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: A novel betacoronavirus associated with lethal respiratory and renal complications was recently identified in patients from several countries in the Middle East. We report the deep genome sequencing of the virus directly from a patient's sputum sample. Our high-throughput sequencing yielded a substantial depth of genome sequence assembly and showed the minority viral variants in the specimen. Detailed phylogenetic analysis of the virus genome (England/ Qatar/2012) revealed its close relationship to European bat coronaviruses circulating among the bat species of the Vespertilionidae family. Molecular clock analysis showed that the 2 human infections of this betacoronavirus in June 2012 (EMC/2012) and September 2012 (England/Qatar/2012) share a common virus ancestor most likely considerably before early 2012, suggesting the human diversity is the result of multiple zoonotic events. T he ability of coronaviruses (CoVs) to infect multiple species and to rapidly change through recombination presents a continuing human health threat. The epidemic of severe acute respiratory syndrome (SARS) during 2003-2004 during which a CoV transmitted from bats to civet cats and then to humans demonstrated this potential (reviewed in [1, 2] ). Recently, a novel human betacoronavirus (betaCoV) was found to be associated with at least 13 human infections, 7 of which were fatal (3-7). One of the viruses, EMC/2012, has been sequenced, and its sequence similarity to several bat CoVs suggested an animal origin, but a definitive bat species of origin has not yet been identified (3). Additional genome sequences from this virus are needed to aid diagnostics, monitor population dynamics, identify the animal source, and characterize mechanisms of pathogenesis. The large size (30,000 nt) and high variability of CoV RNA genomes present a challenge for sequencing. We describe a strategy for rapidly designing the primers necessary for reverse transcription and cDNA amplification of such diverse RNA viruses and report the full-genome determination of the novel CoV directly from patient sputum using next-generation short-read sequencing. Full genomes from 2 epidemiologically unlinked novel CoV infections separated in time by >2 months were analyzed to gain clues to 2 major questions: what are the precursors of the virus, and how long has the virus been circulating in its current form? Materials and Methods Fifteen betaCoV full genomes with the closest homology to EMC/2012 (GenBank accession no. JX869059) were analyzed to identify all possible primer-like sequences (melting temperature 58°C-60°C, guanine plus cytosine content 35%-60%) yielding 357,198 potential primers. The 30-kb JX869059 CoV genome was divided into fifteen 2.5-kb overlapping amplicons, and the 2 highest frequency sequences mapping in the 5′ and 3′ 250 bp of each amplicon were selected. Reverse complements of the 3′ mapping sequences were prepared, resulting in a set of 60 primers for the 15 amplicons (4 primers/amplicon). Three additional primers were added for the extreme termini of the genome. The algorithm also prepared a virtual PCR map of the predicted binding and amplicon size for the primer set on CoV genomes. A map of the primer mapping positions

Output: Full-Genome Deep Sequencing and Phylogenetic Analysis of Novel Human Betacoronavirus


Input: Consider Input: Background: ISG15 is an Ubiquitin-like protein, highly induced by Type I Interferons. Upon the cooperative activity of specific Ubiquitinating enzymes, ISG15 can be conjugated to its substrates. Increasing evidence points to a role for protein ISGylation in anti-viral and anti-tumoral defense. Principal Findings: We identified ISG15 from Old World Monkeys (OWm) as a hyper-efficient protein modifier. Western blot analysis visualized more efficient conjugation of OWmISG15 relative to HuISG15 in human (Hu), monkey and mouse (Mo) cell-lines. Moreover, the substrates of OWmISG15 identified upon Tandem Affinity Purification followed by LC-MS/MS identification largely outnumbered these of HuISG15 itself. Several Ubiquitin-Conjugating enzymes were identified as novel ISGylated substrates. Introduction of a N89D mutation in HuISG15 improved its ISGylation capacity, and additional Q31K/ T33A/D133N mutations yielded a HuISG15 variant with an ISGylation efficiency comparable to OWmISG15. Homology modeling and structural superposition situate N89 in the interaction interface with the Activating enzyme. Analysis of the UbE1L residues in this interface revealed a striking homology between OWmUbE1L and HuUbE1, the Activating enzyme of Ubiquitin. In line with this observation, we found efficient activation of AgmISG15, but not HuISG15 or MoISG15, by HuUbE1, thus providing a likely explanation for OWm hyperISGylation. Conclusions: This study discloses the poor conjugation competence of HuISG15 compared to OWmISG15 and maps the critical determinants for efficient conjugation. HyperISGylation may greatly assist ISGylation studies and may enhance its function as positive regulator of Interferon-related immune responses or as anti-tumoral modulator.

Output: HyperISGylation of Old World Monkey ISG15 in Human Cells


Input: Consider Input: Synthetic biology is an emerging field, which, since its birth, has shown great value and potential in many fields including medicine, energy, environment and agriculture. It is also important for the study of the origin and evolution of life. Since the publication of the first synthetic cell in May, 2010, synthetic biology again attracts high attention and leads to extensive discussions all over the world. There have been a number of researches and achievements on synthetic biology in the United States and European countries. While in China, so far there is no systematic research on synthetic biology. In order to promote the development of this new discipline in China, we organized this review to systematically introduce the concept and research content of synthetic biology, summarize the achievements, and investigate the current situation in both China and abroad. We also analyzed the opportunities and challenges in synthetic biology, and looked forward to the future development of synthetic biology, especially its future development in China. synthetic cell, synthetic biology, minimal genome Zhang L Y, Chang S H, Wang J. Synthetic biology: From the first synthetic cell to see its current situation and future development.


Output: Invited Review Synthetic biology: From the first synthetic cell to see its current situation and future development