A comparative analysis of parechovirus protein structures with other picornaviruses

Parechoviruses belong to the genus Parechovirus within the family Picornaviridae and are non-enveloped icosahedral viruses with a single-stranded RNA genome. Parechoviruses include human and animal pathogens classified into six species. Those that infect humans belong to the Parechovirus A species and can cause infections ranging from mild gastrointestinal or respiratory illness to severe neonatal sepsis. There are no approved antivirals available to treat parechovirus (nor any other picornavirus) infections. In this parechovirus review, we focus on the cleaved protein products resulting from the polyprotein processing after translation comparing and contrasting their known or predicted structures and functions to those of other picornaviruses. The review also includes our original analysis from sequence and structure prediction. This review highlights significant structural differences between parechoviral and other picornaviral proteins, suggesting that parechovirus drug development should specifically be directed to parechoviral targets.Peer reviewe

Structural insights into phosphoprotein chaperoning of nucleoprotein in measles virus

Instruct Biennial Structural Biology Conference Abstract BookletMeasles virus is an important, highly contagious, human pathogen. The nucleoprotein N binds only to viral genomic RNA and forms the helical ribonucleocapsid that serves as a template for viral replication. We address how N is regulated by another protein, the phosphoprotein, P, to prevent newly synthesized N from binding to cellular RNA. Here, we pulled down an N01-408 fragment lacking most of its C-terminal tail domain by several affinity-tagged, N-terminal, P fragments to map the N0-binding region of P to the first 48 amino acids. We showed biochemically and using P mutants the importance of the hydrophobic interactions for the binding. We fused an N0 binding peptide, P1-48, to the C-terminus of an N021-408 fragment lacking both the N-terminal peptide and the C-terminal tail of N protein to reconstitute and crystallize the N0-P complex. We solved the X-ray structure of the resulting N0-P chimeric protein at 2.7 Å resolution. The structure reveals the molecular details of the conserved N0-P interface and explains how P chaperones N0 preventing both self-assembly of N0 and its binding to RNA. We compare the structure of an N0-P complex to atomic model of helical ribonucleocapsid. We thus propose a model how P may help to start viral RNA synthesis. Our results provide a new insight into mechanisms of paramyxovirus replication. New data on the mechanisms of phosphoprotein chaperone action allows better understanding of the virus genome replication and nucleocapsid assembly. We describe a conserved structural interface for the N-P interaction which could be a target for drug development not only to treat measles but also potentially other paramyxovirus diseases.Non peer reviewe

Crystal Structure of the Measles Virus Nucleoprotein Core in Complex with an N-terminal Region of Phosphoprotein

ABSTRACT The enveloped negative-stranded RNA virus measles virus (MeV) is an important human pathogen. The nucleoprotein (N0) assembles with the viral RNA into helical ribonucleocapsids (NC) which are, in turn, coated by a helical layer of the matrix protein. The viral polymerase complex uses the NC as its template. The N0 assembly onto the NC and the activity of the polymerase are regulated by the viral phosphoprotein (P). In this study, we pulled down an N0 1-408 fragment lacking most of its C-terminal tail domain by several affinity-tagged, N-terminal P fragments to map the N0-binding region of P to the first 48 amino acids. We showed biochemically and using P mutants the importance of the hydrophobic interactions for the binding. We fused an N0 binding peptide, P1-48, to the C terminus of an N0 21-408 fragment lacking both the N-terminal peptide and the C-terminal tail of N protein to reconstitute and crystallize the N0-P complex. We solved the X-ray structure of the resulting N0-P chimeric protein at a resolution of 2.7 Å. The structure reveals the molecular details of the conserved N0-P interface and explains how P chaperones N0, preventing both self-assembly of N0 and its binding to RNA. Finally, we propose a model for a preinitiation complex for RNA polymerization. IMPORTANCE Measles virus is an important, highly contagious human pathogen. The nucleoprotein (N) binds only to viral genomic RNA and forms the helical ribonucleocapsid that serves as a template for viral replication. We address how N is regulated by another protein, the phosphoprotein (P), to prevent newly synthesized N from binding to cellular RNA. We describe the atomic model of an N-P complex and compare it to helical ribonucleocapsid. We thus provide insight into how P chaperones N and helps to start viral RNA synthesis. Our results provide a new insight into mechanisms of paramyxovirus replication. New data on the mechanisms of phosphoprotein chaperone action allows better understanding of virus genome replication and nucleocapsid assembly. We describe a conserved structural interface for the N-P interaction which could be a target for drug development to treat not only measles but also potentially other paramyxovirus diseases.Peer reviewe

Formation of Amyloid-Like Fibrils by Y-Box Binding Protein 1 (YB-1) Is Mediated by Its Cold Shock Domain and Modulated by Disordered Terminal Domains

YB-1, a multifunctional DNA- and RNA-binding nucleocytoplasmic protein, is involved in the majority of DNA- and mRNA-dependent events in the cell. It consists of three structurally different domains: its central cold shock domain has the structure of a β-barrel, while the flanking domains are predicted to be intrinsically disordered. Recently, we showed that YB-1 is capable of forming elongated fibrils under high ionic strength conditions. Here we report that it is the cold shock domain that is responsible for formation of YB-1 fibrils, while the terminal domains differentially modulate this process depending on salt conditions. We demonstrate that YB-1 fibrils have amyloid-like features, including affinity for specific dyes and a typical X-ray diffraction pattern, and that in contrast to most of amyloids, they disassemble under nearly physiological conditions

Dynamics of diffusion jet combustion in an ejection burner

In this work we present the results of computational and experimental studies on the burnout dynamics of diffusion gas jets in an ejection burner with a two-stage air ejection scheme. It is shown that usage of this scheme leads to an increase in the uniformity of the distribution of thermogasdynamic parameters at the burner outlet, an increase in the completeness of combustion of the fuel, and a more stable operation of the device

Dynamics of diffusion jet combustion in an ejection burner

In this work we present the results of computational and experimental studies on the burnout dynamics of diffusion gas jets in an ejection burner with a two-stage air ejection scheme. It is shown that usage of this scheme leads to an increase in the uniformity of the distribution of thermogasdynamic parameters at the burner outlet, an increase in the completeness of combustion of the fuel, and a more stable operation of the device

The role of investments for the economy of the Russian Federation

The article analyzes the concept of investments, their forms, types, as well as the impact on the economic climate in the country via comparative quantitative research methods. As a result, the characteristic of the structure of the main investing countries in the economy of Russia, the recipient countries of direct investments from the Russian Federation is given and a high percentage of the process of investing in a country is the returning capital of organizations from abroad. In conclusion, investments are the lever of progressive formation and positive actions for economic processes in the country.El artículo analiza el concepto de inversiones, sus formas, tipos, así como el impacto en el clima económico del país a través de métodos comparativos de investigación cuantitativa. Como resultado, se da la característica de la estructura de los principales países inversores en la economía de Rusia, los países receptores de inversiones directas de la Federación de Rusia y un alto porcentaje del proceso de inversión en un país es el capital de retorno de las organizaciones. desde el extranjero. En conclusión, las inversiones son la palanca de la formación progresiva y las acciones positivas para los procesos económicos en el país

Double-Clad Bismuth-Doped Fiber with a Rectangular Inner Cladding for Laser Application

In this paper, we report the latest research results on the fabrication of double-clad Bi-doped germanosilicate core fibers with a rectangular inner cladding design for improved laser performance in the near-IR spectral region. Detailed comparative analysis of the absorption characteristics of the Bi-doped fibers with a circular- and rectangular-shaped inner cladding was performed. A series of cladding-pumped, Bi-doped fiber lasers emitting near 1.46 µm was developed using the semiconductor’s multi-mode fiber-coupled laser diodes at λ = 808 nm. The peculiarities of the laser parameters of the fabricated active fibers with the double-clad design were thoroughly studied by analyzing the dependencies of the slope efficiency of the lasers, namely the pump power, active fiber length and core-to-inner-cladding area ratio. The obtained results show that the rectangular design provided enhanced cladding absorption and improvements in laser performance. In particular, we achieved maximal slope efficiencies of 5.5% and 4.3% for the absorbed pump power introduced into the inner cladding with cross-section areas of 80 × 80 µm2 and 125 × 125 µm2, respectively. Multi-wavelength lasing operation in a free-running cavity due to a few modes’ propagation regimes was found using the Bi-doped fiber with an 80 × 80 µm2 inner cladding

Double-Clad Bismuth-Doped Fiber with a Rectangular Inner Cladding for Laser Application

In this paper, we report the latest research results on the fabrication of double-clad Bi-doped germanosilicate core fibers with a rectangular inner cladding design for improved laser performance in the near-IR spectral region. Detailed comparative analysis of the absorption characteristics of the Bi-doped fibers with a circular- and rectangular-shaped inner cladding was performed. A series of cladding-pumped, Bi-doped fiber lasers emitting near 1.46 µm was developed using the semiconductor’s multi-mode fiber-coupled laser diodes at λ = 808 nm. The peculiarities of the laser parameters of the fabricated active fibers with the double-clad design were thoroughly studied by analyzing the dependencies of the slope efficiency of the lasers, namely the pump power, active fiber length and core-to-inner-cladding area ratio. The obtained results show that the rectangular design provided enhanced cladding absorption and improvements in laser performance. In particular, we achieved maximal slope efficiencies of 5.5% and 4.3% for the absorbed pump power introduced into the inner cladding with cross-section areas of 80 × 80 µm2 and 125 × 125 µm2, respectively. Multi-wavelength lasing operation in a free-running cavity due to a few modes’ propagation regimes was found using the Bi-doped fiber with an 80 × 80 µm2 inner cladding

Double-clad large mode area Er-doped fiber for high-energy and high-peak power amplifiers

International audienceIn this paper we present a novel design of an Er-doped double-clad fiber for short-pulse amplifiers. It was shown that the P2O5-Al2O3-SiO2 core glass matrix leads to significant increase of the efficiency of cladding pumped amplifiers based on heavily Er-doped fibers. By using such a fiber we have demonstrated, to the best of our knowledge, the first nanosecond mJ-energy level Er-doped fiber amplifier with diffraction limited beam quality. Additionally, we report on the direct amplification of 100 fs pulses with the same fiber achieving of peak powers in excess of 100 k