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\"In 1967, an extraterrestrial microbe came crashing down to Earth and nearly ended the human race. Accidental exposure to the particle--designated The Andromeda Strain--killed every resident of the town of Piedmont, Arizona, save for an elderly man and an infant boy. Over the next five days, a team of top scientists assigned to Project Wildfire worked valiantly to save the world from an epidemic of unimaginable proportions. In the moments before a catastrophic nuclear detonation, they succeeded. In the ensuing decades, research on the microparticle continued. And the world thought it was safe ... Deep inside Fairchild Air Force Base, Project Eternal Vigilance has continued to watch and wait for the Andromeda Strain to reappear. On the verge of being shut down, the project has registered no activity--until now. A Brazilian terrain-mapping drone has detected a bizarre anomaly of otherworldly matter in the middle of the jungle, and, worse yet, the tell-tale chemical signature of the deadly microparticle. With this shocking discovery, the next-generation Project Wildfire is activated, and a diverse team of experts hailing from all over the world is dispatched to investigate the potentially apocalyptic threat. But the microbe is growing--evolving. And if the Wildfire team can't reach the quarantine zone, enter the anomaly, and figure out how to stop it, this new Andromeda Evolution will annihilate all life as we know it\"-- Provided by publisher.

We aimed to verify the “saddle-shaped” dose-survival effect of microbes in response to heavy ion beam irradiation (HI), and further determine the radiation parameter that affects saddle shape formation, and the relationship between the saddle region and the positive mutation rate. A bibliometric analysis was performed based on literature containing the dose-survival effect of microbes in response to HI, from which the data on the particle energies, ionic types, irradiated microbes, survival curves, and maximum positive mutation rates were assembled. Articles reporting a “saddle-shaped” survival curve accounted for 64% of the total relevant articles and possessed a high cited frequency. The predominant articles, authors, and institutions that reported the dose-survival effect of microbes in response to HI proposed the “saddle-shaped” survival curve. It was customarily low-energy (but not moderate- or high-energy) HI that induced the “saddle-shaped” dose-survival effect. In addition, the “saddle-shaped” dose-survival effect was general among ~ 30-genera microbes. More importantly, most of the saddle regions contained the survival fractions within 10–30%, which are customarily used to screen mutants due to a high positive mutation rate. Further, 87% of the maximum positive mutation rates were associated with the saddle region, and 58% were located in the peak of the saddle region. “Saddle-shaped” dose-survival effect is a reliable and general phenomenon among varieties of microbes customarily in response to low-energy HI. Meanwhile, saddle region is always accompanied with high positive mutation rates. Thus, this study will aid in microbial mutation breeding practices.

The SARS-CoV-2 virus rapidly spread worldwide, threatening public health. Since it emerged, the scientific community has been engaged in the development of effective therapeutics and vaccines. The subunit S1 in the spike protein of SARS-CoV-2 mediates the viral entry into the host and is therefore one of the major research targets. The S1 protein is extensively glycosylated, and there is compelling evidence that glycans protect the virus’ active site from the human defense system. Therefore, investigation of the S1 protein glycome alterations in the different virus variants will provide a view of the glycan evolution and its relationship with the virus pathogenesis. In this study, we explored the N-glycosylation expression of the S1 protein for eleven SARS-CoV-2 variants: five variants of concern (VOC), including alpha, beta, gamma, delta, and omicron, and six variants of interest (VOI), including epsilon, eta, iota, lambda, kappa, and mu. The results showed significant differences in the N-glycome abundance of all variants. The N-glycome of the VOC showed a large increase in the abundance of sialofucosylated glycans, with the greatest abundance in the omicron variant. In contrast, the results showed a large abundance of fucosylated glycans for most of the VOI. Two glycan compositions, GlcNAc[sub.4] ,Hex[sub.5] ,Fuc,NeuAc (4-5-1-1) and GlcNAc[sub.6] ,Hex[sub.8] ,Fuc,NeuAc (6-8-1-1), were the most abundant structures across all variants. We believe that our data will contribute to understanding the S1 protein’s structural differences between SARS-CoV-2 mutations.

Uncertainty remains about how long the protective immune responses against severe acute respiratory syndrome coronavirus 2 persists, and suspected reinfection in recovered patients has been reported. We describe a case of reinfection from distinct virus lineages in Brazil harboring the E484K mutation, a variant associated with escape from neutralizing antibodies.

SARS-CoV-2 continues to acquire mutations in the spike receptor-binding domain (RBD) that impact ACE2 receptor binding, folding stability, and antibody recognition. Deep mutational scanning prospectively characterizes the impacts of mutations on these biochemical properties, enabling rapid assessment of new mutations seen during viral surveillance. However, the effects of mutations can change as the virus evolves, requiring updated deep mutational scans. We determined the impacts of all single amino acid mutations in the Omicron BA.1 and BA.2 RBDs on ACE2-binding affinity, RBD folding, and escape from binding by the LY-CoV1404 (bebtelovimab) monoclonal antibody. The effects of some mutations in Omicron RBDs differ from those measured in the ancestral Wuhan-Hu-1 background. These epistatic shifts largely resemble those previously seen in the Alpha variant due to the convergent epistatically modifying N501Y substitution. However, Omicron variants show additional lineage-specific shifts, including examples of the epistatic phenomenon of entrenchment that causes the Q498R and N501Y substitutions present in Omicron to be more favorable in that background than in earlier viral strains. In contrast, the Omicron substitution Q493R exhibits no sign of entrenchment, with the derived state, R493, being as unfavorable for ACE2 binding in Omicron RBDs as in Wuhan-Hu-1. Likely for this reason, the R493Q reversion has occurred in Omicron sub-variants including BA.4/BA.5 and BA.2.75, where the affinity buffer from R493Q reversion may potentiate concurrent antigenic change. Consistent with prior studies, we find that Omicron RBDs have reduced expression, and identify candidate stabilizing mutations that ameliorate this deficit. Last, our maps highlight a broadening of the sites of escape from LY-CoV1404 antibody binding in BA.1 and BA.2 compared to the ancestral Wuhan-Hu-1 background. These BA.1 and BA.2 deep mutational scanning datasets identify shifts in the RBD mutational landscape and inform ongoing efforts in viral surveillance.

Initial optimism regarding the development of COVID-19 vaccines has been tempered by the emergence of new variants of SARS-CoV-2. Will vaccination be able to contain the pandemic? How can we best optimize the limited supplies of vaccines available and what should future COVID-19 vaccines look like?This Comment discusses how the emerging SARS-CoV-2 variants of concern could impact on the hopes of long-term pandemic control through vaccination and the mutations that might be relevant to the design of modified vaccines.

Severe cases of COVID-19 are characterized by development of acute respiratory distress syndrome (ARDS). Water accumulation in the lungs is thought to occur as consequence of an exaggerated inflammatory response. A possible mechanism could involve decreased activity of the epithelial Na.sup.+ channel, ENaC, expressed in type II pneumocytes. Reduced transepithelial Na.sup.+ reabsorption could contribute to lung edema due to reduced alveolar fluid clearance. This hypothesis is based on the observation of the presence of a novel furin cleavage site in the S protein of SARS-CoV-2 that is identical to the furin cleavage site present in the alpha subunit of ENaC. Proteolytic processing of [alpha]ENaC by furin-like proteases is essential for channel activity. Thus, competition between S protein and [alpha]ENaC for furin-mediated cleavage in SARS-CoV-2-infected cells may negatively affect channel activity. Here we present experimental evidence showing that coexpression of the S protein with ENaC in a cellular model reduces channel activity. In addition, we show that bidirectional competition for cleavage by furin-like proteases occurs between (ENaC and S protein. In transgenic mice sensitive to lethal SARS-CoV-2, however, a significant decrease in gamma ENaC expression was not observed by immunostaining of lungs infected as shown by SARS-CoV2 nucleoprotein staining.

Marine microbial communities are engines of globally important processes, such as the marine carbon, nitrogen and sulphur cycles. Recent data on the structures of these communities show that they adhere to universal biological rules. Co-occurrence patterns can help define species identities, and systems-biology tools are revealing networks of interacting microorganisms. Some microbial systems are found to change predictably, helping us to anticipate how microbial communities and their activities will shift in a changing world.

Maximum-depth sequencing (MDS), a new method of detecting extremely rare variants within a bacterial population, is used to show that mutation rates in Escherichia coli vary across the genome by at least an order of magnitude, and also to uncover mechanisms of antibiotic-induced mutagenesis. Direct measurement of low-level bacterial mutation rates Knowledge of the spontaneous mutation rate of bacteria is important for the study of basic evolutionary processes and of potential value in various clinical settings. De novo mutations in bacteria are a difficult target for high-throughput sequencing, but now Justin Jee et al . describe a new method of detecting extremely rare variants within a bacterial population, termed maximum-depth sequencing (MDS), which can detect extremely rare variants within a bacterial population through error-corrected, high-throughput sequencing. The authors use this method to measure locus-specific mutation rates in Escherichia coli and show that they vary across the genome by at least an order of magnitude. MDS shows that certain types of nucleotide misincorporation occur 10 4 -fold more frequently than the basal mutation rate, but are repaired in vivo and are thus undetectable by conventional methods. Using MDS, the authors also uncover mechanisms of antibiotic-induced mutagenesis. In 1943, Luria and Delbrück used a phage-resistance assay to establish spontaneous mutation as a driving force of microbial diversity 1 . Mutation rates are still studied using such assays, but these can only be used to examine the small minority of mutations conferring survival in a particular condition. Newer approaches, such as long-term evolution followed by whole-genome sequencing 2 , 3 , may be skewed by mutational ‘hot’ or ‘cold’ spots 3 , 4 . Both approaches are affected by numerous caveats 5 , 6 , 7 . Here we devise a method, maximum-depth sequencing (MDS), to detect extremely rare variants in a population of cells through error-corrected, high-throughput sequencing. We directly measure locus-specific mutation rates in Escherichia coli and show that they vary across the genome by at least an order of magnitude. Our data suggest that certain types of nucleotide misincorporation occur 10 4 -fold more frequently than the basal rate of mutations, but are repaired in vivo . Our data also suggest specific mechanisms of antibiotic-induced mutagenesis, including downregulation of mismatch repair via oxidative stress, transcription–replication conflicts, and, in the case of fluoroquinolones, direct damage to DNA.

Since the end of 2019, a highly contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has deprived numerous lives worldwide, called COVID-19. Up to date, omicron is the latest variant of concern, and BA.5 is replacing the BA.2 variant to become the main subtype rampaging worldwide. These subtypes harbor an L452R mutation, which increases their transmissibility among vaccinated people. Current methods for identifying SARS-CoV-2 variants are mainly based on polymerase chain reaction (PCR) followed by gene sequencing, making time-consuming processes and expensive instrumentation indispensable. In this study, we developed a rapid and ultrasensitive electrochemical biosensor to achieve the goals of high sensitivity, the ability of distinguishing the variants, and the direct detection of RNAs from viruses simultaneously. We used electrodes made of MXene-AuNP (gold nanoparticle) composites for improved sensitivity and the CRISPR/Cas13a system for high specificity in detecting the single-base L452R mutation in RNAs and clinical samples. Our biosensor will be an excellent supplement to the RT-qPCR method enabling the early diagnosis and quick distinguishment of SARS-CoV-2 Omicron BA.5 and BA.2 variants and more potential variants that might arise in the future.