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BackgroundBiofuel production from plant cell walls offers the potential for sustainable and economically attractive alternatives to petroleum-based products. Fuels from cellulosic biomass are particularly promising, but would benefit from lower processing costs. Clostridium thermocellum can rapidly solubilize and ferment cellulosic biomass, making it a promising candidate microorganism for consolidated bioprocessing for biofuel production, but increases in product yield and titer are still needed.ResultsHere, we started with an engineered C. thermocellum strain where the central metabolic pathways to products other than ethanol had been deleted. After two stages of adaptive evolution, an evolved strain was selected with improved yield and titer. On chemically defined medium with crystalline cellulose as substrate, the evolved strain produced 22.4 ± 1.4 g/L ethanol from 60 g/L cellulose. The resulting yield was about 0.39 gETOH/gGluc eq, which is 75 % of the maximum theoretical yield. Genome resequencing, proteomics, and biochemical analysis were used to examine differences between the original and evolved strains.ConclusionsA two step selection method successfully improved the ethanol yield and the titer. This evolved strain has the highest ethanol yield and titer reported to date for C. thermocellum, and is an important step in the development of this microbe for industrial applications.Electronic supplementary materialThe online version of this article (doi:10.1186/s13068-016-0528-8) contains supplementary material, which is available to authorized users.
During the evolution of SARS-CoV-2 in humans a D614G substitution in the spike (S) protein emerged and became the predominant circulating variant (S-614G) of the COVID-19 pandemic. However, whether the increasing prevalence of the S-614G variant represents a fitness advantage that improves replication and/or transmission in humans or is merely due to founder effects remains elusive. Here, we generated isogenic SARS-CoV-2 variants and demonstrate that the S-614G variant has (i) enhanced binding to human ACE2, (ii) increased replication in primary human bronchial and nasal airway epithelial cultures as well as in a novel human ACE2 knock-in mouse model, and (iii) markedly increased replication and transmissibility in hamster and ferret models of SARS-CoV-2 infection. Collectively, our data show that while the S-614G substitution results in subtle increases in binding and replication in vitro, it provides a real competitive advantage in vivo, particularly during the transmission bottle neck, providing an explanation for the global predominance of S-614G variant among the SARS-CoV-2 viruses currently circulating.
PurposeComprehensive evaluation of anaphylaxis in China is currently lacking. In this study, we characterized the clinical profiles, anaphylactic triggers, and emergency treatment in pediatric and adult patients.MethodsOutpatients diagnosed with "anaphylaxis" or "severe allergic reactions" in the Department of Allergy, Peking Union Medical College Hospital from January 1, 2000 to June 30, 2014 were analyzed retrospectively.ResultsA total of 1,952 episodes of anaphylaxis in 907 patients were analyzed (78% were adults and 22% were children). Foods are the most common cause (77%), followed by idiopathic etiologies (15%), medications (7%) and insects (0.6%). In food-induced anaphylaxis, 62% (13/21) of anaphylaxis in infants and young children (0-3 years of age) were triggered by milk, 59% (36/61) of anaphylaxis in children (4-9 years of age) were triggered by fruits/vegetables, while wheat was the cause of anaphylaxis in 20% (56/282) of teenagers (10-17 years of age) and 42% (429/1,016) in adults (18-50 years of age). Mugwort pollen sensitization was common in patients with anaphylaxis induced by spices, fruits/vegetables, legume/peanuts, and tree nuts/seeds, with the prevalence rates of 75%, 67%, 61%, and 51%, respectively. Thirty-six percent of drug-induced anaphylaxis was attributed to traditional Chinese Medicine. For patients receiving emergency care, only 25% of patients received epinephrine.ConclusionsThe present study showed that anaphylaxis appeared to occur more often in adults than in infants and children, which were in contrast to those found in other countries. In particular, wheat allergens played a prominent role in triggering food-induced anaphylaxis, followed by fruits/vegetables. Traditional Chinese medicine was a cause of drug-induced anaphylaxis. Furthermore, exercise was the most common factor aggravating anaphylaxis. Education regarding the more aggressive use of epinephrine in the emergency setting is clearly needed.
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