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Monoclonal anti‐SARS‐CoV‐2 immunoglobulins represent a treatment option for COVID‐19. However, their production in mammalian cells is not scalable to meet the global demand. Single‐domain (VHH) antibodies (also called nanobodies) provide an alternative suitable for microbial production. Using alpaca immune libraries against the receptor‐binding domain (RBD) of the SARS‐CoV‐2 Spike protein, we isolated 45 infection‐blocking VHH antibodies. These include nanobodies that can withstand 95°C. The most effective VHH antibody neutralizes SARS‐CoV‐2 at 17–50 pM concentration (0.2–0.7 µg per liter), binds the open and closed states of the Spike, and shows a tight RBD interaction in the X‐ray and cryo‐EM structures. The best VHH trimers neutralize even at 40 ng per liter. We constructed nanobody tandems and identified nanobody monomers that tolerate the K417N/T, E484K, N501Y, and L452R immune‐escape mutations found in the Alpha, Beta, Gamma, Epsilon, Iota, and Delta/Kappa lineages. We also demonstrate neutralization of the Beta strain at low‐picomolar VHH concentrations. We further discovered VHH antibodies that enforce native folding of the RBD in the E. coli cytosol, where its folding normally fails. Such “fold‐promoting” nanobodies may allow for simplified production of vaccines and their adaptation to viral escape‐mutations.  相似文献   

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In this study we investigated the phylogenetic relationships within the ‘higher land birds’ by parsimony analysis of nucleotide DNA sequences obtained from the two nuclear, protein-coding genes, c- myc and RAG-1. Nuclear genes have not previously been used to address this phylogenetic question. The results include high jackknife support for a monophyletic Apodiformes (including the Trochilidae). This arrangement was further supported by the observation of an insertion of four amino acids in the c- myc gene in all apodiform taxa. Monophyly was also inferred for each of the two piciform groups Galbulae and Pici. Within Pici, the Capitonidae was found to be paraphyletic, with the New World barbets more closely related to the Ramphastidae than to the Old World barbets. Another clade with high jackknife support consists of the Upupidae, Phoeniculidae and Bucerotidae. The families Momotidae and Todidae, and Coraciidae and Brachypteraciidae, respectively, also form well supported monophyletic clades. The results are inconclusive regarding the monophyly of the orders Coraciiformes and Piciformes, respectively.  相似文献   

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Host‐race formation is promoted by genetic trade‐offs in the ability of herbivores to use alternate hosts, including trade‐offs due to differential timing of host‐plant availability. We examined the role of phenology in limiting host‐plant use in the goldenrod gall fly (Eurosta solidaginis) by determining: (1) whether phenology limits alternate host use, leading to a trade‐off that could cause divergent selection on Eurosta emergence time and (2) whether Eurosta has the genetic capacity to respond to such selection in the face of existing environmental variation. Experiments demonstrated that oviposition and gall induction on the alternate host, Solidago canadensis, were the highest on young plants, whereas the highest levels of gall induction on the normal host, Solidago gigantea, occurred on intermediate‐age plants. These findings indicate a phenological trade‐off for host‐plant use that sets up the possibility of divergent selection on emergence time. Heritability, estimated by parent–offspring regression, indicated that host‐race formation is impeded by the amount of genetic variation, relative to environmental, for emergence time.  相似文献   

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Genetic variation in anti-predator traits has been shown for a variety of species. Aphid alarm pheromone, ( E )-β-farnesene, is released by attacked aphids and causes a variety of behavioral defense reactions in the signal receivers. In pea aphids, Acyrthosiphon pisum Harris (Homoptera: Aphididae), ( E )-β-farnesene mediates the production of winged offspring in the presence of natural enemies. While variation in the propensity for pea aphids to produce winged offspring is well-documented, little quantitative information is available about clonal differences in ( E )-β-farnesene emission or the amount of alarm pheromone released in aphid colonies. We tested the wing induction response of four clones when attacked by a predatory lacewing larva, Chrysoperla carnea (Stephens) (Neuroptera: Chrysopidae), and found that three of the four clones increased the proportion of winged offspring under predator attack. We then investigated the emission of aphid alarm pheromone of these clones of pea aphid under attack. Alarm pheromone emission in aphid colonies of initially 25 adults varied from 81.2 to 10 851.0 ng per aphid colony over 24 h. There were no differences between clones in total emission or in emission per consumption event. These results show that there is substantial variability in alarm pheromone emission within clones and that the propensity to produce winged offspring in some clones is not a simple function of the propensity of alarm pheromone production in these clones.  相似文献   

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In 1947–1949, studies of water chemistry, aquatic macrophytes, bryophytes and algae were performed in a small lake, L. Rudträsket, near Stockholm, but only a few results concerning water chemistry and macrophytes have so far been published. Heinrichs Skuja (1892–1972) left 62 hand-written pages with the results of his analyses from the lake: a list of taxa, some measurements and several algal sketches. The main part of this material is presented here. Skuja identified about 640 taxa with a majority for desmids, ca. 290, followed by ca. 100 chlorophyceans, 65 euglenophytes and 60 cyanophytes. The species composition gives a fairly reflection of the character of the lake: small, shallow, rich in humus, acid and surrounded by swampy areas with Sphagnum. Dimensions of algae as well as drawings from L. Rudträsket have partly been published in publications by Skuja. In this paper seven plates with about 115 figures have been drawn in Indian ink and printed. Today, the lake has a lower pH value, pH 4.6, than in 1947–1949, pH 5.3–6.1, and would be a stimulating object for comparative studies.  相似文献   

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