The SARS-Unique Domain (SUD) of SARS Coronavirus Contains Two Macrodomains That Bind G-Quadruplexes

Since the outbreak of severe acute respiratory syndrome (SARS) in 2003, the three-dimensional structures of several of the replicase/transcriptase components of SARS coronavirus (SARS-CoV), the non-structural proteins (Nsps), have been determined. However, within the large Nsp3 (1922 amino-acid residues), the structure and function of the so-called SARS-unique domain (SUD) have remained elusive. SUD occurs only in SARS-CoV and the highly related viruses found in certain bats, but is absent from all other coronaviruses. Therefore, it has been speculated that it may be involved in the extreme pathogenicity of SARS-CoV, compared to other coronaviruses, most of which cause only mild infections in humans. In order to help elucidate the function of the SUD, we have determined crystal structures of fragment 389–652 (“SUDcore”) of Nsp3, which comprises 264 of the 338 residues of the domain. Both the monoclinic and triclinic crystal forms (2.2 and 2.8 Å resolution, respectively) revealed that SUDcore forms a homodimer. Each monomer consists of two subdomains, SUD-N and SUD-M, with a macrodomain fold similar to the SARS-CoV X-domain. However, in contrast to the latter, SUD fails to bind ADP-ribose, as determined by zone-interference gel electrophoresis. Instead, the entire SUDcore as well as its individual subdomains interact with oligonucleotides known to form G-quadruplexes. This includes oligodeoxy- as well as oligoribonucleotides. Mutations of selected lysine residues on the surface of the SUD-N subdomain lead to reduction of G-quadruplex binding, whereas mutations in the SUD-M subdomain abolish it. As there is no evidence for Nsp3 entering the nucleus of the host cell, the SARS-CoV genomic RNA or host-cell mRNA containing long G-stretches may be targets of SUD. The SARS-CoV genome is devoid of G-stretches longer than 5–6 nucleotides, but more extended G-stretches are found in the 3′-nontranslated regions of mRNAs coding for certain host-cell proteins involved in apoptosis or signal transduction, and have been shown to bind to SUD in vitro. Therefore, SUD may be involved in controlling the host cell's response to the viral infection. Possible interference with poly(ADP-ribose) polymerase-like domains is also discussed

Interdependence between transportation system and power distribution system: a comprehensive review on models and applications

The rapidly increasing penetration of electric vehicles in modern metropolises has been witnessed during the past decade, inspired by financial subsidies as well as public awareness of climate change and environment protection. Integrating charging facilities, especially high-power chargers in fast charging stations, into power distribution systems remarkably alters the traditional load flow pattern, and thus imposes great challenges on the operation of distribution network in which controllable resources are rare. On the other hand, provided with appropriate incentives, the energy storage capability of electric vehicle offers a unique opportunity to facilitate the integration of distributed wind and solar power generation into power distribution system. The above trends call for thorough investigation and research on the interdependence between transportation system and power distribution system. This paper conducts a comprehensive survey on this line of research. The basic models of transportation system and power distribution system are introduced, especially the user equilibrium model, which describes the vehicular flow on each road segment and is not familiar to the readers in power system community. The modelling of interdependence across the two systems is highlighted. Taking into account such interdependence, applications ranging from long-term planning to short-term operation are reviewed with emphasis on comparing the description of traffic-power interdependence. Finally, an outlook of prospective directions and key technologies in future research is summarized.fi=vertaisarvioitu|en=peerReviewed

A Link-Node Discrete-Time Dynamic Second Best Toll Pricing Model with a Relaxation Solution Algorithm

Congestion pricing, Dynamic second best toll pricing, Dynamic user equilibrium, Relaxation algorithm,

A dynamic user equilibrium model for traffic assignment in urban areas

info:eu-repo/semantics/publishe