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.

Input: Consider Input: The endoplasmic reticulum (ER) is an architecturally diverse organelle that serves as a membrane source for the replication of multiple viruses. Flaviviruses, including yellow fever virus, West Nile virus, dengue virus, and Zika virus, induce unique single-membrane ER invaginations that house the viral replication machinery 1 . Whether this virus-induced ER remodeling is vulnerable to antiviral pathways is unknown. Here, we show that flavivirus replication at the ER is targeted by the interferon (IFN) response. Through genome-scale CRISPR screening, we uncovered an antiviral mechanism mediated by a functional gene pairing between IFI6, an interferon-stimulated gene (ISG) cloned over 30 years ago 2 , and HSPA5, which encodes the ER-resident HSP70 chaperone BiP. We reveal that IFI6 is an ERlocalized integral membrane effector that is stabilized through interactions with BiP. Mechanistically, IFI6 prophylactically protects uninfected cells by preventing formation of virus-induced ER membrane invaginations. Notably, IFI6 has little effect on other mammalian RNA viruses, including the related Flaviviridae member hepatitis C virus, which replicates in double-membrane vesicles that protrude outward from the ER. These findings support a model in which the IFN response is armed with a membrane-targeted effector that discriminately blocks the establishment of virus-specific ER microenvironments required for replication. Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Output: A CRISPR screen identifies IFI6 as an ER-resident interferon effector that blocks flavivirus replication HHS Public Access Author manuscript


Input: Consider Input: Compared to classical epidemiologic methods, genomics can be used to precisely monitor virus evolution and transmission in real time across large, diverse populations. Integration of pathogen genomics with data about host genetics and global transcriptional responses to infection allows for comprehensive studies of population-level responses to infection and provides novel methods for predicting clinical outcomes. As genomic technologies become more accessible, these methods will redefine how emerging viruses are studied and outbreaks are contained. Here we review the existing and emerging genomic technologies that are enabling systems epidemiology and systems virology and making it possible to respond rapidly to emerging viruses such as Zika.

Output: Genomic Signatures of Emerging Viruses: A New Era of Systems Epidemiology


Input: Consider Input: Background: The purpose of this study is to determine the incidence and significance of hypouricemia in patients with severe acute respiratory syndrome (SARS). Pulmonary lesions in patients with SARS are thought to result from proinflammatory cytokine dysregulation. Acute renal failure has been reported in patients with SARS, but whether cytokines can injure renal tubules is unknown. Methods: Sixty patients diagnosed with SARS in Taiwan in April 2003 were studied. Patients were identified as hypouricemic when their serum uric acid (UA) level was less than 2.5 mg/dL (<149 mol/L) within 15 days after fever onset. Urine UA and creatinine levels were available for 43 patients; the serum cytokines interleukin-6 (IL-6), IL-8, and tumor necrosis factor-␣ (TNF-␣) were measured in 16 patients. Results: Sixteen patients (26.7%) had hypouricemia (UA, 1.68 ؎ 0.52 mg/dL [100 ؎ 31 mol/L]). No differences in age, sex, symptoms, vital signs, hemogram, or other biochemistry data existed between the hypouricemic and normouricemic groups. Fractional excretion (FE) of UA (FE UA ) in 12 hypouricemic patients was 39.6% ؎ 23.4%, significantly greater than that of 31 normouricemic patients (16.4% ؎ 11.4%; P < 0.0001). After adjustments for age and sex, high FE UA was significantly associated with the lowest blood oxygenation (P ‫؍‬ 0.001; r ‫؍‬ ؊0.624). The number of catastrophic outcomes (endotracheal intubation and/or death) adjusted for older age and sex showed that hypouremic patients had an odds ratio of 10.57 (confidence interval, 2.33 to 47.98; P ‫؍‬ 0.002). Kaplan-Meier curves for catastrophic outcome-free results showed significant differences between patients with normouricemia or hypouricemia (P ‫؍‬ 0.01). Serum IL-8 levels correlated significantly with FE UA (P < 0.001; r ‫؍‬ 0.785) and inversely with serum UA level (P ‫؍‬ 0.044; r ‫؍‬ ؊0.509); neither IL-6 nor TNF-␣ level showed such correlations. Conclusion: One fourth of patients with SARS developed hypouricemia, which might result from a defect in renal UA handling and was associated with a high serum IL-8 level. Renal hypouricemia is an ominous sign in patients with SARS. Am J Kidney Dis 45:88 -95.


Output: Renal Hypouricemia Is an Ominous Sign in Patients With Severe Acute Respiratory Syndrome