Histamine exerts its numerous physiological functions through interaction with G protein-coupled receptors. Three such receptors have been defined at both the pharmacological and molecular level, ...while pharmacological evidence hints at the existence of further subtypes. We report here the cloning and characterization of a fourth histamine receptor subtype. Initially discovered in an expressed-sequence tag database, the full coding sequence (SP9144) was subsequently identified in chromosome 18 genomic sequence. This virtual coding sequence exhibited highest homology to the H(3) histamine receptor and was used to generate a full-length clone by polymerase chain reaction (PCR). The distribution of mRNA encoding SP9144 was restricted to cells of the immune system as determined by quantitative PCR. HEK-293 cells transiently transfected with SP9144 and a chimeric G protein alpha-subunit (Galpha(q/i1,2)) exhibited increases in intracellular Ca(2+) in response to histamine but not other biogenic amines. SP9144-transfected cells exhibited saturable, specific, high-affinity binding of (3)Hhistamine, which was potently inhibited by H(3) receptor-selective compounds. The rank order and potency of these compounds at SP9144 differed from the rank order at the H(3) receptor. Although SP9144 apparently coupled to Galpha(i), HEK-293 cells stably transfected with SP9144 did not exhibit histamine-mediated inhibition of forskolin-stimulated cAMP levels. However, both (35)SGTPgammaS binding and phosphorylation of mitogen-activated protein kinase were stimulated by histamine via SP9144 activation. In both of these assays, SP9144 exhibited evidence of constitutive activation. Taken together, these data demonstrate that SP9144 is a unique, fourth histamine receptor subtype.
The energetics of La‐doping in BaTiO3 are reported for both (electronic) donor‐doping with the creation of Ti3+ cations and ionic doping with the creation of Ti vacancies. The experiments (for ...samples prepared in air) and simulations demonstrate that ionic doping is the preferred mechanism for all concentrations of La‐doping. The apparent disagreement with electrical conduction of these ionic doped samples is explained by subsequent oxygen‐loss, which leads to the creation of Ti3+ cations. Simulations show that oxygen‐loss is much more favorable in the ionic‐doped system than undoped BaTiO3 due to the unique local structure created around the defect site. These findings resolve the so‐called “donor‐doping” anomaly in BaTiO3 and explain the source of semiconductivity in positive temperature coefficient of resistance (PTCR) BaTiO3 thermistors.
The defect structure of 4% La‐doped BaTiO3 with 4 LaBa and a Ti vacancy is shown. The loss of Ti encourages the creation of an oxygen vacancy and the subsequent electron compensation creates Ti3+, which generates the semiconducting behavior seen for the these samples.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
On the orthosilicate join, Li4SiO4–Mn2SiO4, the new phase Li3Mn0.5SiO4 and a range of Li2+2x Mn1–x SiO4 solid solutions with ∼0.76 ≤ x ≤ 1 have been prepared by high-temperature, solid-state reaction ...and characterized. Li3Mn0.5SiO4 is orthorhombic, space group Pnma, with a = 10.722(3) Å, b = 6.239(2) Å, and c = 5.052(3) Å. A combined analysis of X-ray and neutron powder diffraction data show that its structure is derived from the γII tetrahedral structural family typified by Li3PO4, but with additional Li+ in partially occupied, distorted octahedral sites. These octahedral sites are linked by a combination of edge- and face-sharing, similar to that in the nickel arsenide structure and their partial occupancy is responsible for an Li+ ion conductivity of, for example, ∼ 1 × 10–8 S cm–1 at 60 °C, with activation energy 0.93(1) eV, which is many orders of magnitude higher than that of Li2MnSiO4.
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IJS, KILJ, NUK, PNG, UL, UM
Standardised mortality ratios (SMR) are often used to depict cardiovascular care. Data missingness, data quality, temporal variation and case-mix can, however, complicate the assessment of clinical ...performance.
To study Primary Care Trust (PCT) 30-day SMRs for STEMI and NSTEMI whilst considering the impact of missing data for age, sex and IMD score.
Observational study using data from the Myocardial Ischaemia National Audit Project (MINAP) database to generate PCT SMR maps and funnel plots for England, 2004-2007.
217,157
40.4% STEMI and 59.6% NSTEMI.
95% CI 30-day unadjusted mortality: STEMI 5.8% to 6.2%; NSTEMI 6.6% to 6.9%; relative risk, 95% CI 1.14, 1.10 to 1.19. Median (IQR) data missingess by PCT for composite of age, sex and IMD score was 1.4% (0.7% to 2.2%). For STEMI and NSTEMI statistically significant predictors of mortality were mean age (STEMI: P<0.001; NSTEMI: P<0.001), proportion of females (STEMI: P<0.001; NSTEMI: P<0.001) and proportion of missing ages (STEMI: P=0.02; NSTEMI: P<0.001). Proportion of missing sex also predicted 30-day mortality for NSTEMI (P=0.01). Maps of SMRs demonstrated substantial mortality variation, but no evidence of North / South divide. There were significant correlations between STEMI and NSTEMI observed (R² 0.72) and standardised mortality (R² 0.49) rates. PCT data aggregation gave an acceptable model fit in terms of deviance explained. For STEMI there were 33 (21.7%) regions below the 99.8% lower limit of the associated performance funnel plot, and 28 (18.4%) for NSTEMI; the inclusion of missing data did not affect the distribution of SMRs.
The proportion of missing data was associated with 30-day mortality for STEMI and NSTEMI, however it did not influence the distribution of PCTs within the funnel plots. There was considerable variation in mortality not attributable to key patient-specific factors, supporting the notion of regional-dependent variation in STEMI and NSTEMI care.
Thromboembolism is a recognized complication occurring during endovascular coil embolization of intracranial aneurysms. Recently, there has been much interest in glycoprotein IIb/IIIa inhibitors to ...treat such complications, but the evidence is limited. We reviewed our use of one such agent, abciximab, which we commonly administer and believe to be a safe and suitable rescue agent in this setting.
We retrospectively reviewed cases in which abciximab was administered in our institution between 2001 and 2007. Clinical outcome was assessed by the modified Rankin Scale (mRS) at 6 months. Good outcome was defined as no significant clinical sequelae compared with baseline status or clinical improvement (mRS < 2). Poor outcome was defined as no resolution of a new clinical deficit that developed postprocedure at 6 months (mRS > 2). Angiographic appearance of thromboembolic phenomena and posttreatment outcome was assessed with the Thrombolysis in Myocardial Infarction (TIMI) scale.
Thirty-eight patients were included, with good outcome observed in 30 (79%) and poor outcome in 8 (21%) patients. Angiographic improvement based on TIMI scoring was seen in 24 (63%) patients, and no improvement was seen in 14 (37%). In 4 patients (11%), good outcome was obtained at 6 months despite no angiographic improvement on TIMI. No cases of intracranial rebleed or additional neurologic deficit following administration of abciximab were encountered.
In this small retrospective series, abciximab was safe and effective when used as a rescue agent for thromboembolic complications encountered during coiling of intracerebral aneurysms.
Spinal cord injury chronically alters cardiac structure and function and is associated with increased odds for cardiovascular disease. Here, we investigate the cardiac consequences of spinal cord ...injury on the acute-to-chronic continuum, and the contribution of altered bulbospinal sympathetic control to the decline in cardiac function following spinal cord injury. By combining experimental rat models of spinal cord injury with prospective clinical studies, we demonstrate that spinal cord injury causes a rapid and sustained reduction in left ventricular contractile function that precedes structural changes. In rodents, we experimentally demonstrate that this decline in left ventricular contractile function following spinal cord injury is underpinned by interrupted bulbospinal sympathetic control. In humans, we find that activation of the sympathetic circuitry below the level of spinal cord injury causes an immediate increase in systolic function. Our findings highlight the importance for early interventions to mitigate the cardiac functional decline following spinal cord injury.
Cr-doped rutile, Ti1−xCrxO2−x/2−δ, powders and ceramics with 0 ≤ x ≤ 0.05 were prepared by solid state reaction and sintered at 1350 °C. Cr distribution is homogeneous with no evidence of either ...segregation or crystallographic shear plane formation. For high x compositions, >∼0.01, Cr substitution is charge-compensated ionically by oxygen vacancies with two Cr3+ ions for each vacancy and the materials are electronically insulating. For low x compositions, the materials are semiconducting. This is attributed to a new charge compensation mechanism involving Ti3+ ions created in response to the local electroneutrality requirement for two trivalent cations to be in close proximity to each oxygen vacancy. At very low dopant concentrations, ≪0.01, the dopants are well-separated and instead, some Ti3+ ions act as a second dopant to preserve local electroneutrality. For intermediate x compositions, a core–shell structure is proposed consisting of semiconducting grain interiors containing Ti3+ ions surrounded by a more insulating shell with Cr3+ ions as the only acceptor dopant. Lattice parameters show unusual, non-linear Vegard's law behaviour characterised by a maximum in cell volume at intermediate x ∼ 0.005, that is attributed to the composition-dependent presence of Ti3+ ions.
The zebra finch ( Taeniopygia castanotis ) is a songbird sold in the pet trade and commonly used in research. In this report, we describe a set of partially overlapping traits shared by 3 birds in 2 ...broods from the same nest box that included atypical morphologic, developmental, and behavioral characteristics. The most obvious feature of this novel phenotype was feathers exhibiting a clumped appearance, which was accompanied by slow growth, delayed expression of adult plumage traits, and tameness, which we define as a lack of escape response upon handling without behavioral indicators of stress such as rapid breathing. Surprisingly, these birds also displayed a fatal response to nonhuman stressors. In one brood, a male expressed all of these characteristics, 2 females were wild-type, and a male sibling expressed only a hyperactive stress response but was otherwise normal. This indicates that the stress response could be inherited independently of the other abnormalities found in the male nest mate. In a second brood, a male bearing the abnormal feather phenotype behaved similarly to the male in the first brood, supporting the possibility that tameness is genetically associated with the unusual feather phenotype. The 2 other male and 2 female nest mates from this brood were behaviorally and visually normal, although the females developed slowly. Although similar traits have appeared in the aviary previously, such as slow development and small size, these are the first cases documented in detail. This correlated suite of traits suggests a linkage among altered feather growth, developmental rate, and brain and/or physiologic traits influencing normal fear and stress responses in the zebra finch. Awareness and study of the mechanism(s) linking these traits by examination of underlying genetic or environmental factors will allow a better understanding of the relationship between physical and behavioral traits in domesticated laboratory animals.
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