scholarly journals A Protein-Engineered, Enhanced Yeast Display Platform for Rapid Evolution of Challenging Targets

Author(s):  
Jiří Zahradník ◽  
Debabrata Dey ◽  
Shir Marciano ◽  
Lucie Kolářová ◽  
Chloé I. Charendoff ◽  
...  
Author(s):  
Allison J. Greaney ◽  
Tyler N. Starr ◽  
Christopher O. Barnes ◽  
Yiska Weisblum ◽  
Fabian Schmidt ◽  
...  

AbstractMonoclonal antibodies targeting a variety of epitopes have been isolated from individuals previously infected with SARS-CoV-2, but the relative contributions of these different antibody classes to the polyclonal response remains unclear. Here we use a yeast-display system to map all mutations to the viral spike receptor-binding domain (RBD) that escape binding by representatives of three potently neutralizing classes of anti-RBD antibodies with high-resolution structures. We compare the antibody-escape maps to similar maps for convalescent polyclonal plasma, including plasma from individuals from whom some of the antibodies were isolated. The plasma-escape maps most closely resemble those of a single class of antibodies that target an epitope on the RBD that includes site E484. Therefore, although the human immune system can produce antibodies that target diverse RBD epitopes, in practice the polyclonal response to infection is dominated by a single class of antibodies targeting an epitope that is already undergoing rapid evolution.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Allison J. Greaney ◽  
Tyler N. Starr ◽  
Christopher O. Barnes ◽  
Yiska Weisblum ◽  
Fabian Schmidt ◽  
...  

AbstractMonoclonal antibodies targeting a variety of epitopes have been isolated from individuals previously infected with SARS-CoV-2, but the relative contributions of these different antibody classes to the polyclonal response remains unclear. Here we use a yeast-display system to map all mutations to the viral spike receptor-binding domain (RBD) that escape binding by representatives of three potently neutralizing classes of anti-RBD antibodies with high-resolution structures. We compare the antibody-escape maps to similar maps for convalescent polyclonal plasmas, including plasmas from individuals from whom some of the antibodies were isolated. While the binding of polyclonal plasma antibodies are affected by mutations across multiple RBD epitopes, the plasma-escape maps most resemble those of a single class of antibodies that target an epitope on the RBD that includes site E484. Therefore, although the human immune system can produce antibodies that target diverse RBD epitopes, in practice the polyclonal response to infection is skewed towards a single class of antibodies targeting an epitope that is already undergoing rapid evolution.


Swiss Surgery ◽  
1999 ◽  
Vol 5 (3) ◽  
pp. 143-146 ◽  
Author(s):  
Launois ◽  
Maddern ◽  
Tay

The detailed knowledge of the segmental anatomy of the liver has led to a rapid evolution in resectional surgery based on the intrahepatic distribution of the portal trinity (the hepatic artery, hepatic duct and portal vein). The classical intrafascial or extrahepatic approach is to isolate the appropriate branch of the portal vein, hepatic artery and the hepatic duct, outside the liver substance. Another method, the extrafascial approach, is to dissect the whole sheath of the pedicle directly after division of a substantial amount of the hepatic tissue to reach the pedicle, which is surrounded by a sheath, derived from Glisson's capsule. This Glissonian sheath encloses the portal trinity. In the transfissural or intrahepatic approach, these sheaths can be approached either anteriorly (after division of the main, right or umbilical fissure) or posteriorly from behind the porta hepatis. We describe the technique for approaching the Glissonian sheath and hence the hepatic pedicle structures and their branches by the intrahepatic posterior approach that allows early delineation of the liver segment without the need for ancillary techniques. In addition, the indications for the use of this technique in the technical and oncologic settings are also discussed.


Psihiatru ro ◽  
2019 ◽  
Vol 58 (3) (1) ◽  
pp. 18-20
Author(s):  
Cătălina Crişan ◽  
Laura Grosu ◽  
Oana Vanţa

Gayet-Wernicke encephalopathy is an acute neuropsychiatric condition caused by thiamine deficiency. Only a small percentage of patients experience all three symptoms, with ophtalmoplegia, ataxia and confusion, and the full triad occurs more frequently among those who have overused alcohol. The evolution is toward full recovery, Korsakoff syndrome, dementia or death. We present the case of a 56-year-old patient, known with a diagnostic of alcoholism, who was admitted for a complicated withdrawal syndrome with delirium and who developed encephalopathy and dementia syndrome.


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