Nitrite is produced by elicited but not by circulating neutrophils

The generation of nitrite (NO2-) was used as an index of the production of nitric oxide by human and rat polymorphonuclear leukocytes (PMN) and rat peritoneal macrophages. Human peripheral blood PMN did not produce significant levels of NO2-. Attempts to induce NO2- generation in human PMN by incubation with GM–CSF (1 nM), TNFα (0.3 nM), endotoxin (1 μg/ml) or formyl-Met-Leu-Phe (100 nM) for up to 16 h were not successful. Addition of human PMN primed by GM–CSF (1 nM) to rabbit aortic ring preparations precontracted with phenylephrine had no effect on tone. In contrast to these observations, PMN, isolated from the peritoneum of oyster glycogen treated rats, generated NO2- via a pathway sensitive to inhibition by the nitric oxide synthase inhibitor, NG-monomethyl L-arginine. However, peripheral blood rat PMN obtained from the same animals did not produce NO2-, even during prolonged incubation for periods of up to 16 h. It is suggested that detectable NO production by PMN requires NO synthase activity to be induced either by the process of PMN migration or by exposure to certain cytokines produced locally at the site of inflammation

Nox1 oxidase suppresses influenza a virus-induced lung inflammation and oxidative stress

Influenza A virus infection is an ongoing clinical problem and thus, there is an urgent need to understand the mechanisms that regulate the lung inflammation in order to unravel novel generic pharmacological strategies. Evidence indicates that the Nox2-containing NADPH oxidase enzyme promotes influenza A virus-induced lung oxidative stress, inflammation and dysfunction via ROS generation. In addition, lung epithelial and endothelial cells express the Nox1 isoform of NADPH oxidase, placing this enzyme at key sites to regulate influenza A virus-induced lung inflammation. The aim of this study was to investigate whether Nox1 oxidase regulates the inflammatory response and the oxidative stress to influenza infection in vivo in mice. Male WT and Nox1-deficient (Nox1−/y) mice were infected with the moderately pathogenic HkX-31 (H3N2, 1×104 PFU) influenza A virus for analysis of bodyweight, airways inflammation, oxidative stress, viral titre, lung histopathology, and cytokine/chemokine expression at 3 and 7 days post infection. HkX-31 virus infection of Nox1−/y mice resulted in significantly greater: loss of bodyweight (Day 3); BALF neutrophilia, peri-bronchial, peri-vascular and alveolar inflammation; Nox2-dependent inflammatory cell ROS production and peri-bronchial, epithelial and endothelial oxidative stress. The expression of pro-inflammatory cytokines including CCL2, CCL3, CXCL2, IL-1β, IL-6, GM-CSF and TNF-α was higher in Nox1−/y lungs compared to WT mice at Day 3, however, the expression of CCL2, CCL3, CXCL2, IFN-γ and the anti-inflammatory cytokine IL-10 were lower in lungs of Nox1−/y mice vs. WT mice at Day 7. Lung viral titre, and airways infiltration of active CD8+ and CD4+ T lymphocytes, and of Tregs were similar between WT and Nox1−/y mice. In conclusion, Nox1 oxidase suppresses influenza A virus induced lung inflammation and oxidative stress in mice particularly at the early phases of the infection. Nox1 and Nox2 oxidases appear to have opposing roles in the regulation of inflammation caused by influenza A viruses

Long Term Variability of a Black Widow's Eclipses -- A Decade of PSR J2051−-0827

In this paper we report on $\sim10$ years of observations of PSR J2051$-$0827, at radio frequencies in the range 110--4032 MHz. We investigate the eclipse phenomena of this black widow pulsar using model fits of increased dispersion and scattering of the pulsed radio emission as it traverses the eclipse medium. These model fits reveal variability in dispersion features on timescales as short as the orbital period, and previously unknown trends on timescales of months--years. No clear patterns are found between the low-frequency eclipse widths, orbital period variations and trends in the intra-binary material density. Using polarisation calibrated observations we present the first available limits on the strength of magnetic fields within the eclipse region of this system; the average line of sight field is constrained to be $10^{-4}$ G $\lesssim B_{||} \lesssim 10^2$ G, while for the case of a field directed near-perpendicular to the line of sight we find $B_{\perp} \lesssim 0.3$ G. Depolarisation of the linearly polarised pulses during the eclipse is detected and attributed to rapid rotation measure fluctuations of $\sigma_{\text{RM}} \gtrsim 100$ rad m$^{-2}$ along, or across, the line of sights averaged over during a sub-integration. The results are considered in the context of eclipse mechanisms, and we find scattering and/or cyclotron absorption provide the most promising explanation, while dispersion smearing is conclusively ruled out. Finally, we estimate the mass loss rate from the companion to be $\dot{M}_{\text{C}} \sim 10^{-12} M_\odot$ yr$^{-1}$, suggesting that the companion will not be fully evaporated on any reasonable timescale

A LOFAR census of non-recycled pulsars: extending below 80 MHz

We present the results from the low-frequency (40--78 MHz) extension of the first LOFAR pulsar census of non-recycled pulsars. We have used the Low-Band Antennas of the LOFAR core stations to observe 87 pulsars out of 158 that have been detected previously with the High-Band Antennas. Forty-three pulsars have been detected and we present here their flux densities and flux-calibrated profiles. Seventeen of these pulsars have not been, to our knowledge, detected before at such low frequencies. We re-calculate the spectral indices using the new low-frequency flux density measurements from the LOFAR census and discuss the prospects of studying pulsars at the very low frequencies with the current and upcoming facilities, such as NenuFAR

Osteogenesis imperfecta: Ultrastructural and histological findings on examination of skin revealing novel insights into genotype-phenotype correlation

© 2016 Taylor & Francis. Osteogenesis imperfecta (OI) is a heterogeneous group of inherited disorders of bone formation, resulting in low bone mass and an increased propensity to fracture. Over 90% of patients with OI have a mutation in COL1A1/COL1A2, which shows an autosomal dominant pattern of inheritance. In-depth phenotyping and in particular, studies involving manifestations in the skin connective tissue have not previously been undertaken in OI. The aims of the study were to perform histological and ultrastructural examination of skin biopsies in a cohort of patients with OI; to identify common and distinguishing features in order to inform genotype-phenotype correlation; and to identify common and distinguishing features between the different subtypes of OI. As part of the RUDY (Rare Diseases in Bone, Joints and/or Blood Vessels) study, in collaboration with the NIHR Rare Diseases Translational Research Collaboration, we undertook a national study of skin biopsies in patients with OI. We studied the manifestations in the skin connective tissue and undertook in-depth clinical and molecular phenotyping of 16 patients with OI. We recruited 16 patients: analyses have shown that in type 1 collagen mutation positive patients (COL1A1/ COL1A2) (n-4/16) consistent findings included: variable collagen fibril diameter (CFD) and presence of collagen flowers. Histological examination in these patients showed an increase in elastic fibers that are frequently fragmented and clumped. These observations provide evidence that collagen flowers and CFD variability are consistent features in OI due to type 1 collagen defects and reinforce the need for accurate phenotyping in conjunction with genomic analyses

The POlarised GLEAM Survey (POGS) II: Results from an All-Sky Rotation Measure Synthesis Survey at Long Wavelengths

The low-frequency linearly-polarised radio source population is largely unexplored. However, a renaissance in low-frequency polarimetry has been enabled by pathfinder and precursor instruments for the Square Kilometre Array. In this second paper from the POlarised GaLactic and Extragalactic All-Sky Murchison Widefield Array (MWA) Survey -- the POlarised GLEAM Survey, or POGS -- we present the results from our all-sky MWA Phase I Faraday Rotation Measure survey. Our survey covers nearly the entire Southern sky in the Declination range $-82^{\circ}$ to $+30^{\circ}$ at a resolution between around three and seven arcminutes (depending on Declination) using data in the frequency range 169$-$231 MHz. We have performed two targeted searches: the first covering 25,489 square degrees of sky, searching for extragalactic polarised sources; the second covering the entire sky South of Declination $+30^{\circ}$, searching for known pulsars. We detect a total of 517 sources with 200 MHz linearly-polarised flux densities between 9.9 mJy and 1.7 Jy, of which 33 are known radio pulsars. All sources in our catalogues have Faraday rotation measures in the range $-328.07$ rad m$^{-2}$ to $+279.62$ rad m$^{-2}$. The Faraday rotation measures are broadly consistent with results from higher-frequency surveys, but with typically more than an order of magnitude improvement in the precision, highlighting the power of low-frequency polarisation surveys to accurately study Galactic and extragalactic magnetic fields. We discuss the properties of our extragalactic and known-pulsar source population, how the sky distribution relates to Galactic features, and identify a handful of new pulsar candidates among our nominally extragalactic source population.Comment: Replacement of previous version. Only change is minor updates to catalogues (see ancillary files) which now contain bib code of finalised manuscript (published in PASA). Manuscript has 31 pages, 10 figures, 5 tables. Four Appendices are included in the ancillary material, showing further Figures, continuum spectra for a handful of selected sources, and RM spectra for all 517 source

The POlarised GLEAM Survey (POGS) II: Results from an all-sky rotation measure synthesis survey at long wavelengths

The low-frequency linearly polarised radio source population is largely unexplored. However, a renaissance in low-frequency polarimetry has been enabled by pathfinder and precursor instruments for the Square Kilometre Array. In this second paper from the POlarised GaLactic and Extragalactic All-Sky MWA Survey-the POlarised GLEAM Survey, or POGS-we present the results from our all-sky MWA Phase I Faraday Rotation Measure survey. Our survey covers nearly the entire Southern sky in the Declination range to at a resolution between around three and seven arcminutes (depending on Declination) using data in the frequency range 169-231 MHz. We have performed two targeted searches: the first covering 25 489 square degrees of sky, searching for extragalactic polarised sources; the second covering the entire sky South of Declination, searching for known pulsars. We detect a total of 517 sources with 200 MHz linearly polarised flux densities between 9.9 mJy and 1.7 Jy, of which 33 are known radio pulsars. All sources in our catalogues have Faraday rotation measures in the range to rad m-2. The Faraday rotation measures are broadly consistent with results from higher-frequency surveys, but with typically more than an order of magnitude improvement in the precision, highlighting the power of low-frequency polarisation surveys to accurately study Galactic and extragalactic magnetic fields. We discuss the properties of our extragalactic and known-pulsar source population, how the sky distribution relates to Galactic features, and identify a handful of new pulsar candidates among our nominally extragalactic source population