TASK DEFINITION: In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.
PROBLEM: Among RNA viruses, the order Nidovirales stands out for including viruses with the largest RNA genomes currently known. Nidoviruses employ a complex RNAsynthesizing machinery comprising a variety of non-structural proteins (nsps). One of the postulated drivers of the expansion of nidovirus genomes is the presence of a proofreading 3 -to-5 exoribonuclease (ExoN) belonging to the DEDDh family. ExoN may enhance the fidelity of RNA synthesis by correcting nucleotide incorporation errors made by the RNA-dependent RNA polymerase. Here, we review our current understanding of ExoN evolution, structure, and function. Most experimental data are derived from studies of the ExoN domain of coronaviruses (CoVs), which were triggered by the bioinformatics-based identification of ExoN in the genome of severe acute respiratory syndrome coronavirus (SARS-CoV) and its relatives in 2003. Although convincing data supporting the proofreading hypothesis have been obtained, from biochemical assays and studies with CoV mutants lacking ExoN functionality, the features of ExoN from most other nidovirus families remain to be characterized. Remarkably, viable ExoN knockout mutants were obtained only for two CoVs, mouse hepatitis virus (MHV) and SARS-CoV, whose RNA synthesis and replication kinetics were mildly affected by the lack of ExoN function. In several other CoV species, ExoN inactivation was not tolerated, and knockout mutants could not be rescued when launched using a reverse genetics system. This suggests that ExoN is also critical for primary viral RNA synthesis, a property that poorly matches the profile of an enzyme that would merely boost longterm replication fidelity. In CoVs, ExoN resides in a bifunctional replicase subunit (nsp14) whose C-terminal part has (N7-guanine)-methyltransferase activity. The crystal structure of SARS-CoV nsp14 has shed light on the interplay between these two domains, and on nsp14's interactions with nsp10, a co-factor that strongly enhances ExoN activity in vitro assays. Further elucidation of the structure-function relationships of ExoN and its interactions with other (viral and/or host) members of the CoV replication machinery will be key to understanding the enzyme's role in viral RNA synthesis and pathogenesis, and may contribute to the design of new approaches to combat emerging nidoviruses.

SOLUTION: The Curious Case of the Nidovirus Exoribonuclease: Its Role in RNA Synthesis and Replication Fidelity

PROBLEM: BACKGROUND: Despite the high risk for patient harm during unanticipated ICU evacuations, critical care providers receive little to no training on how to perform safe and eff ective ICU evacuations. We reviewed the pertinent published literature and off er suggestions for the critical care provider regarding ICU evacuation. Th e suggestions in this article are important for all who are involved in pandemics or disasters with multiple critically ill or injured patients, including front-line clinicians, hospital administrators, and public health or government offi cials. Th e Evacuation and Mobilization topic panel used the American College of Chest Physicians (CHEST) Guidelines Oversight Committee's methodology to develop seven key questions for which specifi c literature searches were conducted to identify studies upon which evidence-based recommendations could be made. No studies of suffi cient quality were identifi ed. Th erefore, the panel developed expert opinion-based suggestions using a modifi ed Delphi process. RESULTS: Based on current best evidence, we provide 13 suggestions outlining a systematic approach to prepare for and execute an eff ective ICU evacuation during a disaster. Interhospital and intrahospital collaboration and functional ICU communication are critical for success. Pre-event planning and preparation are required for a no-notice evacuation. A Critical Care Team Leader must be designated within the Hospital Incident Command System. A threestage ICU Evacuation Timeline, including (1) no immediate threat, (2) evacuation threat, and (3) evacuation implementation, should be used. Detailed suggestions on ICU evacuation, including regional planning, evacuation drills, patient transport preparation and equipment, patient prioritization and distribution for evacuation, patient information and tracking, and federal and international evacuation assistance systems, are also provided. CONCLUSIONS: Successful ICU evacuation during a disaster requires active preparation, participation, communication, and leadership by critical care providers. Critical care providers have a professional obligation to become better educated, prepared, and engaged with the processes of ICU evacuation to provide a safe continuum of critical care during a disaster. CHEST 2014; 146( 4_Suppl ): e44S -e60S ABBREVIATIONS : CCTL 5 Critical Care Team Leader ; ECMO 5 extracorporeal membrane oxygenation ; EOC 5 emergency operations center ; NDMS 5 National Disaster Medical System Form Hospital and Transport Agreements 1a. We suggest local and regional mutual-aid agreements should be established with other appropriately staff ed and resourced hospitals to redistribute critically ill and injured patients from an evacuating hospital(s), and these agreements should be integrated within the framework of disaster preparedness plans. 1b. We suggest creation of predisaster formal agreements between hospitals and transport agencies or between Health Coalitions or Regional Health Authorities and transport agencies for air or ground transport of critically ill patients during a disaster. Prepare for and Simulate Critical Care Evacuation 2a. We suggest staffi ng requirements within disaster plans should take into account the staffi ng resources necessary for desired surge capability to both safely move patients and to provide continuous care for patients remaining in the ICU. . COI grids refl ecting the confl icts of interest that were current as of the date of the conference and voting are posted in the online supplementary materials. DISCLAIMER: American College of Chest Physicians guidelines and consensus statements are intended for general information only, are not medical advice, and do not replace professional care and physician advice, which always should be sought for any medical condition. Th e complete disclaimer for this consensus statement can be accessed at

SOLUTION: Evacuation of the ICU Care of the Critically Ill and Injured During Pandemics and Disasters: CHEST Consensus Statement

PROBLEM: Cytotoxic CD8+ T-cell immunosurveillance for intracellular pathogens, such as viruses, is controlled by classical major histocompatibility complex (MHC) class Ia molecules, and ideally, these antiviral T-cell populations are defined by the specific peptide and restricting MHC allele. Surprisingly, despite the utility of the cat in modeling human viral immunity, little is known about the Feline Leukocyte Antigen class I complex (FLAI). Only a few coding sequences with uncertain locus origin and expression patterns have been reported. Of 19 class I genes, 3 loci -FLAI-E, -H and -K -are predicted to encode classical molecules, and our objective was to evaluate their status by analyzing polymorphisms and tissue expression. Using locus-specific, PCR-based genotyping, we amplified 33 FLAI-E, -H, and -K alleles from 12 cats of various breeds, identifying, for the first time, alleles across 3 distinct loci in a feline species. Alleles shared the expected polymorphic and invariant sites in the 1/ 2 domains, and full-length cDNA clones possessed all characteristic class Ia exons. Alleles could be assigned to a specific locus with reasonable confidence, although there was evidence of potentially confounding interlocus recombination between FLAI-E and -K. Only FLAI-E, -H and -K-origin alleles were amplified from cDNAs of multiple tissue types. We also defined hypervariable regions across these genes, which permitted the assignment of names to both novel and established alleles. As predicted, FLAI-E, -H, and -K fulfill the major criteria of class Ia genes. These data represent a necessary prerequisite for studying epitope-specific antiviral CD8+ T-cell responses in cats.

SOLUTION:
Polymorphisms and Tissue Expression of the Feline Leukocyte Antigen Class I Loci FLAI-E, -H and -K