166 research outputs found

    Evidence for endohedral muonium in Kx C60 and consequences for electronic structure

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    Positive muons injected into solid C60, K4C60, and K6C60 form vacuumlike muonium (μ+e-) with a (6–12)% probability. Observation of coherent spin precession of muonium establishes that all three materials are nonmagnetic and nonconducting at low temperatures. From the temperature dependence of the signals we estimate the electronic band gaps in K4C60 and K6C60 to be considerably smaller than in C60. The similarity of the muonium centers supports a model in which a muonium atom is caged inside the C60 molecule in pure C60 or the C60x molecular ion in KxC60

    A common behavior of thermoelectric layered cobaltites: incommensurate spin density wave states in [Ca2_2Co4/3_{4/3}Cu2/3_{2/3}O4_4]0.62_{0.62}[CoO2_2] and [Ca2_2CoO3_3]0.62_{0.62}[CoO2_2]

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    Magnetism of a misfit layered cobaltite [Ca2_2Co4/3_{4/3}Cu2/3_{2/3}O4_4]xRS_x^{\rm RS}[CoO2_2] (xx \sim 0.62, RS denotes a rocksalt-type block) was investigated by a positive muon spin rotation and relaxation (μ+\mu^+SR) experiment. A transition to an incommensurate ({\sf IC}) spin density wave ({\sf SDW}) state was found below 180 K (= TConT_{\rm C}^{\rm on}); and a clear oscillation due to a static internal magnetic field was observed below 140 K (= TCT_{\rm C}). Furthermore, an anisotropic behavior of the zero-field μ+\mu^+SR experiment indicated that the {\sf IC-SDW} propagates in the aa-bb plane, with oscillating moments directed along the c axis. These results were quite similar to those for the related compound [Ca2_2CoO3_3]0.62RS_{0.62}^{\rm RS}[CoO2_2], {\sl i.e.}, Ca3_3Co4_4O9_9. Since the {\sf IC-SDW} field in [Ca2_2Co4/3_{4/3}Cu2/3_{2/3}O4_4]0.62RS_{0.62}^{\rm RS}[CoO2_2] was approximately same to those in pure and doped [Ca2_2CoO3_3]0.62RS_{0.62}^{\rm RS}[CoO2_2], it was concluded that the {\sf IC-SDW} exist in the [CoO2_2] planes.Comment: 15 pages, 6 figures. accepted for publication in J. Phys.: Condens. Matte

    Muon spin relaxation studies of incommensurate magnetism and superconductivity in stage-4 La2_{2}CuO4.11_{4.11} and La1.88_{1.88}Sr0.12_{0.12}CuO4_{4}

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    This paper reports muon spin relaxation (MuSR) measurements of two single crystals of the title high-Tc cuprate systems where static incommensurate magnetism and superconductivity coexist. By zero-field MuSR measurements and subsequent analyses with simulations, we show that (1) the maximum ordered Cu moment size (0.36 Bohr magneton) and local spin structure are identical to those in prototypical stripe spin systems with the 1/8 hole concentration; (2) the static magnetism is confined to less than a half of the volume of the sample, and (3) regions with static magnetism form nano-scale islands with the size comparable to the in-plane superconducting coherence length. By transverse-field MuSR measurements, we show that Tc of these systems is related to the superfluid density, in the same way as observed in cuprate systems without static magnetism. We discuss a heuristic model involving percolation of these nanoscale islands with static magnetism as a possible picture to reconcile heterogeneity found by the present MuSR study and long-range spin correlations found by neutron scattering.Comment: 19 pages, 15 figures, submitted to Phys. Rev. B. E-mail: [email protected]

    A LINE-1 insertion situated in the promoter of IMPG2 is associated with autosomal recessive progressive retinal atrophy in Lhasa Apso dogs

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    Funder: Lhasa Apso Breed CouncilFunder: Kennel Club Charitable Trust UKAbstract: Background: Canine progressive retinal atrophies are a group of hereditary retinal degenerations in dogs characterised by depletion of photoreceptor cells in the retina, which ultimately leads to blindness. PRA in the Lhasa Apso (LA) dog has not previously been clinically characterised or described in the literature, but owners in the UK are advised to have their dog examined through the British Veterinary Association/ Kennel Club/ International Sheep Dog Society (BVA/KC/ISDS) eye scheme annually, and similar schemes that are in operation in other countries. After the exclusion of 25 previously reported canine retinal mutations in LA PRA-affected dogs, we sought to identify the genetic cause of PRA in this breed. Results: Analysis of whole-exome sequencing data of three PRA-affected LA and three LA without signs of PRA did not identify any exonic or splice site variants, suggesting the causal variant was non-exonic. We subsequently undertook a genome-wide association study (GWAS), which identified a 1.3 Mb disease-associated region on canine chromosome 33, followed by whole-genome sequencing analysis that revealed a long interspersed element-1 (LINE-1) insertion upstream of the IMPG2 gene. IMPG2 has previously been implicated in human retinal disease; however, until now no canine PRAs have been associated with this gene. The identification of this PRA-associated variant has enabled the development of a DNA test for this form of PRA in the breed, here termed PRA4 to distinguish it from other forms of PRA described in other breeds. This test has been used to determine the genotypes of over 900 LA dogs. A large cohort of genotyped dogs was used to estimate the allele frequency as between 0.07–0.1 in the UK LA population. Conclusions: Through the use of GWAS and subsequent sequencing of a PRA case, we have identified a LINE-1 insertion in the retinal candidate gene IMPG2 that is associated with a form of PRA in the LA dog. Validation of this variant in 447 dogs of 123 breeds determined it was private to LA dogs. We envisage that, over time, the developed DNA test will offer breeders the opportunity to avoid producing dogs affected with this form of PRA

    Two additive mechanisms impair the differentiation of 'substrate-selective' p38 inhibitors from classical p38 inhibitors in vitro

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    <p>Abstract</p> <p>Background</p> <p>The success of anti-TNF biologics for the treatment of rheumatoid arthritis has highlighted the importance of understanding the intracellular pathways that regulate TNF production in the quest for an orally-available small molecule inhibitor. p38 is known to strongly regulate TNF production via MK2. The failure of several p38 inhibitors in the clinic suggests the importance of other downstream pathways in normal cell function. Recent work has described a 'substrate-selective' p38 inhibitor that is able to preferentially block the activity of p38 against one substrate (MK2) versus another (ATF2). Using a combined experimental and computational approach, we have examined this mechanism in greater detail for two p38 substrates, MK2 and ATF2.</p> <p>Results</p> <p>We found that in a dual (MK2 and ATF2) substrate assay, MK2-p38 interaction reduced the activity of p38 against ATF2. We further constructed a detailed kinetic mechanistic model of p38 phosphorylation in the presence of multiple substrates and successfully predicted the performance of classical and so-called 'substrate-selective' p38 inhibitors in the dual substrate assay. Importantly, it was found that excess MK2 results in a stoichiometric effect in which the formation of p38-MK2-inhibitor complex prevents the phosphorylation of ATF2, despite the preference of the compound for the p38-MK2 complex over the p38-ATF2 complex. MK2 and p38 protein expression levels were quantified in U937, Thp-1 and PBMCs and found that [MK2] > [p38].</p> <p>Conclusion</p> <p>Our integrated mechanistic modeling and experimental validation provides an example of how systems biology approaches can be applied to drug discovery and provide a basis for decision-making with limited chemical matter. We find that, given our current understanding, it is unlikely that 'substrate-selective' inhibitors of p38 will work as originally intended when placed in the context of more complex cellular environments, largely due to a stoichiometric excess of MK2 relative to p38.</p

    Abscess of adrenal gland caused by disseminated subacute Nocardia farcinica pneumonia. A case report and mini-review of the literature

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    <p>Abstract</p> <p>Background</p> <p>Infections caused by <it>Nocardia farcinica </it>are uncommon and show a great variety of clinical manifestations in immunocompetent and immunocompromised patients. Because of its unspecific symptoms and tendency to disseminate it may mimic the clinical symptoms and radiologic findings of a tumour disease and the diagnosis of nocardiosis can easily be missed, because there are no characteristic symptoms.</p> <p>Case presentation</p> <p>We present a case of an adrenal gland abscess caused by subacute disseminated <it>N. farcinica </it>pneumonia.</p> <p>Conclusion</p> <p>An infection with <it>N. farcinica </it>is potentially lethal because of its tendency to disseminate -particularly in the brain- and its high resistance to antibiotics. Awareness of this differential diagnosis allows early and appropriate treatment to be administered.</p

    Systematic Identification of Spontaneous Preterm Birth-Associated RNA Transcripts in Maternal Plasma

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    <div><h3>Background</h3><p>Spontaneous preterm birth (SPB, before 37 gestational weeks) is a major cause of perinatal mortality and morbidity, but its pathogenesis remains unclear. Studies on SPB have been hampered by the limited availability of markers for SPB in predelivery clinical samples that can be easily compared with gestational age-matched normal controls. We hypothesize that SPB involves aberrant placental RNA expression, and that such RNA transcripts can be detected in predelivery maternal plasma samples, which can be compared with gestational age-matched controls.</p> <h3>Principal Findings</h3><p>Using gene expression microarray to profile essentially all human genes, we observed that 426 probe signals were changed by >2.9-fold in the SPB placentas, compared with the spontaneous term birth (STB) placentas. Among the genes represented by those probes, we observed an over-representation of functions in RNA stabilization, extracellular matrix binding, and acute inflammatory response. Using RT-quantitative PCR, we observed differences in the RNA concentrations of certain genes only between the SPB and STB placentas, but not between the STB and term elective cesarean delivery placentas. Notably, 36 RNA transcripts were observed at placental microarray signals higher than a threshold, which indicated the possibility of their detection in maternal plasma. Among them, the <em>IL1RL1</em> mRNA was tested in plasma samples taken from 37 women. It was detected in 6 of 10 (60%) plasma samples collected during the presentation of preterm labor (≤32.9 weeks) in women eventually giving SPB, but was detected in only 1 of 27 (4%) samples collected during matched gestational weeks from women with no preterm labor (Fisher exact test, p = 0.00056).</p> <h3>Conclusion</h3><p>We have identified 36 SPB-associated RNA transcripts, which are possibly detectable in maternal plasma. We have illustrated that the <em>IL1RL1</em> mRNA was more frequently detected in predelivery maternal plasma samples collected from women resulting in SPB than the gestational-age matched controls.</p> </div

    TRBP and eIF6 Homologue in Marsupenaeus japonicus Play Crucial Roles in Antiviral Response

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    Plants and invertebrates can suppress viral infection through RNA silencing, mediated by RNA-induced silencing complex (RISC). Trans-activation response RNA-binding protein (TRBP), consisting of three double-stranded RNA-binding domains, is a component of the RISC. In our previous paper, a TRBP homologue in Fenneropenaeus chinensis (Fc-TRBP) was reported to directly bind to eukaryotic initiation factor 6 (Fc-eIF6). In this study, we further characterized the function of TRBP and the involvement of TRBP and eIF6 in antiviral RNA interference (RNAi) pathway of shrimp. The double-stranded RNA binding domains (dsRBDs) B and C of the TRBP from Marsupenaeus japonicus (Mj-TRBP) were found to mediate the interaction of TRBP and eIF6. Gel-shift assays revealed that the N-terminal of Mj-TRBP dsRBD strongly binds to double-stranded RNA (dsRNA) and that the homodimer of the TRBP mediated by the C-terminal dsRBD increases the affinity to dsRNA. RNAi against either Mj-TRBP or Mj-eIF6 impairs the dsRNA-induced sequence-specific RNAi pathway and facilitates the proliferation of white spot syndrome virus (WSSV). These results further proved the important roles of TRBP and eIF6 in the antiviral response of shrimp
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