A fijivirus major viroplasm protein shows RNA-Stimulated ATPase activity by adopting pentameric and hexameric assemblies of dimers

Fijiviruses replicate and package their genomes within viroplasms in a pro cess involving RNA-RNA and RNA-protein interactions. Here, we demonstrate that the 24 C-terminal residues (C-arm) of the P9-1 major viroplasm protein of the mal de Río Cuarto virus (MRCV) are required for its multimerization and the formation of viroplasm like structures. Using an integrative structural approach, the C-arm was found to be dis pensable for P9-1 dimer assembly but essential for the formation of pentamers and hexamers of dimers (decamers and dodecamers), which favored RNA binding. Although both P9-1 and P9-1DC-arm catalyzed ATP with similar activities, an RNA-stimulated ATPase activity was only detected in the full-length protein, indicating a C-arm-mediated interaction between the ATP catalytic site and the allosteric RNA binding sites in the (do)decameric assemblies. A stronger preference to bind phosphate moieties in the dec amer was predicted, suggesting that the allosteric modulation of ATPase activity by RNA is favored in this structural conformation. Our work reveals the structural versatility of a fijivirus major viroplasm protein and provides clues to its mechanism of action.Instituto de BiotecnologíaFil: Llauger, Gabriela. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Llauger, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Melero, Roberto. Consejo Superior de Investigaciones Científicas (CSIC). Centro Nacional de Biotecnología. Biocomputing Unit. Campus Universidad Autónoma de Madrid; EspañaFil: Monti, Demian Esteban. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Monti, Demian Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sycz, Gabriela. Fundación Instituto Leloir; ArgentinaFil: Sycz, Gabriela. Instituto de Investigaciones Bioquímicas de Buenos Aires (IIBBA); ArgentinaFil: Sycz, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Huck-Iriart, Cristian. Universidad Nacional de San Martín. Instituto de Tecnologías Emergentes y Ciencias Aplicadas (ITECA); ArgentinaFil: Huck-Iriart, Cristian. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cerutti, Maria Laura. Fundación Instituto Leloir; ArgentinaFil: Cerutti, Maria Laura. Instituto de Investigaciones Bioquímicas de Buenos Aires (IIBBA); ArgentinaFil: Cerutti, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cerutti, Maria Laura. Plataforma Argentina de Biología Estructural y Metabolómica (PLABEM); ArgentinaFil: Klinke, Sebastián. Fundación Instituto Leloir; ArgentinaFil: Klinke, Sebastián. Instituto de Investigaciones Bioquímicas de Buenos Aires (IIBBA); ArgentinaFil: Klinke, Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Klinke, Sebastián. Plataforma Argentina de Biología Estructural y Metabolómica (PLABEM); ArgentinaFil: Mikkelsen, Evelyn. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Fisicoquímica Biológicas (IQUIFIB). Departamento de Química Biológica; ArgentinaFil: Mikkelsen, Evelyn. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Tijman, Ariel. Universidad de la República (UdelaR). Department of Biological Sciences. Computational Biophysics Lab; UruguayFil: Tijman, Ariel. Universidad de la República (UdelaR). Facultad de Química. Bioscience Department. Molecular Microbiology Lab; UruguayFil: Tijman, Ariel. Universidad de la República (UdelaR). Facultad de Química. Organic Chemistry Department and Bioscience Department. Biocatalysis and Biotransformation Lab; UruguayFil: Arranz, Rocío. Universidad Autónoma de Madrid. Centro Nacional de Biotecnología. Departamento de Estructura de Macromoléculas; EspañaFil: Arranz, Rocío. Consejo Superior de Investigaciones Científicas (CSIC); EspañaFil: Alfonso, Victoria. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Alfonso, Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Arellano, Sofía Maité. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Arellano, Sofía Maité. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Goldbaum, Fernando Alberto. Fundación Instituto Leloir; ArgentinaFil: Goldbaum, Fernando Alberto. Instituto de Investigaciones Bioquímicas de Buenos Aires (IIBBA); ArgentinaFil: Goldbaum, Fernando Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Goldbaum, Fernando Alberto. Plataforma Argentina de Biología Estructural y Metabolómica (PLABEM); ArgentinaFil: Sterckx, Yann G. J. University of Antwerp. Laboratory of Medical Biochemistry and the Infla-Med; BélgicaFil: Carazo, José María. Consejo Superior de Investigaciones Científicas (CSIC). Centro Nacional de Biotecnología. Biocomputing Unit. Campus Universidad Autónoma de Madrid; EspañaFil: Kaufman, Sergio B. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Fisicoquímica Biológicas (IQUIFIB). Departamento de Química Biológica; ArgentinaFil: Kaufman, Sergio B. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Dans, Pablo D. Universidad de la República (UdelaR). Department of Biological Sciences. Computational Biophysics Lab; UruguayFil: Dans, Pablo D. Institut Pasteur de Montevideo. Bioinformatics Unit; UruguayFil: Dans, Pablo D. Institute for Research in Biomedicine. Molecular Modelling and Bioinformatics Group; EspañaFil: Del Vas, Mariana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Del Vas, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Otero, Lisandro H. Fundación Instituto Leloir; ArgentinaFil: Otero, Lisandro H. Instituto de Investigaciones Bioquímicas de Buenos Aires (IIBBA); ArgentinaFil: Otero, Lisandro H. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Otero, Lisandro H. Plataforma Argentina de Biología Estructural y Metabolómica (PLABEM); Argentin

The management of acute venous thromboembolism in clinical practice - study rationale and protocol of the European PREFER in VTE Registry

Background: Venous thromboembolism (VTE) is a major health problem, with over one million events every year in Europe. However, there is a paucity of data on the current management in real life, including factors influencing treatment pathways, patient satisfaction, quality of life (QoL), and utilization of health care resources and the corresponding costs. The PREFER in VTE registry has been designed to address this and to understand medical care and needs as well as potential gaps for improvement. Methods/design: The PREFER in VTE registry was a prospective, observational, multicenter study conducted in seven European countries including Austria, France Germany, Italy, Spain, Switzerland, and the UK to assess the characteristics and the management of patients with VTE, the use of health care resources, and to provide data to estimate the costs for 12 months treatment following a first-time and/or recurrent VTE diagnosed in hospitals or specialized or primary care centers. In addition, existing anticoagulant treatment patterns, patient pathways, clinical outcomes, treatment satisfaction, and health related QoL were documented. The centers were chosen to reflect the care environment in which patients with VTE are managed in each of the participating countries. Patients were eligible to be enrolled into the registry if they were at least 18 years old, had a symptomatic, objectively confirmed first time or recurrent acute VTE defined as either distal or proximal deep vein thrombosis, pulmonary embolism or both. After the baseline visit at the time of the acute VTE event, further follow-up documentations occurred at 1, 3, 6 and 12 months. Follow-up data was collected by either routinely scheduled visits or by telephone calls. Results: Overall, 381 centers participated, which enrolled 3,545 patients during an observational period of 1 year. Conclusion: The PREFER in VTE registry will provide valuable insights into the characteristics of patients with VTE and their acute and mid-term management, as well as into drug utilization and the use of health care resources in acute first-time and/or recurrent VTE across Europe in clinical practice. Trial registration: Registered in DRKS register, ID number: DRKS0000479

All-sky search for continuous gravitational waves from isolated neutron stars using Advanced LIGO and Advanced Virgo O3 data

We present results of an all-sky search for continuous gravitational waves which can be produced by spinning neutron stars with an asymmetry around their rotation axis, using data from the third observing run of the Advanced LIGO and Advanced Virgo detectors. Four different analysis methods are used to search in a gravitational-wave frequency band from 10 to 2048 Hz and a first frequency derivative from −10^−8 to 10^−9 Hz/s. No statistically significant periodic gravitational-wave signal is observed by any of the four searches. As a result, upper limits on the gravitational-wave strain amplitude h0 are calculated. The best upper limits are obtained in the frequency range of 100 to 200 Hz and they are ∼1.1×10^−25 at 95% confidence level. The minimum upper limit of 1.10×10^−25 is achieved at a frequency 111.5 Hz. We also place constraints on the rates and abundances of nearby planetary- and asteroid-mass primordial black holes that could give rise to continuous gravitational-wave signals

All-sky search for gravitational wave emission from scalar boson clouds around spinning black holes in LIGO O3 data

This paper describes the first all-sky search for long-duration, quasimonochromatic gravitational-wave signals emitted by ultralight scalar boson clouds around spinning black holes using data from the third observing run of Advanced LIGO. We analyze the frequency range from 20 to 610 Hz, over a small frequency derivative range around zero, and use multiple frequency resolutions to be robust towards possible signal frequency wanderings. Outliers from this search are followed up using two different methods, one more suitable for nearly monochromatic signals, and the other more robust towards frequency fluctuations. We do not find any evidence for such signals and set upper limits on the signal strain amplitude, the most stringent being ???10???25 at around 130 Hz. We interpret these upper limits as both an ???exclusion region??? in the boson mass/black hole mass plane and the maximum detectable distance for a given boson mass, based on an assumption of the age of the black hole/boson cloud system

Search for continuous gravitational wave emission from the Milky??Way center in O3 LIGO-Virgo data

We present a directed search for continuous gravitational wave (CW) signals emitted by spinning neutron stars located in the inner parsecs of the Galactic Center (GC). Compelling evidence for the presence of a numerous population of neutron stars has been reported in the literature, turning this region into a very interesting place to look for CWs. In this search, data from the full O3 LIGO-Virgo run in the detector frequency band [10, 2000] Hz have been used. No significant detection was found and 95% confidence level upper limits on the signal strain amplitude were computed, over the full search band, with the deepest limit of about 7.6 x 10(-26) at similar or equal to 142 Hz. These results are significantly more constraining than those reported in previous searches. We use these limits to put constraints on the fiducial neutron star ellipticity and r-mode amplitude. These limits can be also translated into constraints in the black hole mass-boson mass plane for a hypothetical population of boson clouds around spinning black holes located in the GC