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Sökning: WFRF:(Liu Geoffrey) > Stockholms universitet

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1.
  • Elliott, Mark, et al. (författare)
  • Engineered botulinum neurotoxin B with improved binding to human receptors has enhanced efficacy in preclinical models
  • 2019
  • Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 5:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Although botulinum neurotoxin serotype A (BoNT/A) products are common treatments for various disorders, there is only one commercial BoNT/B product, whose low potency, likely stemming from low affinity toward its human receptor synaptotagmin 2 (hSyt2), has limited its therapeutic usefulness. We express and characterize two full-length recombinant BoNT/B1 proteins containing designed mutations E1191M/S1199Y (rBoNT/B1(MY)) and E1191Q/S1199W (rBoNT/B1(QW)) that enhance binding to hSyt2. In preclinical models including human-induced pluripotent stem cell neurons and a humanized transgenic mouse, this increased hSyt2 affinity results in high potency, comparable to that of BoNT/A. Last, we solve the cocrystal structure of rBoNT/B1(MY) in complex with peptides of hSyt2 and its homolog hSyt1. We demonstrate that neuronal surface receptor binding limits the clinical efficacy of unmodified BoNT/B and that modified BoNT/B proteins have promising clinical potential.
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2.
  • Rocchetti, Giulia Albani, et al. (författare)
  • Selecting the best candidates for resurrecting extinct-in-the-wild plants from herbaria
  • 2022
  • Ingår i: Nature Plants. - : Springer Science and Business Media LLC. - 2055-0278. ; 8:12, s. 1385-1393
  • Tidskriftsartikel (refereegranskat)abstract
    • Resurrecting extinct species is a fascinating and challenging idea for scientists and the general public. Whereas some theoretical progress has been made for animals, the resurrection of extinct plants (de-extinction sensu lato) is a relatively recently discussed topic. In this context, the term ‘de-extinction’ is used sensu lato to refer to the resurrection of ‘extinct in the wild’ species from seeds or tissues preserved in herbaria, as we acknowledge the current impossibility of knowing a priori whether a herbarium seed is alive and can germinate. In plants, this could be achieved by germinating or in vitro tissue-culturing old diaspores such as seeds or spores available in herbarium specimens. This paper reports the first list of plant de-extinction candidates based on the actual availability of seeds in herbarium specimens of globally extinct plants. We reviewed globally extinct seed plants using online resources and additional literature on national red lists, resulting in a list of 361 extinct taxa. We then proposed a method of prioritizing candidates for seed-plant de-extinction from diaspores found in herbarium specimens and complemented this with a phylogenetic approach to identify species that may maximize evolutionarily distinct features. Finally, combining data on seed storage behaviour and longevity, as well as specimen age in the novel ‘best de-extinction candidate’ score (DEXSCO), we identified 556 herbarium specimens belonging to 161 extinct species with available seeds. We expect that this list of de-extinction candidates and the novel approach to rank them will boost research efforts towards the first-ever plant de-extinction. 
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