Global S&T Development Trend Analysis Platform of Resources and Environment
Activation of RIPK1 controls TNF-mediated apoptosis, necroptosis and inflammatory pathways(1). Cleavage of human and mouse RIPK1 after residues D324 and D325, respectively, by caspase-8 separates the RIPK1 kinase domain from the intermediate and death domains. The D325A mutation in mouse RIPK1 leads to embryonic lethality during mouse development(2,3). However, the functional importance of blocking caspase-8-mediated cleavage of RIPK1 on RIPK1 activation in humans is unknown. Here we identify two families with variants in RIPK1 (D324V and D324H) that lead to distinct symptoms of recurrent fevers and lymphadenopathy in an autosomaldominant manner. Impaired cleavage of RIPK1 D324 variants by caspase-8 sensitized patients'
Reverse genetics has been an indispensable tool to gain insights into viral pathogenesis and vaccine development. The genomes of large RNA viruses, such as those from coronaviruses, are cumbersome to clone and manipulate inEscherichia coliowing to the size and occasional instability of the genome(1-3). Therefore, an alternative rapid and robust reverse-genetics platform for RNA viruses would benefit the research community. Here we show the full functionality of a yeast-based synthetic genomics platform to genetically reconstruct diverse RNA viruses, including members of theCoronaviridae,FlaviviridaeandPneumoviridaefamilies. Viral subgenomic fragments were generated using viral isolates, cloned viral DNA, clinical samples or synthetic DNA, and these fragments were then reassembled in one step inSaccharomyces cerevisiaeusing transformation-associated recombination cloning to maintain the genome as a yeast artificial chromosome. T7 RNA polymerase was then used to generate infectious RNA to rescue viable virus. Using this platform, we were able to engineer and generate chemically synthesized clones of the virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)(4), which has caused the recent pandemic of coronavirus disease (COVID-19), in only a week after receipt of the synthetic DNA fragments. The technical advance that we describe here facilitates rapid responses to emerging viruses as it enables the real-time generation and functional characterization of evolving RNA virus variants during an outbreak.
A yeast-based synthetic genomics platform is used to reconstruct and characterize large RNA viruses from synthetic DNA fragments
Our understanding of the earliest stages of crown bird evolution is hindered by an exceedingly sparse avian fossil record from the Mesozoic era. The most ancient phylogenetic divergences among crown birds are known to have occurred in the Cretaceous period(1-3), but stem-lineage representatives of the deepest subclades of crown birds-Palaeognathae (ostriches and kin), Galloanserae (landfowl and waterfowl) and Neoaves (all other extant birds)-are unknown from the Mesozoic era. As a result, key questions related to the ecology(4,5), biogeography(3,6,7) and divergence times(1,8-10) of ancestral crown birds remain unanswered. Here we report a new Mesozoic fossil that occupies a position close to the last common ancestor of Galloanserae and fills a key phylogenetic gap in the early evolutionary history of crown birds(10,11). Asteriornis maastrichtensis, gen. et sp. nov., from the Maastrichtian age of Belgium (66.8-66.7 million years ago), is represented by a nearly complete, three-dimensionally preserved skull and associated postcranial elements. The fossil represents one of the only well-supported crown birds from the Mesozoic era(12), and is the first Mesozoic crown bird with well-represented cranial remains. Asteriornis maastrichtensis exhibits a previously undocumented combination of galliform (landfowl)-like and anseriform (waterfowl)-like features, and its presence alongside a previously reported Ichthyornis-like taxon from the same locality(13) provides direct evidence of the co-occurrence of crown birds and avialan stem birds. Its occurrence in the Northern Hemisphere challenges biogeographical hypotheses of a Gondwanan origin of crown birds(3), and its relatively small size and possible littoral ecology may corroborate proposed ecological filters(4,5,9) that influenced the persistence of crown birds through the end-Cretaceous mass extinction.
A newly discovered fossil from the Cretaceous of Belgium is the oldest modern bird ever found, showing a unique combination of features and suggesting attributes shared by avian survivors of the end-Cretaceous extinction.
Structurally intact tropical forests sequestered about half of the global terrestrial carbon uptake over the 1990s and early 2000s, removing about 15 per cent of anthropogenic carbon dioxide emissions(1-3). Climate-driven vegetation models typically predict that this tropical forest '