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Antonio Muruato Michelle N. Vu Bryan A. Johnson Meredith E. Davis-Gardner Abigail Vanderheiden Kumari Lokugamage Craig Schindewolf Patricia A. Crocquet-Valdes Rose M. Langsjoen Jessica A. Plante Kenneth S. Plante Scott C. Weaver Kari Debbink Andrew L. Routh David Walker Mehul S. Suthar Pei-Yong Shi Xuping Xie Vineet D. Menachery 《PLoS biology》2021,19(11)
The emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has resulted in a pandemic causing significant damage to public health and the economy. Efforts to understand the mechanisms of Coronavirus Disease 2019 (COVID-19) have been hampered by the lack of robust mouse models. To overcome this barrier, we used a reverse genetic system to generate a mouse-adapted strain of SARS-CoV-2. Incorporating key mutations found in SARS-CoV-2 variants, this model recapitulates critical elements of human infection including viral replication in the lung, immune cell infiltration, and significant in vivo disease. Importantly, mouse adaptation of SARS-CoV-2 does not impair replication in human airway cells and maintains antigenicity similar to human SARS-CoV-2 strains. Coupled with the incorporation of mutations found in variants of concern, CMA3p20 offers several advantages over other mouse-adapted SARS-CoV-2 strains. Using this model, we demonstrate that SARS-CoV-2–infected mice are protected from lethal challenge with the original Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), suggesting immunity from heterologous Coronavirus (CoV) strains. Together, the results highlight the use of this mouse model for further study of SARS-CoV-2 infection and disease.Studying cross-protection from different coronaviruses is important to inform the research for a universal vaccine. This study uses a mouse-adapted SARS-CoV-2 strain to show that it confers protection from SARS-CoV challenge, suggesting possible immunity from heterologous challenge following natural infection. 相似文献
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Bitinaite J Rubino M Varma KH Schildkraut I Vaisvila R Vaiskunaite R 《Nucleic acids research》2007,35(6):1992-2002
Here we report a PCR-based DNA engineering technique for seamless assembly of recombinant molecules from multiple components. We create cloning vector and target molecules flanked with compatible single-stranded (ss) extensions. The vector contains a cassette with two inversely oriented nicking endonuclease sites separated by restriction endonuclease site(s). The spacer sequences between the nicking and restriction sites are tailored to create ss extensions of custom sequence. The vector is then linearized by digestion with nicking and restriction endonucleases. To generate target molecules, a single deoxyuridine (dU) residue is placed 6–10nt away from the 5′-end of each PCR primer. 5′ of dU the primer sequence is compatible either with an ss extension on the vector or with the ss extension of the next-in-line PCR product. After amplification, the dU is excised from the PCR products with the USER enzyme leaving PCR products flanked by 3′ ss extensions. When mixed together, the linearized vector and PCR products directionally assemble into a recombinant molecule through complementary ss extensions. By varying the design of the PCR primers, the protocol is easily adapted to perform one or more simultaneous DNA manipulations such as directional cloning, site-specific mutagenesis, sequence insertion or deletion and sequence assembly. 相似文献
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Intrasexual competition is an important selective force that can favor the evolution of honest signals of fighting ability. Research has focused predominantly on male birds, but many female birds also possess plumage ornaments that could mediate the outcome of competitive interactions. We examined the relationship between blue and white structural coloration and aggression in female tree swallows Tachycineta bicolor. Tree swallows are secondary cavity nesters and females show delayed plumage maturation which may be related to intense competition for nest sites. We compared plumage reflectance of second‐year (SY) and after‐second year (ASY) females, and within‐individual changes in plumage reflectance of ASY females in two successive years. We assessed aggression by placing a caged SY female 2 m from the nest box of an ASY female and quantified the ASY female's response in relation to her own plumage coloration. We found substantial differences in plumage reflectance of SY and ASY females, but found that ASY females became greener with duller white coloration in the second year. This may be due to poor weather that made reproduction particularly costly in the first year of the study and suggests coloration is influenced by condition. We found no relationship between dorsal coloration and aggressiveness. Rather, brighter white females spent more time on their nest box and within 2 m of the intruder than females with dull breasts. Our findings suggest that brighter white ASY females may perceive a SY female as less of a threat or that there may be a trade‐off associated with aggression and parental care that is related to white brightness. 相似文献
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Summary
Sedum wrightii is one of only a few species in the Crassulaceae for which there is evidence for a high degree of variability in the ratio of daytime to nighttime CO2 assimilation. There are both environmental and genetic components to this variability. S. wrightii grows over a wide altitudinal gradient. The purpose of this study was to compare low, intermediate, and high altitude populations with respect to the degree of CAM expression and the capability to tolerate limited water availability. We utilized clonallyreplicated genotypes of plants from each population in common environment greenhouse experiments. Genetic differences among the populations were found in long-term water use efficiency, in 24 hour CO2 exchange patterns, in biomass 13C values, in carbon allocation, and in water status and ultimately survival during prolonged drought. The differences among the populations appear to be closely related to differences in the native habitats. The low altitude, desert plants had the greatest ability to grow and survive under conditions of limited water availability and appear to have the greatest shift to nighttime CO2 uptake during periods without water, while the high altitude plants had the poorest performance under these conditions and appear to shut down net carbon uptake when severely water limited. 相似文献
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Albert L. Harting Michelle M. Barbieri Jason D. Baker Tracy A. Mercer Thea C. Johanos Stacie J. Robinson Charles L. Littnan Katie M. Colegrove Dave S. Rotstein 《Marine Mammal Science》2021,37(1):235-250
Identifying, assessing, and ranking the impact of individual threats is fundamental to the conservation and recovery of rare and endangered species. In this analysis, we quantify not only the frequency of specific causes-of-death (CODs) among Main Hawaiian Island (MHI) monk seals, but also assess the impact of individual CODs on the intrinsic growth rate, λ, of the MHI population. We used gross necropsy results, histopathology, and other evidence to assign probabilities of 11 COD types to each mortality and then used Monte Carlo sampling to evaluate the influence of each COD on λ. By right censoring realizations involving specific CODs, we were able to estimate λ (and its associated uncertainty) when CODs were selectively removed from influencing survival. Applying the analysis to all known and inferred deaths believed to have occurred 2004–2019, the CODs with the largest influence on λ were anthropogenic trauma, anthropogenic drowning, and protozoal disease. In aggregate, anthropogenic CODs had a larger effect on the growth rate than either natural or disease CODs. Possible bias associated with differential carcass detection, recovery, and COD classification are discussed. 相似文献