Anisotropic spin fluctuations and multiple superconducting gaps in hole-doped Ba_0.7K_0.3Fe_2As_2: NMR in a single crystal

We report the first ^{75}As-NMR study on a single crystal of the hole-doped iron-pnictide superconductor Ba_{0.7}K_{0.3}Fe_2As_{2} (T_c = 31.5 K). We find that the Fe antiferromagnetic spin fluctuations are anisotropic and are weaker compared to underdoped copper-oxides or cobalt-oxide superconductors. The spin lattice relaxation rate 1/T_1 decreases below T_c with no coherence peak and shows a step-wise variation at low temperatures, which is indicative of multiple superconducting gaps, as in the electron-doped Pr(La)FeAsO$_{1-x}$F$_{x}$. Furthermore, no evidence was obtained for a microscopic coexistence of a long-range magnetic and superconductivity

Doping Dependence of Collective Spin and Orbital Excitations in Spin 1 Quantum Antiferromagnet La2−x_{2-x}Srx_xNiO4_4 Observed by X-rays

We report the first empirical demonstration that resonant inelastic x-ray scattering (RIXS) is sensitive to \emph{collective} magnetic excitations in $S=1$ systems by probing the Ni $L_3$-edge of La$_{2-x}$Sr$_x$NiO$_4$ ($x = 0, 0.33, 0.45$). The magnetic excitation peak is asymmetric, indicating the presence of single and multi spin-flip excitations. As the hole doping level is increased, the zone boundary magnon energy is suppressed at a much larger rate than that in hole doped cuprates. Based on the analysis of the orbital and charge excitations observed by RIXS, we argue that this difference is related to the orbital character of the doped holes in these two families. This work establishes RIXS as a probe of fundamental magnetic interactions in nickelates opening the way towards studies of heterostructures and ultra-fast pump-probe experiments.Comment: 8 pages, 4 figures, see ancillary files for the supplemental materia

A prospective study of decline in fat free mass and skeletal muscle strength in chronic obstructive pulmonary disease

BACKGROUND: Skeletal muscle depletion is an important complication of chronic obstructive pulmonary disease (COPD) but little prospective data exists about the rate at which it occurs and the factors that promote its development. We therefore prospectively investigated the impact of disease severity, exacerbation frequency and treatment with corticosteroids on change in body composition and maximum isometric quadriceps strength (QMVC) over one year. METHODS: 64 patients with stable COPD (FEV(1 )mean (SD) 35.8(18.4) %predicted) were recruited from clinic and studied on two occasions one year apart. Fat free mass was determined using bioelectrical impedance analysis and a disease specific regression equation. RESULTS: QMVC fell from 34.8(1.5) kg to 33.3(1.5) kg (p = 0.04). The decline in quadriceps strength was greatest in those with the highest strength at baseline (R -0.28 p = 0.02) and was not correlated with lung function, exacerbation frequency or steroid treatment. Decline in fat free mass was similarly higher in those with largest FFM at baseline (R = -0.31 p = 0.01) but was more strongly correlated with greater gas trapping (R = -0.4 p = 0.001). Patients with frequent exacerbations (>1 per year) (n = 36) experienced a greater decline in fat free mass compared to infrequent exacerbators (n = 28) -1.3(3.7)kg vs. +1.2(3.1)kg (p = 0.005), as did patients on maintenance oral steroids (n = 8) -2.8(3.3) kg vs. +0.2(3.5) kg (p = 0.024) whereas in those who stopped smoking (n = 7) fat free mass increased; +2.7(3.1) kg vs. -0.51(3.5) kg (p = 0.026). CONCLUSION: Decline in fat free mass in COPD is associated with worse lung function, continued cigarette consumption and frequent exacerbations. Factors predicting progression of quadriceps weakness could not be identified from the present cohort

Aspartoacylase-LacZ Knockin Mice: An Engineered Model of Canavan Disease

Canavan Disease (CD) is a recessive leukodystrophy caused by loss of function mutations in the gene encoding aspartoacylase (ASPA), an oligodendrocyte-enriched enzyme that hydrolyses N-acetylaspartate (NAA) to acetate and aspartate. The neurological phenotypes of different rodent models of CD vary considerably. Here we report on a novel targeted aspa mouse mutant expressing the bacterial β-Galactosidase (lacZ) gene under the control of the aspa regulatory elements. X-Gal staining in known ASPA expression domains confirms the integrity of the modified locus in heterozygous aspa lacZ-knockin (aspalacZ/+) mice. In addition, abundant ASPA expression was detected in Schwann cells. Homozygous (aspalacZ/lacZ) mutants are ASPA-deficient, show CD-like histopathology and moderate neurological impairment with behavioural deficits that are more pronounced in aspalacZ/lacZ males than females. Non-invasive ultrahigh field proton magnetic resonance spectroscopy revealed increased levels of NAA, myo-inositol and taurine in the aspalacZ/lacZ brain. Spongy degeneration was prominent in hippocampus, thalamus, brain stem, and cerebellum, whereas white matter of optic nerve and corpus callosum was spared. Intracellular vacuolisation in astrocytes coincides with axonal swellings in cerebellum and brain stem of aspalacZ/lacZ mutants indicating that astroglia may act as an osmolyte buffer in the aspa-deficient CNS. In summary, the aspalacZ mouse is an accurate model of CD and an important tool to identify novel aspects of its complex pathology

The Warburg Effect Is Genetically Determined in Inherited Pheochromocytomas

The Warburg effect describes how cancer cells down-regulate their aerobic respiration and preferentially use glycolysis to generate energy. To evaluate the link between hypoxia and Warburg effect, we studied mitochondrial electron transport, angiogenesis and glycolysis in pheochromocytomas induced by germ-line mutations in VHL, RET, NF1 and SDH genes. SDH and VHL gene mutations have been shown to lead to the activation of hypoxic response, even in normoxic conditions, a process now referred to as pseudohypoxia. We observed a decrease in electron transport protein expression and activity, associated with increased angiogenesis in SDH- and VHL-related, pseudohypoxic tumors, while stimulation of glycolysis was solely observed in VHL tumors. Moreover, microarray analyses revealed that expression of genes involved in these metabolic pathways is an efficient tool for classification of pheochromocytomas in accordance with the predisposition gene mutated. Our data suggest an unexpected association between pseudohypoxia and loss of p53, which leads to a distinct Warburg effect in VHL-related pheochromocytomas

Glucose Depletion in the Airway Surface Liquid Is Essential for Sterility of the Airways

Diabetes mellitus predisposes the host to bacterial infections. Moreover, hyperglycemia has been shown to be an independent risk factor for respiratory infections. The luminal surface of airway epithelia is covered by a thin layer of airway surface liquid (ASL) and is normally sterile despite constant exposure to bacteria. The balance between bacterial growth and killing in the airway determines the outcome of exposure to inhaled or aspirated bacteria: infection or sterility. We hypothesized that restriction of carbon sources –including glucose– in the ASL is required for sterility of the lungs. We found that airway epithelia deplete glucose from the ASL via a novel mechanism involving polarized expression of GLUT-1 and GLUT-10, intracellular glucose phosphorylation, and low relative paracellular glucose permeability in well-differentiated cultures of human airway epithelia and in segments of airway epithelia excised from human tracheas. Moreover, we found that increased glucose concentration in the ASL augments growth of P. aeruginosa in vitro and in the lungs of hyperglycemic ob/ob and db/db mice in vivo. In contrast, hyperglycemia had no effect on intrapulmonary bacterial growth of a P. aeruginosa mutant that is unable to utilize glucose as a carbon source. Our data suggest that depletion of glucose in the airway epithelial surface is a novel mechanism for innate immunity. This mechanism is important for sterility of the airways and has implications in hyperglycemia and conditions that result in disruption of the epithelial barrier in the lung