The Nearby Neutron Star RX J0720.4-3125 from Radio to X-rays

We present radio, optical, ultraviolet, and X-ray observations of the isolated, thermally-emitting neutron star RX J0720.4-3125 using the Parkes radio telescope, the Very Large Array, the Hubble Space Telescope, and the Chandra X-ray Observatory. From these data we show that the optical/UV spectrum of RX J0720.4-3125 is not well fit by a Rayleigh-Jeans tail as previously thought, but is instead best fit by either a single non-thermal power-law or a combination of a Rayleigh-Jeans tail and a non-thermal power-law. Taken together with the X-ray spectrum, we find the best model for RX J0720.4-3125 to be two blackbodies plus a power-law, with the cool blackbody implying a radius of 11-13 km at an assumed distance of 300 pc. This is similar to many middle aged (10^{5-6} yr) radio pulsars such as PSR B0656+14, evidence supporting the hypothesis that RX J0720.4-3125 is likely to be an off-beam radio pulsar. The radio data limit the flux at 1.4 GHz to be <0.24 mJy, or a luminosity limit of 4*pi*d^2*F < 3e25*d_300^2 ergs/s, and we see no sign of extended nebulosity, consistent with expectations for a pulsar like RX J0720.4-3125.Comment: 13 pages, 9 figures. Uses emulateapj5.sty and onecolfloat5.sty. Accepted for publication in Ap

EC 11481-2303 - A Peculiar Subdwarf OB Star Revisited

EC 11481-2303 is a peculiar, hot, high-gravity pre-white dwarf. Previous optical spectroscopy revealed that it is a sdOB star with an effective temperature (Teff) of 41790 K, a surface gravity log(g)= 5.84, and He/H = 0.014 by number. We present an on-going spectral analysis by means of non-LTE model-atmosphere techniques based on high-resolution, high-S/N optical (VLT-UVES) and ultraviolet (FUSE, IUE) observations. We are able to reproduce the optical and UV observations simultaneously with a chemically homogeneous NLTE model atmosphere with a significantly higher effective temperature and lower He abundance (Teff = 55000 K, log (g) = 5.8, and He / H = 0.0025 by number). While C, N, and O appear less than 0.15 times solar, the iron-group abundance is strongly enhanced by at least a factor of ten.Comment: 8 pages, 11 figure

A T-type channel-calmodulin complex triggers αCaMKII activation

Abstract Calmodulin (CaM) is an important signaling molecule that regulates a vast array of cellular functions by activating second messengers involved in cell function and plasticity. Low voltage-activated calcium channels of the Cav3 family have the important role of mediating low threshold calcium influx, but were not believed to interact with CaM. We find a constitutive association between CaM and the Cav3.1 channel at rest that is lost through an activity-dependent and Cav3.1 calcium-dependent CaM dissociation. Moreover, Cav3 calcium influx is sufficient to activate αCaMKII in the cytoplasm in a manner that depends on an intact Cav3.1 C-terminus needed to support the CaM interaction. Our findings thus establish that T-type channel calcium influx invokes a novel dynamic interaction between CaM and Cav3.1 channels to trigger a signaling cascade that leads to αCaMKII activation

Hot subdwarfs from the ESO Supernova Ia Progenitor Survey: II. Atmospheric parameters of subdwarf O stars

We address the origin and evolutionary status of hot subdwarf stars by studying the optical spectral properties of 58 subdwarf O (sdO) stars. Combining them with the results of our previously studied subdwarf B (sdB) stars, we aim at investigating possible evolutionary links. We analyze high-resolution ESO VLT UVES spectra from the ESO Supernova Ia Progenitor Survey (SPY). Effective temperatures, gravities, and helium abundances are determined simultaneously by fitting the profiles of H and He lines using dedicated synthetic spectra in NLTE. Evidence for cool companions to 8 sdOs as well as a binary consisting of two sdO stars is found. A correlation between He abundances and the presence of carbon and/or nitrogen lines emerges: below solar He abundance, no sdO shows C or N lines. In contrast, C and/or N lines are present in ALL sdOs with super- solar He abundance. We thus use the solar He abundance to divide our sample into He-deficient and He-enriched sdOs. While He-deficient sdOs are scattered in a wide range of the Teff-log(g)-diagram, most of the He-enriched sdOs cluster in a narrow region at Teff = 40,000 ... 50,000K and log(g)=5.5 ... 6.0. An evolu- tionary link between sdBs and sdOs appears plausible only for the He-deficient sdOs indicating that they are the likely successors to sdBs. The properties of He-enriched sdOs cannot be explained with canonical single star evolutionary models. Alternative scenarios (late hot flasher) as well as for binary evolution (white dwarf merger; post-RGB evolution) are tested. While we regard the post-RGB scenario as inappropriate, the white dwarf merger and the late hot flasher scenarios remain viable to explain the origin of He-enriched sdOs.Comment: 14 pages, 10 figures, Astronomy & Astrophysics accepte

Mitochondrial changes within axons in multiple sclerosis

Multiple sclerosis is the most common cause of non-traumatic neurological impairment in young adults. An energy deficient state has been implicated in the degeneration of axons, the pathological correlate of disease progression, in multiple sclerosis. Mitochondria are the most efficient producers of energy and play an important role in calcium homeostasis. We analysed the density and function of mitochondria using immunohistochemistry and histochemistry, respectively, in chronic active and inactive lesions in progressive multiple sclerosis. As shown before in acute pattern III and Balo’s lesions, the mitochondrial respiratory chain complex IV activity is reduced despite the presence of mitochondria in demyelinated axons with amyloid precursor protein accumulation, which are predominantly located at the active edge of chronic active lesions. Furthermore, the strong non-phosphorylated neurofilament (SMI32) reactivity was associated with a significant reduction in complex IV activity and mitochondria within demyelinated axons. The complex IV defect associated with axonal injury may be mediated by soluble products of innate immunity, as suggested by an inverse correlation between complex IV activity and macrophage/microglial density in chronic lesions. However, in inactive areas of chronic multiple sclerosis lesions the mitochondrial respiratory chain complex IV activity and mitochondrial mass, judged by porin immunoreactivity, are increased within approximately half of large (>2.5 μm diameter) chronically demyelinated axons compared with large myelinated axons in the brain and spinal cord. The axon-specific mitochondrial docking protein (syntaphilin) and phosphorylated neurofilament-H were increased in chronic lesions. The lack of complex IV activity in a proportion of Na+/K+ ATPase α-1 positive demyelinated axons supports axonal dysfunction as a contributor to neurological impairment and disease progression. Furthermore, in vitro studies show that inhibition of complex IV augments glutamate-mediated axonal injury (amyloid precursor protein and SMI32 reactivity). Our findings have important implications for both axonal degeneration and dysfunction during the progressive stage of multiple sclerosis

Expressed sequence tag analysis of adult human optic nerve for NEIBank: Identification of cell type and tissue markers

<p>Abstract</p> <p>Background</p> <p>The optic nerve is a pure white matter central nervous system (CNS) tract with an isolated blood supply, and is widely used in physiological studies of white matter response to various insults. We examined the gene expression profile of human optic nerve (ON) and, through the NEIBANK online resource, to provide a resource of sequenced verified cDNA clones. An un-normalized cDNA library was constructed from pooled human ON tissues and was used in expressed sequence tag (EST) analysis. Location of an abundant oligodendrocyte marker was examined by immunofluorescence. Quantitative real time polymerase chain reaction (qRT-PCR) and Western analysis were used to compare levels of expression for key calcium channel protein genes and protein product in primate and rodent ON.</p> <p>Results</p> <p>Our analyses revealed a profile similar in many respects to other white matter related tissues, but significantly different from previously available ON cDNA libraries. The previous libraries were found to include specific markers for other eye tissues, suggesting contamination. Immune/inflammatory markers were abundant in the new ON library. The oligodendrocyte marker QKI was abundant at the EST level. Immunofluorescence revealed that this protein is a useful oligodendrocyte cell-type marker in rodent and primate ONs. L-type calcium channel EST abundance was found to be particularly low. A qRT-PCR-based comparative mammalian species analysis reveals that L-type calcium channel expression levels are significantly lower in primate than in rodent ON, which may help account for the class-specific difference in responsiveness to calcium channel blocking agents. Several known eye disease genes are abundantly expressed in ON. Many genes associated with normal axonal function, mRNAs associated with axonal transport, inflammation and neuroprotection are observed.</p> <p>Conclusion</p> <p>We conclude that the new cDNA library is a faithful representation of human ON and EST data provide an initial overview of gene expression patterns in this tissue. The data provide clues for tissue-specific and species-specific properties of human ON that will help in design of therapeutic models.</p

One year follow-up of patients with refractory angina pectoris treated with enhanced external counterpulsation

BACKGROUND: Enhanced external counterpulsation (EECP) is a non-invasive technique that has been shown to be effective in reducing both angina and myocardial ischemia in patients not responding to medical therapy and without revascularization alternatives. The aim of the present study was to assess the long-term outcome of EECP treatment at a Scandinavian centre, in relieving angina in patients with chronic refractory angina pectoris. METHODS: 55 patients were treated with EECP. Canadian cardiovascular society (CCS) class, antianginal medication and adverse clinical events were collected prior to EECP, at the end of the treatment, and at six and 12 months after EECP treatment. Clinical signs and symptoms were recorded. RESULTS: EECP treatment significantly improved the CCS class in 79 ± 6% of the patients with chronic angina pectoris (p < 0.001). The reduction in CCS angina class was seen in patients with CCS class III and IV and persisted 12 months after EECP treatment. There was no significant relief in angina in patients with CCS class II prior to EECP treatment. 73 ± 7% of the patients with a reduction in CCS class after EECP treatment improved one CCS class, and 22 ± 7% of the patients improved two CCS classes. The improvement of two CCS classes could progress over a six months period and tended to be more prominent in patients with CCS class IV. In accordance with the reduction in CCS classes there was a significant decrease in the weekly nitroglycerin usage (p < 0.05). CONCLUSION: The results from the present study show that EECP is a safe treatment for highly symptomatic patients with refractory angina. The beneficial effects were sustained during a 12-months follow-up period

Effects of the high-density lipoprotein mimetic agent CER-001 on coronary atherosclerosis in patients with acute coronary syndromes: a randomized trial†

Aim High-density lipoproteins (HDLs) have several potentially protective vascular effects. Most clinical studies of therapies targeting HDL have failed to show benefits vs. placebo. Objective To investigate the effects of an HDL-mimetic agent on atherosclerosis by intravascular ultrasonography (IVUS) and quantitative coronary angiography (QCA). Design and setting A prospective, double-blinded, randomized trial was conducted at 51 centres in the USA, the Netherlands, Canada, and France. Intravascular ultrasonography and QCA were performed to assess coronary atherosclerosis at baseline and 3 (2-5) weeks after the last study infusion. Patients Five hundred and seven patients were randomized; 417 and 461 had paired IVUS and QCA measurements, respectively. Intervention Patients were randomized to receive 6 weekly infusions of placebo, 3 mg/kg, 6 mg/kg, or 12 mg/kg CER-001. Main outcome measures The primary efficacy parameter was the nominal change in the total atheroma volume. Nominal changes in per cent atheroma volume on IVUS and coronary scores on QCA were also pre-specified endpoints. Results The nominal change in the total atheroma volume (adjusted means) was −2.71, −3.13, −1.50, and −3.05 mm3 with placebo, CER-001 3 mg/kg, 6 mg/kg, and 12 mg/kg, respectively (primary analysis of 12 mg/kg vs. placebo: P = 0.81). There was also no difference among groups for the nominal change in per cent atheroma volume (0.02, −0.02, 0.01, and 0.19%; nominal P = 0.53 for 12 mg/kg vs. placebo). Change in the coronary artery score was −0.022, −0.036, −0.022, and −0.015 mm (nominal P = 0.25, 0.99, 0.55), and change in the cumulative coronary stenosis score was −0.51, 2.65, 0.71, and −0.77% (compared with placebo, nominal P = 0.85 for 12 mg/kg and nominal P = 0.01 for 3 mg/kg). The number of patients with major cardiovascular events was 10 (8.3%), 16 (13.3%), 17 (13.7%), and 12 (9.8%) in the four groups. Conclusion CER-001 infusions did not reduce coronary atherosclerosis on IVUS and QCA when compared with placebo. Whether CER-001 administered in other regimens or to other populations could favourably affect atherosclerosis must await further study. Name of the trial registry: Clinicaltrials.gov; Registry's URL: http://clinicaltrials.gov/ct2/show/NCT01201837?term=cer-001&rank=2; Trial registration number: NCT0120183