1,133 research outputs found

    Analysis of hepatitis C virus RNA dimerization and core–RNA interactions

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    The core protein of hepatitis C virus (HCV) has been shown previously to act as a potent nucleic acid chaperone in vitro, promoting the dimerization of the 3′-untranslated region (3′-UTR) of the HCV genomic RNA, a process probably mediated by a small, highly conserved palindromic RNA motif, named DLS (dimer linkage sequence) [G. Cristofari, R. Ivanyi-Nagy, C. Gabus, S. Boulant, J. P. Lavergne, F. Penin and J. L. Darlix (2004) Nucleic Acids Res., 32, 2623–2631]. To investigate in depth HCV RNA dimerization, we generated a series of point mutations in the DLS region. We find that both the plus-strand 3′-UTR and the complementary minus-strand RNA can dimerize in the presence of core protein, while mutations in the DLS (among them a single point mutation that abolished RNA replication in a HCV subgenomic replicon system) completely abrogate dimerization. Structural probing of plus- and minus-strand RNAs, in their monomeric and dimeric forms, indicate that the DLS is the major if not the sole determinant of UTR RNA dimerization. Furthermore, the N-terminal basic amino acid clusters of core protein were found to be sufficient to induce dimerization, suggesting that they retain full RNA chaperone activity. These findings may have important consequences for understanding the HCV replicative cycle and the genetic variability of the virus

    Prevalence and mechanism of adverse reactions to colistin in patients with cystic fibrosis

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    Citizen Science Time Domain Astronomy with Astro-COLIBRI

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    Astro-COLIBRI is an innovative tool designed for professional astronomers to facilitate the study of transient astronomical events. Transient events - such as supernovae, gamma-ray bursts and stellar mergers - are fleeting cataclysmic phenomena that can offer profound insights into the most violent processes in the universe. Revealing their secrets requires rapid and precise observations: Astro-COLIBRI alerts its users of new transient discoveries from observatories all over the world in real-time. The platform also provides observers the details they need to make follow-up observations. Some of the transient phenomena available through Astro-COLIBRI are accessible by amateur astronomers and citizen scientists. A subset of the features dedicated to this growing group of users are highlighted here. They include the possibility of receiving only alerts on very bright events, the possibility of defining custom observer locations, as well as the calculation of optimized observation plans for searches for optical counterparts to gravitational wave events.Comment: Proceedings Atelier Pro-AM Gemini, Journ\'ees SF2A 2023. arXiv admin note: text overlap with arXiv:2308.0704

    Role of brachytherapy in the treatment of cancers of the anal canal. Long-term follow-up and multivariate analysis of a large monocentric retrospective series.

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    BACKGROUND AND PURPOSE: There are few data on long-term clinical results and tolerance of brachytherapy in anal canal cancer. We present one of the largest retrospective analyses of anal canal cancers treated with external beam radiotherapy with/without (±) chemotherapy followed by a brachytherapy boost. MATERIALS AND METHODS: We performed a retrospective analysis of clinical results in terms of efficacy and toxicity. The impact of different clinical and therapeutic variables on these outcomes was studied. RESULTS: From May 1992 to December 2009, 209 patients received brachytherapy after external beam radiotherapy ± chemotherapy. Of these patients, 163 were stage II or stage IIIA (UICC 2002) and 58 were N1-3. According to age, ECOG performance status (PS), and comorbidities, patients received either radiotherapy alone (58/209) or radiochemotherapy (151/209). The median follow-up was 72.8 months. The 5- and 10-year local control rates were 78.6 and 73.9 %, respectively. Globally, severe acute and late G3-4 reactions (NCI-CTC scale v. 4.0) occurred in 11.2 and 6.3 % of patients, respectively. Univariate analysis showed the statistical impact of the pelvic treatment volume (p = 0.046) and of the total dose (p = 0.02) on the risk of severe acute and late toxicities, respectively. Only six patients required permanent colostomy because of severe late anorectal toxicities. CONCLUSION: After a long follow-up time, brachytherapy showed an acceptable toxicity profile and high local control rates in patients with anal canal cancer

    The seasonal cycle of ocean-atmosphere CO2 Flux in Ryder Bay, West Antarctic Peninsula

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    Approximately 15 million km2 of the Southern Ocean is seasonally ice covered, yet the processes affecting carbon cycling and gas exchange in this climatically important region remain inadequately understood. Here, 3 years of dissolved inorganic carbon (DIC) measurements and carbon dioxide (CO2) fluxes from Ryder Bay on the west Antarctic Peninsula (WAP) are presented. During spring and summer, primary production in the surface ocean promotes atmospheric CO2 uptake. In winter, higher DIC, caused by net heterotrophy and vertical mixing with Circumpolar Deep Water, results in outgassing of CO2 from the ocean. Ryder Bay is found to be a net sink of atmospheric CO2 of 0.59–0.94 mol C m−2 yr−1 (average of 3 years). Seasonal sea ice cover increases the net annual CO2 uptake, but its effect on gas exchange remains poorly constrained. A reduction in sea ice on the WAP shelf may reduce the strength of the oceanic CO2 sink in this region

    Changes in global ocean bottom properties and volume transports in CMIP5 models under climate change scenarios

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    Changes in bottom temperature, salinity and density in the global ocean by 2100 for CMIP5 climate models are investigated for the climate change scenarios RCP4.5 and RCP8.5. The mean of 24 models shows a decrease in density in all deep basins except the North Atlantic which becomes denser. The individual model responses to climate change forcing are more complex: regarding temperature, the 24 models predict a warming of the bottom layer of the global ocean; in salinity, there is less agreement regarding the sign of the change, especially in the Southern Ocean. The magnitude and equatorward extent of these changes also vary strongly among models. The changes in properties can be linked with changes in the mean transport of key water masses. The Atlantic Meridional Overturning Circulation weakens in most models and is directly linked to changes in bottom density in the North Atlantic. These changes are due to the intrusion of modified Antarctic Bottom Water, made possible by the decrease in North Atlantic Deep Water formation. In the Indian, Pacific and South Atlantic, changes in bottom density are congruent with the weakening in Antarctic Bottom Water transport through these basins. We argue that the greater the 1986-2005 meridional transports, the more changes have propagated equatorwards by 2100. However, strong decreases in density over 100 years of climate change cause a weakening of the transports. The speed at which these property changes reach the deep basins is critical for a correct assessment of the heat storage capacity of the oceans as well as for predictions of future sea level rise
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