Neuroprotection by erythropoietin administration after experimental traumatic brain injury.

A large body of evidence indicates that the hormone erythropoietin (EPO) exerts beneficial effects in the central nervous system (CNS). To date, EPO's effect has been assessed in several experimental models of brain and spinal cord injury. This study was conducted to validate whether treatment with recombinant human EPO (rHuEPO) would limit the extent of injury following experimental TBI. Experimental TBI was induced in rats by a cryogenic injury model. rHuEPO or placebo was injected intraperitoneally immediately after the injury and then every 8 h until 2 or 14 days. Forty-eight hours after injury brain water content, an indicator of brain edema, was measured with the wet-dry method and blood-brain barrier (BBB) breakdown was evaluated by assay of Evans blue extravasation. Furthermore, extent of cerebral damage was assessed. Administration of rHuEPO markedly improved recovery from motor dysfunction compared with placebo group (P < 0.05). Brain edema was significantly reduced in the cortex of the EPO-treated group relative to that in the placebo-treated group (80.6 \ub1 0.3% versus 91.8% \ub1 0.8% respectively, P < 0.05). BBB breakdown was significantly lower in EPO-treated group than in the placebo-treated group (66.2 \ub1 18.7 \u3bcg/g versus 181.3 \ub1 21 \u3bcg/g, respectively, P < 0.05). EPO treatment reduced injury volume significantly compared with placebo group (17.4 \ub1 5.4 mm3 versus 37.1 \ub1 5.3 mm3, P < 0.05). EPO, administered in its recombinant form, affords significant neuroprotection in experimental TBI model and may hold promise for future clinical applications. \ua9 2007 Elsevier B.V. All rights reserved

Arcsecond-resolution 12CO mapping of the yellow hypergiants IRC +10420 and AFGL 2343

IRC +10420 and AFGL 2343 are the unique, known yellow hypergiants (YHGs) presenting a heavy circumstellar envelope (CSE). We aim to study the morphology, exceptional kinematics, and excitation conditions of their CSEs, and the implications for mass-loss processes. We have mapped the 12CO J=2-1 and 1-0 emission in these YHGs with the IRAM Plateau de Bure interferometer and the 30m telescope. We developed LVG models in order to analyze their circumstellar characteristics. The maps show that the overall shape of both CSEs is approximately spherical, although they also reveal several aspherical features. The CSE around IRC +10420 shows a rounded extended halo surrounding a bright inner region, with both components presenting aspherical characteristics. It presents a brightness minimum at the center. The envelope around AFGL 2343 is a detached shell, showing spherical symmetry and clumpiness at a level of about 15% of the maximum brightness. The envelopes expand isotropically at about 35 km/s, about two or three times faster than typical CSEs around AGB stars. High temperatures (~ 200 K) are derived for the innermost regions in IRC +10420, while denser and cooler (~ 30 K) gas is found in AFGL 2343. The mass-loss processes in these YHGs have been found to be similar. The deduced mass-loss rates (~ 10E-4 - 10E-3 Msun/yr) are much higher than those obtained in AGB stars, and they present significant variations on time scales of ~ 1000 yr

Eliminating Hepatitis C Virus From a Prevalent Kidney Transplant Recipient Population: A Single-Center Study in Belgium in the Direct-Acting Antivirals Era

Background: Direct-acting antivirals (DAAs) have revolutionized the treatment of hepatitis C virus (HCV) infection. Although previous studies have reported positive results with DAAs after kidney transplantation (KT), their impact on the prevalence of HCV viremia (HCVv) in prevalent kidney transplant recipients (KTRs) remains ill defined. Methods: We retrospectively reviewed the HCV status of all patients followed at Cliniques Universitaires Saint-Luc, Brussels, Belgium, outpatient KT clinic between January 2014 and December 2018. We collected the clinical features of KTRs treated with DAAs during this period and calculated the annual prevalence of HCVv over this period. Results: Out of 1451 KTRs, 22 (1.52%) had HCVv in 2014 to 2018. From 2014 to 2018, the annual prevalence of HCVv dropped from 1.97% to 0.43%, (P < .001). Fourteen KTRs were treated with DAAs a median of 197 months (range: 5-374) after KT, mostly (79%) in 2017 after reimbursement restrictions of DAAs for KTRs in Belgium were removed. DAA treatment was safe with a sustained virological response rate at 12 weeks after treatment (SVR12) of 93%. Two patients died 14 months (lymphoma, despite SVR12) and 7 months (hepatocarcinoma, no SVR12) after DAAs initiation, respectively. Among HCVv KTRs not treated with DAAs (n = 8), 2 lost their graft, 5 died, and 1 is initiating therapy. The current prevalence of HCVv in the cohort is 0.08%, with a single patient currently on treatment. Conclusion: Treatment with DAAs led to a dramatic decrease of HCVv prevalence in this KTR cohort. DAA use was safe and effective. Elimination of HCV is possible at KT clinics

TGS1 mediates 2,2,7-trimethyl guanosine capping of the human telomerase RNA to direct telomerase dependent telomere maintenance

Pathways that direct the selection of the telomerase-dependent or recombination-based, alternative lengthening of telomere&nbsp;(ALT) maintenance pathway in cancer cells are poorly understood. Using human lung cancer cells and tumor organoids we show that formation of the 2,2,7-trimethylguanosine (TMG) cap structure at the human telomerase RNA 5′ end by the Trimethylguanosine Synthase 1 (TGS1) is central for recruiting telomerase to telomeres and engaging Cajal bodies in telomere maintenance. TGS1 depletion or inhibition by the natural nucleoside sinefungin impairs telomerase recruitment to telomeres leading to Exonuclease 1 mediated generation of telomere 3′ end protrusions that engage in RAD51-dependent, homology directed recombination and the activation of key features of the ALT pathway. This indicates a critical role for 2,2,7-TMG capping of the RNA component of human telomerase (hTR) in enforcing telomerase-dependent telomere maintenance to restrict the formation of telomeric substrates conductive to ALT. Our work introduces a targetable pathway of telomere maintenance that holds relevance for telomere-related diseases such as cancer and aging

Multiwavelength Observations of the Gamma-Ray Blazar PKS 0528+134 in Quiescence

We present multiwavelength observations of the ultraluminous blazar-type radio loud quasar PKS 0528+134 in quiescence during the period July to December 2009. Significant flux variability on a time scale of several hours was found in the optical regime, accompanied by a weak trend of spectral softening with increasing flux. We suggest that this might be the signature of a contribution from the accretion disk at the blue end of the optical spectrum. The optical flux is weakly polarized with rapid variations of the degree and direction of polarization, while the polarization of the 43 GHz radio core remains steady. Optical spectropolarimetry suggests a trend of increasing degree of polarization with increasing wavelength, providing additional evidence for an accretion disc contribution towards the blue end of the optical spectrum. We constructed four SEDs indicating that even in the quiescent state, the bolometric luminosity of PKS 0528+134 is dominated by its gamma-ray emission. A leptonic single-zone jet model produced acceptable fits to the SEDs with contributions to the high-energy emission from synchrotron self-Compton radiation and Comptonization of direct accretion disk emission. Fit parameters close to equipartition were obtained. The moderate variability on long time scales implies the existence of on-going particle acceleration, while the observed optical polarization variability seems to point towards a turbulent acceleration process. Turbulent particle acceleration at stationary features along the jet therefore appears to be a viable possibility for the quiescent state of PKS 0528+134.Comment: Accepted for Publication in The Astrophysical Journal. - Acknowledgement adde

Another look at the BL Lacertae flux and spectral variability

The GLAST-AGILE Support Program (GASP) of the Whole Earth Blazar Telescope (WEBT) monitored BL Lacertae in 2008-2009 at radio, near-IR, and optical frequencies. During this period, high-energy observations were performed by XMM-Newton, Swift, and Fermi. We analyse these data with particular attention to the calibration of Swift UV data, and apply a helical jet model to interpret the source broad-band variability. The GASP-WEBT observations show an optical flare in 2008 February-March, and oscillations of several tenths of mag on a few-day time scale afterwards. The radio flux is only mildly variable. The UV data from both XMM-Newton and Swift seem to confirm a UV excess that is likely caused by thermal emission from the accretion disc. The X-ray data from XMM-Newton indicate a strongly concave spectrum, as well as moderate flux variability on an hour time scale. The Swift X-ray data reveal fast (interday) flux changes, not correlated with those observed at lower energies. We compare the spectral energy distribution (SED) corresponding to the 2008 low-brightness state, which was characterised by a synchrotron dominance, to the 1997 outburst state, where the inverse-Compton emission was prevailing. A fit with an inhomogeneous helical jet model suggests that two synchrotron components are at work with their self inverse-Compton emission. Most likely, they represent the radiation from two distinct emitting regions in the jet. We show that the difference between the source SEDs in 2008 and 1997 can be explained in terms of pure geometrical variations. The outburst state occurred when the jet-emitting regions were better aligned with the line of sight, producing an increase of the Doppler beaming factor. Our analysis demonstrates that the jet geometry can play an extremely important role in the BL Lacertae flux and spectral variability.Comment: 12 pages, 10 figures, accepted for publication in A&

Radio-to-UV monitoring of AO 0235+164 by the WEBT and Swift during the 2006--2007 outburst

The blazar AO 0235+164 was claimed to show a quasi-periodic behaviour in the radio and optical bands. Moreover, an extra emission component contributing to the UV and soft X-ray flux was detected, whose nature is not yet clear. A predicted optical outburst was observed in late 2006/early 2007. We here present the radio-to-optical WEBT light curves during the outburst, together with UV data acquired by Swift in the same period. We found the optical outburst to be as strong as the big outbursts of the past: starting from late September 2006, a brightness increase of 5 mag led to the outburst peak in February 19-21, 2007. We also observed an outburst at mm and then at cm wavelengths, with an increasing time delay going toward lower frequencies during the rising phase. Cross-correlation analysis indicates that the 1 mm and 37 GHz flux variations lagged behind the R-band ones by about 3 weeks and 2 months, respectively. These short time delays suggest that the corresponding jet emitting regions are only slightly separated and/or misaligned. In contrast, during the outburst decreasing phase the flux faded contemporaneously at all cm wavelengths. This abrupt change in the emission behaviour may suggest the presence of some shutdown mechanism of intrinsic or geometric nature. The behaviour of the UV flux closely follows the optical and near-IR one. By separating the synchrotron and extra component contributions to the UV flux, we found that they correlate, which suggests that the two emissions have a common origin.Comment: 9 pages, 7 figures, in press for Astronomy and Astrophysic

Multifrequency monitoring of the blazar 0716+714 during the GASP-WEBT-AGILE campaign of 2007

Since the CGRO operation in 1991-2000, one of the primary unresolved questions about the blazar gamma-ray emission has been its possible correlation with the low-energy (in particular optical) emission. To help answer this problem, the Whole Earth Blazar Telescope (WEBT) consortium has organized the GLAST-AGILE Support Program (GASP) to provide the optical-to-radio monitoring data to be compared with the gamma-ray detections by the AGILE and GLAST satellites. This new WEBT project started in early September 2007, just before a strong gamma-ray detection of 0716+714 by AGILE. We present the GASP-WEBT optical and radio light curves of this blazar obtained in July-November 2007, about various AGILE pointings at the source. We construct NIR-to-UV spectral energy distributions (SEDs), by assembling GASP-WEBT data together with UV data from the Swift ToO observations of late October. We observe a contemporaneous optical-radio outburst, which is a rare and interesting phenomenon in blazars. The shape of the SEDs during the outburst appears peculiarly wavy because of an optical excess and a UV drop-and-rise. The optical light curve is well sampled during the AGILE pointings, showing prominent and sharp flares. A future cross-correlation analysis of the optical and AGILE data will shed light on the expected relationship between these flares and the gamma-ray events.Comment: 5 pages, 5 figures, to be published in A&A (Letters); revised to match the final version (changes in Fig. 5 and related text

The correlated optical and radio variability of BL Lacertae. WEBT data analysis 1994-2005

Since 1997, BL Lacertae has undergone a phase of high optical activity, with the occurrence of several prominent outbursts. Starting from 1999, the Whole Earth Blazar Telescope (WEBT) consortium has organized various multifrequency campaigns on this blazar, collecting tens of thousands of data points. One of the main issues in the study of this huge dataset has been the search for correlations between the optical and radio flux variations, and for possible periodicities in the light curves. The analysis of the data assembled during the first four campaigns (comprising also archival data to cover the period 1968-2003) revealed a fair optical-radio correlation in 1994-2003, with a delay of the hard radio events of ~100 days. Moreover, various statistical methods suggested the existence of a radio periodicity of ~8 years. In 2004 the WEBT started a new campaign to extend the dataset to the most recent observing seasons, in order to possibly confirm and better understand the previous results. In this campaign we have collected and assembled about 11000 new optical observations from twenty telescopes, plus near-IR and radio data at various frequencies. Here, we perform a correlation analysis on the long-term R-band and radio light curves. In general, we confirm the ~100-day delay of the hard radio events with respect to the optical ones, even if longer (~200-300 days) time lags are also found in particular periods. The radio quasi-periodicity is confirmed too, but the "period" seems to progressively lengthen from 7.4 to 9.3 years in the last three cycles. The optical and radio behaviour in the last forty years suggests a scenario where geometric effects play a major role. In particular, the alternation of enhanced and suppressed optical activity (accompanied by hard and soft radio events, respectively) canComment: 6 pages, 4 figure