Cu ores

Composition, structure and stability of RuO_2(110) as a function of oxygen pressure

Using density-functional theory (DFT) we calculate the Gibbs free energy to determine the lowest-energy structure of a RuO_2(110) surface in thermodynamic equilibrium with an oxygen-rich environment. The traditionally assumed stoichiometric termination is only found to be favorable at low oxygen chemical potentials, i.e. low pressures and/or high temperatures. At realistic O pressure, the surface is predicted to contain additional terminal O atoms. Although this O excess defines a so-called polar surface, we show that the prevalent ionic model, that dismisses such terminations on electrostatic grounds, is of little validity for RuO_2(110). Together with analogous results obtained previously at the (0001) surface of corundum-structured oxides, these findings on (110) rutile indicate that the stability of non-stoichiometric terminations is a more general phenomenon on transition metal oxide surfaces.Comment: 12 pages including 5 figures. Submitted to Phys. Rev. B. Related publications can be found at http://www.fhi-berlin.mpg.de/th/paper.htm

Relaxation dynamics in a Fe7 nanomagnet

We investigate the phonon-induced relaxation dynamics in the Fe 7 magnetic molecule, which is made of two Fe 3 + triangles bridged together by a central Fe 3 + ion. The competition between different antiferromagnetic exchange interactions leads to a low-spin ground state multiplet with a complex pattern of low-lying excited levels. We theoretically investigate the decay of the time correlation function of molecular observables, such as the cluster magnetization, due to the spin-phonon interaction. We find that more than one time contributes to the decay of the molecular magnetization. The relaxation dynamics is probed by measurements of the nuclear spin-lattice relaxation rate 1 /T 1 . The interpretation of these measurements allows the determination of the magnetoelastic coupling strength and to set the scale factor of the relaxation dynamics time scales. In our theoretical interpretation of 1 /T 1 data we also take into account the wipeout effect at low temperature

Association between canine leishmaniosis and Ehrlichia canis co-infection: a prospective case-control study

Abstract Background In the Mediterranean basin, Leishmania infantum is a major cause of disease in dogs, which are frequently co-infected with other vector-borne pathogens (VBP). However, the associations between dogs with clinical leishmaniosis (ClinL) and VBP co-infections have not been studied. We assessed the risk of VBP infections in dogs with ClinL and healthy controls. Methods We conducted a prospective case-control study of dogs with ClinL (positive qPCR and ELISA antibody for L. infantum on peripheral blood) and clinically healthy, ideally breed-, sex- and age-matched, control dogs (negative qPCR and ELISA antibody for L. infantum on peripheral blood) from Paphos, Cyprus. We obtained demographic data and all dogs underwent PCR on EDTA-blood extracted DNA for haemoplasma species, Ehrlichia/Anaplasma spp., Babesia spp., and Hepatozoon spp., with DNA sequencing to identify infecting species. We used logistic regression analysis and structural equation modelling (SEM) to evaluate the risk of VBP infections between ClinL cases and controls. Results From the 50 enrolled dogs with ClinL, DNA was detected in 24 (48%) for Hepatozoon spp., 14 (28%) for Mycoplasma haemocanis, 6 (12%) for Ehrlichia canis and 2 (4%) for Anaplasma platys. In the 92 enrolled control dogs, DNA was detected in 41 (45%) for Hepatozoon spp., 18 (20%) for M. haemocanis, 1 (1%) for E. canis and 3 (3%) for A. platys. No Babesia spp. or “Candidatus Mycoplasma haematoparvum” DNA was detected in any dog. No statistical differences were found between the ClinL and controls regarding age, sex, breed, lifestyle and use of ectoparasitic prevention. A significant association between ClinL and E. canis infection (OR = 12.4, 95% CI: 1.5–106.0, P = 0.022) was found compared to controls by multivariate logistic regression. This association was confirmed using SEM, which further identified that younger dogs were more likely to be infected with each of Hepatozoon spp. and M. haemocanis, and dogs with Hepatozoon spp. were more likely to be co-infected with M. haemocanis. Conclusions Dogs with ClinL are at a higher risk of co-infection with E. canis than clinically healthy dogs. We recommend that dogs diagnosed with ClinL should be tested for E. canis co-infection using PCR

First-principles study of the polar O-terminated ZnO surface in thermodynamic equilibrium with oxygen and hydrogen

Using density-functional theory in combination with a thermodynamic formalism we calculate the relative stability of various structural models of the polar O-terminated (000-1)-O surface of ZnO. Model surfaces with different concentrations of oxygen vacancies and hydrogen adatoms are considered. Assuming that the surfaces are in thermodynamic equilibrium with an O2 and H2 gas phase we determine a phase diagram of the lowest-energy surface structures. For a wide range of temperatures and pressures we find that hydrogen will be adsorbed at the surface, preferentially with a coverage of 1/2 monolayer. At high temperatures and low pressures the hydrogen can be removed and a structure with 1/4 of the surface oxygen atoms missing becomes the most stable one. The clean, defect-free surface can only exist in an oxygen-rich environment with a very low hydrogen partial pressure. However, since we find that the dissociative adsorption of molecular hydrogen and water (if also the Zn-terminated surface is present) is energetically very preferable, it is very unlikely that a clean, defect-free (000-1)-O surface can be observed in experiment.Comment: 10 pages, 4 postscript figures. Uses REVTEX and epsf macro

Young people's uses of celebrity: Class, gender and 'improper' celebrity

This is an Author's Accepted Manuscript of an article published in Discourse: Studies in the Cultural Politics of Education, 34(1), 2013, copyright Taylor & Francis, available online at: http://www.tandfonline.com/10.1080/01596306.2012.698865.In this article, we explore the question of how celebrity operates in young people's everyday lives, thus contributing to the urgent need to address celebrity's social function. Drawing on data from three studies in England on young people's perspectives on their educational and work futures, we show how celebrity operates as a classed and gendered discursive device within young people's identity work. We illustrate how young people draw upon class and gender distinctions that circulate within celebrity discourses (proper/improper, deserving/undeserving, talented/talentless and respectable/tacky) as they construct their own identities in relation to notions of work, aspiration and achievement. We argue that these distinctions operate as part of neoliberal demands to produce oneself as a ‘subject of value’. However, some participants produced readings that show ambivalence and even resistance to these dominant discourses. Young people's responses to celebrity are shown to relate to their own class and gender position.The Arts and Humanities Research Council, the British Academy, the Economic and Social Research Council, and the UK Resource Centre for Women in Science Engineering and Technology